Alberto Pivetta

Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years

ACE‐inhibitors, β‐blockers, implantable cardioverter–defibrillator (ICD) and cardiac resynchronization therapy (CRT) improved prognosis of heart failure. We sought to analyse the long‐term prognostic impact of evidence‐based integrated therapeutic strategies in patients with idiopathic dilated cardiomyopathy (IDCM).

Are Nonsustained Ventricular Tachycardias Predictive of Major Arrhythmias in Patients with Dilated Cardiomyopathy on Optimal Medical Treatment

Background: To evaluate the role of nonsustained ventricular tachycardias (NSVT) for the prediction of major ventricular arrhythmias (MVA) in patients with idiopathic dilated cardiomyopathy (DCM) after optimization of medical treatment.

Right Ventricular Cardiomyocyte Apoptosis in Patients With Acute Myocardial Infarction of the Left Ventricular Wall

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.

Radiofrequency Ablation of Atrioventricular Nodal Tachycardia in a Patient with Dextrocardia, Inferior Vena Cava Interruption, and Azygos Continuation

The prevalence of dextrocardia is 0.2% in the general population and can be associated to inferior vena cava (IVC) stenosis or interruption in 8–18% cases. The anomalies of the IVC can coexist with azygos continuation in about 0.6% of cases. Radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT) rarely has been reported in patients with dextrocardia, while no case was previously described in patients with dextrocardia, IVC interruption, and azygos continuation. We report a case of a 79-year-old man with paroxysmal drug-refractory SVT and previously known dextrocardia

Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy

Objective To explore the genetic landscape of a well selected dilated cardiomyopathy (DCM) cohort, assessing the possible relation between different genotypes and left ventricular reverse remodelling (LVRR). Methods A cohort of 152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been studied by next-generation sequencing (NGS). Patients were grouped into different ‘gene-clusters’ with functionally homogeneous genetic backgrounds. LVRR was defined by left ventricular ejection fraction normalisation or increase ≥10% associated with normalisation in indexed left ventricular end-diastolic diameter or relative decrease ≥10% at 24 months follow-up. Results A pathogenic disease-related gene variant was identified in 57% of patients: 28 (18%) TTN; 7 (5%) LMNA; 16 (11%) structural cytoskeleton Z-disk genes; 9 (6%) desmosomal genes; 18 (12%) motor sarcomeric genes and 9 (6%) other genes. Baseline clinical features were similar throughout the different genotypes. A significant relationship was found between gene cluster subgroups and LVRR, with a lower rate of LVRR in structural cytoskeleton Z-disk gene mutation carriers (1/16 patients, 6%, p<0.05 vs the other subgroups). Of note, structural cytoskeleton Z-disk gene rare variants were independently and inversely associated with LVRR when adjusted for clinical predictors of LVRR (OR 0.065; 95% CI 0.008 to 0.535, p=0.011). Conclusions NGS confirmed a high genetic diagnostic yield in DCM. A specific ‘gene-clusters’ classification based on functional similarities in different genes might be helpful in the clinical management of genetically determined DCM. In this study, structural cytoskeleton Z-disk gene rare variants were independently associated with a lower rate of LVRR at follow-up.

Focus on cardiac amyloidosis: a single-center experience with a long-term follow-up.

Aim Amyloidosis is a systemic disease, related to different underlying causes, with frequent cardiac involvement. Clinical evaluation, echocardiography and electrocardiography represent important noninvasive tools in identification of cardiac involvement. The aim of this study was to assess the clinical–laboratory features of a series of patients affected by cardiac amyloidosis in order to evaluate the risk of cardiac mortality. Methods We evaluated 48 patients (men 65%, mean age 63 ± 11 years) with biopsy-proven diagnosis of amyloidosis and heart involvement observed from 1991 to 2009. All patients underwent clinical–laboratory evaluation at baseline and were followed up. Results During a median follow-up of 9.5 months (first to third interquartile: 3–41.5 months), 24 patients (50%) died as a result of a cardiac cause. Survival free from cardiac death was 69, 50, 48 and 41% at 6, 12, 24 and 60 months from diagnosis, respectively. At multivariable Cox regression analysis, the presence of heart failure at enrolment [hazard ratio (HR) 4.67, 95% confidence interval (CI) 1.07–20.27, P = 0.04] and history of recent syncope (HR 3.97, 95% CI 1.28–12.34, P = 0.017) emerged as independent predictors of cardiac death. By using the equation derived from the multivariate analysis, individual survival probability at different times of follow-up was calculated. Conclusion We confirm the particularly poor outcome of cardiac amyloidosis in the short term. A careful clinical evaluation emerges as the most important tool for the prognostic stratification and quantification of risk in patients with cardiac amyloidosis.

Lifelong arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy: distribution of events and impact of periodical reassessment

Aims The arrhythmic risk stratification of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains controversial. We evaluated the long-term distribution of life-threatening arrhythmic events assessing the impact of periodical risk reassessment. Methods and results Ninety-eight ARVC patients with no previous major ventricular arrhythmias were retrospectively analysed. Patients were assessed at baseline, at 22 [inter-quartile range (IQR) 16-26], 49 (IQR 41-55) and 97 months (IQR 90-108). The primary endpoint was a composite of sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or appropriate implanted cardioverter-defibrillator intervention. During a median follow-up of 91 months (IQR 34-222) 28 patients (29%) experienced the composite endpoint. The median time for the primary event was 35 months (IQR 18-86 months), and 39% of events occurred beyond 49 months of follow-up. History of syncope (HR 4.034; 95% CI, 1.488 to 10.932; P-value = 0.006), non-sustained ventricular tachycardia (NSVT; HR 3.534; 95% CI 1.265-9.877; P-value = 0.016), premature ventricular contractions (PVC) >1000/24h (HR 2.761; 95% CI 1.120-6.807; P-value = 0.027), and right ventricular fractional area change (RVFAC; HR 0.945; 95% CI 0.906-0.985; P-value = 0.008) were found as independent predictors at baseline multivariate analysis. Nevertheless, when the prognostic impact of each variable was reassessed overtime only NSVT (HR 3.282; 95% CI, 1.122 to 9.598, P-value = 0.023) and RVFAC (HR 0.351, 95% CI, 0.157 to 0.780; P-value = 0.010) remained independent predictors throughout the whole follow-up. Conclusion In our cohort of ARVC patients only NSVT and RVFAC maintained their independent prognostic impact in predicting arrhythmic events during the long-term follow-up. Periodical re-assessment of risk in these patients is strongly recommended.

Arrhythmogenic Right Ventricular Cardiomyopathy: Clinical Assessment and Differential Diagnosis

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiovascular disorder leading to life-threatening ventricular arrhythmias, progressive biventricular dysfunction, and heart failure. Sudden death can be the unique feature of the disease. Genetic studies indicate that ARVC should be considered a disease of desmosome dysfunction. Diagnosis remains a clinical challenge mainly in its early stages and in patients with minimal imaging structural abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow tract ventricular tachycardia, Brugada syndrome, dilated cardiomyopathy, and myocarditis, due to arrhythmic expressivity and biventricular involvement. Diagnosis is based on major and minor criteria listed in the Revised Task Force Criteria.