Background: Low cardiorespiratory fitness is an established risk predictor for chronic non-communicable diseases. We aimed to investigate the prognostic significance of fitness level on the risk of major adverse cardiac events (MACE, the composite of myocardial infarction, stroke, or all-cause death), in a contemporary cohort of middle-aged subjects without cardiovascular disease. Methods: Retrospective analysis of patients aged 40–60 years without a history of cardiovascular disease. Degree of fitness was determined according to a graded, maximal treadmill exercise stress testing (EST) time achieved, classified into age- and sex-specific quintiles (Q), and categorized as low (Q1), moderate (Q2–Q4) or high (Q5) fitness groups. A multivariable Cox proportional hazard regression model was used to assess the association of fitness level with the risk of MACE. Results: A total of 6836 patients were included, of which 44.5% were women, and the mean age was 52 years. Overall, 289 MACE events occurred during a median follow-up of 7 years. Level of fitness was inversely associated with the presence of cardiovascular risk factors. The multivariable adjusted hazard ratio (95% confidence interval) for MACE was 1.65 (1.12–2.44) and 2.17 (1.40–3.38) in those at moderate and low fitness levels, compared to the high-fitness group (reference), respectively. For each decrease of one metabolic equivalent (MET) unit achieved at peak exercise, the relative risk for MACE increased by 18%. The association between low fitness and MACE was not modified by other risk factors (P-for-interaction non-significant). Conclusions: Low fitness level, as captured by a maximal treadmill EST, is an independent risk predictor for MACE among middle-age individuals without known cardiovascular disease. The association of low fitness with high burden of cardiometabolic risk factors highlight the importance of lifestyle intervention in this patient population.

Aims The effect of elevated heart rate (HR) on morbidity and mortality is evident in chronic stable heart failure; data in this regard in acute decompensated heart failure (ADHF) setting are scarce. In this single-centre study, we sought to address the prognostic value of HR and beta-blocker dosage at discharge on all-cause mortality among patients with heart failure and reduced ejection fraction and ADHF. Methods and results In this retrospective observational study, 2945 patients were admitted for the first time with the primary diagnosis of ADHF between January 2008 and February 2018. Patients were divided by resting HR at discharge into three groups (HR < 70 b.p.m., HR 70–90 b.p.m., and HR > 90 b.p.m.). Evidence-based beta-blockers were defined as metoprolol, bisoprolol, and carvedilol. The doses of prescribed beta-blockers were calculated into a percentage target dose of each beta-blocker and divided to four quartiles: 0 < Dose ≤ 25%, 25% < Dose ≤ 50%, 50% < Dose ≤ 75%, and >75% of the target dose. Cox regression was used to calculate the hazard ratio for various HR categories and adjusting for clinical and laboratory variables. At discharge, 1226 patients had an HR < 70 b.p.m., 1347 patients had an HR at range 70–90 b.p.m., and 372 patients with an HR > 90 b.p.m. The 30 day mortality rate was 2.2%, 3.7%, and 12.1% (P < 0.001), respectively. Concordantly, 1 year mortality rate was 14.6%, 16.7%, and 30.4% (P < 0.001) among patients with HR < 70 b.p.m., HR 70–90 b.p.m., and HR > 90 b.p.m., respectively. The adjusted hazard ratio was significantly increased only in HR above 90 b.p.m. category (hazard ratio, 2.318; 95% confidence interval, 1.794–2.996). Conclusions Patients with ADHF and an HR of <90 b.p.m. at discharge had significantly a lower 1 year mortality independent of the dosage of beta-blocker at discharge. It is conceivable to discharge these patients with lower HR.

Background: Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS). Few real-world data are available regarding the early implementation of HF therapies in patients with ACS and reduced LVEF. Methods: Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). The utilization of HF therapies at discharge or 90 days following ACS was analyzed in relation to LVEF [reduced ≤40% (n = 406) or mildly-reduced 41–49% (n = 255)] and short-term adverse outcomes. Results: History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p < 0.001) were more prevalent in those with reduced compared to mildly-reduced LVEF. ACEI/ARB/ARNI and beta-blockers were used by the majority of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF ≤ 40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41–49%, respectively, and SGLT2I in about a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p = 0.084. No association was observed between the number of HF drug classes or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions: In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.

Polymicrobial endocarditis is uncommon, and polymicrobial endocarditis in combination with Coxiella burnetii is very rare. We herein describe an extremely rare case of polymicrobial bivalvular endocarditis due to coinfection with Enterococcus faecalis and Coxiella burnetii in a 62-year-old male patient, and extensively review the relevant medical literature. To the best of our knowledge, only three similar cases have been previously reported. Q fever is a worldwide endemic bacterial zoonosis, but it and its most common chronic complication, endocarditis, are still underestimated and underdiagnosed worldwide. This situation reflects the paucity of reported cases of polymicrobial endocarditis in combination with Coxiella burnetii. Clinical presentation of Q fever endocarditis is highly nonspecific, and diagnosis may be delayed or missed, leading to severe and potentially fatal disease. Our case and the previously reported similar cases emphasize the need for further evaluation of infective endocarditis due to Coxiella burnetii, in all cases of culture-negative endocarditis, and in prolonged oligo-symptomatic inflammatory syndrome, particularly in the presence of valvular heart disease. This approach should be applied even when typical pathogens are isolated, especially in endemic areas of Q fever, and with atypical presentation.

Introduction: A direct head-to-head comparison between potent P2Y12 inhibitors: prasugrel versus ticagrelor is still lacking. Purpose: In this single-center study, we sought to address the efficacy and safety of these two third-generation antiplatelet drugs, after about a decade of practical use. Methods: A retrospective observational study included all patients who were admitted with acute coronary syndrome between January 2010 and December 2019 and were discharged with aspirin and either prasugrel or ticagrelor after percutaneous coronary intervention. Patients were divided into two groups based on the dual antiplatelet drugs prescribed. Primary endpoint: A composite endpoint of cardiovascular death, recurrent coronary syndrome, or ischemic stroke at one year. Secondary endpoint: Significant bleeding according to the BARC classification (types 3, 4, or 5). Results: During this period, 746 patients met the inclusion criteria. The primary endpoint was reached in 70 patients (9.4%): 24 patients (8.0%) in the group treated with ticagrelor and 46 patients (10.3%) in the group treated with prasugrel (p-value = 0.303). In terms of safety events, significant bleeding was not statistically different between the ticagrelor and prasugrel groups: 13 (2.9%) vs. 9 (3%), respectively (p-value = 0.9). More patients discontinued their treatment before the end of the year among those treated with ticagrelor compared to those treated with prasugrel (16.7% vs. 9.6%, p-value = 0.003). Conclusions: There was no significant difference in the occurrence of recurrent cardiac events, stroke, or cardiovascular death, nor significant bleeding among ACS patients treated either with prasugrel or ticagrelor.

Background: Guideline-directed medical therapies for heart failure (HF) may benefit patients with reduced left ventricular ejection fraction (LVEF) following acute coronary syndromes (ACS), even in the absence of overt HF. Few real-world data are available regarding early implementation of HF therapies in patients with ACS and reduced LVEF. Methods: Data collected from the 2021 nationwide, prospective ACS Israeli Survey (ACSIS). Drug classes included: (a) angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI); (b) beta-blockers; (c) mineralocorticoid receptor antagonist (MRA) and (d) sodium-glucose cotransporter-2 inhibitors (SGLT2I). Utilization of HF therapies at discharge or 90-days following ACS was analyzed in relation to LVEF [reduced ≤40% (n=406) or mildly-reduced 41-49% (n=255)] and short-term adverse outcomes. Results: History of HF, anterior wall myocardial infarction and Killip class II-IV (32% vs. 14% p85% of patients in both LVEF groups, though ARNI was prescribed to only 3.9% (LVEF≤40%). MRA was used by 42.9% and 12.2% of patients with LVEF ≤40% and 41-49%, respectively, and SGLT2I in a quarter of both LVEF groups. Overall, ≥3 HF drug classes were documented in 44% of the patients. A trend towards higher rates of 90-day HF rehospitalizations, recurrent ACS or all-cause death was noted in those with reduced (7.6%) vs. mildly-reduced (3.7%) LVEF, p=0.084. No association was observed between the number of HF drug classes, or the use of ARNI and/or SGLT2I with adverse clinical outcomes. Conclusions: In current clinical practice, the majority of patients with reduced and mildly-reduced LVEF are treated by ACEI/ARB and beta-blockers early following ACS, whereas MRA is underutilized and the adoption of SGLT2I and ARNI is low. A greater number of therapeutic classes was not associated with reduced short-term rehospitalizations or mortality.Drug therapies for heart failure