Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Coronary Artery Bypass Grafting Following Acute Coronary Syndrome: Impact of Gender.

The impact of gender on clinical outcomes after coronary artery bypass grafting (CABG) has generated conflicting results. We investigated the impact of gender, on 30 day mortality, complications and late survival in patients with acute coronary syndrome (ACS) undergoing CABG. The study included 1308 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 1045 (80%) were men and 263 (20%) women. While women were older and had more hypertension and hyperlipidemia, they demonstrated less diabetes mellitus, previous ischemic heart disease, smoking, and fewer implicated coronary arteries. Women presented with more atypical symptoms as compared to men (26.3% vs 19.4%, p = 0.017). Overall multivariable-adjusted 30 day mortality was higher in women than in men (OR 2.47 95% CI 1.19-5.1, p = 0.015). Among patients with ST-elevation myocardial infarction (STEMI) or non-STEMI, women had a higher 10 year mortality rate than men (42.5% vs 19.2%, log-rank p < 0.001 and 31.5% vs 20.7%, log-rank, p = 0.012). However, in patients with unstable angina pectoris on admission, these differences were not seen (16.9% vs 13.4%, log-rank p = 0.540). Multivariable analysis demonstrated that female gender was a significant predictor for 10 year mortality (HR 1.39, 95% CI 1.02-1.9, p = 0.038). In a real-life setting, women constitute an independent predictor for short- and long-term mortality following ACS treated by CABG surgery. The reasons for a higher mortality in women should be further investigated as well as specific and/or more intensive therapies after CABG in this high-risk group of patients.

Keratin 8 is a potential self-antigen in the coronary artery disease immunopeptidome: A translational approach.

BACKGROUND: Inflammation is an important risk factor in atherosclerosis, the underlying cause of coronary artery disease (CAD). Unresolved inflammation may result in maladaptive immune responses and lead to immune reactivity to self-antigens. We hypothesized that inflammation in CAD patients would manifest in immune reactivity to self-antigens detectable in soluble HLA-I/peptide complexes in the plasma. METHODS: Soluble HLA-I/peptide complexes were immuno-precipitated from plasma of male acute coronary syndrome (ACS) patients or age-matched controls and eluted peptides were subjected to mass spectrometry to generate the immunopeptidome. Self-peptides were ranked according to frequency and signal intensity, then mouse homologs of selected peptides were used to test immunologic recall in spleens of male apoE-/- mice fed either normal chow or high fat diet. The peptide detected with highest frequency in patient plasma samples and provoked T cell responses in mouse studies was selected for use as a self-antigen to stimulate CAD patient peripheral blood mononuclear cells (PBMCs). RESULTS: The immunopeptidome profile identified self-peptides unique to the CAD patients. The mouse homologs tested showed immune responses in apoE-/- mice. Keratin 8 was selected for further study in patient PBMCs which elicited T Effector cell responses in CAD patients compared to controls, associated with reduced PD-1 mRNA expression. CONCLUSION: An immunopeptidomic strategy to search for self-antigens potentially involved in CAD identified Keratin 8. Self-reactive immune response to Keratin 8 may be an important factor in the inflammatory response in CAD.

Immediate response to prasugrel loading in patients with ST-elevation myocardial infarction: Predictors and outcome.

INTRODUCTION: Information regarding immediate response to novel P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) is scarce and has been associated with adequate reperfusion. Recent studies have shown that the onset of anti-platelet effects of novel P2Y12 inhibitors in patients with STEMI might be slower and more variable than in stable coronary syndrome. We aimed to assess the predictors and significance of immediate platelet response to prasugrel loading in STEMI. METHODS: Platelet aggregation (PA) was prospectively evaluated in STEMI patients upon prasugrel loading and at primary percutaneous coronary intervention (PPCI). Early platelet responsiveness was defined as percent reduction of PA from baseline to PPCI, divided by the time lapse from loading to PPCI. High- and low-platelet responsiveness was defined as above and below the median value respectively. RESULTS: Fifty consecutive STEMI patients (age 58±8, 90% male) underwent PPCI with a mean door-to-balloon time of 42±15min. Mean PA upon prasugrel loading and at PPCI was 76±9% and 63±19%, respectively. Older age and prior aspirin use were predictors of low platelet responsiveness to prasugrel [ß=(-0.33), p=0.02 and ß=(-0.28), p=0.04, respectively]. Fast compared with slow responders demonstrated more frequent early ST resolution (93% vs. 72%, p=0.02) and lower peak troponin levels (76±62µg/L vs. 48±28µg/L, p=0.05). CONCLUSIONS: Immediate platelet responsiveness to prasugrel among STEMI patients is highly variable and inversely associated with older age and prior aspirin use. Fast compared with slow responders have improved reperfusion and infarct size markers.

Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

Risk factors and outcomes associated with the development of myocardial ischemic events in patients who receive cardiac resynchronization therapy.

There are limited data regarding risk factors for the development of ischemic events (IEs) among patients with ischemic cardiomyopathy (IC) who receive cardiac resynchronization therapy with a defibrillator (CRT-D) and their effect on the efficacy of the device. The present study population comprised 1,045 patients with IC enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy. We used multivariate Cox proportional hazards regression modeling to identify risk factors for the development of IE (comprising hospitalization for acute coronary syndromes and/or coronary interventions during the trial) among study patients. Time-dependent analysis was performed to identify the effect of IE on the risk for subsequent heart failure (HF) or death in CRT-D recipients. Independent predictors for the development of IE among study patients included previous revascularization (coronary artery bypass surgery: hazard ratio [HR] 1.88, p = 0.003; percutaneous coronary intervention: HR 3.21, p <0.001) and increased systolic blood pressure (HR 1.67, p = 0.02), whereas a left bundle branch block pattern on the baseline electrocardiogram was associated with reduced risk for IE (HR 0.62, p = 0.02). Treatment with CRT-D did not have a significant effect on IE risk compared with defibrillator-only therapy (HR 0.87, p = 0.51). Time-dependent analysis showed that the development of IEs among CRT-D recipients was associated with more than twofold (p = 0.01) increased risk for subsequent heart failure or death. In conclusion, our data suggest that treatment with CRT-D does not reduce the risk of IE in patients with IC and that the benefit of CRT-D is attenuated after the development of IEs in this population.