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Vol. 37. Num. 2.February 2018
Pages 97-212
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Vol. 37. Num. 2.February 2018
Pages 97-212
Editorial comment
DOI: 10.1016/j.repce.2018.01.005
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Reduction of systemic inflammation after cardiac resynchronization therapy: A new form of response?
Redução da inflamação sistémica após terapêutica de ressincronização cardíaca: uma nova forma de resposta?
Natália Antónioa,b
a Serviço de Cardiologia A, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
b Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal
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Chronic heart failure (CHF) is the final common pathway for various cardiac pathologies and, despite significant progress in its treatment in recent years, this complex clinical syndrome still has a poor prognosis.1,2

Cardiac resynchronization therapy (CRT) is a well-established option in the treatment of CHF that results in significant clinical improvements, ventricular reverse remodeling, and lower mortality in selected patients.2–4 However, based on current selection criteria, a significant proportion of patients with CHF do not respond positively to CRT.5 It is therefore important to identify new predictors that will improve the selection of potential responders to this therapy.

Although the pathophysiology of CHF is still poorly understood, neurohormonal stimulation and immune activation have been shown to be involved in the development and progression of this systemic disease.6,7 There is growing evidence that levels of various pro-inflammatory cytokines are elevated in patients with CHF, and that this inflammatory response has negative prognostic implications. C-reactive protein (CRP) has been widely studied and is present at higher levels in patients with CHF than in healthy controls.8 Furthermore, high CRP levels in patients with CHF are associated with a worse prognosis.8

However, the impact of CRT on the progression of the systemic inflammatory status associated with CHF has been little investigated, and the scarce information available is contradictory. The study by Almeida-Morais et al. published in this issue of the Journal is thus of considerable relevance.9

The authors present a prospective cohort study involving 115 patients with advanced heart failure of different etiologies and with indication for CRT. The primary aim of the study was to assess changes in inflammatory response based on B-type natriuretic peptide (BNP) and CRP levels following CRT. The secondary aim was to determine the association between changes in inflammatory parameters and functional and echocardiographic response to CRT. The authors defined patients with a minimum increase of 10% in peak oxygen consumption as functional responders, and used the conventional definition of echocardiographic responders as those in whom a reduction of at least 15% in left ventricular end-systolic volume was seen six months after device implantation.

This new study reports innovative and interesting results with regard to the behavior of the inflammatory response in patients undergoing CRT. Overall, CRT was associated with a significant reduction in plasma BNP and CRP levels, suggesting that, in addition to slowing progression of CHF, CRT may also help directly or indirectly to reduce systemic inflammation.

Previous studies have assessed the impact of CRT on the systemic inflammatory response associated with CHF, showing a significant reduction in many inflammatory mediators.10–13 In some of these studies, this reduction was only seen in CRT responders.14,15 However, the literature also includes other studies in which the effect of CRT on inflammatory markers was neutral, even in responders.16,17

The authors of the study observed that functional and echocardiographic responses to CRT were not correlated and that, oddly, only functional responders presented a significant post-CRT reduction in inflammatory parameters. According to these innovative results, improvement in inflammatory status may occur in response to functional improvement in CHF, even in the absence of ventricular reverse remodeling.

Despite the limitations arising from the heterogeneity of the study population in terms of CHF etiology, which may lead to differences in immune activation, this study had the advantage of including a population under optimal pharmacological CHF therapy and with very similar clinical presentations in both responders and non-responders, by both echocardiographic and functional criteria.

We are far from fully understanding the mechanisms behind the effect of CRT on the systemic inflammatory response in CHF, and many questions remain that merit further investigation. If CRT reduces the inflammatory status of patients with CHF, what are the mechanisms underlying this improvement, and what prognostic impact could that reduction in systemic inflammation have? Moreover, can systemic inflammation determine the functional response to CRT? Can immune mechanisms also influence the ability of CRT to induce ventricular reverse remodeling?

Uncertainties remain concerning the impact of CRT on systemic inflammation. However, there is increasing evidence to support the promising hypothesis of a new form of response to CRT – the reduction of inflammatory status associated with CHF.

Conflicts of interest

The author has no conflicts of interest to declare.

D.R. Murray, G.L. Freeman
Proinflammatory cytokines: predictors of a failing heart?
Circulation, 107 (2003), pp. 1460-1462
P. Ponikowski, A.A. Voors, S.D. Anker, Authors/Task Force Members
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC
Eur Heart J, 37 (2016), pp. 2129-2200
F.A. McAlister, J.A. Ezekowitz, N. Wiebe
Systematic review: cardiac resynchronization in patients with symptomatic heart failure
Ann Intern Med, 141 (2004), pp. 381-390
A. Viveiros Monteiro, M. Martins Oliveira
Time to left ventricular reverse remodeling after cardiac resynchronization therapy: better late than never
Rev Port Cardiol, 35 (2016), pp. 161-167
Y. Cheuk-Man, G. John, B.B. Gabe
Usefulness of tissue Doppler velocity and strain dyssynchrony for predicting left ventricular reverse remodeling response after cardiac resynchronization therapy
Am J Cardiol, 100 (2007), pp. 1263-1270
A. Yndestad, J.K. Damås, H. Geir Eiken
Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure
Cardiovasc Res, 54 (2002), pp. 175-182
Seixas-Cambão M., A.F. Leite-Moreira
Pathophysiology of chronic heart failure
Rev Port Cardiol, 28 (2009), pp. 439-471
I.S. Anand, R. Latini, V.G. Florea, Val-HeFT Investigators
C-reactive protein in heart failure: prognostic value and the effect of valsartan
Circulation, 112 (2005), pp. 1428-1434
L. Almeida-Morais, A. Abreu, M. Oliveira
Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: the paradox of functional and echocardiographic response
Rev Port Cardiol, 37 (2018), pp. 105-113
C. Brouwers, H. Versteeg, M. Meine
Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy
Brain Behav Immun, 40 (2014), pp. 211-218
K.T. Lappegård, H. Bjørnstad
Anti-inflammatory effect of cardiac resynchronization therapy
Pacing Clin Electrophysiol, 29 (2006), pp. 753-758
P. Osmancik, D. Herman, P. Stros
Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy
Cardiology, 124 (2013), pp. 190-198
G.N. Theodorakis, P. Flevari, C. Kroupis
Antiinflammatory effects of cardiac resynchronization therapy in patients with chronic heart failure
Pacing Clin Electrophysiol, 29 (2006), pp. 255-261
A. Michelucci, G. Ricciardi, F. Sofi
Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy
T. Shinohara, N. Takahashi, S. Saito
Effect of cardiac resynchronization therapy on cardiac sympathetic nervous dysfunction and serum C-reactive protein level
Pacing Clin Electrophysiol, 34 (2011), pp. 1225-1230
R. Tarquini, C.T. Guerra, M.C. Porciani
Effects of cardiac resynchronization therapy on systemic inflammation and neurohormonal pathways in heart failure
Cardiol J, 16 (2009), pp. 545-552
G. Boriani, F. Regoli, D. Saporito
Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response

Please cite this article as: António N. Redução da inflamação sistémica após terapêutica de ressincronização cardíaca: uma nova forma de resposta? Rev Port Cardiol. 2018;37:115–116.

Copyright © 2018. Sociedade Portuguesa de Cardiologia
Revista Portuguesa de Cardiologia (English edition)

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