ID in cardiomyocytes impairs mitochondrial respiration and adaptation to acute and chronic increases in workload. Iron supplementation restores cardiac energy reserve and function in iron-deficient hearts.

Aims Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non‐advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non‐advanced HFrEF and explored CI association with systemic iron status and disease severity. Methods and results We enrolled 80 consecutive patients with non‐ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18–33)%. CI was 304 (262–373) μg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2–4). CIQ1 patients had higher serum N‐terminal pro‐B‐type natriuretic peptide levels than CIQ2–4 patients [3566 (1513–6412) vs. 1542 (526–2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end‐diastolic (P = 0.001) and end‐systolic diameter indices (P = 0.003) and higher LV end‐diastolic pressures (P = 0.046) than CIQ2–4 patients. Conclusion Low CI is associated with greater disease severity in patients with non‐advanced non‐ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored.

BackgroundIn patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS) there is scarce evidence for mechanical circulatory support (MCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps in rCS complicating influenza-related myocarditis.MethodsThis is a prospective and observational analysis from the single center Hannover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza virus infection-associated myocarditis complicated by rCS admitted to our ICU on MCS. Subsequently, we performed a propensity score matched analysis to patients with acute myocardial infarction complicated by rCS and non-ischemic cardiomyopathy related rCS.ResultsWe describe a series of seven patients with rCS complicating influenza-related myocarditis (mean age: 56±10 years, 58% males, Influenza A/B n=2/5). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella. In two patients with out-of-hospital cardiac arrest VA-ECMO had been implanted for extracorporeal-cardiopulmonary resuscitation. All patients died within 18 days after hospital admission. By propensity score-based comparison to patients with myocardial infarction- or non-ischemic cardiomyopathy related rCS with combined MCS, 30-day mortality was significantly higher in influenza-related rCS.ConclusionDespite initial stabilisation with combined MCS in patients with rCS complicating influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Potentially, influenza virus infection critically affects other organs besides the heart leading to irreversible end-organ damage, which MCS cannot compensate and, therefore, resulted in a devastating outcome.

Herein we report the case of a young man, admitted to the Department of Cardiology and Angiology at Hannover Medical School with shortness of breath and elevated troponin. Few weeks earlier the patient received the first dose of BioNTech's mRNA vaccine (Comirnaty, BNT162b2). After diagnostic work-up revealed giant cell myocarditis, the patient received immunosuppressive therapy. In the present context of myocarditis after mRNA vaccination we discuss this rare aetiology and the patient's treatment strategy in the light of current recommendations.

Aims Heart failure (HF) after myocardial infarction (MI) is a major cause of morbidity and mortality. We sought to investigate the functional importance of cardiac iron status after MI and the potential of preemptive iron supplementation in preventing cardiac iron deficiency (ID) and attenuating left ventricular (LV) remodelling. Methods and results MI was induced in C57BL/6J male mice by left anterior descending coronary artery ligation. Cardiac iron status in the non-infarcted LV myocardium was dynamically regulated after MI: non-haem iron and ferritin increased at 4 weeks but decreased at 24 weeks after MI. Cardiac ID at 24 weeks was associated with reduced expression of iron-dependent electron transport chain (ETC) complex I compared with sham-operated mice. Hepcidin expression in the non-infarcted LV myocardium was elevated at 4 weeks and suppressed at 24 weeks. Hepcidin suppression at 24 weeks was accompanied by more abundant expression of membrane-localised ferroportin, the iron exporter, in the non-infarcted LV myocardium. Notably, similarly dysregulated iron homeostasis was observed in LV myocardium from failing human hearts, which displayed lower iron content, reduced hepcidin expression, and increased membrane-bound ferroportin. Injecting ferric carboxymaltose (15 µg/g body weight) intravenously at 12, 16, and 20 weeks after MI preserved cardiac iron content and attenuated LV remodelling and dysfunction at 24 weeks compared with saline-injected mice. Conclusion We demonstrate, for the first time, that dynamic changes in cardiac iron status after MI are associated with local hepcidin suppression, leading to cardiac ID long-term after MI. Preemptive iron supplementation maintained cardiac iron content and attenuated adverse remodelling after MI. Our results identify the spontaneous development of cardiac ID as a novel disease mechanism and therapeutic target in postinfarction LV remodelling and HF.