Contribution of concomitant myocarditis to the development of various clinical types of arrhythmogenic right ventricular cardiomyopathy

Aim. To assess the contribution of genetic and inflammatory factors to the development of arrhythmogenic right ventricular cardiomyopathy (ARVC).Material and methods. The study involved 54 patients with ARVC (age, 38,7±14,1 years; men, 42,6%; mean follow-up period, 21 [6; 60] months). All patients underwent electrocardiography (ECG), 24-hour ECG monitoring, echocardiography, determination of anticardiac antibodies and DNA of cardiotropic viruses in the blood, molecular genetic ARVC testing, as well as cardiac magnetic resonance imaging (n=49), high-resolution ECG (n=18), right ventricular endomyocardial biopsy (n=2), and autopsy (n=2).Results. Following four clinical types of ARVC were identified: I. Latent arrhythmic form: characterized by frequent premature ventricular contractions and/or nonsustained ventricular tachycardia (VT). II. Manifested arrhythmic form (n=11) — SVT/ventricular fibrillation (VF). III. ARVC with progressive heart failure (HF, n=8). IV. Combination of ARVC with left ventricular noncompaction (LVNC, n=8). Superimposed myocarditis was identified in 74%, 36%, 87,5% and 85,7% of patients in forms I-IV, respectively. Mutations were detected in 11%, 46%, 50%, and 38% of patients in forms I-IV, respectively. Clinical forms were stable: there was no transition from one clinical form to another during follow-up period.Conclusion. The contribution of genetic and inflammatory mechanisms to the clinical picture is different: in the latent arrhythmic form, the leading role belongs to inflammation; in the manifested arrhythmic form, the contribution of pathogenic mutations prevails, and in ARVC with progressive HF and in combination with LVNC, the contribution of genetic and inflammatory factors is equally important.

Virus-Negative Necrotizing Coronary Vasculitis with Aneurysm Formation in Human SARS-CoV-2 Infection

We report a case of myopericarditis associated to SARS-CoV-2 infection with necrotizing coronary vasculitis of intramural vessels, giving rise to biventricular apical microaneurysms and to electrical instability. Negativity of myocardial polymerase chain reaction for the most common cardiotropic viruses and for SARS-CoV-2 suggested an immune-mediated myocardial and pericardial inflammatory disease. High dose (1 mg/Kg daily) prednisone and anti-viral (Remdesivir, IDA Business, Carrigtohill, County Cork, T45 DP77, Ireland) therapy led to resolution of cardiac inflammation and ventricular arrhythmias. Morpho-molecular characterization of endomyocardial tissue may improve the outcome in subjects with SARS-CoV-2-associated myopericarditis and coronary vasculitis.

Fulminant myocarditis: COVID or not COVID? Reinfection or co-infection?

We describe a unique case of fulminant myocarditis in a patient with presumed SARS-CoV-2 reinfection. Patient had initial infection 4 months backand had COVID-19 antibody at the time of presentation. Endomyocardial biopsy showed lymphocytic myocarditis, that is usually seen in viral myocarditis. The molecular diagnostic testing of the endomyocardial biopsy for cardiotropic viruses was positive for Parvovirus and negative for SARS-CoV-2. Authors highly suspect co-infection of SARS-CoV-2 and Parvovirus, that possibly triggered the immune cascade resulting in fulminant myocarditis. Patient was hemodynamically unstable with ventricular tachycardia and was supported on VA ECMO and Impella CP. There was impressive recovery of left ventricular function within 48 hours, leading to decannulation of VA ECMO in 72 h. This unique case was written by the survivor herself.

The role of inflammation in recent-onset dilated cardiomyopathy

Background The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification. Purpose We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up. Methods 83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of >7 CD3+ lymphocytes/mm2 and/or >14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction > +10% and a relative decrease of LV end-diastolic diameter >−10% at 12 months. Results LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1) Conclusion Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months. Figure 1 Funding Acknowledgement Type of funding source: None

Serological and Molecular Biological Studies of Parvovirus B19, Coxsackie B Viruses, and Adenoviruses as Potential Cardiotropic Viruses in Bulgaria

Background:Inflammatory diseases of the heart (myocarditis, pericarditis) are commonly caused by viruses. Among the human cardiotropic viruses, parvovirus B19, Coxsackie B viruses, and adenoviruses play a leading role.Aim:The aim of the present study was to determine the presumptive causative role of parvovirus B19, Coxsackie B viruses, and adenoviruses in the development of myocarditis, pericarditis and dilated cardiomyopathy by demonstrating the presence of specific antiviral antibodies or viral DNA in patients’ serum samples.Materials and methods:We tested serum samples collected between 2010 and 2014 from 235 patients with myocarditis (n=108), pericarditis (n=79), myopericarditis (n=19), dilated cardiomyopathy (n=7), and fever of unknown origin accompanied by cardiac complaints (n=22). The mean age of patients with the standard deviation was 33 ± 18 years. Serological and molecular methods (ELISA for specific IgM/IgG antibodies to parvovirus B19 and IgM antibodies to Coxsackie B viruses and adenoviruses, and PCR for detection of parvovirus B19 in serum samples, respectively) were used in the study.Results:Of all tested 235 serum samples, in 60 (25.5%) positive results for at least one of the three tested viruses were detected. Forty out of these 235 serum samples (17%) were Coxsackie B virus IgM positive. They were found in 17% (18/108) of the patients with myocarditis, in 15% (12/79) of those with pericarditis, in 16% (3/19) of those with myopericarditis and in 32% (7/22) in those with fever of unknown origin. The 63 Coxsackie B virus IgM negative patient’s serum samples were tested by ELISA for presence of adenovirus IgM antibodies. Such were found in 4 patients with pericarditis and in 2 patients with fever of unknown origin. Every IgM negative sample (n=189) for Coxsackie B and adenovirus was further tested by ELISA for parvovirus B19 IgM/IgG antibodies. B19-IgM antibodies were detected in 14 patients (7.4%). The percentages for B19-IgM antibodies was 8% (7/90), 5% (3/63) and 31% (4/13) in the patients affected with myocarditis, pericarditis, and fever of unknown origin, respectively. Protective B19-IgG antibodies were found in 108 (57%) of the samples. A B19-PCR signal was detected in all the patients who were B19-IgM positive, and in only 1 patient with positive B19-IgG result, the latter presenting with dilated cardiomyopathy.Conclusion:The present study shows the involvement of Coxsackie B, parvovirus B19 and adenoviruses in the development of inflammatory diseases of the heart (myocarditis and pericarditis). It is the first ever study in the country that simultaneously analyzes the prevalence of the three major human cardiotropic viruses.

Acute myopericarditis presenting as effusive-constrictive pericarditis– a case report

Myopericarditis is primarily a pericardial inflammatory syndrome occurring when clinical diagnostic criteria for pericarditis are satisfied and concurrent mild myocardial involvement is documented by elevation of biomarkers of myocardial damage (i.e. increased troponins). Limited clinical data on the causes of myopericarditis suggest that viral infections are among the most common causes in developed countries. Cardiotropic viruses can cause pericardial and myocardial in!ammation via direct cytolytic or cytotoxic effects and/or subsequent immune-mediated mechanisms. Many cases of myopericarditis are subclinical. In other patients, cardiac symptoms and signs are over shadowed by systemic manifestations of infection or inflammation. The increased sensitivity of troponin assay and contemporary widespread use of troponins has greatly increased the reported number of cases. Management is similar to that reported for pericarditis, generally with a empiric anti-inflammatory drugs mainly aimed to control symptoms. Rest and avoidance of physical activity beyond normal sedentary activities has been recommended for 6 months is recommended as for myocarditis. At present, there is no evidence that troponin elevation confers worse prognosis (i.e. a greater risk of recurrence, death or transplantation) in patients with preserved left ventricular function. Usually complete remission is seen in 3 to 6 months. We report here a case of a 18 year young man with acute myopericarditis who presented with transient effusive-constrictive pericarditis.Bangladesh Med J. 2015 Sep; 44 (3): 165-167

Role of Inflammation, Viruses and Tissue Macrophages in the Development of Idiopathic Arrhythmia and Heart Failure

Endomyocardial biopsy is the gold standard in the diagnosis of myocardial pathology. Intravital study of endomyocardial samples offers the possibility to determine the morphological substrate and etiology of disease, to monitor the effectiveness of treatment. We studied morphological features, viral antigens, macrophages and specifically alternatively activated macrophages in endomyocardial biopsies of 25 patients with idiopathic arrhythmias and heart failure. Immunohistological study was performed to identify type of lymphocytes, macrophages and antigens of cardiotropic viruses. We observed the presence of alternatively activated macrophages in myocardium of patients with myocarditis and without it. We detected the presence of viral antigens in the myocardium of patients with myocardial fibrosis without of histological criteria myocarditis. Small focal infiltration of the myocardial CD68+ macrophages associated with heart failure and ventricular arrhythmias. The presence of virus antigens in myocardium associated with fewer myocardial stabilin-1+ macrophages [negative correlation]. On the other side small focal infiltration of stabilin-1+ macrophages correlated with severity of myocardial interstitial fibrosis [positive correlation]