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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Standard exercise testing remains a clinical tool with many applications in clinical practice&#44; providing important information for patients with a wide spectrum of conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> Combining this test with ventilatory gas exchange measurements provides incremental information&#44; leading to more accurate quantification of cardiorespiratory fitness &#40;CRF&#41; and to the identification of exercise-limiting pathophysiological mechanisms&#44; both of which are highly useful in clinical practice for cardiology&#44; as well as several other areas&#44; including pneumology&#44; internal medicine&#44; oncology&#44; surgery&#44; neurology&#44; sports medicine&#44; and physical medicine and rehabilitation&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; provides a noninvasive and dynamic integrative assessment of the exercise responses involving the respiratory&#44; cardiovascular &#40;CV&#41;&#44; and musculoskeletal systems&#46; It is considered the gold standard in the assessment of cardiorespiratory function and is extremely useful in the diagnostic investigation of unexplained exercise intolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> However&#44; its utility goes beyond diagnosis as it also helps with prognostic stratification and therapeutic evaluation in different clinical contexts&#44; and in guiding exercise prescription&#44; not only in patients undergoing cardiac or pulmonary rehabilitation&#44; but also in healthy athletes who aim to enhance their performance&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite being recommended by several scientific societies across a wide range of settings&#44; CPET is still underused for multiple reasons such as its complexity and the lack of trained personnel to interpret it&#44; lack of awareness of practicing clinicians of its utility&#44; its availability&#44; and costs&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This article aims to address some of those barriers by reviewing the main indications&#44; applications&#44; and basic interpretation skills concerning CPET in contemporary clinical practice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">How to perform cardiopulmonary exercise testing</span><p id="par0025" class="elsevierStylePara elsevierViewall">Given the wide range of physiological data and differential diagnosis&#44; knowing the clinical context of the individual and the question of the referring physician is a critical step when performing a CPET&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#8211;7</span></a> CPET should be performed by healthcare professionals qualified and trained in emergency situations&#46; A physician must be present during the test and an emergency cart with a defibrillator must be quickly available&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;8</span></a> The laboratory where a CPET is carried out must have a controlled environment with a temperature between 16 and 24<span class="elsevierStyleHsp" style=""></span>&#176;C and humidity between 30 and 60&#37;&#44; while the equipment must be correctly calibrated&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The test should be clearly explained&#44; potential doubts clarified&#44; and informed consent obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> It is also important to agree on the type of gestural communication to adopt during the test and to emphasize the relevance of performing maximum effort&#46; Before a CPET session or test&#44; the gas analyzer must be calibrated&#58; gas volume at the beginning of each session of tests and gas concentration before each test&#46; Also&#44; immediately before&#44; a spirometry and&#47;or a maximal voluntary ventilation &#40;MVV&#41; test should be performed&#44; which are essential to determine the breathing reserve &#40;BR&#41; and identify possible ventilatory limitations at rest and during exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> In addition to continuous gas exchange assessment&#44; during CPET&#44; the electrocardiogram &#40;ECG&#41;&#44; blood pressure &#40;BP&#41; and peripheral oxygen saturation &#40;SpO<span class="elsevierStyleInf">2</span>&#41; are also monitored&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Ergometers and protocols</span><p id="par0035" class="elsevierStylePara elsevierViewall">Ergometers are mechanical or electrical types of equipment that allow the definition of the work &#40;intensity of effort&#41; that the user will perform during the test&#46; The most used are the cycle and treadmill ergometers&#44; but there are others available&#44; such as arm and ergometers for athletes&#8217; evaluation in specific sports such as swimming&#44; rowing&#44; cross-country skiing&#44; or kayaking&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">6&#44;8&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In a hospital environment the treadmill and cycle ergometers are preferred as they can replicate the most common physical activity types&#46; The treadmill&#44; which also involves upper limb muscles&#44; enables users to attain 5&#8211;10&#37; higher oxygen consumption &#40;VO<span class="elsevierStyleInf">2</span>&#41; and represents an activity that most people do in their daily lives &#40;walking or running&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> A comparison of the main advantages of these two types of ergometers is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Exercise protocols need to be individualized considering the characteristics of the person who performs it and the indication for the exam&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a> According to the load application&#44; protocols can be classified as constant or progressive &#40;incremental&#41;&#46; Progressive or incremental load protocols can be intermittent &#40;with pauses&#41; or continuous&#44; while the latter can be performed on a ramp or by stages &#40;levels&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Most laboratories perform incremental ramp or stagged tests&#46; Ramp tests have the advantage of increasing the speed or resistance in a gradual and linear way&#44; without jumps between stages&#44; which allows a greater individualization of the protocol&#46; With this methodology it is possible to obtain a linear increase in VO<span class="elsevierStyleInf">2</span>&#44; improving the precision to determine maximal VO<span class="elsevierStyleInf">2</span> &#40;VO<span class="elsevierStyleInf">2</span>max&#41; and submaximal parameters&#44; namely the ventilatory thresholds &#40;VTs&#41;&#44; which increases the reproducibility of the test&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Constant load protocols can be used in specific situations&#44; such as for the diagnosis of exercise-induced bronchospasm&#44; evaluation of the contribution of carotid bodies in exercise hyperpnea&#44; assessment of the lactate threshold &#40;constant low-intensity work lasting 10 minutes&#41;&#44; and determination of the VO<span class="elsevierStyleInf">2</span>max&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a></p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Key cardiopulmonary exercise testing variables to analyze</span><p id="par0060" class="elsevierStylePara elsevierViewall">Modern day gas analyzers perform breath-by-breath measurements of respiratory gases&#44; which provide data with large variability and justifies performing data averaging&#58; 20- or 30-second averaging are the most recommended modalities since they are a good balance between data variability and accuracy&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing can generate a large number of variables&#44; but there is a group of those that are more pertinent in current clinical practice&#46; A general overview of normalized values&#44; based on the most recent recommendations&#44; is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; but the values described may vary&#44; depending on the literature and the population under study&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">8&#44;11&#8211;14</span></a> Some of these parameters are already evaluated in conventional exercise testing &#40;i&#46;e&#46; without respiratory gas assessment&#44; such as BP&#44; heart rate &#40;HR&#41; and rhythm&#44; and the ST-segment of the ECG&#41;&#44; but others are associated with gas exchange and only available with a CPET&#46; The most important parameters in clinical practice will be discussed later in this document&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Oxygen consumption is a key parameter providing a refined measure of CRF which is of major value in different settings&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> Optimal oxygen &#40;O<span class="elsevierStyleInf">2</span>&#41; delivery is central to exercise performance&#44; being influenced by several factors ranging from CV and respiratory function to hemoglobin plasma concentration&#44; autonomic inputs&#44; mitochondrial efficiency&#44; and thermoregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> Furthermore&#44; age&#44; gender&#44; genetic background&#44; and training can also affect peak VO<span class="elsevierStyleInf">2</span> &#40;pVO<span class="elsevierStyleInf">2</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Oxygen consumption can be expressed as an absolute value or adjusted to body weight and should also be reported in relation to age&#44; gender&#44; weight&#44; height&#44; and ergometer predicted values&#44; through specific formulas&#46; Many of these equations provided by the gas analyzer software are inaccurate and outdated&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;5</span></a> Today&#44; the FRIEND trial equation is accepted as the best one to calculate the predicted value of VO<span class="elsevierStyleInf">2</span>max&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Importantly&#44; pVO<span class="elsevierStyleInf">2</span> is the highest VO<span class="elsevierStyleInf">2</span> obtained during exercise&#44; while VO<span class="elsevierStyleInf">2</span>max corresponds to a state of a VO<span class="elsevierStyleInf">2</span> plateau&#44; despite increases in workload&#46; Notably&#44; while pVO<span class="elsevierStyleInf">2</span> provides a comprehensive overview of CRF&#44; it should be acknowledged that exercise economy&#44; encompassing cardiorespiratory efficiency&#44; but also factors such as biomechanics&#44; neuromuscular efficiency&#44; and training&#44; should be considered&#44; as two subjects with a similar pVO<span class="elsevierStyleInf">2</span> may have different performances&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a> Likewise&#44; individuals with better exercise economy could require a different VO<span class="elsevierStyleInf">2</span> for the same workloads&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O<span class="elsevierStyleInf">2</span> pulse reflects the amount of O<span class="elsevierStyleInf">2</span> extracted at each heartbeat&#44; providing information on both stroke volume &#40;SV&#41; and the arteriovenous oxygen difference&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">19</span></a> In the absence of factors such as anemia&#44; hypoxia&#44; and mitochondrial disorders&#44; the O<span class="elsevierStyleInf">2</span> pulse trajectory parallels the one of SV&#46; During exercise&#44; the curve is expected to increase linearly almost till the end of the exercise period where a plateau is normally expected&#46; An early flattening or decrease of its trajectory are abnormal responses&#46; Indeed&#44; a plateau or decrease in the O<span class="elsevierStyleInf">2</span> pulse trajectory during incremental exercise may reflect a reduction in SV in the setting of myocardial ischemia or left ventricle outflow obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">20</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Respiratory exchange ratio &#40;RER&#41; is the ratio between carbon dioxide production &#40;VCO<span class="elsevierStyleInf">2</span>&#41; and VO<span class="elsevierStyleInf">2</span>&#44; providing information on the type of energy substrate being metabolized&#46; When calculated at peak effort it offers an objective insight on whether effort was maximal&#46; Though different cut-offs may be considered&#44; a value &#8805;1&#46;10 has been considered a criterion for maximal effort attainment&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;21</span></a> A low peak RER suggests submaximal CV effort&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The ratio of minute ventilation &#40;VE&#41; to VO<span class="elsevierStyleInf">2</span> is called the ventilatory equivalent for O<span class="elsevierStyleInf">2</span> &#40;EqO<span class="elsevierStyleInf">2</span>&#41;&#44; and the ratio of VE to VCO<span class="elsevierStyleInf">2</span> is called the ventilatory equivalent for CO<span class="elsevierStyleInf">2</span> &#40;EqCO<span class="elsevierStyleInf">2</span>&#41;&#44; providing information about ventilatory efficiency&#46; During CPET&#44; the normal pattern of change in ventilatory equivalent for oxygen &#40;VE&#47;VO<span class="elsevierStyleInf">2</span>&#41; is a drop early in exercise to its nadir at the first VT &#40;VT1&#41;&#44; followed by an increase as the maximal exercise capacity approaches&#46; This behavior is due to a steeper rise in ventilation in response to increased CO<span class="elsevierStyleInf">2</span> production in proportion to VO<span class="elsevierStyleInf">2</span> increase&#46; Ventilatory equivalent for carbon dioxide &#40;VE&#47;VCO<span class="elsevierStyleInf">2</span>&#41; correspondingly decreases hyperbolically as the work rate increases&#46; This balance may be disturbed in several clinical conditions&#44; including chronic obstructive pulmonary disease &#40;COPD&#41;&#44; pulmonary hypertension &#40;PH&#41; and heart failure &#40;HF&#41;&#46; In these conditions&#44; VE&#47;VO<span class="elsevierStyleInf">2</span> and VE&#47;VCO<span class="elsevierStyleInf">2</span> are increased due to an augmented dead space and&#47;or alveolar hyperventilation&#46; A steep VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;a high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; is associated with several cardiorespiratory diseases and is an independent marker of poor prognosis&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Ventilatory thresholds &#40;VT&#41; provide pivotal data on the metabolic response to exercise&#44; and are paramount in exercise prescription&#46; The first VT &#40;VT1&#41; represents a transition to a mixed aerobic and anaerobic metabolism&#44; being characterized by increases in lactate and decreases in pH&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> This is accompanied by lactate buffering&#44; with ensuing increases in VCO<span class="elsevierStyleInf">2</span> and ventilation&#44; to maintain acid&#8211;base homeostasis&#46; The second VT &#40;VT2&#41; represents a point where lactate increases rapidly and more substantially &#40;as buffering becomes insufficient&#41;&#44; with ensuing hyperventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">22</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">While different terms are sometimes used&#44; such as anaerobic threshold &#40;for VT1&#41; and respiratory compensation point &#40;for VT2&#41;&#44; respectively&#44; the terminology &#8220;VT&#8221; was adopted in the current literature&#46; These metabolic transition points can be determined invasively &#40;by blood analysis&#41; or non-invasively&#46; VT1 is commonly determined by the ventilatory equivalent method as the lowest point before an ensuing increase in the curve&#44; or by the V-slope method &#40;by an increase in the slope between VCO<span class="elsevierStyleInf">2</span> and VO<span class="elsevierStyleInf">2</span>&#44; which previously had a linear relationship&#44; representing the increase in VCO<span class="elsevierStyleInf">2</span> due to lactate buffering&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">23&#44;24</span></a> VT2 can be assessed by the ventilatory equivalent method&#44; as the lowest point before a continuous increase&#44; by a marked increase in ventilation &#40;in relation to VCO<span class="elsevierStyleInf">2</span>&#41; and by the end-tidal carbon dioxide pressure &#40;P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41;&#44; where a deflection occurs reflecting the marked ventilation increase&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> illustrates the methods recommended for determining VTs&#46; Importantly&#44; an integrative approach employing different methods should be considered&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Partial pressure of end-tidal oxygen &#40;P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; reflects the gas exhaled precisely at the end of expiration&#44; originating from the deep lung&#46; The reported concentrations of end-tidal gas represent a mixture of gases from all alveoli&#44; with some being well-perfused and others under-perfused&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a> During the initial stages of moderate exercise&#44; levels of end-tidal O<span class="elsevierStyleInf">2</span> &#40;P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#41; typically decrease and start to rise during later stages due to increased CO<span class="elsevierStyleInf">2</span> production&#44; resulting in acidemia and subsequently increased ventilation&#46; P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> levels increase initially&#44; reflecting the rising CO<span class="elsevierStyleInf">2</span> production at the beginning of exercise&#44; followed by a drop when acidemia stimulates ventilation beyond what is necessary to eliminate CO<span class="elsevierStyleInf">2</span>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Minute ventilation is a measure of the total volume of air breathed in one minute&#46; During exercise&#44; VE increases initially due to an increase in tidal volume&#44; which can increase three to fivefold&#44; reaching approximately 60&#37; of the vital capacity&#46; In later stages of exercise&#44; breathing frequency will at least double&#44; while tidal volume remains relatively unchanged&#46; Younger and fitter individuals may experience a considerably higher increase in respiratory rate&#44; reaching around 30&#8211;40 breaths per minute&#46; A frequency higher than 55 breaths per minute is generally considered abnormal&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">25</span></a> If the tidal volume does not increase significantly during a CPET&#44; it suggests the presence of lung disease&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Breathing reserve &#40;BR&#41; can be defined as the difference between the MVV at rest and the maximum ventilation achieved during exercise&#46; MVV&#44; measured in liters per minute&#44; can be obtained through direct measurement &#40;by instructing the individual to breathe as deeply and quickly as possible for 12 or 15 seconds and then multiplying the value by five or by four&#44; respectively&#41; or by estimation &#40;MVV&#61;forced expiratory volume in the first second &#40;FEV1&#41;&#215;35 or 40&#41;&#46; During a CPET&#44; maximal VE should not exceed 80&#8211;85&#37; of the predicted value in a healthy individual&#46; If maximal VE exceeds 80&#37; of the predicted value&#44; it indicates a low BR&#44; meaning there is little capacity for further increase in ventilation&#46; A reduced &#40;&#60;15&#8211;20&#37;&#41; or absent BR suggests that the limitation to exercise is likely due to respiratory disease&#46; However&#44; it is important to note that BR tends to decrease with age and lower fitness levels&#46; In cases of CV disease or other factors limiting exercise performance&#44; BR is typically higher&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Interpretation of cardiopulmonary exercise testing results</span><p id="par0125" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing has a large array of measured and calculated parameters that can be interpreted&#46; To provide a simple yet comprehensive and visual information&#44; Wasserman et al&#46; arranged the CPET values into nine graphs&#44; hence the name &#8220;9-panel plot&#8221; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">11&#44;25</span></a><a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a> presents the classic and most used sequence&#44; but other alignments may also be applied&#46; Following a plot order and understanding the normal response and the most frequent abnormal patterns is essential for proper CPET interpretation&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 3</span>&#58; The first question to be asked in a CPET is whether the test was maximal&#46; The gold standard definition of a maximal CPET is a plateau or a VO<span class="elsevierStyleInf">2</span> curve drop&#44; despite load increase&#46; However&#44; this finding may be difficult to attain in patients&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 8</span>&#58; When a VO<span class="elsevierStyleInf">2</span> plateau is not identifiable&#44; we look at this plot to check whether a RER &#40;black dots&#41; over 1&#46;10 was attained at peak effort &#40;the vertical red line&#41;&#46; A RER of 1&#46;10 may not be reached in cases of insufficient effort or causes of limitation other than circulatory limitation &#40;e&#46;g&#46;&#44; respiratory&#44; vascular PH&#44; or musculoskeletal limitation&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 3</span>&#58; We then inspect VO<span class="elsevierStyleInf">2</span> &#40;blue dots&#41; at peak exercise&#46; While cut-off values differ&#44; a value under 85&#37; in the setting of a maximal CPET &#40;RER &#62;1&#46;10&#41; suggests a clear exercise limitation&#46; In cycle-ergometer testing&#44; it is possible to evaluate the VO<span class="elsevierStyleInf">2</span>&#47;work &#40;W&#41; ratio&#46; Normal value is typically around 10 mL&#47;W&#46; However&#44; in cases of heart disease&#44; this relationship may decrease&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plots 8 and 7</span>&#58; In the setting of dyspnea or the presence of exercise limitation&#44; we then proceed to ascertain its etiology&#46; A BR &#40;panel 8&#44; brown dots&#41; &#60;15&#8211;20&#37; at peak exercise&#44; defined after a good quality spirometry or MVV determination&#44; suggests ventilatory limitation&#46; It should be noted that in highly conditioned individuals with substantial tolerance to discomfort &#40;e&#46;g&#46;&#44; athletes&#41;&#44; a BR &#60;20&#37; can be reached without having true ventilatory limitation &#40;usually in these cases a significant exercise time is attained&#44; with a RER above 1&#46;10&#41;&#46; The pattern of the tidal volume &#40;panel 7&#44; brown dots&#41; may inform whether the pattern of respiratory limitation is restrictive or obstructive&#46; SpO<span class="elsevierStyleInf">2</span> is not always depicted in the 9-panel plot&#44; but a decrease greater than 5&#37; is abnormal and suggestive of limitations in gas exchange&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plots 4&#44; 6&#44; and 9</span>&#58; Ventilation-perfusion &#40;V&#47;Q&#41; mismatch due to low cardiac output &#40;CO&#41; or PH can also be a cause of exercise limitation&#46; Ventilatory efficiency can be measured using two methods&#58; &#40;1&#41; VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;plot 4&#41; between VT1 and VT2&#59; &#40;2&#41; nadir &#40;VT2&#41; of the ventilatory equivalents of CO<span class="elsevierStyleInf">2</span> &#40;plot 6&#44; red line&#41;&#46; The results are usually similar&#46; P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span> and P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#40;plot 9&#41; are also useful for assessing V&#47;Q matching and detecting gas exchange abnormalities in the lungs&#46; The more pronounced the ventilation&#44; the lower the P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> and the higher the P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 1</span>&#58; VE increases proportionally with the load and CO<span class="elsevierStyleInf">2</span> concentration&#46; In the case of a ramp protocol&#44; it is expected to increase steadily from rest to VT1&#44; have a steep increase from VT1 to VT2&#44; and an even steeper increase after VT2&#46; This pattern is difficult to observe when a staged protocol &#40;e&#46;g&#46;&#44; Bruce&#41; rather than a ramp protocol is used&#46; If the patient has cyclic fluctuations with an oscillatory pattern in VE and expired gases&#44; that persist &#8805;60&#37; of the test with an amplitude &#8805;15&#37; of the average resting value&#44; exercise oscillatory ventilation &#40;EOV&#41; is noted&#46; This is an important prognostic marker&#44; especially in HF patients&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 2</span>&#58; Peak HR &#40;pink dots&#41; can inform on the presence or absence of chronotropic incompetence&#46; However&#44; this information is difficult to interpret in the setting of beta-blocker therapy and may have little therapeutic impact&#46; It can be useful in patients with pacemakers or cardiac resynchronization therapy &#40;CRT&#41;&#44; to identify insufficient rate response to exercise&#44; which requires optimization in programming&#46; More than the absolute and predicted value of peak O<span class="elsevierStyleInf">2</span> pulse &#40;blue dots&#41;&#44; the pattern of O<span class="elsevierStyleInf">2</span> pulse progression may be informative&#46; It should increase and may have a plateau at maximal exercise&#46; A marked and consistent decrease in O<span class="elsevierStyleInf">2</span> pulse during exercise&#44; in non-athlete subjects&#44; suggests a decrease in SV that may be caused by different phenomena such as myocardial ischemia&#44; left ventricular outflow obstruction&#44; or exercise-induced mitral regurgitation&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 5</span>&#58; Like the VE curve in plot 1&#44; the VO<span class="elsevierStyleInf">2</span>&#47;VCO<span class="elsevierStyleInf">2</span> relationship can be useful to identify VT1&#44; and VT2&#44; using the V-slope method&#46; A low VT1 usually suggests circulatory limitation or severe muscular deconditioning&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Maximal versus submaximal test</span><p id="par0170" class="elsevierStylePara elsevierViewall">The usual target of a CPET is to perform a maximal test&#46; Submaximal tests should only be considered as an alternative for specific cases since their value for risk stratification is much less studied and reduced regarding a maximal test&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">8&#44;26</span></a> It is widely accepted that a CPET may be considered maximal if a VO<span class="elsevierStyleInf">2</span> plateau or drop can be found at peak exercise despite by increasing workload&#46; If a VO<span class="elsevierStyleInf">2</span> plateau or drop is not seen&#44; but a RER &#62;1&#46;10&#44; a BR &#60;15&#37;&#44; a peak exercise HR over 90&#37; of the predicted&#44; or peak exercise lactate concentration &#8805;8 mmol&#47;L &#40;if measured&#41; are reached&#44; one may consider that an intense effort was achieved&#44; and a near-maximal test was performed&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;10</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Indications for cardiopulmonary exercise testing</span><p id="par0175" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing has multiple clinical indications&#44; covering a broad spectrum of specialties and diseases&#46; It is an important tool for diagnosis&#44; risk stratification&#44; exercise prescription&#44; evaluation of the effect of several therapeutic interventions &#40;pharmacological&#44; percutaneous&#44; and surgical&#41; and prognosis assessment&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a> shows some of the main indications for CPET&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Athlete evaluation</span><p id="par0180" class="elsevierStylePara elsevierViewall">In asymptomatic athletes&#44; CPET is important to detect subclinical cardiac disease&#44; particularly in master athletes&#44; in the assessment of baseline functional capacity&#44; in revealing the sporting ability of young athletes&#44; or when evaluating performance in different modalities&#44; and training monitoring&#46; CPET can assist in the diagnostic process and evaluation of non-specific symptoms such as exertional dyspnea&#44; chest discomfort&#44; or tiredness&#46; Indeed&#44; during their sporting careers&#44; many athletes may experience these symptoms and the etiology may be cardiac&#44; respiratory&#44; muscular&#44; or even psychological&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">In the context of sports performance&#44; CPET allows the prescription of exercise through the documentation of VTs and the corresponding HR&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">27&#44;28</span></a> In this way&#44; this methodology helps to individualize the intensity of training&#44; through the determination of different training zones&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 1</span>&#58; below the VT1 &#40;light exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 2</span>&#58; between VT1 and VT2 &#40;moderate to high-intensity exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 3</span>&#58; above the VT2 &#40;very high-intensity exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 4</span>&#58; corresponds to sprints and efforts above those previously mentioned&#46;</p></li></ul></p><p id="par0210" class="elsevierStylePara elsevierViewall">Additionally&#44; it plays an important role in diagnosing training overload and thus preventing overtraining syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cardiac rehabilitation</span><p id="par0215" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing should be performed whenever available to stratify the risk for exercise&#44; to prescribe exercise and to quantify the training benefits of cardiac rehabilitation&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">28&#44;30</span></a> CPET is the gold standard to prescribe aerobic exercise&#44; whether moderate continuous training &#40;corresponding to the training zone between the two VTs&#41;&#44; or interval training with low-intensity &#40;below VT1&#41; and high-intensity &#40;above VT2&#41; training intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> Higher duration of the test and values of VO<span class="elsevierStyleInf">2</span> and HR at VTs and peak exercise&#44; together with lower values of VE&#47;VCO<span class="elsevierStyleInf">2</span> slope are some of the expected gains for a cardiac rehabilitation program&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ischemic heart disease</span><p id="par0220" class="elsevierStylePara elsevierViewall">The role of classical exercise testing in the diagnosis of coronary artery disease &#40;CAD&#41; has been progressively superseded by imaging modalities across several scenarios&#46; CPET may add useful ancillary data&#44; such as the O<span class="elsevierStyleInf">2</span> pulse trajectory&#44; that can provide information concurring with possible ischemic contributions to exercise intolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">32</span></a> Moreover&#44; an abnormal relationship between pVO<span class="elsevierStyleInf">2</span> and work rate can also be of value in this setting&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Data derived from CPET can also provide prognostic information in CAD patients&#44; namely with parameters such as pVO<span class="elsevierStyleInf">2</span> and the VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#44; giving inputs on the risk of further events and reinforcing its value in their comprehensive assessment&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Cardiomyopathies</span><p id="par0230" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is a safe and useful tool in patients with suspected&#47;confirmed hypertrophic cardiomyopathy &#40;HCM&#41; to provide information on symptoms&#44; severity&#44; and prognosis&#44; to aid planning management&#44; and to monitor therapeutic efficacy&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">3&#44;33&#44;34</span></a> pVO<span class="elsevierStyleInf">2</span> can also help to distinguish left ventricular hypertrophy &#40;LVH&#41; associated with HCM from other forms of secondary LVH&#44; such as hypertensive cardiomyopathy&#44; &#8220;athlete&#39;s heart&#8221;&#44; and athletes with HCM&#46; It is suggested that in these cases&#44; a pVO<span class="elsevierStyleInf">2</span> &#60;84&#37; of the age-gender predicted &#40;AGP&#41; is indicative of pathological LVH&#46; A pVO<span class="elsevierStyleInf">2</span> &#62;50 mL&#47;kg&#47;min or 120&#37; of the AGP is proposed as a standard for differentiating an &#8220;athlete&#39;s heart&#8221; from HCM&#46; Only a small percentage of athletes with HCM achieve &#62;100&#37; of the AGP pVO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">33</span></a> The functional information provided by the CPET should be integrated with data derived from other investigations for the appropriate differential diagnosis between &#8220;athlete&#39;s heart&#8221; and cardiomyopathies&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Although the application of CPET in arrhythmogenic cardiomyopathy is scarce&#44; it has proven to be safe and potentially useful for risk stratification when considering advanced therapies &#40;such as heart transplantation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Heart failure</span><p id="par0240" class="elsevierStylePara elsevierViewall">In patients with HF with reduced ejection fraction &#40;HFrEF&#41;&#44; pVO<span class="elsevierStyleInf">2</span> has a prominent role in the prognostic stratification&#46; However&#44; submaximal exercise gas exchange variables have emerged that rival the prognostic utility of pVO<span class="elsevierStyleInf">2</span>&#46; Some of these encompass the VO<span class="elsevierStyleInf">2</span>&#47;W ratio &#40;aerobic efficiency&#41;&#44; VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;ventilatory efficiency&#41;&#44; VO<span class="elsevierStyleInf">2</span> at VT1&#44; oxygen uptake efficiency slope &#40;OUES&#41;&#44; and EOV&#46; EOV represents a strong negative prognostic parameter in HF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">The 2012 EACPR&#47;AHA Scientific Statement<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> proposed a multiparametric CPET data table developed by Arena et al&#46;&#44; with an iteration of the figures by proposing color-coded interpretive tables applied to different diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> A CPET score utilizing VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#8805;34 &#40;7 points&#41;&#44; HR decay in the first minute of recovery &#8804;6 bpm &#40;5 points&#41;&#44; OUES &#8804;1&#46;4 &#40;3 points&#41;&#44; resting P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#60;33 mmHg &#40;3 points&#41;&#44; and a pVO<span class="elsevierStyleInf">2</span> &#8804;14 mL&#47;kg&#47;min &#40;2 points&#41; has been validated to predict transplant&#47;mechanical circulatory support-free survival in HF patients better than pVO<span class="elsevierStyleInf">2</span> alone&#44; with a summed score &#62;15 indicating the poorest prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">39&#44;40</span></a> The use of this CPET score is helpful in risk stratifying HF patients in Weber class B &#40;with pVO<span class="elsevierStyleInf">2</span> 16&#8211;20 mL&#47;kg&#47;min&#41; into low-risk and higher-risk subgroups&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">41</span></a> The latest criteria proposed two different pVO<span class="elsevierStyleInf">2</span> cut-offs for heart transplantation depending on whether the patient is &#40;pVO<span class="elsevierStyleInf">2</span> &#8804;14 mL&#47;kg&#47;min&#41; or not &#40;pVO<span class="elsevierStyleInf">2</span> &#8804;12 mL&#47;kg&#47;min&#41; on &#946;-blocker treatment &#40;Cl I&#44; LOE B&#41;&#59; in outpatients aged &#60;50 years&#44; a pVO<span class="elsevierStyleInf">2</span> &#60;50&#37; of the expected value &#40;Cl IIa&#44; LOE B&#41;&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The International Society for Heart and Lung Transplantation &#40;ISHLT&#41; guidelines indicate the use of a VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#62;35 as a determinant in listing for heart transplantation in the presence of a submaximal CPET &#40;Cl IIb&#44; LOE&#58; C&#41;&#46; The presence of a CRT does not alter the current pVO<span class="elsevierStyleInf">2</span> cut-off recommendations &#40;Cl I&#44; LOE&#58; B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">42&#44;43</span></a> HF with preserved ejection fraction &#40;HFpEF&#41; represents worldwide most patients with HF&#46; These patients may be functionally very limited&#44; a limitation that can be objectively quantified by CPET&#46; However&#44; because CPET findings in HFpEF are nonspecific regarding HFrEF patients&#44; the clinical utility of CPET in a patient with HFpEF suspicion is low&#46; CPET can help to understand the nature and magnitude of symptoms&#44; the pathophysiological mechanism&#44; and the impact of noncardiac comorbidities that frequently limit elderly HFpEF patients&#46; Lastly&#44; CPET is also mandatory to correctly prescribe exercise to HFpEF patients integrated in cardiac rehabilitation programs&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Valvular heart disease</span><p id="par0255" class="elsevierStylePara elsevierViewall">In valvular diseases&#44; CPET can help unveil unreported symptoms&#44; understand the mechanism&#39;s underlying symptoms&#44; and better outline prognosis that helps to define treatment timings more appropriately&#46; The ventilatory classification system may provide additional information in detecting elevated pulmonary pressures&#44; with higher values indicating greater severity of the valvular heart disease and poorer prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> Combined stress echocardiography and CPET can be helpful in determining the mechanisms of exercise intolerance in patients with mitral stenosis&#46; Those patients show the expected exercise-induced PH that may lead to hyperventilation and increased VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#46; Also&#44; O<span class="elsevierStyleInf">2</span> pulse stops increasing due to lack of increase of ventricular filling during exercise because the valvular stenosis&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Current guidelines support the use of stress testing in asymptomatic severe aortic stenosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">45</span></a> A pVO<span class="elsevierStyleInf">2</span> &#8804;19 mL&#47;kg&#47;min for men and &#8804;15 mL&#47;kg&#47;min for women&#59; O<span class="elsevierStyleInf">2</span> pulse &#8804;15 mL&#47;beat for men and &#8804;11 mL&#47;beat for women&#44; were strong predictors of mortality in patients with moderate to severe aortic stenosis&#44; irrespective of whether they undergo aortic valve replacement&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">46</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Pulmonary hypertension</span><p id="par0265" class="elsevierStylePara elsevierViewall">When evaluating a patient with an established or suspected PH diagnosis&#44; CPET can be useful to elucidate the underlying pathophysiologic mechanism of exercise intolerance&#44; to assess the severity of PH&#44; to quantify the response to treatment&#44; and to stratify mortality risk&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The pathophysiology of PH is characterized by reduced CO reserve due to increased right ventricle afterload and increased physiologic dead space due to marked inefficient ventilation&#46; Variables such as pVO<span class="elsevierStyleInf">2</span>&#44; O<span class="elsevierStyleInf">2</span> pulse&#44; and VO<span class="elsevierStyleInf">2</span>&#47;W ratio will be abnormally reduced due to the limited CO reserve&#46; Likewise&#44; the significant changes in VE&#44; VE&#47;VCO<span class="elsevierStyleInf">2</span> and P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> during exercise&#44; reflect the impaired ventilatory efficiency so distinctive of PAH&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Congenital heart diseases</span><p id="par0275" class="elsevierStylePara elsevierViewall">It is safe to perform a CPET in the spectrum of congenital heart disease &#40;CHD&#41;&#44; not only for risk stratification&#44; but also in assisting in the decision of timing of surgical or percutaneous interventions&#44; as well as exercise counseling and training&#46; The most reported CPET findings in CHD are reduced pVO<span class="elsevierStyleInf">2</span>&#44; early VT1&#44; blunt HR increase&#44; reduced tidal volume increase&#44; and increased VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">As a general guideline&#44; it is recommended to stop testing in the presence of severe desaturation &#40;SpO<span class="elsevierStyleInf">2</span> &#8804;80&#37;&#41; when accompanied by symptoms and signs of severe hypoxemia&#46; However&#44; data concerning specific recommendations regarding cyanotic CHD are limited&#46; A right-to-left shunt can manifest itself during the CPET by the onset or worsening of systemic arterial desaturation&#44; augmentation of VE&#44; usually associated with an abrupt decrease in P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> and simultaneous increases in P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#44; RER&#44; and ventilatory equivalents&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Dyspnea of unknown cause</span><p id="par0285" class="elsevierStylePara elsevierViewall">Dyspnea is a complex and multifactorial symptom characterized by the subjective feeling of breathing discomfort&#46; It is a commonly reported symptom&#44; and the underlying causes can be diverse and may include respiratory&#44; CV&#44; metabolic&#44; or psychological factors&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">50</span></a> In fact&#44; dyspnea experienced during exercise and daily activities may be an early symptom of various cardiopulmonary and neuromuscular diseases&#44; leading to progressively less intense activities&#44; resulting in muscle deconditioning and a decline in quality of life&#46; Dyspnea is a predictor of quality of life&#44; exercise tolerance&#44; and mortality in several pathologies&#44; being a better predictor than FEV1 in COPD or angina in ischemic heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">51</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">During CPET&#44; dyspnea can be assessed using scales which are helpful to monitor its intensity throughout the test and to compare the severity of breathing discomfort with the level of exercise&#46; The most used scale is the modified Borg scale&#44; which ranges from 0 to 10&#46; This scale has been widely validated and correlates well with aerobic stress and blood lactate levels during exercise&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Due to its subjective nature and multiple potential underlying causes&#44; dyspnea requires a comprehensive evaluation to identify the factors contributing to the symptom&#46; CPET plays a crucial role to clarify the underlying mechanisms of dyspnea during exertion&#46; Interpretative algorithms enable identifying patterns of findings that are typical for different clinical conditions and allow clinicians to differentiate patterns of various conditions&#44; such as COPD&#44; asthma&#44; HF&#44; obesity&#44; PH&#44; and interstitial lung diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">52</span></a> In some cases&#44; modified protocols can be employed during CPET to detect specific conditions&#44; which are suspected based on clinical data &#40;e&#46;g&#46;&#44; identification of exercise-induced bronchoconstriction&#44; and exercise-induced laryngeal obstruction&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Pulmonary disease</span><p id="par0300" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is extremely useful in the evaluation of patients with lung disease for quantifying exercise capacity and level of disability&#44; providing diagnostic information&#44; evaluating hypoxemia during exercise and underlying mechanisms&#44; defining therapeutic strategies &#40;such as pulmonary rehabilitation&#41;&#44; assessing the preoperative risk of complications in lung surgery&#44; and providing prognostic information&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">52&#44;53</span></a> If BR is significantly reduced&#44; it suggests that the respiratory system may be a limiting factor for exercise performance&#46; It is possible to measure the flow-volume curve during exercise to detect ventilatory constraints&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">In healthy individuals&#44; as exercise intensity increases&#44; the volume of air remaining in the lungs at the end of expiration declines while the inspiratory capacity increases&#44; leading to improved ventilatory efficiency&#46; However&#44; patients with obstructive lung disease may have difficulty in emptying their lungs during incremental exercise compared to rest due to expiratory flow limitation &#40;EFL&#41; and increased respiratory rate&#44; resulting in reduced expiratory time&#46; Consequently&#44; there is an increase in end-expiratory volume&#44; in contrast to the decrease observed in individuals without lung disease&#44; leading to a reduction in inspiratory capacity of at least 250 mL&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">54</span></a> Additionally&#44; other measurements&#44; including EFL &#62;25&#37; at peak effort&#44; a lung volume ratio at the end of inspiration greater &#62;90&#37; of total lung capacity&#44; and a tidal volume &#62;70&#37; of inspiratory capacity can be obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">53</span></a> Assessing these parameters during exercise helps to identify the presence of dynamic hyperinflation&#44; which can be responsible for dyspnea and a limiting factor for exercise&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The decision to perform arterial blood gas measurements during CPET depends on the specific goals of the test&#46; In general&#44; measuring partial pressure of O<span class="elsevierStyleInf">2</span> &#40;PaO<span class="elsevierStyleInf">2</span>&#41; allows the calculation of gas exchange indices&#44; such as the alveolar-arterial gradient&#46; Measuring the partial pressure of CO<span class="elsevierStyleInf">2</span> &#40;PaCO<span class="elsevierStyleInf">2</span>&#41; allows the calculation of the dead space over tidal volume &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; ratio&#44; which is a measure of the efficiency of carbon dioxide exchange&#46; Inefficient CO<span class="elsevierStyleInf">2</span> exchange is manifested by the high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> ratio&#44; often signaled by the high VE&#47;VCO<span class="elsevierStyleInf">2</span> ratio with exercise&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Contraindications for cardiopulmonary exercise testing</span><p id="par0315" class="elsevierStylePara elsevierViewall">Beyond knowing the potential indications for CPET&#44; it is also fundamental to know the main contraindications for this exam&#44; especially corresponding to severe or uncontrolled CV conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;13</span></a> In general&#44; absolute contraindications for CPET encompass&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0320" class="elsevierStylePara elsevierViewall">Acute myocardial infarction &#40;3&#8211;5 days&#41;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0325" class="elsevierStylePara elsevierViewall">Unstable angina</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall">Uncontrolled arrhythmia causing symptoms or hemodynamic instability</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0335" class="elsevierStylePara elsevierViewall">Active endocarditis</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0340" class="elsevierStylePara elsevierViewall">Acute myocarditis or pericarditis</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0345" class="elsevierStylePara elsevierViewall">Symptomatic severe aortic stenosis</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0350" class="elsevierStylePara elsevierViewall">Decompensated HF</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0355" class="elsevierStylePara elsevierViewall">Acute aortic dissection</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0360" class="elsevierStylePara elsevierViewall">Uncontrolled asthma</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0365" class="elsevierStylePara elsevierViewall">Acute pulmonary embolism</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0370" class="elsevierStylePara elsevierViewall">Arterial desaturation at rest on room air &#60;85&#37;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0375" class="elsevierStylePara elsevierViewall">Physical disability that precludes safe and adequate testing</p></li></ul></p><p id="par0380" class="elsevierStylePara elsevierViewall">Other conditions represent relative contraindications for CPET&#44; reinforcing the need of direct supervision by a physician&#46; Among the relative contraindications&#44; the following conditions are included&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0385" class="elsevierStylePara elsevierViewall">Untreated left main coronary stenosis or its equivalent</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0390" class="elsevierStylePara elsevierViewall">Asymptomatic severe aortic stenosis</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0395" class="elsevierStylePara elsevierViewall">Severe untreated arterial hypertension at rest &#40;SBP &#62;200 mmHg&#59; SBP &#62;110 mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0400" class="elsevierStylePara elsevierViewall">Significant tachyarrhythmias</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0405" class="elsevierStylePara elsevierViewall">High-degree atrioventricular block or other significant bradyarrhythmia</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0410" class="elsevierStylePara elsevierViewall">Thrombosis of the lower limb until treated</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0415" class="elsevierStylePara elsevierViewall">Severe abdominal aortic aneurysm</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0420" class="elsevierStylePara elsevierViewall">Recent stroke or transient ischemic attack</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Advanced or complicated pregnancy</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Psychiatric or mental impairment &#40;inability to cooperate&#41;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall">Uncorrected medical conditions&#44; such as significant anemia&#44; important electrolyte imbalance&#44; and hyperthyroidism&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0440" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is a comprehensive exam aimed at clarifying patient symptoms&#44; differentiating underlying pathophysiological mechanisms&#44; and estimating CRF&#44; disease severity and prognosis&#46; Standardization of CPET-derived data can optimize its accessibility and improve the individualized management of patients across a wide range of clinical contexts&#46; Knowledge of the main indications&#44; applications&#44; and basic interpretation of CPET results is essential to harness its remarkable potential and apply its principal advantages in clinical practice&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0445" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Indications for cardiopulmonary exercise testing"
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          "titulo" => "Contraindications for cardiopulmonary exercise testing"
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            0 => "Prova de esfor&#231;o cardiorrespirat&#243;ria"
            1 => "Indica&#231;&#245;es"
            2 => "Aplica&#231;&#245;es"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; provides a noninvasive and integrated assessment of the response of the respiratory&#44; cardiovascular&#44; and musculoskeletal systems to exercise&#46; This information improves the diagnosis&#44; risk stratification&#44; and therapeutic management of several clinical conditions&#46; Additionally&#44; CPET is the gold standard test for cardiorespiratory fitness quantification and exercise prescription&#44; both in patients with cardiopulmonary disease undergoing cardiac or pulmonary rehabilitation programs and in healthy individuals&#44; such as high-level athletes&#46; In this setting&#44; the relevance of practical knowledge about this exam is useful and of interest to several medical specialties other than cardiology&#46; However&#44; despite its multiple established advantages&#44; CPET remains underused&#46; This article aims to increase awareness of the value of CPET in clinical practice and to inform clinicians about its main indications&#44; applications&#44; and basic interpretation&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prova de esfor&#231;o cardiorrespirat&#243;ria &#40;PECR&#41; fornece uma avalia&#231;&#227;o n&#227;o invasiva e integrada das respostas ao exerc&#237;cio dos sistemas respirat&#243;rio&#44; cardiovascular e m&#250;sculo-esquel&#233;tico&#46; Essas informa&#231;&#245;es melhoram o diagn&#243;stico&#44; a estratifica&#231;&#227;o de risco e a abordagem terap&#234;utica de diversas condi&#231;&#245;es cl&#237;nicas&#46; Al&#233;m disso&#44; a PECR &#233; o teste <span class="elsevierStyleItalic">gold standard</span> para a quantifica&#231;&#227;o da aptid&#227;o cardiorrespirat&#243;ria e a prescri&#231;&#227;o de exerc&#237;cio&#44; tanto em doentes com doen&#231;a cardiopulmonar em programas de reabilita&#231;&#227;o card&#237;aca ou pulmonar&#44; como em indiv&#237;duos saud&#225;veis&#44; incluindo atletas de alto rendimento&#46; Neste contexto&#44; o conhecimento pr&#225;tico da relev&#226;ncia deste exame &#233; &#250;til e transversal a diversas especialidades m&#233;dicas para al&#233;m da cardiologia&#46; No entanto&#44; apesar das suas m&#250;ltiplas vantagens reconhecidas&#44; a PECR continua subutilizada&#46; Este artigo tem como objetivo aumentar a consciencializa&#231;&#227;o do valor da PECR para a pr&#225;tica cl&#237;nica e informar os m&#233;dicos sobre as suas principais indica&#231;&#245;es&#44; aplica&#231;&#245;es e interpreta&#231;&#227;o b&#225;sica&#46;</p></span>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">CRT&#58; cardiac resynchronization therapy&#59; ICD&#58; implanted cardioverter-defibrillator&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Feature&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cycle&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treadmill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Familiarity with exercise&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Predicted VO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quantification of external work&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With some algorithms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quality of ECG monitoring&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With artifacts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BP measurement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Harder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ease to take arterial blood gas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Harder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muscles in lower limbs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dependent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less dependent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with pacemakers&#44; ICDs&#44; or CRTs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less appropriate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">More appropriate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Safety&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower &#40;risk of falls&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Size of equipment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mobility of equipment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "etiqueta" => "Table 2"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal reference values&#47;risk stratification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pVO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; 85&#8211;115&#37; of the predicted valueMild impairment&#58; 75&#8211;84&#37; of the predicted valueModerate impairment&#58; 50&#8211;74&#37; of the predicted valueSevere impairment&#58; &#60;50&#37; of the predicted value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO<span class="elsevierStyleInf">2</span> at VT1&#47;predicted pVO<span class="elsevierStyleInf">2</span>&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; 40&#8211;80&#37;Impairment&#58; &#60;40&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">O<span class="elsevierStyleInf">2</span> pulse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; increase&#59; &#8805;80&#37; of the predicted valueImpairment&#58; early plateau or decrease&#59; &#60;80&#37; of the predicted value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VE&#47;VCO<span class="elsevierStyleInf">2</span> slope<span class="elsevierStyleItalic">for the assessment of V&#47;Q mismatch &#40;only between VT1 and VT2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; &#60;30Mild impairment&#58; 30&#8211;35&#46;9Moderate impairment&#58; 36&#8211;45Severe impairment&#58; &#8805;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VE&#47;VCO<span class="elsevierStyleInf">2</span> slope<span class="elsevierStyleItalic">for the assessment of prognosis in patients with HF &#40;the whole slope&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-significant risk&#58; &#60;30&#46;0Mild risk&#58; 30&#46;0&#8211;35&#46;9Moderate risk&#58; 36&#8211;44&#46;9High risk&#58; <span class="elsevierStyleUnderline">&#62;</span>45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EOV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal or mild impairment&#58; absentModerate or severe impairment&#58; present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BR at peak exercise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;30&#37; of the predicted valueRespiratory limitation if below 15&#8211;20&#37; BR &#40;estimated by MVV or FEV1&#215;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drop &#60;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MHR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bike</span>&#58;220-age&#177;10 beats&#47;min<span class="elsevierStyleItalic">Treadmill</span>&#58;General population &#40;MHR&#61;208&#8722;0&#46;7&#215;age&#41;Women &#40;MHR&#61;206&#8722;0&#46;88&#215;age&#41;Patients on beta-blockers or other bradycardic drugs&#58; &#40;164&#8722;0&#46;7&#215;age&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;85&#37; of the predicted MHR&#40;MHR&#8722;HR at rest&#41;&#47;&#40;predicted MHR&#8722;HR at rest&#41; &#62;80&#37;MHR &#8805;62&#37; on beta-blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR decay in the 1st minute of recovery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;12 bpm &#40;upright cool-down&#41;&#62;18 bpm &#40;immediate supine&#41;&#62;22 bpm &#40;sitting&#41;&#44; at 2 minutes into the recovery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BP increase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SBP increase &#8805;40 mmHg &#40;upper limit 210 mmHg in men and 190 mmHg in women&#41;DBP remains the same or slightly decreases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic repolarization changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ST-segment depression that is horizontal or downsloping &#8805;1 mm&#44; extending 60&#8211;80 ms beyond the J-point&#46;Upsloping ST-segment depression &#8805;1&#46;5 mm&#44; extending 80 ms beyond the J-point&#46;ST-segment elevation &#8805;1 mmST&#47;HR index &#8805;1&#46;6 V&#47;bpmST&#47;HR loop in clockwise fashionExercise-induced ST-segment elevation&#44; either isolated or associated with ST-segment depression in a mirror territory in a non-Q wave territory&#44; suggests severe coronary stenosis or a spasm&#46;ST-segment elevation in Q wave leads may represent reversible ischemia&#44; dyskinesis or akinetic left ventricular segmental wall motion in postinfarction patients&#46;Enlargement of the QRS complex during exercise&#46;Exercise-induced left anterior hemiblock suggests stenosis of either the LM or proximal LAD&#46;Exercise induced a left posterior hemiblock can be a marker for RCA or Cx artery stenosis&#46;&nbsp;\t\t\t\t\t\t\n
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Review Article
Cardiopulmonary exercise testing in clinical practice: Principles, applications, and basic interpretation
Prova de esforço cardiorrespiratória na prática clínica: princípios, aplicações e interpretação básica
Hélder Doresa,b,c,
Autor para correspondência
heldores@hotmail.com

Corresponding author.
, Miguel Mendesd, Ana Abreue,f,g,h,i,j, Anaí Durazzod, Cidália Rodriguesk, Eduardo Vilelal, Gonçalo Cunhad, José Gomes Pereiram,n,o, Luísa Bentop, Luís Morenoq,r, Paulo Diniss,t, Sandra Amorimu,v, Susana Clementew,x, Mário Santosy,z,aa,ab
a Department of Cardiology, Hospital da Luz, Lisbon, Portugal
b CHRC, NOVA Medical School, Lisbon, Portugal
c NOVA Medical School, Lisbon, Portugal
d Department of Cardiology, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
e Cardiovascular Rehabilitation Center, Department of Cardiology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, CHULN/Faculdade de Medicina da Universidade de Lisboa, FMUL/CRECUL, Lisbon, Portugal
f Ergometry Department, Department of Cardiology, Hospital de Santa Maria, CHULN, Lisbon, Portugal
g Instituto de Saúde Ambiental, ISAMB, FMUL/Laboratório Associado Terra, Lisbon, Portugal
h Instituto de Medicina Preventiva e Saúde Pública, IMPSP, FMUL, Lisbon, Portugal
i Instituto de Medicina Nuclear, IMN, FMUL, Lisbon, Portugal
j Cardiovascular Center, Universidade de Lisboa, CCUL, Centro Académico de Medicina da Universidade de Lisboa, CAML, Lisbon, Portugal
k Department of Pulmonology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
l Department of Cardiology, Unidade Local de Saúde Gaia/Espinho, Vila Nova de Gaia, Portugal
m Faculdade de Motricidade Humana, Universidade de Lisboa, Oeiras, Portugal
n Comité Olímpico de Portugal, Lisbon, Portugal
o Desporsano – Sports Clinic, Lisbon, Portugal
p Hospital Garcia de Orta, Almada, Portugal
q Regimento de Comandos, Exército Português, Belas, Portugal
r Hospital CUF Tejo, Lisbon, Portugal
s Department of Cardiology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
t Centro de Saúde Militar de Coimbra, Exército Português, Coimbra, Portugal
u Centro Hospitalar Universitário São João, Porto, Portugal
v Faculdade de Medicina da Universidade do Porto, Porto, Portugal
w Department of Pulmonology, Hospital da Luz, Lisbon, Portugal
x Department of Pulmonology, Hospital Beatriz Ângelo, Loures, Portugal
y Department of Cardiology, Pulmonary Vascular Disease Unit, Centro Hospitalar Universitário de Santo António, Porto, Portugal
z CAC ICBAS-CHP – Centro Académico Clínico Instituto de Ciências Biomédicas Abel Salazar – Centro Hospitalar Universitário de Santo António, Porto, Portugal
aa Department of Immuno-Physiology and Pharmacology, UMIB – Unit for Multidisciplinary Research in Biomedicine, ICBAS – School of Medicine and Biomedical Sciences, Universidade do Porto, Porto, Portugal
ab ITR – Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Standard exercise testing remains a clinical tool with many applications in clinical practice&#44; providing important information for patients with a wide spectrum of conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">1</span></a> Combining this test with ventilatory gas exchange measurements provides incremental information&#44; leading to more accurate quantification of cardiorespiratory fitness &#40;CRF&#41; and to the identification of exercise-limiting pathophysiological mechanisms&#44; both of which are highly useful in clinical practice for cardiology&#44; as well as several other areas&#44; including pneumology&#44; internal medicine&#44; oncology&#44; surgery&#44; neurology&#44; sports medicine&#44; and physical medicine and rehabilitation&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; provides a noninvasive and dynamic integrative assessment of the exercise responses involving the respiratory&#44; cardiovascular &#40;CV&#41;&#44; and musculoskeletal systems&#46; It is considered the gold standard in the assessment of cardiorespiratory function and is extremely useful in the diagnostic investigation of unexplained exercise intolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> However&#44; its utility goes beyond diagnosis as it also helps with prognostic stratification and therapeutic evaluation in different clinical contexts&#44; and in guiding exercise prescription&#44; not only in patients undergoing cardiac or pulmonary rehabilitation&#44; but also in healthy athletes who aim to enhance their performance&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Despite being recommended by several scientific societies across a wide range of settings&#44; CPET is still underused for multiple reasons such as its complexity and the lack of trained personnel to interpret it&#44; lack of awareness of practicing clinicians of its utility&#44; its availability&#44; and costs&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">This article aims to address some of those barriers by reviewing the main indications&#44; applications&#44; and basic interpretation skills concerning CPET in contemporary clinical practice&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">How to perform cardiopulmonary exercise testing</span><p id="par0025" class="elsevierStylePara elsevierViewall">Given the wide range of physiological data and differential diagnosis&#44; knowing the clinical context of the individual and the question of the referring physician is a critical step when performing a CPET&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#8211;7</span></a> CPET should be performed by healthcare professionals qualified and trained in emergency situations&#46; A physician must be present during the test and an emergency cart with a defibrillator must be quickly available&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;8</span></a> The laboratory where a CPET is carried out must have a controlled environment with a temperature between 16 and 24<span class="elsevierStyleHsp" style=""></span>&#176;C and humidity between 30 and 60&#37;&#44; while the equipment must be correctly calibrated&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The test should be clearly explained&#44; potential doubts clarified&#44; and informed consent obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> It is also important to agree on the type of gestural communication to adopt during the test and to emphasize the relevance of performing maximum effort&#46; Before a CPET session or test&#44; the gas analyzer must be calibrated&#58; gas volume at the beginning of each session of tests and gas concentration before each test&#46; Also&#44; immediately before&#44; a spirometry and&#47;or a maximal voluntary ventilation &#40;MVV&#41; test should be performed&#44; which are essential to determine the breathing reserve &#40;BR&#41; and identify possible ventilatory limitations at rest and during exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> In addition to continuous gas exchange assessment&#44; during CPET&#44; the electrocardiogram &#40;ECG&#41;&#44; blood pressure &#40;BP&#41; and peripheral oxygen saturation &#40;SpO<span class="elsevierStyleInf">2</span>&#41; are also monitored&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Ergometers and protocols</span><p id="par0035" class="elsevierStylePara elsevierViewall">Ergometers are mechanical or electrical types of equipment that allow the definition of the work &#40;intensity of effort&#41; that the user will perform during the test&#46; The most used are the cycle and treadmill ergometers&#44; but there are others available&#44; such as arm and ergometers for athletes&#8217; evaluation in specific sports such as swimming&#44; rowing&#44; cross-country skiing&#44; or kayaking&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">6&#44;8&#44;9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In a hospital environment the treadmill and cycle ergometers are preferred as they can replicate the most common physical activity types&#46; The treadmill&#44; which also involves upper limb muscles&#44; enables users to attain 5&#8211;10&#37; higher oxygen consumption &#40;VO<span class="elsevierStyleInf">2</span>&#41; and represents an activity that most people do in their daily lives &#40;walking or running&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">8</span></a> A comparison of the main advantages of these two types of ergometers is presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Exercise protocols need to be individualized considering the characteristics of the person who performs it and the indication for the exam&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a> According to the load application&#44; protocols can be classified as constant or progressive &#40;incremental&#41;&#46; Progressive or incremental load protocols can be intermittent &#40;with pauses&#41; or continuous&#44; while the latter can be performed on a ramp or by stages &#40;levels&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Most laboratories perform incremental ramp or stagged tests&#46; Ramp tests have the advantage of increasing the speed or resistance in a gradual and linear way&#44; without jumps between stages&#44; which allows a greater individualization of the protocol&#46; With this methodology it is possible to obtain a linear increase in VO<span class="elsevierStyleInf">2</span>&#44; improving the precision to determine maximal VO<span class="elsevierStyleInf">2</span> &#40;VO<span class="elsevierStyleInf">2</span>max&#41; and submaximal parameters&#44; namely the ventilatory thresholds &#40;VTs&#41;&#44; which increases the reproducibility of the test&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Constant load protocols can be used in specific situations&#44; such as for the diagnosis of exercise-induced bronchospasm&#44; evaluation of the contribution of carotid bodies in exercise hyperpnea&#44; assessment of the lactate threshold &#40;constant low-intensity work lasting 10 minutes&#41;&#44; and determination of the VO<span class="elsevierStyleInf">2</span>max&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">10&#44;11</span></a></p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Key cardiopulmonary exercise testing variables to analyze</span><p id="par0060" class="elsevierStylePara elsevierViewall">Modern day gas analyzers perform breath-by-breath measurements of respiratory gases&#44; which provide data with large variability and justifies performing data averaging&#58; 20- or 30-second averaging are the most recommended modalities since they are a good balance between data variability and accuracy&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing can generate a large number of variables&#44; but there is a group of those that are more pertinent in current clinical practice&#46; A general overview of normalized values&#44; based on the most recent recommendations&#44; is presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; but the values described may vary&#44; depending on the literature and the population under study&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">8&#44;11&#8211;14</span></a> Some of these parameters are already evaluated in conventional exercise testing &#40;i&#46;e&#46; without respiratory gas assessment&#44; such as BP&#44; heart rate &#40;HR&#41; and rhythm&#44; and the ST-segment of the ECG&#41;&#44; but others are associated with gas exchange and only available with a CPET&#46; The most important parameters in clinical practice will be discussed later in this document&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Oxygen consumption is a key parameter providing a refined measure of CRF which is of major value in different settings&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> Optimal oxygen &#40;O<span class="elsevierStyleInf">2</span>&#41; delivery is central to exercise performance&#44; being influenced by several factors ranging from CV and respiratory function to hemoglobin plasma concentration&#44; autonomic inputs&#44; mitochondrial efficiency&#44; and thermoregulation&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">15</span></a> Furthermore&#44; age&#44; gender&#44; genetic background&#44; and training can also affect peak VO<span class="elsevierStyleInf">2</span> &#40;pVO<span class="elsevierStyleInf">2</span>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Oxygen consumption can be expressed as an absolute value or adjusted to body weight and should also be reported in relation to age&#44; gender&#44; weight&#44; height&#44; and ergometer predicted values&#44; through specific formulas&#46; Many of these equations provided by the gas analyzer software are inaccurate and outdated&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;5</span></a> Today&#44; the FRIEND trial equation is accepted as the best one to calculate the predicted value of VO<span class="elsevierStyleInf">2</span>max&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Importantly&#44; pVO<span class="elsevierStyleInf">2</span> is the highest VO<span class="elsevierStyleInf">2</span> obtained during exercise&#44; while VO<span class="elsevierStyleInf">2</span>max corresponds to a state of a VO<span class="elsevierStyleInf">2</span> plateau&#44; despite increases in workload&#46; Notably&#44; while pVO<span class="elsevierStyleInf">2</span> provides a comprehensive overview of CRF&#44; it should be acknowledged that exercise economy&#44; encompassing cardiorespiratory efficiency&#44; but also factors such as biomechanics&#44; neuromuscular efficiency&#44; and training&#44; should be considered&#44; as two subjects with a similar pVO<span class="elsevierStyleInf">2</span> may have different performances&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">18</span></a> Likewise&#44; individuals with better exercise economy could require a different VO<span class="elsevierStyleInf">2</span> for the same workloads&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">O<span class="elsevierStyleInf">2</span> pulse reflects the amount of O<span class="elsevierStyleInf">2</span> extracted at each heartbeat&#44; providing information on both stroke volume &#40;SV&#41; and the arteriovenous oxygen difference&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">19</span></a> In the absence of factors such as anemia&#44; hypoxia&#44; and mitochondrial disorders&#44; the O<span class="elsevierStyleInf">2</span> pulse trajectory parallels the one of SV&#46; During exercise&#44; the curve is expected to increase linearly almost till the end of the exercise period where a plateau is normally expected&#46; An early flattening or decrease of its trajectory are abnormal responses&#46; Indeed&#44; a plateau or decrease in the O<span class="elsevierStyleInf">2</span> pulse trajectory during incremental exercise may reflect a reduction in SV in the setting of myocardial ischemia or left ventricle outflow obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">20</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Respiratory exchange ratio &#40;RER&#41; is the ratio between carbon dioxide production &#40;VCO<span class="elsevierStyleInf">2</span>&#41; and VO<span class="elsevierStyleInf">2</span>&#44; providing information on the type of energy substrate being metabolized&#46; When calculated at peak effort it offers an objective insight on whether effort was maximal&#46; Though different cut-offs may be considered&#44; a value &#8805;1&#46;10 has been considered a criterion for maximal effort attainment&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;21</span></a> A low peak RER suggests submaximal CV effort&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The ratio of minute ventilation &#40;VE&#41; to VO<span class="elsevierStyleInf">2</span> is called the ventilatory equivalent for O<span class="elsevierStyleInf">2</span> &#40;EqO<span class="elsevierStyleInf">2</span>&#41;&#44; and the ratio of VE to VCO<span class="elsevierStyleInf">2</span> is called the ventilatory equivalent for CO<span class="elsevierStyleInf">2</span> &#40;EqCO<span class="elsevierStyleInf">2</span>&#41;&#44; providing information about ventilatory efficiency&#46; During CPET&#44; the normal pattern of change in ventilatory equivalent for oxygen &#40;VE&#47;VO<span class="elsevierStyleInf">2</span>&#41; is a drop early in exercise to its nadir at the first VT &#40;VT1&#41;&#44; followed by an increase as the maximal exercise capacity approaches&#46; This behavior is due to a steeper rise in ventilation in response to increased CO<span class="elsevierStyleInf">2</span> production in proportion to VO<span class="elsevierStyleInf">2</span> increase&#46; Ventilatory equivalent for carbon dioxide &#40;VE&#47;VCO<span class="elsevierStyleInf">2</span>&#41; correspondingly decreases hyperbolically as the work rate increases&#46; This balance may be disturbed in several clinical conditions&#44; including chronic obstructive pulmonary disease &#40;COPD&#41;&#44; pulmonary hypertension &#40;PH&#41; and heart failure &#40;HF&#41;&#46; In these conditions&#44; VE&#47;VO<span class="elsevierStyleInf">2</span> and VE&#47;VCO<span class="elsevierStyleInf">2</span> are increased due to an augmented dead space and&#47;or alveolar hyperventilation&#46; A steep VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;a high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; is associated with several cardiorespiratory diseases and is an independent marker of poor prognosis&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Ventilatory thresholds &#40;VT&#41; provide pivotal data on the metabolic response to exercise&#44; and are paramount in exercise prescription&#46; The first VT &#40;VT1&#41; represents a transition to a mixed aerobic and anaerobic metabolism&#44; being characterized by increases in lactate and decreases in pH&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">5</span></a> This is accompanied by lactate buffering&#44; with ensuing increases in VCO<span class="elsevierStyleInf">2</span> and ventilation&#44; to maintain acid&#8211;base homeostasis&#46; The second VT &#40;VT2&#41; represents a point where lactate increases rapidly and more substantially &#40;as buffering becomes insufficient&#41;&#44; with ensuing hyperventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">22</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">While different terms are sometimes used&#44; such as anaerobic threshold &#40;for VT1&#41; and respiratory compensation point &#40;for VT2&#41;&#44; respectively&#44; the terminology &#8220;VT&#8221; was adopted in the current literature&#46; These metabolic transition points can be determined invasively &#40;by blood analysis&#41; or non-invasively&#46; VT1 is commonly determined by the ventilatory equivalent method as the lowest point before an ensuing increase in the curve&#44; or by the V-slope method &#40;by an increase in the slope between VCO<span class="elsevierStyleInf">2</span> and VO<span class="elsevierStyleInf">2</span>&#44; which previously had a linear relationship&#44; representing the increase in VCO<span class="elsevierStyleInf">2</span> due to lactate buffering&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">23&#44;24</span></a> VT2 can be assessed by the ventilatory equivalent method&#44; as the lowest point before a continuous increase&#44; by a marked increase in ventilation &#40;in relation to VCO<span class="elsevierStyleInf">2</span>&#41; and by the end-tidal carbon dioxide pressure &#40;P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41;&#44; where a deflection occurs reflecting the marked ventilation increase&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a><a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a> illustrates the methods recommended for determining VTs&#46; Importantly&#44; an integrative approach employing different methods should be considered&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Partial pressure of end-tidal oxygen &#40;P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span>&#41; reflects the gas exhaled precisely at the end of expiration&#44; originating from the deep lung&#46; The reported concentrations of end-tidal gas represent a mixture of gases from all alveoli&#44; with some being well-perfused and others under-perfused&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">11</span></a> During the initial stages of moderate exercise&#44; levels of end-tidal O<span class="elsevierStyleInf">2</span> &#40;P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#41; typically decrease and start to rise during later stages due to increased CO<span class="elsevierStyleInf">2</span> production&#44; resulting in acidemia and subsequently increased ventilation&#46; P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> levels increase initially&#44; reflecting the rising CO<span class="elsevierStyleInf">2</span> production at the beginning of exercise&#44; followed by a drop when acidemia stimulates ventilation beyond what is necessary to eliminate CO<span class="elsevierStyleInf">2</span>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Minute ventilation is a measure of the total volume of air breathed in one minute&#46; During exercise&#44; VE increases initially due to an increase in tidal volume&#44; which can increase three to fivefold&#44; reaching approximately 60&#37; of the vital capacity&#46; In later stages of exercise&#44; breathing frequency will at least double&#44; while tidal volume remains relatively unchanged&#46; Younger and fitter individuals may experience a considerably higher increase in respiratory rate&#44; reaching around 30&#8211;40 breaths per minute&#46; A frequency higher than 55 breaths per minute is generally considered abnormal&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">25</span></a> If the tidal volume does not increase significantly during a CPET&#44; it suggests the presence of lung disease&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Breathing reserve &#40;BR&#41; can be defined as the difference between the MVV at rest and the maximum ventilation achieved during exercise&#46; MVV&#44; measured in liters per minute&#44; can be obtained through direct measurement &#40;by instructing the individual to breathe as deeply and quickly as possible for 12 or 15 seconds and then multiplying the value by five or by four&#44; respectively&#41; or by estimation &#40;MVV&#61;forced expiratory volume in the first second &#40;FEV1&#41;&#215;35 or 40&#41;&#46; During a CPET&#44; maximal VE should not exceed 80&#8211;85&#37; of the predicted value in a healthy individual&#46; If maximal VE exceeds 80&#37; of the predicted value&#44; it indicates a low BR&#44; meaning there is little capacity for further increase in ventilation&#46; A reduced &#40;&#60;15&#8211;20&#37;&#41; or absent BR suggests that the limitation to exercise is likely due to respiratory disease&#46; However&#44; it is important to note that BR tends to decrease with age and lower fitness levels&#46; In cases of CV disease or other factors limiting exercise performance&#44; BR is typically higher&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Interpretation of cardiopulmonary exercise testing results</span><p id="par0125" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing has a large array of measured and calculated parameters that can be interpreted&#46; To provide a simple yet comprehensive and visual information&#44; Wasserman et al&#46; arranged the CPET values into nine graphs&#44; hence the name &#8220;9-panel plot&#8221; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">11&#44;25</span></a><a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a> presents the classic and most used sequence&#44; but other alignments may also be applied&#46; Following a plot order and understanding the normal response and the most frequent abnormal patterns is essential for proper CPET interpretation&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 3</span>&#58; The first question to be asked in a CPET is whether the test was maximal&#46; The gold standard definition of a maximal CPET is a plateau or a VO<span class="elsevierStyleInf">2</span> curve drop&#44; despite load increase&#46; However&#44; this finding may be difficult to attain in patients&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 8</span>&#58; When a VO<span class="elsevierStyleInf">2</span> plateau is not identifiable&#44; we look at this plot to check whether a RER &#40;black dots&#41; over 1&#46;10 was attained at peak effort &#40;the vertical red line&#41;&#46; A RER of 1&#46;10 may not be reached in cases of insufficient effort or causes of limitation other than circulatory limitation &#40;e&#46;g&#46;&#44; respiratory&#44; vascular PH&#44; or musculoskeletal limitation&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 3</span>&#58; We then inspect VO<span class="elsevierStyleInf">2</span> &#40;blue dots&#41; at peak exercise&#46; While cut-off values differ&#44; a value under 85&#37; in the setting of a maximal CPET &#40;RER &#62;1&#46;10&#41; suggests a clear exercise limitation&#46; In cycle-ergometer testing&#44; it is possible to evaluate the VO<span class="elsevierStyleInf">2</span>&#47;work &#40;W&#41; ratio&#46; Normal value is typically around 10 mL&#47;W&#46; However&#44; in cases of heart disease&#44; this relationship may decrease&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plots 8 and 7</span>&#58; In the setting of dyspnea or the presence of exercise limitation&#44; we then proceed to ascertain its etiology&#46; A BR &#40;panel 8&#44; brown dots&#41; &#60;15&#8211;20&#37; at peak exercise&#44; defined after a good quality spirometry or MVV determination&#44; suggests ventilatory limitation&#46; It should be noted that in highly conditioned individuals with substantial tolerance to discomfort &#40;e&#46;g&#46;&#44; athletes&#41;&#44; a BR &#60;20&#37; can be reached without having true ventilatory limitation &#40;usually in these cases a significant exercise time is attained&#44; with a RER above 1&#46;10&#41;&#46; The pattern of the tidal volume &#40;panel 7&#44; brown dots&#41; may inform whether the pattern of respiratory limitation is restrictive or obstructive&#46; SpO<span class="elsevierStyleInf">2</span> is not always depicted in the 9-panel plot&#44; but a decrease greater than 5&#37; is abnormal and suggestive of limitations in gas exchange&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plots 4&#44; 6&#44; and 9</span>&#58; Ventilation-perfusion &#40;V&#47;Q&#41; mismatch due to low cardiac output &#40;CO&#41; or PH can also be a cause of exercise limitation&#46; Ventilatory efficiency can be measured using two methods&#58; &#40;1&#41; VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;plot 4&#41; between VT1 and VT2&#59; &#40;2&#41; nadir &#40;VT2&#41; of the ventilatory equivalents of CO<span class="elsevierStyleInf">2</span> &#40;plot 6&#44; red line&#41;&#46; The results are usually similar&#46; P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span> and P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#40;plot 9&#41; are also useful for assessing V&#47;Q matching and detecting gas exchange abnormalities in the lungs&#46; The more pronounced the ventilation&#44; the lower the P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> and the higher the P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 1</span>&#58; VE increases proportionally with the load and CO<span class="elsevierStyleInf">2</span> concentration&#46; In the case of a ramp protocol&#44; it is expected to increase steadily from rest to VT1&#44; have a steep increase from VT1 to VT2&#44; and an even steeper increase after VT2&#46; This pattern is difficult to observe when a staged protocol &#40;e&#46;g&#46;&#44; Bruce&#41; rather than a ramp protocol is used&#46; If the patient has cyclic fluctuations with an oscillatory pattern in VE and expired gases&#44; that persist &#8805;60&#37; of the test with an amplitude &#8805;15&#37; of the average resting value&#44; exercise oscillatory ventilation &#40;EOV&#41; is noted&#46; This is an important prognostic marker&#44; especially in HF patients&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 2</span>&#58; Peak HR &#40;pink dots&#41; can inform on the presence or absence of chronotropic incompetence&#46; However&#44; this information is difficult to interpret in the setting of beta-blocker therapy and may have little therapeutic impact&#46; It can be useful in patients with pacemakers or cardiac resynchronization therapy &#40;CRT&#41;&#44; to identify insufficient rate response to exercise&#44; which requires optimization in programming&#46; More than the absolute and predicted value of peak O<span class="elsevierStyleInf">2</span> pulse &#40;blue dots&#41;&#44; the pattern of O<span class="elsevierStyleInf">2</span> pulse progression may be informative&#46; It should increase and may have a plateau at maximal exercise&#46; A marked and consistent decrease in O<span class="elsevierStyleInf">2</span> pulse during exercise&#44; in non-athlete subjects&#44; suggests a decrease in SV that may be caused by different phenomena such as myocardial ischemia&#44; left ventricular outflow obstruction&#44; or exercise-induced mitral regurgitation&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Plot 5</span>&#58; Like the VE curve in plot 1&#44; the VO<span class="elsevierStyleInf">2</span>&#47;VCO<span class="elsevierStyleInf">2</span> relationship can be useful to identify VT1&#44; and VT2&#44; using the V-slope method&#46; A low VT1 usually suggests circulatory limitation or severe muscular deconditioning&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Maximal versus submaximal test</span><p id="par0170" class="elsevierStylePara elsevierViewall">The usual target of a CPET is to perform a maximal test&#46; Submaximal tests should only be considered as an alternative for specific cases since their value for risk stratification is much less studied and reduced regarding a maximal test&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">8&#44;26</span></a> It is widely accepted that a CPET may be considered maximal if a VO<span class="elsevierStyleInf">2</span> plateau or drop can be found at peak exercise despite by increasing workload&#46; If a VO<span class="elsevierStyleInf">2</span> plateau or drop is not seen&#44; but a RER &#62;1&#46;10&#44; a BR &#60;15&#37;&#44; a peak exercise HR over 90&#37; of the predicted&#44; or peak exercise lactate concentration &#8805;8 mmol&#47;L &#40;if measured&#41; are reached&#44; one may consider that an intense effort was achieved&#44; and a near-maximal test was performed&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">5&#44;10</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Indications for cardiopulmonary exercise testing</span><p id="par0175" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing has multiple clinical indications&#44; covering a broad spectrum of specialties and diseases&#46; It is an important tool for diagnosis&#44; risk stratification&#44; exercise prescription&#44; evaluation of the effect of several therapeutic interventions &#40;pharmacological&#44; percutaneous&#44; and surgical&#41; and prognosis assessment&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Figure 4</a> shows some of the main indications for CPET&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Athlete evaluation</span><p id="par0180" class="elsevierStylePara elsevierViewall">In asymptomatic athletes&#44; CPET is important to detect subclinical cardiac disease&#44; particularly in master athletes&#44; in the assessment of baseline functional capacity&#44; in revealing the sporting ability of young athletes&#44; or when evaluating performance in different modalities&#44; and training monitoring&#46; CPET can assist in the diagnostic process and evaluation of non-specific symptoms such as exertional dyspnea&#44; chest discomfort&#44; or tiredness&#46; Indeed&#44; during their sporting careers&#44; many athletes may experience these symptoms and the etiology may be cardiac&#44; respiratory&#44; muscular&#44; or even psychological&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">6</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">In the context of sports performance&#44; CPET allows the prescription of exercise through the documentation of VTs and the corresponding HR&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">27&#44;28</span></a> In this way&#44; this methodology helps to individualize the intensity of training&#44; through the determination of different training zones&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 1</span>&#58; below the VT1 &#40;light exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 2</span>&#58; between VT1 and VT2 &#40;moderate to high-intensity exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 3</span>&#58; above the VT2 &#40;very high-intensity exercise&#41;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Zone 4</span>&#58; corresponds to sprints and efforts above those previously mentioned&#46;</p></li></ul></p><p id="par0210" class="elsevierStylePara elsevierViewall">Additionally&#44; it plays an important role in diagnosing training overload and thus preventing overtraining syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Cardiac rehabilitation</span><p id="par0215" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing should be performed whenever available to stratify the risk for exercise&#44; to prescribe exercise and to quantify the training benefits of cardiac rehabilitation&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">28&#44;30</span></a> CPET is the gold standard to prescribe aerobic exercise&#44; whether moderate continuous training &#40;corresponding to the training zone between the two VTs&#41;&#44; or interval training with low-intensity &#40;below VT1&#41; and high-intensity &#40;above VT2&#41; training intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">31</span></a> Higher duration of the test and values of VO<span class="elsevierStyleInf">2</span> and HR at VTs and peak exercise&#44; together with lower values of VE&#47;VCO<span class="elsevierStyleInf">2</span> slope are some of the expected gains for a cardiac rehabilitation program&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ischemic heart disease</span><p id="par0220" class="elsevierStylePara elsevierViewall">The role of classical exercise testing in the diagnosis of coronary artery disease &#40;CAD&#41; has been progressively superseded by imaging modalities across several scenarios&#46; CPET may add useful ancillary data&#44; such as the O<span class="elsevierStyleInf">2</span> pulse trajectory&#44; that can provide information concurring with possible ischemic contributions to exercise intolerance&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">32</span></a> Moreover&#44; an abnormal relationship between pVO<span class="elsevierStyleInf">2</span> and work rate can also be of value in this setting&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Data derived from CPET can also provide prognostic information in CAD patients&#44; namely with parameters such as pVO<span class="elsevierStyleInf">2</span> and the VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#44; giving inputs on the risk of further events and reinforcing its value in their comprehensive assessment&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Cardiomyopathies</span><p id="par0230" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is a safe and useful tool in patients with suspected&#47;confirmed hypertrophic cardiomyopathy &#40;HCM&#41; to provide information on symptoms&#44; severity&#44; and prognosis&#44; to aid planning management&#44; and to monitor therapeutic efficacy&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">3&#44;33&#44;34</span></a> pVO<span class="elsevierStyleInf">2</span> can also help to distinguish left ventricular hypertrophy &#40;LVH&#41; associated with HCM from other forms of secondary LVH&#44; such as hypertensive cardiomyopathy&#44; &#8220;athlete&#39;s heart&#8221;&#44; and athletes with HCM&#46; It is suggested that in these cases&#44; a pVO<span class="elsevierStyleInf">2</span> &#60;84&#37; of the age-gender predicted &#40;AGP&#41; is indicative of pathological LVH&#46; A pVO<span class="elsevierStyleInf">2</span> &#62;50 mL&#47;kg&#47;min or 120&#37; of the AGP is proposed as a standard for differentiating an &#8220;athlete&#39;s heart&#8221; from HCM&#46; Only a small percentage of athletes with HCM achieve &#62;100&#37; of the AGP pVO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">33</span></a> The functional information provided by the CPET should be integrated with data derived from other investigations for the appropriate differential diagnosis between &#8220;athlete&#39;s heart&#8221; and cardiomyopathies&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Although the application of CPET in arrhythmogenic cardiomyopathy is scarce&#44; it has proven to be safe and potentially useful for risk stratification when considering advanced therapies &#40;such as heart transplantation&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Heart failure</span><p id="par0240" class="elsevierStylePara elsevierViewall">In patients with HF with reduced ejection fraction &#40;HFrEF&#41;&#44; pVO<span class="elsevierStyleInf">2</span> has a prominent role in the prognostic stratification&#46; However&#44; submaximal exercise gas exchange variables have emerged that rival the prognostic utility of pVO<span class="elsevierStyleInf">2</span>&#46; Some of these encompass the VO<span class="elsevierStyleInf">2</span>&#47;W ratio &#40;aerobic efficiency&#41;&#44; VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#40;ventilatory efficiency&#41;&#44; VO<span class="elsevierStyleInf">2</span> at VT1&#44; oxygen uptake efficiency slope &#40;OUES&#41;&#44; and EOV&#46; EOV represents a strong negative prognostic parameter in HF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">The 2012 EACPR&#47;AHA Scientific Statement<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">3</span></a> proposed a multiparametric CPET data table developed by Arena et al&#46;&#44; with an iteration of the figures by proposing color-coded interpretive tables applied to different diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">38</span></a> A CPET score utilizing VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#8805;34 &#40;7 points&#41;&#44; HR decay in the first minute of recovery &#8804;6 bpm &#40;5 points&#41;&#44; OUES &#8804;1&#46;4 &#40;3 points&#41;&#44; resting P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> &#60;33 mmHg &#40;3 points&#41;&#44; and a pVO<span class="elsevierStyleInf">2</span> &#8804;14 mL&#47;kg&#47;min &#40;2 points&#41; has been validated to predict transplant&#47;mechanical circulatory support-free survival in HF patients better than pVO<span class="elsevierStyleInf">2</span> alone&#44; with a summed score &#62;15 indicating the poorest prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">39&#44;40</span></a> The use of this CPET score is helpful in risk stratifying HF patients in Weber class B &#40;with pVO<span class="elsevierStyleInf">2</span> 16&#8211;20 mL&#47;kg&#47;min&#41; into low-risk and higher-risk subgroups&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">41</span></a> The latest criteria proposed two different pVO<span class="elsevierStyleInf">2</span> cut-offs for heart transplantation depending on whether the patient is &#40;pVO<span class="elsevierStyleInf">2</span> &#8804;14 mL&#47;kg&#47;min&#41; or not &#40;pVO<span class="elsevierStyleInf">2</span> &#8804;12 mL&#47;kg&#47;min&#41; on &#946;-blocker treatment &#40;Cl I&#44; LOE B&#41;&#59; in outpatients aged &#60;50 years&#44; a pVO<span class="elsevierStyleInf">2</span> &#60;50&#37; of the expected value &#40;Cl IIa&#44; LOE B&#41;&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">The International Society for Heart and Lung Transplantation &#40;ISHLT&#41; guidelines indicate the use of a VE&#47;VCO<span class="elsevierStyleInf">2</span> slope &#62;35 as a determinant in listing for heart transplantation in the presence of a submaximal CPET &#40;Cl IIb&#44; LOE&#58; C&#41;&#46; The presence of a CRT does not alter the current pVO<span class="elsevierStyleInf">2</span> cut-off recommendations &#40;Cl I&#44; LOE&#58; B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0480"><span class="elsevierStyleSup">42&#44;43</span></a> HF with preserved ejection fraction &#40;HFpEF&#41; represents worldwide most patients with HF&#46; These patients may be functionally very limited&#44; a limitation that can be objectively quantified by CPET&#46; However&#44; because CPET findings in HFpEF are nonspecific regarding HFrEF patients&#44; the clinical utility of CPET in a patient with HFpEF suspicion is low&#46; CPET can help to understand the nature and magnitude of symptoms&#44; the pathophysiological mechanism&#44; and the impact of noncardiac comorbidities that frequently limit elderly HFpEF patients&#46; Lastly&#44; CPET is also mandatory to correctly prescribe exercise to HFpEF patients integrated in cardiac rehabilitation programs&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Valvular heart disease</span><p id="par0255" class="elsevierStylePara elsevierViewall">In valvular diseases&#44; CPET can help unveil unreported symptoms&#44; understand the mechanism&#39;s underlying symptoms&#44; and better outline prognosis that helps to define treatment timings more appropriately&#46; The ventilatory classification system may provide additional information in detecting elevated pulmonary pressures&#44; with higher values indicating greater severity of the valvular heart disease and poorer prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">44</span></a> Combined stress echocardiography and CPET can be helpful in determining the mechanisms of exercise intolerance in patients with mitral stenosis&#46; Those patients show the expected exercise-induced PH that may lead to hyperventilation and increased VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#46; Also&#44; O<span class="elsevierStyleInf">2</span> pulse stops increasing due to lack of increase of ventricular filling during exercise because the valvular stenosis&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Current guidelines support the use of stress testing in asymptomatic severe aortic stenosis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">45</span></a> A pVO<span class="elsevierStyleInf">2</span> &#8804;19 mL&#47;kg&#47;min for men and &#8804;15 mL&#47;kg&#47;min for women&#59; O<span class="elsevierStyleInf">2</span> pulse &#8804;15 mL&#47;beat for men and &#8804;11 mL&#47;beat for women&#44; were strong predictors of mortality in patients with moderate to severe aortic stenosis&#44; irrespective of whether they undergo aortic valve replacement&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">46</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Pulmonary hypertension</span><p id="par0265" class="elsevierStylePara elsevierViewall">When evaluating a patient with an established or suspected PH diagnosis&#44; CPET can be useful to elucidate the underlying pathophysiologic mechanism of exercise intolerance&#44; to assess the severity of PH&#44; to quantify the response to treatment&#44; and to stratify mortality risk&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">The pathophysiology of PH is characterized by reduced CO reserve due to increased right ventricle afterload and increased physiologic dead space due to marked inefficient ventilation&#46; Variables such as pVO<span class="elsevierStyleInf">2</span>&#44; O<span class="elsevierStyleInf">2</span> pulse&#44; and VO<span class="elsevierStyleInf">2</span>&#47;W ratio will be abnormally reduced due to the limited CO reserve&#46; Likewise&#44; the significant changes in VE&#44; VE&#47;VCO<span class="elsevierStyleInf">2</span> and P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> during exercise&#44; reflect the impaired ventilatory efficiency so distinctive of PAH&#46;<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">47</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Congenital heart diseases</span><p id="par0275" class="elsevierStylePara elsevierViewall">It is safe to perform a CPET in the spectrum of congenital heart disease &#40;CHD&#41;&#44; not only for risk stratification&#44; but also in assisting in the decision of timing of surgical or percutaneous interventions&#44; as well as exercise counseling and training&#46; The most reported CPET findings in CHD are reduced pVO<span class="elsevierStyleInf">2</span>&#44; early VT1&#44; blunt HR increase&#44; reduced tidal volume increase&#44; and increased VE&#47;VCO<span class="elsevierStyleInf">2</span> slope&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">48</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">As a general guideline&#44; it is recommended to stop testing in the presence of severe desaturation &#40;SpO<span class="elsevierStyleInf">2</span> &#8804;80&#37;&#41; when accompanied by symptoms and signs of severe hypoxemia&#46; However&#44; data concerning specific recommendations regarding cyanotic CHD are limited&#46; A right-to-left shunt can manifest itself during the CPET by the onset or worsening of systemic arterial desaturation&#44; augmentation of VE&#44; usually associated with an abrupt decrease in P<span class="elsevierStyleInf">ET</span>CO<span class="elsevierStyleInf">2</span> and simultaneous increases in P<span class="elsevierStyleInf">ET</span>O<span class="elsevierStyleInf">2</span>&#44; RER&#44; and ventilatory equivalents&#46;<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Dyspnea of unknown cause</span><p id="par0285" class="elsevierStylePara elsevierViewall">Dyspnea is a complex and multifactorial symptom characterized by the subjective feeling of breathing discomfort&#46; It is a commonly reported symptom&#44; and the underlying causes can be diverse and may include respiratory&#44; CV&#44; metabolic&#44; or psychological factors&#46;<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">50</span></a> In fact&#44; dyspnea experienced during exercise and daily activities may be an early symptom of various cardiopulmonary and neuromuscular diseases&#44; leading to progressively less intense activities&#44; resulting in muscle deconditioning and a decline in quality of life&#46; Dyspnea is a predictor of quality of life&#44; exercise tolerance&#44; and mortality in several pathologies&#44; being a better predictor than FEV1 in COPD or angina in ischemic heart disease&#46;<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">51</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">During CPET&#44; dyspnea can be assessed using scales which are helpful to monitor its intensity throughout the test and to compare the severity of breathing discomfort with the level of exercise&#46; The most used scale is the modified Borg scale&#44; which ranges from 0 to 10&#46; This scale has been widely validated and correlates well with aerobic stress and blood lactate levels during exercise&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Due to its subjective nature and multiple potential underlying causes&#44; dyspnea requires a comprehensive evaluation to identify the factors contributing to the symptom&#46; CPET plays a crucial role to clarify the underlying mechanisms of dyspnea during exertion&#46; Interpretative algorithms enable identifying patterns of findings that are typical for different clinical conditions and allow clinicians to differentiate patterns of various conditions&#44; such as COPD&#44; asthma&#44; HF&#44; obesity&#44; PH&#44; and interstitial lung diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">52</span></a> In some cases&#44; modified protocols can be employed during CPET to detect specific conditions&#44; which are suspected based on clinical data &#40;e&#46;g&#46;&#44; identification of exercise-induced bronchoconstriction&#44; and exercise-induced laryngeal obstruction&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Pulmonary disease</span><p id="par0300" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is extremely useful in the evaluation of patients with lung disease for quantifying exercise capacity and level of disability&#44; providing diagnostic information&#44; evaluating hypoxemia during exercise and underlying mechanisms&#44; defining therapeutic strategies &#40;such as pulmonary rehabilitation&#41;&#44; assessing the preoperative risk of complications in lung surgery&#44; and providing prognostic information&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">52&#44;53</span></a> If BR is significantly reduced&#44; it suggests that the respiratory system may be a limiting factor for exercise performance&#46; It is possible to measure the flow-volume curve during exercise to detect ventilatory constraints&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">In healthy individuals&#44; as exercise intensity increases&#44; the volume of air remaining in the lungs at the end of expiration declines while the inspiratory capacity increases&#44; leading to improved ventilatory efficiency&#46; However&#44; patients with obstructive lung disease may have difficulty in emptying their lungs during incremental exercise compared to rest due to expiratory flow limitation &#40;EFL&#41; and increased respiratory rate&#44; resulting in reduced expiratory time&#46; Consequently&#44; there is an increase in end-expiratory volume&#44; in contrast to the decrease observed in individuals without lung disease&#44; leading to a reduction in inspiratory capacity of at least 250 mL&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">54</span></a> Additionally&#44; other measurements&#44; including EFL &#62;25&#37; at peak effort&#44; a lung volume ratio at the end of inspiration greater &#62;90&#37; of total lung capacity&#44; and a tidal volume &#62;70&#37; of inspiratory capacity can be obtained&#46;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">53</span></a> Assessing these parameters during exercise helps to identify the presence of dynamic hyperinflation&#44; which can be responsible for dyspnea and a limiting factor for exercise&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">The decision to perform arterial blood gas measurements during CPET depends on the specific goals of the test&#46; In general&#44; measuring partial pressure of O<span class="elsevierStyleInf">2</span> &#40;PaO<span class="elsevierStyleInf">2</span>&#41; allows the calculation of gas exchange indices&#44; such as the alveolar-arterial gradient&#46; Measuring the partial pressure of CO<span class="elsevierStyleInf">2</span> &#40;PaCO<span class="elsevierStyleInf">2</span>&#41; allows the calculation of the dead space over tidal volume &#40;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>&#41; ratio&#44; which is a measure of the efficiency of carbon dioxide exchange&#46; Inefficient CO<span class="elsevierStyleInf">2</span> exchange is manifested by the high <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">D</span>&#47;<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> ratio&#44; often signaled by the high VE&#47;VCO<span class="elsevierStyleInf">2</span> ratio with exercise&#46;</p></span></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Contraindications for cardiopulmonary exercise testing</span><p id="par0315" class="elsevierStylePara elsevierViewall">Beyond knowing the potential indications for CPET&#44; it is also fundamental to know the main contraindications for this exam&#44; especially corresponding to severe or uncontrolled CV conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">1&#44;13</span></a> In general&#44; absolute contraindications for CPET encompass&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0320" class="elsevierStylePara elsevierViewall">Acute myocardial infarction &#40;3&#8211;5 days&#41;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0325" class="elsevierStylePara elsevierViewall">Unstable angina</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0330" class="elsevierStylePara elsevierViewall">Uncontrolled arrhythmia causing symptoms or hemodynamic instability</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0335" class="elsevierStylePara elsevierViewall">Active endocarditis</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0340" class="elsevierStylePara elsevierViewall">Acute myocarditis or pericarditis</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0345" class="elsevierStylePara elsevierViewall">Symptomatic severe aortic stenosis</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0350" class="elsevierStylePara elsevierViewall">Decompensated HF</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0355" class="elsevierStylePara elsevierViewall">Acute aortic dissection</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0360" class="elsevierStylePara elsevierViewall">Uncontrolled asthma</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0365" class="elsevierStylePara elsevierViewall">Acute pulmonary embolism</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0370" class="elsevierStylePara elsevierViewall">Arterial desaturation at rest on room air &#60;85&#37;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0375" class="elsevierStylePara elsevierViewall">Physical disability that precludes safe and adequate testing</p></li></ul></p><p id="par0380" class="elsevierStylePara elsevierViewall">Other conditions represent relative contraindications for CPET&#44; reinforcing the need of direct supervision by a physician&#46; Among the relative contraindications&#44; the following conditions are included&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0385" class="elsevierStylePara elsevierViewall">Untreated left main coronary stenosis or its equivalent</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0390" class="elsevierStylePara elsevierViewall">Asymptomatic severe aortic stenosis</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0395" class="elsevierStylePara elsevierViewall">Severe untreated arterial hypertension at rest &#40;SBP &#62;200 mmHg&#59; SBP &#62;110 mmHg&#41;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0400" class="elsevierStylePara elsevierViewall">Significant tachyarrhythmias</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0405" class="elsevierStylePara elsevierViewall">High-degree atrioventricular block or other significant bradyarrhythmia</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">&#8226;</span><p id="par0410" class="elsevierStylePara elsevierViewall">Thrombosis of the lower limb until treated</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">&#8226;</span><p id="par0415" class="elsevierStylePara elsevierViewall">Severe abdominal aortic aneurysm</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">&#8226;</span><p id="par0420" class="elsevierStylePara elsevierViewall">Recent stroke or transient ischemic attack</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">Advanced or complicated pregnancy</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">Psychiatric or mental impairment &#40;inability to cooperate&#41;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall">Uncorrected medical conditions&#44; such as significant anemia&#44; important electrolyte imbalance&#44; and hyperthyroidism&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0440" class="elsevierStylePara elsevierViewall">Cardiopulmonary exercise testing is a comprehensive exam aimed at clarifying patient symptoms&#44; differentiating underlying pathophysiological mechanisms&#44; and estimating CRF&#44; disease severity and prognosis&#46; Standardization of CPET-derived data can optimize its accessibility and improve the individualized management of patients across a wide range of clinical contexts&#46; Knowledge of the main indications&#44; applications&#44; and basic interpretation of CPET results is essential to harness its remarkable potential and apply its principal advantages in clinical practice&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0445" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "How to perform cardiopulmonary exercise testing"
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          "titulo" => "Key cardiopulmonary exercise testing variables to analyze"
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          "titulo" => "Indications for cardiopulmonary exercise testing"
          "secciones" => array:10 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Athlete evaluation"
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            1 => array:2 [
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              "titulo" => "Cardiac rehabilitation"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Ischemic heart disease"
            ]
            3 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Cardiomyopathies"
            ]
            4 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Heart failure"
            ]
            5 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Valvular heart disease"
            ]
            6 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Pulmonary hypertension"
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            7 => array:2 [
              "identificador" => "sec0075"
              "titulo" => "Congenital heart diseases"
            ]
            8 => array:2 [
              "identificador" => "sec0080"
              "titulo" => "Dyspnea of unknown cause"
            ]
            9 => array:2 [
              "identificador" => "sec0085"
              "titulo" => "Pulmonary disease"
            ]
          ]
        ]
        9 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Contraindications for cardiopulmonary exercise testing"
        ]
        10 => array:2 [
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          "titulo" => "Conclusions"
        ]
        11 => array:2 [
          "identificador" => "sec0100"
          "titulo" => "Conflicts of interest"
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        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
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    "fechaRecibido" => "2024-01-08"
    "fechaAceptado" => "2024-01-13"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1868111"
          "palabras" => array:6 [
            0 => "Cardiopulmonary exercise testing"
            1 => "Indications"
            2 => "Applications"
            3 => "Interpretation"
            4 => "Cardiovascular"
            5 => "Oxygen consumption"
          ]
        ]
      ]
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        0 => array:4 [
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          "palabras" => array:6 [
            0 => "Prova de esfor&#231;o cardiorrespirat&#243;ria"
            1 => "Indica&#231;&#245;es"
            2 => "Aplica&#231;&#245;es"
            3 => "Interpreta&#231;&#227;o"
            4 => "Cardiovascular"
            5 => "Consumo de oxig&#233;nio"
          ]
        ]
      ]
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      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cardiopulmonary exercise testing &#40;CPET&#41; provides a noninvasive and integrated assessment of the response of the respiratory&#44; cardiovascular&#44; and musculoskeletal systems to exercise&#46; This information improves the diagnosis&#44; risk stratification&#44; and therapeutic management of several clinical conditions&#46; Additionally&#44; CPET is the gold standard test for cardiorespiratory fitness quantification and exercise prescription&#44; both in patients with cardiopulmonary disease undergoing cardiac or pulmonary rehabilitation programs and in healthy individuals&#44; such as high-level athletes&#46; In this setting&#44; the relevance of practical knowledge about this exam is useful and of interest to several medical specialties other than cardiology&#46; However&#44; despite its multiple established advantages&#44; CPET remains underused&#46; This article aims to increase awareness of the value of CPET in clinical practice and to inform clinicians about its main indications&#44; applications&#44; and basic interpretation&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prova de esfor&#231;o cardiorrespirat&#243;ria &#40;PECR&#41; fornece uma avalia&#231;&#227;o n&#227;o invasiva e integrada das respostas ao exerc&#237;cio dos sistemas respirat&#243;rio&#44; cardiovascular e m&#250;sculo-esquel&#233;tico&#46; Essas informa&#231;&#245;es melhoram o diagn&#243;stico&#44; a estratifica&#231;&#227;o de risco e a abordagem terap&#234;utica de diversas condi&#231;&#245;es cl&#237;nicas&#46; Al&#233;m disso&#44; a PECR &#233; o teste <span class="elsevierStyleItalic">gold standard</span> para a quantifica&#231;&#227;o da aptid&#227;o cardiorrespirat&#243;ria e a prescri&#231;&#227;o de exerc&#237;cio&#44; tanto em doentes com doen&#231;a cardiopulmonar em programas de reabilita&#231;&#227;o card&#237;aca ou pulmonar&#44; como em indiv&#237;duos saud&#225;veis&#44; incluindo atletas de alto rendimento&#46; Neste contexto&#44; o conhecimento pr&#225;tico da relev&#226;ncia deste exame &#233; &#250;til e transversal a diversas especialidades m&#233;dicas para al&#233;m da cardiologia&#46; No entanto&#44; apesar das suas m&#250;ltiplas vantagens reconhecidas&#44; a PECR continua subutilizada&#46; Este artigo tem como objetivo aumentar a consciencializa&#231;&#227;o do valor da PECR para a pr&#225;tica cl&#237;nica e informar os m&#233;dicos sobre as suas principais indica&#231;&#245;es&#44; aplica&#231;&#245;es e interpreta&#231;&#227;o b&#225;sica&#46;</p></span>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Some of the main indications for cardiopulmonary exercise testing&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">CRT&#58; cardiac resynchronization therapy&#59; ICD&#58; implanted cardioverter-defibrillator&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Feature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cycle&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treadmill&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Familiarity with exercise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Predicted VO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quantification of external work&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With some algorithms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Quality of ECG monitoring&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">With artifacts&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BP measurement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Harder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ease to take arterial blood gas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Easier&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Harder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Muscles in lower limbs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dependent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less dependent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Patients with pacemakers&#44; ICDs&#44; or CRTs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less appropriate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">More appropriate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Safety&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower &#40;risk of falls&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Size of equipment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mobility of equipment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lower&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Higher&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Normal reference values&#47;risk stratification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">pVO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Normal&#58; 85&#8211;115&#37; of the predicted valueMild impairment&#58; 75&#8211;84&#37; of the predicted valueModerate impairment&#58; 50&#8211;74&#37; of the predicted valueSevere impairment&#58; &#60;50&#37; of the predicted value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO<span class="elsevierStyleInf">2</span> at VT1&#47;predicted pVO<span class="elsevierStyleInf">2</span>&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; 40&#8211;80&#37;Impairment&#58; &#60;40&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">O<span class="elsevierStyleInf">2</span> pulse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Normal&#58; increase&#59; &#8805;80&#37; of the predicted valueImpairment&#58; early plateau or decrease&#59; &#60;80&#37; of the predicted value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">VE&#47;VCO<span class="elsevierStyleInf">2</span> slope<span class="elsevierStyleItalic">for the assessment of V&#47;Q mismatch &#40;only between VT1 and VT2&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal&#58; &#60;30Mild impairment&#58; 30&#8211;35&#46;9Moderate impairment&#58; 36&#8211;45Severe impairment&#58; &#8805;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VE&#47;VCO<span class="elsevierStyleInf">2</span> slope<span class="elsevierStyleItalic">for the assessment of prognosis in patients with HF &#40;the whole slope&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-significant risk&#58; &#60;30&#46;0Mild risk&#58; 30&#46;0&#8211;35&#46;9Moderate risk&#58; 36&#8211;44&#46;9High risk&#58; <span class="elsevierStyleUnderline">&#62;</span>45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EOV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Normal or mild impairment&#58; absentModerate or severe impairment&#58; present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BR at peak exercise&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;30&#37; of the predicted valueRespiratory limitation if below 15&#8211;20&#37; BR &#40;estimated by MVV or FEV1&#215;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SpO<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drop &#60;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MHR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bike</span>&#58;220-age&#177;10 beats&#47;min<span class="elsevierStyleItalic">Treadmill</span>&#58;General population &#40;MHR&#61;208&#8722;0&#46;7&#215;age&#41;Women &#40;MHR&#61;206&#8722;0&#46;88&#215;age&#41;Patients on beta-blockers or other bradycardic drugs&#58; &#40;164&#8722;0&#46;7&#215;age&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;85&#37; of the predicted MHR&#40;MHR&#8722;HR at rest&#41;&#47;&#40;predicted MHR&#8722;HR at rest&#41; &#62;80&#37;MHR &#8805;62&#37; on beta-blockers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HR decay in the 1st minute of recovery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;12 bpm &#40;upright cool-down&#41;&#62;18 bpm &#40;immediate supine&#41;&#62;22 bpm &#40;sitting&#41;&#44; at 2 minutes into the recovery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BP increase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SBP increase &#8805;40 mmHg &#40;upper limit 210 mmHg in men and 190 mmHg in women&#41;DBP remains the same or slightly decreases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic repolarization changes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ST-segment depression that is horizontal or downsloping &#8805;1 mm&#44; extending 60&#8211;80 ms beyond the J-point&#46;Upsloping ST-segment depression &#8805;1&#46;5 mm&#44; extending 80 ms beyond the J-point&#46;ST-segment elevation &#8805;1 mmST&#47;HR index &#8805;1&#46;6 V&#47;bpmST&#47;HR loop in clockwise fashionExercise-induced ST-segment elevation&#44; either isolated or associated with ST-segment depression in a mirror territory in a non-Q wave territory&#44; suggests severe coronary stenosis or a spasm&#46;ST-segment elevation in Q wave leads may represent reversible ischemia&#44; dyskinesis or akinetic left ventricular segmental wall motion in postinfarction patients&#46;Enlargement of the QRS complex during exercise&#46;Exercise-induced left anterior hemiblock suggests stenosis of either the LM or proximal LAD&#46;Exercise induced a left posterior hemiblock can be a marker for RCA or Cx artery stenosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Reference values for selected cardiopulmonary exercise testing parameters&#46;</p>"
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                            0 => "K&#46; Albouaini"
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                            2 => "A&#46; Alahmar"
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                      "titulo" => "Clinician&#39;s guide to cardiopulmonary exercise testing in adults&#58; a scientific statement from the American Heart Association"
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "G&#46;J&#46; Balady"
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                            2 => "K&#46; Sietsema"
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                    0 => array:1 [
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                        "tituloSerie" => "Circulation"
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                      "titulo" => "EACPR&#47;AHA scientific statement&#58; clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations"
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                          "etal" => true
                          "autores" => array:3 [
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                      "titulo" => "2016 focused update&#58; clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations"
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                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehw180"
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                        "tituloSerie" => "Eur Heart J"
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                      "titulo" => "Practical guide to cardiopulmonary exercise testing in adults"
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                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Glaab"
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                    0 => array:2 [
                      "doi" => "10.1186/s12931-021-01895-6"
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                        "tituloSerie" => "Respir Res"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35022059"
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                      "titulo" => "Exercise testing in sports medicine"
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                        "tituloSerie" => "Dtsc Aerzteblatt Int"
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ISSN: 08702551
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