Background-Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis. Methods and Results-From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation-free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months model: area under the curve 0.79 versus 0.90, P=0.03). Conclusions-Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset,and its reassessment at 6 months appears useful for assessing longer-term outcome.

In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.

Objective: There is a paucity and inconsistency of data regarding the natural history of patients affected by idiopathic dilated cardiomyopathy (IDCM) and atrial fibrillation (AF). We examined the prognostic implications of AF in a subset of patients with IDCM. Methods:We analyzed the data of 539 patients with IDCM enrolled in the Heart Muscle Disease Registry of Trieste.Results: At baseline, 52 (9.6%) of 539 patients had AF. There was no difference in survival of patients with either AF or sinus rhythm at enrollment (P=.28). During long-term follow-up (90±58 months), AF was detected on ECG/ECG-Holter monitoring in 28 (5.7%) of 487 patients in sinus rhythm at baseline. Predictors of new onset of AF at multivariate analysis were a more dilated left atrium (OR 1.35, 95% CI 1.06-1.72; P=.01) and a lower left ventricle ejection fraction (for 10% decrease, OR 2.41, 95% CI 1.24-4.69, P=.016). Patients developing AF had higher mortality/heart transplantation rate compared to patients who maintained sinus rhythm during follow-up (P<.001). At multivariate analysis, new onset AF (HR 3.67, 95% CI 2.07-6.5; P<.001) in the first three years after diagnosis, but not baseline AF, was found to be independently associated with a worse outcome. Conclusions:Atrial fibrillation is relatively frequent in patients with IDCM. The early development of AF during follow-up, but not its presence at baseline, is associated with poor survival.

Cardiac remodeling after acute myocardial infarction (AMI) is characterized by molecular and cellular mechanisms involving both the left (LV) and right ventricular (RV) walls. Cardiomyoycte apoptosis in the peri-infarct and remote LV myocardium has a central role in cardiac remodeling. Whether apoptosis also occurs in the right ventricle of patients with ischemic heart disease has not been investigated. The aim of the present study was to investigate the presence of cardiomyocyte apoptosis in the right ventricle in patients with AMI. We assessed the number of apoptotic cardiomyocytes using multiple samplings in the LV and RV walls of 12 patients selected at autopsy who died 4 to 42 days after AMI. Five patients without cardiac disease were also selected at autopsy as controls. Apoptotic rates were calculated from the number of cardiomyocytes showing double positive staining for in situ end-labeling of DNA fragmentation (TUNEL) and for activated caspase-3. Potentially false-positive results (DNA synthesis and RNA splicing) were excluded from cell counts. The apoptotic rate in the right ventricle in patients with AMI was significantly higher than in control hearts (median 0.8%, interquartile range 0.3 to 1.0 vs median 0.01%, interquartile range 0.01 to 0.03, p <0.001). RV apoptosis significantly correlated with such parameters of global adverse remodeling as cardiac diameter to LV free wall thickness (R = +0.57, p = 0.050). RV apoptosis was significantly higher in five cases (42%) with infarct involving the ventricular septum and an adjacent small area of the RV walls (median 1.0%, interquartile range 0.8 to 2.2 vs median 0.5%, interquartile range 0.2 to 1.0, p = 0.048, p <0.001 vs controls). The association between apoptotic rate in the right ventricle and cardiac remodeling was apparent even after exclusion of cases with RV AMI involvement (R = +0.82, p = 0.023 for diameter to LV wall thickness ratio and R = -0.91, p = 0.002 for RV free wall thickness). In conclusion, patients with cardiac remodeling after AMI had a significant increase in RV apoptosis even when ischemic involvement of the RV wall was not apparent.

The proportion of asymptomatic patients with DCM at the moment of first evaluation at our center is significant (30%). Among them, those without a previous history of heart failure had a less advanced disease and a trend for a better long-term outcome on optimal medical treatment. Therefore, early diagnosis may offer better long-term quality of life and even better survival. Further studies on larger populations are indicated.