No abstract

Cardiac amyloidosis is a serious and progressive infiltrative disease that is caused by the deposition of amyloid fibrils at the cardiac level. It can be due to rare genetic variants in the hereditary forms or as a consequence of acquired conditions. Thanks to advances in imaging techniques and the possibility of achieving a non-invasive diagnosis, we now know that cardiac amyloidosis is a more frequent disease than traditionally considered. In this position paper the Working Group on Myocardial and Pericardial Disease proposes an invasive and non-invasive definition of cardiac amyloidosis, addresses clinical scenarios and situations to suspect the condition and proposes a diagnostic algorithm to aid diagnosis. Furthermore, we also review how to monitor and treat cardiac amyloidosis, in an attempt to bridge the gap between the latest advances in the field and clinical practice.

Myocarditis is an inflammatory disease of the heart frequently resulting from viral infections and/or post-viral immune-mediated responses. It is one of the important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed on clinical presentation and noninvasive diagnostic methods such as cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic benefits of endomyocardial biopsy results have recently been demonstrated in several clinical trials. Although remarkable advances in diagnosis, understanding of pathophysiological mechanisms, and treatment of acute myocarditis were gained during the last years, no standard treatment strategies could be defined as yet, apart from standard heart failure therapy and physical rest. In severe cases, mechanical support or heart transplantation may become necessary. There is some evidence that immunosuppressive and immunomodulating therapy are effective for chronic, virus-negative inflammatory cardiomyopathy. Further investigations by controlled, randomized studies are needed to definitively determine their role in the treatment of myocarditis.

Background-The objective of this study was to identify the prognostic indicators in patients with suspected myocarditis who underwent endomyocardial biopsy. Methods and Results-Between 1994 and 2007, 181 consecutive patients (age, 42Ϯ15 years) with clinically suspected viral myocarditis were enrolled and followed up for a mean of 59Ϯ42 months. Endomyocardial biopsies were studied for inflammation with histological (Dallas) and immunohistological criteria. Virus genome was detected by polymerase chain reaction. The primary end point was time to cardiac death or heart transplantation. In 38% of the patients (nϭ69), the Dallas criteria were positive. Immunohistological signs of inflammation were shown in 50% (nϭ91). Genomes of cardiotropic virus species were detected in 79 patients (44%). During follow-up, 22% of the patients (nϭ40) reached the primary end point. Three independent predictors were identified for the primary end point, namely New York Heart Association class III or IV at entry (hazard ratio, 3.20; 95% confidence interval,

Background-Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results-We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96Ϯ3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by Ϫ28/Ϫ10 mm Hg (PϽ0.001) and Ϫ32/Ϫ12 mm Hg (PϽ0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118Ϯ3.4 to 108Ϯ3.8 mg/dL (Pϭ0.039). Insulin levels were decreased from 20.8Ϯ3.0 to 9.3Ϯ2.5 IU/mL (Pϭ0.006) and C-peptide levels from 5.3Ϯ0.6 to 3.0Ϯ0.9 ng/mL (Pϭ0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0Ϯ0.9 to 2.4Ϯ0.8 (Pϭ0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (Pϭ0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions-Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.

Background-Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results-In this 2-center study, 755 patients with clinically suspected myocarditis (nϭ481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (nϭ274) underwent either selective LV-EMB (nϭ265; 35.1%), selective RV-EMB (nϭ133; 17.6%), or biventricular EMB (nϭ357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; PϽ0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (Pϭ0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV-and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement. Conclusions-Both

AimsAn anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM.Methods and resultsIn this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died.ConclusionBromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.Clinical trial registrationClinicalTrials.gov, study number: NCT00998556.

The initial mechanism for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the binding of the virus to the membrane-bound form of ACE2, which is mainly expressed in the lung. Since the heart and the vessels also express ACE2, they both could become targets of the virus. However, at present the extent and importance of this potential involvement are unknown. Cardiac troponin levels are significantly higher in patients with more severe infections, patients admitted to intensive care units or in those who have died. In the setting of COVID-19, myocardial injury, defined by an increased troponin level, occurs especially due to non-ischaemic myocardial processes, including severe respiratory infection with hypoxia, sepsis, systemic inflammation, pulmonary thrombosis and embolism, cardiac adrenergic hyperstimulation during cytokine storm syndrome, and myocarditis. At present, there are limited reports on definite diagnosis of myocarditis caused by SARS-CoV-2 in humans and limited demonstration of the virus in the myocardium. In conclusion, although the heart and the vessels are potential targets in COVID-19, there is currently limited evidence on the direct infection of the myocardium by SARS-CoV-2. Additional pathological studies and autopsy series will be very helpful to clarify the potentiality of COVID-19 to directly infect the myocardium and cause myocarditis.