Vaccine-carditis study: Spanish multicenter registry of inflammatory heart disease after COVID-19 vaccination.

INTRODUCTION AND OBJECTIVES: Vaccines against SARS-CoV-2 have been a major scientific and medical achievement in the control of the COVID-19 pandemic. However, very infrequent cases of inflammatory heart disease have been described as adverse events, leading to uncertainty in the scientific community and in the general population. METHODS: The Vaccine-Carditis Registry has included all cases of myocarditis and pericarditis diagnosed within 30 days after COVID-19 vaccination since August 1, 2021 in 29 centers throughout the Spanish territory. The definitions of myocarditis (probable or confirmed) and pericarditis followed the consensus of the Centers for Disease Control and the Clinical Practice Guidelines of the European Society of Cardiology. A comprehensive analysis of clinical characteristics and 3-month evolution is presented. RESULTS: From August 1, 2021, to March 10, 2022, 139 cases of myocarditis or pericarditis were recorded (81.3% male, median age 28 years). Most cases were detected in the 1st week after administration of an mRNA vaccine, the majority after the second dose. The most common presentation was mixed inflammatory disease (myocarditis and pericarditis). 11% had left ventricular systolic dysfunction, 4% had right ventricular systolic dysfunction, and 21% had pericardial effusion. In cardiac magnetic resonance studies, left ventricular inferolateral involvement was the most frequent pattern (58%). More than 90% of cases had a benign clinical course. After a 3-month follow-up, the incidence of adverse events was 12.78% (1.44% mortality). CONCLUSIONS: In our setting, inflammatory heart disease after vaccination against SARS-CoV-2 predominantly affects young men in the 1st week after the second dose of RNA-m vaccine and presents a favorable clinical course in most cases.

Neutrophil extracellular traps (NETs) in patients with STEMI. Association with percutaneous coronary intervention and antithrombotic treatments.

BACKGROUND: Neutrophil extracellular traps (NETs) are formed by DNA, histones and proteolytic enzymes, and are produced by activated neutrophils through different mechanisms. In turn, NETs can activate platelets and coagulation cascade favoring thrombotic processes. The aims of this study were to analyze levels and kinetics of NETs in ST-segment elevation myocardial infarction (STEMI) patients and correlate them with antithrombotic therapy and cardiovascular outcomes at follow-up. METHODS: 150 consecutive STEMI patients referred to primary percutaneous coronary intervention (pPCI) were included. Citrate anticoagulated blood was extracted immediately before pPCI, 30 min and 24 h after the procedure. As markers of NETS cell free DNA (cfDNA), nucleosomes and citrullinated Histone 3 (citH3) were determined. 46 healthy subjects were included as controls. Patients were follow-up for 1.4 ± 0.56 years. RESULTS: Before pPCI, NETs markers were elevated in STEMI patients compared to healthy controls (p < 0.05); these increased significantly 30 min post pPCI (p ≤ 0.001) and decreased at 24 h but remained elevated compared with the control group (p < 0.05). Patients treated with bivalirudin presented a lower increase of NETs 30 min post pPCI compared to patients treated with heparin (p < 0.05). Cardiovascular risk factors or type of stent implanted did not modify NETs levels. Cit3H (HR = 3.74; 95%CI 1.05-13.4; p = 0.042) and left ventricular ejection fraction ≤35% (HR = 6.84; 95%CI 2-23; p = 0.002) were independent predictors of composite endpoint of myocardial infarction, stroke, stent thrombosis and/or cardiovascular-cause death. CONCLUSIONS: NETs were elevated in STEMI patients, increased by pPCI and decreased thereafter. One of the most specific NETs markers was associated with cardiovascular outcomes.

Glycoprotein and Lipoprotein Profiles Assessed by 1H-NMR and Its Relation to Ascending Aortic Dilatation in Bicuspid Aortic Valve Disease.

INTRODUCTION: The bicuspid aortic valve (BAV) confers a high risk of ascending aorta dilatation (AAoD), although its progression seems highly variable. Furthermore, the implication of lipoprotein metabolism and inflammation in the mechanisms that underlie AAoD is not fully established. The aim of this study consisted of evaluating the impact of the lipoprotein and glycoprotein profiles in AAOD as well as its progression in BAV aortopathy. METHODS: Using 1H-nuclear magnetic resonance (1H-NMR), we analyzed and compared the lipoprotein and glycoprotein profiles of plasma samples from 152 BAV patients with dilated and nondilated ascending aorta. Additionally, these profiles were also compared for 119 of these patients who were prospectively followed-up clinically and by echocardiography in the long-term (5 years). Ascending aorta dilation velocity (mm/year) was calculated for this analysis. RESULTS: Several parameters related to the lipoprotein profile including remnant cholesterol, small LDL and IDL-cholesterol were found to be significantly increased in the dilated group compared to those in the nondilated group. The glycoprotein A-nuclear magnetic resonance (NMR) signal, a novel inflammation biomarker, was also observed to be increased in the dilated group. After performing multivariate analysis, remnant cholesterol remained an independent variable related to AAoD. In the long-term follow-up, proatherogenic lipoprotein parameters were related to ascending aorta dilatation velocity ascending. After a lineal regression analysis, non-HDL particles remained as an independent predictor of ascending aorta dilation velocity. CONCLUSIONS: Patients with BAV and AAoD presented a more pro-atherogenic profile assessed by 1H-NMR, especially related to triglyceride-rich lipoproteins. This pro-atherogenic profile seems to contribute to the higher growth rate of ascending aorta diameter.

Improvement in Atrial Fibrillation-Related Symptoms After Cardioversion: Role of NYHA Functional Class and Maintenance of Sinus Rhythm.

BACKGROUND: The European Heart Rhythm Association (EHRA) score is a proven and validated tool for assessing the symptoms of atrial fibrillation (AF). Little is known about the variables related to this score and how it changes after cardioversion. METHODS: We analyzed 744 patients undergoing elective cardioversion in whom AF-related symptoms were assessed at baseline and after 6 months of follow-up using the EHRA score. We assessed the association between the EHRA score and other clinical and echocardiographic variables at baseline and after 6 months of follow-up. RESULTS: At 6 months of follow-up, we observed a reduction in the EHRA score in 50% and worsening in 2.8% of patients who remained in sinus rhythm (SR) compared with 34.6% and 11.3%, respectively, of patients with AF episodes (p<0.0001). Patients who maintained SR at 6 months were less symptomatic than those with AF (EHRA score 1.13 ± 0.35 vs 1.42 ± 0.59; p<0.0001). The independent predictors for reduction in the EHRA score after cardioversion were NYHA ≥II at baseline and maintenance of SR (p<0.0001). CONCLUSION: The greatest improvement in AF-related symptoms was in patients who remained in SR at 6 months after cardioversion and in patients with worse NYHA functional class at baseline.

Prognostic value and clinical predictors of intramyocardial hemorrhage measured by CMR T2* sequences in STEMI.

Recent studies show that microvascular injury consists of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). In patients with reperfused ST-segment elevation myocardial infarction (STEMI) quantitative assessment of IMH with T2* cardiovascular magnetic resonance imaging (CMR) appears to be useful in evaluation of microvascular damage. The current study aimed to investigate feasibility of this approach and to correlate IMH with clinical and CMR parameters. A single center observational cohort study was performed in reperfused STEMI patients with CMR examination 7 days (IQR: 5 to 8 days) after percutaneous coronary intervention. Infarct size (IS) and MVO were evaluated in short-axis late gadolinium enhancement sequences and IMH with whole LV volume T2* mapping sequences. Of the 94 patients, MVO was identified in 52% of patients and the median size of MVO was 3% of LV mass (IQR: 1.5 to 5.4%). IMH was present in 28% of patients and the median size of IMH was 1.1% of LV mass (IQR: 0.5 to 2.9%). IMH extent was independently associated with anterior myocardial infarction (p = 0.022) and thrombectomy (p = 0.049). IMH was correlated with MVO (R = 0.62, p < 0.001), necrosis (R = 0.58, p < 0.001) and LVEF (R = -0.21, p = 0.04). Patients with IMH presented higher incidence of MACE events, independently of LVEF (p = 0.022). T2* mapping is a novel imaging approach that proves useful to asses IMH in the setting of reperfused STEMI. T2* IMH extent was associated with anterior infarction and thrombectomy. T2* IMH was associated with higher incidence of MACE events regardless preserved or reduced LVEF.

Sacubitril-Valsartan in a routine community population: attention to volume status critical to achieving target dose.

AIMS: In the PARADIGM-heart failure trial, sacubitril-valsartan demonstrated a reduction in heart failure admissions and reduced all-cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear. This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population. METHODS AND RESULTS: This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of ≥30%, or an increase in left ventricular ejection fraction of ≥5% compared with baseline values. To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL/min/1.72 m2 [36.8, 60.2] vs 60 mL/min/1.72 m2 [47, 77]; P ≤ 0.001). Of the remaining 257 patients, TD (97/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49/51 mg BD and 26 patients (8.1%) remained on 24/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD. CONCLUSIONS: Sacubitril-valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril-valsartan.