Cardiomyopathies are a heterogeneous group of primary diseases of the myocardium, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC), with higher morbidity and mortality. These diseases are genetically diverse and associated with rare mutations in a large number of genes, many of which overlap among the phenotypes. To better investigate the genetic overlap between these three phenotypes and to identify new genotype–phenotype correlations, we designed a custom gene panel consisting of 115 genes known to be associated with cardiomyopathic phenotypes and channelopathies. A cohort of 38 unrelated patients, 16 affected by DCM, 14 by HCM and 8 by ARVC, was recruited for the study on the basis of more severe phenotypes and family history of cardiomyopathy and/or sudden death. We detected a total of 142 rare variants in 40 genes, and all patients were found to be carriers of at least one rare variant. Twenty-eight of the 142 rare variants were also predicted as potentially pathogenic variants and found in 26 patients. In 23 out of 38 patients, we found at least one novel potential gene–phenotype association. In particular, we detected three variants in OBSCN gene in ARVC patients, four variants in ANK2 gene and two variants in DLG1, TRPM4, and AKAP9 genes in DCM patients, two variants in PSEN2 gene and four variants in AKAP9 gene in HCM patients. Overall, our results confirmed that cardiomyopathic patients could carry multiple rare gene variants; in addition, our investigation of the genetic overlap among cardiomyopathies revealed new gene–phenotype associations. Furthermore, as our study confirms, data obtained using targeted next-generation sequencing could provide a remarkable contribution to the molecular diagnosis of cardiomyopathies, early identification of patients at risk for arrhythmia development, and better clinical management of cardiomyopathic patients.

BackgroundThe assessment of myocardial perfusion (MP) and wall motion (WM) using contrast dipyridamole echocardiography (cSE‐WMP) improves the sensitivity to detect coronary artery disease and the stratification of cardiac events, but its long‐term value for fatal and nonfatal ischemic cardiac events, also with respect to patients undergoing revascularization or not, remains to be determined.Methods and ResultsOne‐thousand three‐hundred and twenty‐nine patients with suspect or known CAD who underwent cSE‐WMP were followed for a median 5.5 years. The independent prognostic value of cSE‐WMP regarding cardiac death or nonfatal myocardial infarction was related to stress WM and MP, rest ejection fraction, clinical risk factors, and medications. Patients revascularized after cSE‐WMP were separately analyzed to determine whether the procedure influenced outcome and whether this depends on cSE‐WMP results. A total of 125 cardiac fatal and nonfatal ischemic events (9.4%) occurred during the follow‐up (61 deaths, 64 myocardial infarctions). The 5‐year event rate with normal MP and WM was 5.9%, 9.9% with isolated MP defects (normal WM), and 15.5% with both MP and WM abnormalities. In patients not undergoing revascularization (n=1111), reversible MP defects added discrimination value over WM response and clinical factors/medication data (P=0.001), while in the cohort undergoing revascularization (n=218), cSE‐WMP results did not influence outcome.Conclusions cSE‐WMP, with both contrast MP and WM assessments, provides independent, incremental prognostic information regarding ischemic cardiac events at 5 years in patients with known or suspected coronary artery disease. Revascularization reduces cardiac events after an abnormal cSE‐WMP, resulting in outcomes not different from those in patients with normal cSE‐WMP.

No abstract

The detection of embolic sources in patients with atrial fibrillation (AF) is important to guide anticoagulant therapy. Two-dimensional transesophageal echocardiography (TEE) is the gold standard to study left atrial appendage (LAA) anatomy and morphology, despite some false-positive diagnosis. We hypothesized that real time 3D TEE (RT3DTEE) is superior to 2DTEE in detecting and/or excluding LAA thrombi. We studied 93 patients with non-valvular AF (60 males, age = 67.1 ± 14.2 years) referred for electric cardioversion with transthoracic, 2DTEE and RT3DTEE. Before cardioversion, TTE allowed a confident measurement of emptying velocity of LAA (LAAeV) only in 59/93 patients (63%). On the contrary a good quality TEE LAAeV was obtained in all patients with 49/93 (53%) dysfunctional LAA (LAAeV < 40 cm/s). A subgroup of 5 patients (7.2% of the 69 effective cardioversion) presented a persistent dysfunction after cardioversion (with LAAeV values of <40 cm/s on the TEE post-CV). TEE allowed to observe a bilobed shape in 45 patients (48.4%) and three lobes in 22 patients (23.7%). In addition, besides to several additional findings, 2DTEE managed to detect thrombi with certainty in 8/93 patients (8.6%). In other 5 cases with diagnostic doubts for thrombi with 2DTEE (5/93 patients: 5.4%), the addition of the RT3DTEE mode allowed to discriminate with certainty the presence of just pectinate muscles in 4 patients RT3DTEE in patients with AF at risk of embolism is feasible, accurate and showed an additional diagnostic capability in the differential diagnosis of selected cases with suspected LAA thrombi.

The prognostic impact of diabetes mellitus (DM) on cardiovascular outcomes is well known. As a consequence of previous studies showing the high incidence of coronary artery disease (CAD) in diabetic patients and the relatively poor outcome compared to nondiabetic populations, DM is considered as CAD equivalent which means that diabetic patients are labeled as asymptomatic individuals at high cardiovascular risk. Lessons learned from the analysis of prognostic studies over the past decade have challenged this dogma and now support the idea that diabetic population is not uniformly distributed in the highest risk box. Detecting CAD in asymptomatic high risk individuals is controversial and, what is more, in patients with diabetes is challenging, and that is why the reliability of traditional cardiac stress tests for detecting myocardial ischemia is limited. Cardiac computed tomography angiography (CCTA) represents an emerging noninvasive technique able to explore the atherosclerotic involvement of the coronary arteries and, thus, to distinguish different risk categories tailoring this evaluation on each patient. The aim of the review is to provide a wide overview on the clinical meaning of CCTA in this field and to integrate the anatomical information with a reliable therapeutic approach.