Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series.

Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14-39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.

Right ventricular myocardial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.

OBJECTIVE: We hypothesized that in patients with heart failure with normal left ventricular (LV) ejection fraction (HFNEF), the same fibrotic processes that affect the subendocardial layer of the LV could also alter the subendocardial fibers of the right ventricle (RV). Consequently, these alterations and to a lesser extent chronically elevated pulmonary arterial pressures would lead to both systolic and diastolic subendocardial dysfunction of the RV (i.e., impaired RV longitudinal systolic and diastolic function) in patients with HFNEF. METHODS: Patients with HFNEF and a control group consisting of asymptomatic patients with LV diastolic dysfunction (asymptomatic LVDD) matched by age, gender, and LV ejection fraction were studied by two-dimensional speckle-tracking echocardiography. RESULTS: A total of 565 patients were included (201 with HFNEF and 364 with asymptomatic LVDD). RV longitudinal diastolic (RV global longitudinal early-diastolic strain rate [RV-SRe]) and systolic (RV global longitudinal systolic strain [RV-Strain]) function were significantly more impaired in patients with HFNEF than in patients with asymptomatic LVDD (HFNEF: RV-Strain -14.41% ± 3.80% and RV-SRe 0.86 ± 0.33 s(-1); asymptomatic LVDD: RV-Strain -16.90% ± 4.28% and RV-SRe 1.02 ± 0.34 s(-1); all P < .0001). On multiple regression analysis, LV global longitudinal systolic strain was the most important independent predictor of RV longitudinal systolic and diastolic function, in contrast with pulmonary arterial systolic pressure, which was weakly related to these functions. Furthermore, in patients with HFNEF the subendocardial function of both the LV and RV were significantly impaired in similar proportions. In that regard, in patients with HFNEF the prevalences of RV longitudinal systolic and diastolic dysfunction were 75% and 48%, whereas the rates of LV longitudinal systolic and diastolic dysfunction were 80% and 60%, respectively. In addition, patients with both systolic and diastolic longitudinal dysfunction of the RV presented worse New York Heart Association functional class. CONCLUSION: In patients with HFNEF, RV subendocardial systolic and diastolic dysfunction are common and possibly associated with the same fibrotic processes that affect the subendocardial layer of the LV and to a lesser extent with RV pressure overload. Furthermore, our findings suggest that RV longitudinal systolic and diastolic dysfunction could contribute to the symptomatology of patients with HFNEF.

Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.

BACKGROUND: The authors hypothesized that in patients with heart failure with normal left ventricular (LV) ejection fraction (HFNEF), the same fibrotic processes that affect the subendocardial layer of the left ventricle could also alter the subendocardial fibers of the left atrium. Consequently, these fibrotic alterations, together with chronically elevated LV filling pressures, would lead to both systolic and diastolic subendocardial dysfunction of the left atrium (i.e., impaired left atrial [LA] longitudinal systolic and diastolic function) in patients with HFNEF. METHODS: Patients with HFNEF and a control group consisting of asymptomatic patients with LV diastolic dysfunction (LVDD) matched by age, gender, and LV ejection fraction were studied using two-dimensional speckle-tracking echocardiography. RESULTS: A total of 420 patients were included (119 with HFNEF and 301 with asymptomatic LVDD). LA longitudinal systolic (LA late diastolic strain rate) and diastolic (LA systolic strain and strain rate) function was significantly more impaired in patients with HFNEF (LA late diastolic strain rate, -1.17 ± 0.63 s(-1); LA systolic strain, 19.9 ± 7.3%; LA systolic strain rate, 1.17 ± 0.46 s(-1)) compared with those with asymptomatic LVDD (-1.80 ± 0.70 s(-1), 30.8 ± 11.4%, and 1.67 ± 0.59 s(-1), respectively) (all P values < .0001). On multiple regression analysis, LV global longitudinal systolic strain and diastolic strain rate were the most important independent predictors of LA longitudinal systolic and diastolic function, in contrast to noninvasive LV filling pressures (i.e., mitral E/e' average septal-lateral ratio), which were modestly related to LA longitudinal systolic and diastolic function. Furthermore, in patients with HFNEF, the subendocardial function of both the left atrium and the left ventricle was significantly impaired in high proportions. In that regard, in patients with HFNEF, the rate of LA longitudinal systolic and diastolic dysfunction was 65.5% and 28.5%, whereas the prevalence of LV longitudinal systolic and diastolic dysfunction was 81.5% and 58%, respectively. In addition, patients with both systolic and diastolic longitudinal dysfunction of the left atrium presented worse NYHA functional class as compared with those with normal LA longitudinal function. CONCLUSIONS: In patients with HFNEF, LA subendocardial systolic and diastolic dysfunction is common and possibly associated with the same fibrotic processes that affect the subendocardial fibers of the left ventricle and to a lesser extent with elevated LV filling pressures. Furthermore, these findings suggest that LA longitudinal systolic and diastolic dysfunction could be related to reduced functional capacity during effort in patients with HFNEF.

Plasma HER2 levels are not associated with cardiac function or hypertrophy in control subjects and heart failure patients.

A proper interaction between the endocardial-derived ligand Neuregulin-1 and the myocardial "Human Epidermal growth factor Receptor 2" (HER2) is essential for maintaining heart function. The shed extracellular domain (ECD) of HER2 circulates in blood and serves as a surrogate marker for breast cancer. Altered cardiac loading conditions are accompanied by dysregulation of the myocardial HER2 gene expression. We studied 193 controls with preserved ejection fraction (EF>55%) and 572 patients with different degrees of systolic heart failure: 98 had EF 45-55%, 138 patients EF 35-44%, and 336 patients, EF <35%, respectively. The corresponding mean HER2 levels were 6.44 ± 0.46 ng/mL, 6.07 ± 0.76 ng/mL and 6.57 ± 0.87 ng/mL, and 6.17 ± 0.71 ng/mL, respectively. Furthermore, there was no significant association between plasma HER2 levels and left ventricular filling pressures or the left ventricular wall thickness. The HER2 plasma levels do not reflect the cardiac function and are therefore not useful as a biomarker for heart failure.