Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients. METHODS AND RESULTS: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non-sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high-risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow-up of 6 years (interquartile range 1.6-12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. CONCLUSION: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life-threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes.

Outpatient tricuspid regurgitation in the community: Clinical context and outcome.

BACKGROUND AND AIMS: Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts. METHODS: We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardiography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (isolated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF. RESULTS: Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 ± 7% for postop-TR subgroup, 75 ± 7% for isolated-TR, 67 ± 6% for PHTN-TR, 58 ± 6% for LHVD -TR and 52 ± 11% for HF-TR. CONCLUSION: Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.

Correlation between epicardial adipose tissue and atrial fibrillation burden in coronary artery bypass graft surgery.

AIMS: Recent studies suggest an association between epicardial adipose tissue (EAT) and atrial fibrillation. The aim of the study is to evaluate the quantitative and qualitative characteristics of EAT in relation to atrial fibrillation burden after coronary artery bypass graft (CABG). METHODS: This prospective single-centre study included patients undergoing CABG. The patients underwent transthoracic echocardiography and collection of a bioptic sample containing right appendage and EAT during CABG for histological characterization. After surgery, clinical and telemetry data were collected. RESULTS: Fifty-six consecutive patients were enrolled. The mean postsurgical hospitalization was 7.9 ±â€Š3.7 days. Twenty-two patients had at least one episode of atrial fibrillation. In the atrial fibrillation group, there was a bigger atrial volume, a higher degree of diastolic disfunction, a thicker layer of EAT and an older median age in comparison with the group that did not develop it. EAT with a cut-off of 4 mm was a predictor of atrial fibrillation with an odds ratio (OR) of 1.49 (confidence interval (CI) 1.09-2.04), 73% of sensibility and 89% of specificity. From the histological analyses, the patients with atrial fibrillation had a significantly higher percentage of fibrosis. At univariate analysis, atrial volume [OR 1.05, CI 1.01-1.09, P = 0.022], E/A rate (OR 0.04, CI 0.02-0.72 P = 0.29), the percentage of fibrosis (OR 1.12, CI 1.00-1.25, P = 0.045) and age (OR 1.17, CI 1.07-1.28, P = 0.001) were predictors of atrial fibrillation. At multivariate analysis, atrial volume (P = 0.027), fibrosis (P = 0.003) and age (P = 0.039) were independent predictors of atrial fibrillation. CONCLUSION: Postcardiac surgical atrial fibrillation is frequent. EAT thickness, atrial volume, fibrosis and age are predictors of postcardiac surgical atrial fibrillation.

RAS inhibitors and renal and general mortality in patients with heart failure supported by left ventricular assist devices: a registry study.

BACKGROUND: The aim of our study was to analyze the association between renin-angiotensin system inhibitor (RASi) therapy and renal outcomes and mortality in patients with heart failure (HF) supported by left ventricular assist device (LVAD) using a large, nationwide prospective cohort. To date, no studies have comprehensively analyzed the association between RASi and renal outcomes and mortality in patients with HF supported by LVAD. METHODS: We performed a retrospective observational study on LVAD patients in the Interagency Registry for Mechanically Assisted Circulatory Support. The main outcome was a composite of renal event and all-cause mortality. Secondary outcomes were the individual components of the composite outcome. A renal event was defined as a composite of doubling serum creatinine, eGFR decrease ≥ 40%, or need for dialysis. The exposure of interest was RASi therapy, updated during follow-up. Cox regression models adjusted for potential confounders were used to estimate the association between time-updated RASi therapy and the outcomes of interest. RESULTS: The analysis included 6448 patients. During a median follow-up of 12.7 months (IQR 19.8 months), 1632 patients developed the composite outcome. RASi therapy was associated with a lower risk of developing the composite outcome (HR 0.61, 95% CI 0.55, 0.68, P < 0.001). A significant association was confirmed between RASi therapy and renal outcomes (HR 0.74, 95% CI 0.61, 0.89, P = 0.002) and all-cause mortality (HR 0.56, 95% CI 0.50, 0.63, P < 0.001). CONCLUSIONS: Our data suggest a beneficial role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD.

Vascular complications after transcatheter aortic valve implantation: treatment modalities and long-term clinical impact.

OBJECTIVES: Vascular complications (VC) are the most frequent drawback of transcatheter aortic valve implantation (TAVI), affecting up to 20% of overall procedures. Data on the treatment and their long-term impact are scarce. The goal of this study was to report on the incidence, management and impact on the long-term outcomes of VC following TAVI. METHODS: This was a multicentric retrospective analysis of consecutive patients undergoing TAVI. The primary endpoint was freedom from major adverse cardiac and cerebrovascular events at long-term follow-up. Adverse events were evaluated according to Valve Academic Research Consortium-2 criteria. RESULTS: A total of 2145 patients were included: VC occurred in 188 (8.8%); of which 180 were limited to the access site. Two-thirds of the VC were minor; 8% required surgical treatment; the remaining were repaired percutaneously. The major adverse cardiac and cerebrovascular events-free survival at 2 years was 83.0% for patients with VC and 86.7% for those without (P = 0.143), but 71.9% for patients with major compared to 89.0% in those with minor VC (P = 0.022). Major VC and diabetes mellitus independently predicted worse outcomes at 2 years. The major adverse cardiac and cerebrovascular events-free survival rate and the occurrence of vascular adverse events in the long term among patients with VC at the access site treated by endovascular techniques (covered stent implantation or angioplasty) were similar to those without VC (84.2% vs 86.7%; P = 0.635). CONCLUSIONS: Major but not minor VC impact long-term survival after TAVI. Covered stents implanted to manage VC at the access site have no impact on the long-term clinical outcome of TAVI.

Bicuspid Aortic Valve Disease from Infancy to Older Age: A 25-Year Experience from an Italian Referral Center.

AIM: Bicuspid aortic valve (BAV) is the most common congenital heart defect, with considerable risk of morbidity and mortality. The purpose of the study was to analyze clinical and echocardiographic presentation of BAV in a large-volume tertiary Italian center and to test their interaction with full age span, sex, and first diagnosis versus second referral. METHODS: Consecutive patients of all ages diagnosed with BAV at our center from January 1988 to December 2012 were retrospectively included. Exclusion criteria were as follows: associated complex congenital cardiac disease, systemic syndrome, and previous cardiac surgery. RESULTS: Eligible patients were 790, divided by age quartiles. Seventy-two percent of patients had any grade BAV dysfunction. Aortic valve stenosis was more frequent in the first (24%) and fourth (24%) quartiles. This corresponds to a double-peak stenosis severity curve, being more severe at a very young age and in the elderly. Aortic valve regurgitation was more prevalent in each quartile than stenosis, with a prevalence of 72% in the second quartile and 77% in the third quartile. This corresponds to a single-peak regurgitation severity curve, being more severe in the fourth and fifth decades of life. Patients with previously diagnosed BAV had more significant valve dysfunction in comparison to patients with first diagnosis of BAV, either stenosis (15% vs. 21%, P = 0.024) or regurgitation (58% vs. 68%, P = 0.006). CONCLUSION: The dominant BAV dysfunction in this large Northern Italian community is regurgitation, with higher severity of disease in the fourth and fifth decades of life.

Leadless pacemaker through tricuspid bioprosthetic valve: Early experience.

BACKGROUND: Leadless pacemaker (LP) therapy has been proved effective in cases where traditional transvenous right pacing (TRP) failed. TRP through a bioprosthetic tricuspid valve (BTV) has always been considered an unpreferable solution because of possible deleterious effect of permanent pacing leads on BTV function and specifically on tricuspid regurgitation (TR). Very limited data exist about the feasibility and safety of LP implantation in this setting. METHODS: We describe two cases of LP implantation through BTV in patients with failure of epicardial pacemaker implanted after cardiac surgery. The focus is on technical description of the procedure and on electrical and echocardiographic evaluation at implantation and at the follow-up. RESULTS: In both cases, skilled and careful handling of the delivery system as well as proper use of X-ray oblique views was determinant for atraumatic successful valve crossing. Likewise, an accurate selection of the deployment site inside the right ventricle, far enough from the valve to avoid valvular dysfunction, was important for successful implantation. Electrical parameters of LP were satisfying at implantation and at the follow-up. The echocardiogram after implantation and at the follow-up showed no mechanical interference of LP with prosthetic valve, no significant TR, and absence of significant changes in the biventricular function. CONCLUSION: Our data seem to support feasibility and safety of this type of procedure in skilled hands, allowing efficacious pacing without valvular dysfunction or right ventricular (RV) physiology impairment.

Mitral regurgitation and dyspnoea: the expanding role of mitral effective regurgitant orifice among un-selected patients.

AIMS: Mitral regurgitation is frequent in the general population and among suspected heart failure patients; however, to what extent it contributes to dyspnoea is unclear. We hypothesized mitral regurgitation to have a role in determining dyspnoea in unselected ambulatory patients. METHODS: Consecutive outpatients referred for echocardiography were retrospectively screened and included. We excluded patients with mitral stenosis or prosthesis, congenital heart disease, cardiac surgery (previous 6 months) and atrial fibrillation. Patients were classified into four dyspnoea grades based on how they perceived their disability. We assessed mitral regurgitation severity through the effective regurgitant orifice area (ERO). RESULTS: One hundred and fifty-four patients (58% men; age 67 ±â€Š14 years; mean ejection fraction 54 ±â€Š12%) formed the study population; 76 (49%) classified asymptomatic (grade I), 63 (41%) dyspnoea grade II and 15 (10%) grade III; none was in grade IV. Mitral regurgitation was present in 102 patients (66%): primary in 14 (14%) and secondary in 88 (86%); among grades I, II and III patients, mitral regurgitation was present in 35 (46%; ERO 0.05 ±â€Š0.10 cm), 52 (82%; ERO 0.10 ±â€Š0.13 cm) and 15 (100%; ERO 0.20 ±â€Š0.11 cm) patients, respectively (P < 0.0001). After adjusting for clinical (age, hypertension, ischemic heart disease, chronic kidney injury, chronic pulmonary disease) and echocardiographic confounders (ejection fraction, E/e'), ERO remained associated with symptoms presence (grade I versus II - III; P = 0.01 and P = 0.03, respectively). CONCLUSION: Among unselected heterogeneous ambulatory patients, mitral ERO was associated with the presence of dyspnoea and could therefore help in identifying symptomatic patients and in clinical characterization of patients with perceived dyspnoea.

Chronic venous obstruction during cardiac device revision: Incidence, predictors, and efficacy of percutaneous techniques to overcome the stenosis.

BACKGROUND: In recent years, upgrade and revision procedures of cardiac implantable electronic devices (CIEDs) have become increasingly frequent. Patency of the access veins is critical for procedural success. OBJECTIVE: The purpose of this study was to determine the incidence of venous obstruction at the time of system revision, to identify predictors of venous stenosis, and to evaluate the efficacy and safety of percutaneous techniques for overcoming stenosis. METHODS: All patients admitted to our division from January 2004 to January 2017 for CIED revision with the intent to add 1 or more leads were included. Each patient underwent ipsilateral contrast venography. The degree of venous stenosis was determined with the support of quantitative coronary angiography and categorized as significant (75%-90%), subocclusive (90%-99%), or occlusive (100%). RESULTS: Of 227 patients, 61 (27%) showed a stenosis >75%. Different techniques were performed to overcome stenosis: direct vein access, distal venous puncture central to the stenosis, and percutaneous venoplasty in 25 (41%), 26 (43%) and 9 (15%) cases. respectively. All procedures were successful, without major complications. At multivariate analysis, having 3 leads before revision (odds ratio 0.444; 95% confidence interval 0.212-0.920; P = .029) and a previous system revision with lead insertion (odds ratio 0.323; 95% confidence interval 0.124-0.841; P = .021) were independent predictors of venous stenosis. CONCLUSION: Chronic venous obstruction is a relatively frequent finding after CIED implantation. The number of implanted leads seems to be an independent predictor of venous obstruction. In case of stenosis, the preprocedural angiography-guided structured approach allowed preservation of both contralateral access and functioning leads.

Role of Speckle Tracking Echocardiography in the Evaluation of Breast Cancer Patients Undergoing Chemotherapy: Review and Meta-analysis of the Literature.

Diagnosis and management of Cancer therapeutics-related cardiac dysfunction is of crucial importance in breast cancer (BC) patients. The role of advanced echocardiographic techniques, such as deformation imaging, in the diagnosis and characterization of patients receiving cancer therapy has so far involved relatively small studies in the research setting. Therefore, we conducted a meta-analysis and systematic review of observational studies evaluating myocardial changes during chemotherapy detected through conventional echocardiographic parameters, such as 2D left ventricular ejection fraction (2D LVEF), and 2D Speckle tracking echocardiography (STE). The literature search retrieved 487 research works, articles, of which 17 were found to be pertinent with this topic. After full article review, 16 studies were considered suitable for the present analysis. Two separate analyses, one for the anthracyclines-based therapeutic regimen and one for the trastuzumab based therapeutic regimen, were performed. A significant reduction in 2D LVEF and 2D STE parameters during cancer therapy was found in both the investigations. Peak systolic global longitudinal strain demonstrated to be the most consistent 2D STE parameter in detecting early myocardial changes among all the studies. Thus, we confirmed the role of 2D STE for the early detection of myocardial damage, suggesting its crucial role in monitoring BC patients and eventually driving the introduction of cardioprotective treatment.

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.