ABSTRACT
Purpose: The Multicentre observational REgistry of patients hospitalized for heart failure and reAL-life adherence to international guidelines for the management of patients with acute and chronic Heart Failure (REAL-HF) aims to provide a comprehensive overview of hospital management of HF patients in Italy. Method(s): The registry involves 11 cardiology centers from seven Italian regions, including all adult patients hospitalized for HF in the period 2020-2026. Data are derived from hospital discharge letters and electronic records. Patients are included in the registry based on Diagnosis Related Groups codes. Result(s): This preliminary analysis included 1600 patients hospitalized for HF in 2020 in two Italian tertiary university hospitals. Males were 851(53%) with a median age of 81(71-87) years. Less than one-third of the patients (n=461[29%]) was hospitalized in a cardiology unit, while almost half of the patients (n=783[49%]) was admitted to an internal medicine ward. Median hospital length of stay was 9(6-14) days. Readmission rates were 9% and 29% at 30 days and within the same year, respectively. In-hospital mortality was 9%, while 28% of the patients died within the same year. According to HF categories, 501(31%) patients were diagnosed as having HFrEF, 193(12%) mildly reduced ejection fraction (HFmrEF) and 689(43%) preserved ejection fraction (HFpEF). Median left ventricular EF was 49%(35-55%) and was significantly lower in patients with HFrEF (30%[25-35%]) compared to those with HFmrEF (45%[43-45%]) and HFpEF (55%[55-60%]) - p<0.001. Coronary artery disease proved to be the leading cause (n=460[29%]) of HF. Atrial fibrillation was highly prevalent (history -13%;during hospitalization -37%). Arterial hypertension was the most prevalent (71%) cardiovascular risk factor. Chronic kidney disease (51%) and chronic obstructive pulmonary disease (27%) were frequent comorbidities. Apparently, COVID-19 had a low impact, being present in only 3% of patients hospitalized for HF in 2020 at both centers. At discharge, 56% of patients were treated with angiotensin-converting enzyme inhibitors-ACEi (n=490[34%]), angiotensin receptor blockers-ARB (n=221[15%]) or angiotensin-neprilysin inhibitors-ARNi (n=100[7%]), 67%(n=964) with beta-blockers, while mineralocorticoid receptor antagonists- MRAs were prescribed for 56%(n=809) of patients. Loop diuretics were frequently prescribed (89%). When we considered patients with HFrEF, we found that only 69% were treated with ACEi/ARB/ARNi, 82% with a beta-blocker, and 67% with MRAs. Only 48% (n=240) were treated with all three of the abovementioned classes of drugs. Among patients with HFrEF, only 5% had an implantable cardioverter defibrillator, and only 4% were treated with cardiac resynchronization therapy. Patients hospitalized in wards other than cardiology were older (83vs70 years, p<0.0001), more frequently females (52%vs44%, p<0.001), and with HFpEF (51%vs24%, p<0.0001). In-hospital mortality and death within the same year resulted significantly lower in patients hospitalized in cardiology units (5%vs11% - p<0.001, and 17%vs32% - p<0.001). Overall, drugs indicated in HF were less frequently prescribed in patients hospitalized in non-specialist cardiac units. Conclusion(s): Preliminary data from the multicentre REAL-HF registry confirm that HF constitutes a clinical issue. Adherence to the guidelines is still inadequate and this may impact on patients' outcomes. Moreover, the significant differences in terms of patients' profiles might further increase the gap between highly specialized cardiology units and internal medicine departments.
ABSTRACT
Background and purpose: Increased inflammatory cytokines, including interleukin 6 (IL-6), are associated to enhanced arrhythmogenic risk, including atrial fibrillation [1]. Moreover, direct effects of cytokines on ion channels are emerging as important mediators of arrhythmogenic remodeling [2]. In line with this, enhanced arrhythmogenesis in COVID-19 patients is hypothesized to be driven by cytokine storms, a well demonstrated condition in this setting [3]. To dissect the underlying mechanisms explaining such an association, we evaluated the proarrhythmogenic alterations of IL-6, assessing the impact on the expression of Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, of the regulatory subunits MiRP1, and on the action potential (AP) profile in HL-1 cardiomyocytes (CMs). In human left atrial samples we studied the relation occurring between the expression levels of IL-6 and of HCN channels. In human induced pluripotent stem cell (hiPSC)-derived CMs we evaluated the acute effects of IL-6 on pacemaker activity. Methods: HL-1 CMs exposed to 50 ng/ml IL-6 or vehicle were collected after 0, 0.5, 6, 12, 24 and 48 h to study intracellular signaling, ion channel expression and AP profile. The latter was assessed through a high-throughput system allowing optical detection of APs with optical stimulation. In human atrial samples obtained from patients undergoing surgery, IL-6 and HCN mRNA expression were analyzed by quantitative RT-PCR. The acute effects on pacemaker activity were evaluated in hiPSC-derived CMs exposed to increasing concentrations of IL-6. Results: In HL1 CMs IL-6 rapidly induces STAT3 phosphorylation, demonstrating the activation of IL-6 signaling cascade. IL-6 modifies HCN channel transcript and proteins at different time points, evidencing a significant downregulation of HCN4 isoform and significant upregulations of HCN1, HCN2 and MiRP1. In line with this, in human left atrial samples, expression levels of IL-6 were linearly and directly related to HCN1 channel, while they were linearly and inversely related to HCN4. Electrophysiological recordings on HL-1 CMs showed a decreasing trend of AP amplitude and of maximum diastolic potential, while AP durations tended to increase. In hiPSC-derived CMs IL-6 reduces the frequency of AP in a concentration-dependent manner. Conclusions: Our data demonstrate that in HL-1 CMs IL-6 activates a STAT3 dependent intracellular signaling that is associated to subsequent variation of HCN channel expression and a concurrent alteration of AP profile. The relation between IL-6 and HCN1,4 expression in human samples suggests a mechanistic link between IL-6 levels and ionic channel targets, including HCN channels. The reduction of AP frequency in hiPSC-derived CMs suggests a direct interaction with ion channels. We hypothesize that these modifications may lay the basis to enhance the propensity of atria to develop arrhythmias in condition of elevate IL-6 levels.
ABSTRACT
Background: SARS-CoV-2 infection might be associated with cardiac complications in low-risk populations, such as in competitive athletes. However, data obtained in adults cannot be directly transferred to preadolescents and adolescents that are less susceptible to adverse clinical outcomes and are often asymptomatic. Purpose: We conducted this prospective multi-centre study to describe the incidence of cardiovascular complications following SARS-CoV-2 infection in a large cohort of junior athletes and to examine the effectiveness of a screening protocol for a safe return-to-play. Methods: Junior competitive athletes suffering from asymptomatic or mildly symptomatic SARS-CoV-2 infection underwent cardiac screening, including physical examination, 12-lead resting electrocardiogram (ECG), echocardiogram, and exercise ECG testing. Further investigations were performed in cases of abnormal findings. Results: A total of 571 competitive junior athletes (14.3±2.5 years) were evaluated. About half of the population (50.3%) was mildly symptomatic during SARS-CoV-2 infection, and the average duration of symptoms was 4±1 days. Pericardial involvement was found in 3.2% of junior athletes: small pericardial effusion (2.6%), moderate pericardial effusion (0.2%), and pericarditis (0.4%). No relevant arrhythmias or myocardial inflammation were found in subjects with pericardial involvement. Athletes with pericarditis or moderate pericardial effusion were temporarily disqualified, and a gradual return-to-play was achieved after complete clinical resolution. Conclusions: The prevalence of cardiac involvement was low in junior athletes after asymptomatic or mild SARS-CoV-2 infection. A screening strategy primarily driven by cardiac symptoms, ECG abnormalities and arrhythmias at rest and/or during exercise should detect cardiac involvement from SARS-CoV-2 infection in most junior athletes. Systematic echocardiographic screening is not recommended in junior athletes. (Figure Presented).
ABSTRACT
Background and aims: The clinical adverse events of COVID-19 among clergy worldwide have been found higher than among ordinary communities, probably because of the nature of their work. The aim of this study, was to assess the impact of cardiac risk factors on COVID-19-related mortality and the need for mechanical ventilation in Coptic clergy. Methods: Of 1576 Coptic clergy participating in the COVID-19-Clergy study, serving in Egypt, USA and Europe, 213 had the infection and were included in this analysis. Based on the presence of systemic arterial hypertension (AH), participants were divided into two groups: Group- I, Clergy with AH (n=77) and Group-II, without AH (n=136).Participants' demographic indices, cardiovascular risk factors, COVID-19 management details and related mortality were assessed. Results: Clergy with AH were older (p<0.001), more obese (p=0.04), had frequent type 2 diabetes (DM) (p=0.001), dyslipidemia (p=0.001) and coronary heart disease (CHD) (p=0.04) compared to those without AH. COVID- 19 treatment at home, hospital or in intensive care did not differ between the patient groups (p>0.05 for all). Clergy serving in Northern and Southern Egypt had a higher mortality rate compared to those from Europe and the USA combined (5.22%, 6.38%, 0%;p=0.001). The impact of AH on mortality was significant only in Southern Egypt (10% vs. 3.7%;p=0.01) but not in Northern Egypt (4.88% vs. 5.81%;p=0.43). In multivariate analysis, CHD OR 1.607 [(0.982 to 3.051);p=0.02] and obesity, OR 3.403 [(1.902 to 4.694);p=0.04]predicted COVID-19 related mortality. A model combining cardiac risk factors (systolic blood pressure (SBP) ≥160 mmHg, DM, obesity, dyslipidemia and history of CHD), was the most powerful independent predictor of COVID-19-related mortality, OR 4.813 [(2.011 to 7.017);p=0.008]. The same model also proved the best independent multivariate predictor of mechanical ventilation OR 1.444 [(0.949 to 11.88);p=0.001]. Conclusion: In Coptic clergy, the cumulative impact of risk factors is the most powerful predictor of mortality and the need for mechanical ventilation in Coptic clergy.