Elsevier

International Journal of Cardiology

Volume 300, 1 February 2020, Pages 14-19
International Journal of Cardiology

Iron deficiency in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

https://doi.org/10.1016/j.ijcard.2019.07.083Get rights and content

Highlights

  • Iron deficiency (ID) is a frequent condition in patients with STEMI.

  • It is associated with mitochondrial injury, as reflected by higher levels of mitochondrial DNA.

  • ID is paradoxically associated with a better in-hospital outcome.

  • This result is associated with a lower myocardial reperfusion injury, as assessed by CMR.

Abstract

Background

Iron deficiency (ID) is a known co-morbidity and a potential therapeutic target in heart failure. Whether ID is frequent also in ST-segment elevation acute myocardial infarction (STEMI) patients and is associated with worse in-hospital outcomes has never been evaluated.

Methods

We defined ID as a serum ferritin < 100 μg/L or transferrin saturation < 20% at hospital admission. We assessed the association between ID and the primary endpoint (a composite of in-hospital mortality and Killip class ≥ 3). We explored the potential association between ID, circulating cell-free mitochondrial DNA (mtDNA), and cardiac magnetic resonance (CMR) parameters.

Results

Four-hundred-twenty STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were included. Of them, 237 (56%) had ID. They had significantly higher admission high-sensitivity troponin and mtDNA levels as compared to non-ID patients (145 ± 35 vs. 231 ± 66 ng/L, P < 0.001; 917 [404–1748] vs. 1368 [908–4260] copies/μL; P < 0.003, respectively). A lower incidence of the primary endpoint (10% vs. 18%, P = 0.01) was observed in ID patients (adjusted OR 0.50 [95% CI 0.27–0.93]; P = 0.02). At CMR (n = 192), ID patients had a similar infarct size (21 ± 18 vs. 21 ± 19 g; P = 0.95), but a higher myocardial salvage index (0.56 ± 0.30 vs. 0.43 ± 0.27; P = 0.002), and a smaller microvascular obstruction extent (3.6 ± 2.2 vs. 6.9 ± 3.9 g; P < 0.001).

Conclusions

Iron deficiency is frequent in STEMI patients, it is coupled with mitochondrial injury, and, paradoxically, with a better in-hospital outcome. This unexpected clinical result seems to be associated with a smaller myocardial reperfusion injury. The mechanisms underlying our findings and their potential clinical implications warrant further investigation.

Introduction

Primary percutaneous coronary intervention (pPCI) is the most effective strategy for reducing infarct size and ventricular dysfunction, demonstrating improved clinical outcomes in patients with ST-segment elevation acute myocardial infarction (STEMI) [1]. Myocardial reperfusion, however, can induce further injury to the myocardium, so that the benefit of pPCI may be partially thwarted [2].

Mitochondria play a key role in cardiac function. They supply the necessary biological energy to the cell by contributing to the production of myocardial adenosine-triphosphate (ATP), a process requiring iron availability [3]. In addition to its role in oxygen uptake and transport as an element of hemoglobin, iron has an important function in cellular oxygen metabolism, acting as a key mitochondrial enzymatic cofactor of the respiratory chain [4]. Thus, iron is crucial for the homeostasis of every cell, particularly for the highly energy-demanding cardiac myocytes [4]. As mitochondrial dysfunction has been identified as a central mechanism underlying myocardial ischemia-reperfusion injury [5], it can be hypothesized that iron deficiency (ID) may exacerbate myocardial damage in STEMI. Notably, ID has been shown to be a frequent condition in heart failure, even in non-anemic patients [6,7], and to be associated with poorer cardiac function and higher mortality [7,8]. However, no data are available on whether ID is also common in STEMI patients and is associated with mitochondrial dysfunction, impaired cardiac function, and worse in-hospital outcomes.

The purpose of this prospective study was to determine the prevalence, clinical predictors, and in-hospital clinical consequences of ID in unselected consecutive STEMI patients undergoing pPCI. In order to explore the possible association between ID and mitochondrial impairment, we also measured the plasma levels of circulating cell-free mitochondrial DNA (mtDNA) [9].

Section snippets

Study population

This prospective study was conducted at Centro Cardiologico Monzino, University of Milan between October 1, 2015 and September 30, 2018. During this time, we enrolled all the consecutive STEMI patients undergoing pPCI. Patients were included if they were admitted within 12 h (24 h for those with cardiogenic shock) from symptom onset, and had at least 1-mm ST-segment elevation in two or more contiguous leads or a new left bundle branch block. Patients with known hemochromatosis, history of

Results

A total of 420 consecutive STEMI patients undergoing pPCI (mean age 65 ± 12 years, 325 men) were included in the study. Of them, 237 (56%) had ID. Table 1 shows the baseline characteristics of patients with and without ID. The two groups were similar regarding clinical and laboratory parameters, except for diabetes mellitus and anemia, which were more likely in patients with ID. Moreover, patients with ID had significantly higher hs-TnI and mtDNA levels at hospital admission than those without

Discussion

The present study indicates that ID is a frequent condition in STEMI patients and is unexpectedly associated with a better in-hospital outcome.

Iron deficiency is now recognized as an important comorbidity in acute and chronic heart failure, and many studies have reported a high (30–50%) prevalence, even among patients without anemia [[6], [7], [8]]. In chronic heart failure, ID has been associated with impaired exercise capacity, reduced quality of life, and worse prognosis [[6], [7], [8]].

Funding sources

This work was supported by the Centro Cardiologico Monzino, I.R.C.C.S., Milan, Italy. This work was supported by the Centro Cardiologico Monzino, Italy. The study's sponsor had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Disclosures

None.

Conflict of interest

None.

Acknowledgments

We acknowledge Michela Palmieri, MA, for her precious help in revising the manuscript.

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    All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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