Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.

Bariatric surgery and cardiovascular disease: a systematic review and meta-analysis.

AIMS: Obesity is a global health problem, associated with significant morbidity and mortality, often due to cardiovascular (CV) diseases. While bariatric surgery is increasingly performed in patients with obesity and reduces CV risk factors, its effect on CV disease is not established. We conducted a systematic review and meta-analysis to evaluate the effect of bariatric surgery on CV outcomes, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. METHODS AND RESULTS: PubMed and Embase were searched for literature until August 2021 which compared bariatric surgery patients to non-surgical controls. Outcomes of interest were all-cause and CV mortality, atrial fibrillation (AF), heart failure (HF), myocardial infarction, and stroke. We included 39 studies, all prospective or retrospective cohort studies, but randomized outcome trials were not available. Bariatric surgery was associated with a beneficial effect on all-cause mortality [pooled hazard ratio (HR) of 0.55; 95% confidence interval (CI) 0.49-0.62, P < 0.001 vs. controls], and CV mortality (HR 0.59, 95% CI 0.47-0.73, P < 0.001). In addition, bariatric surgery was also associated with a reduced incidence of HF (HR 0.50, 95% CI 0.38-0.66, P < 0.001), myocardial infarction (HR 0.58, 95% CI 0.43-0.76, P < 0.001), and stroke (HR 0.64, 95% CI 0.53-0.77, P < 0.001), while its association with AF was not statistically significant (HR 0.82, 95% CI 0.64-1.06, P = 0.12). CONCLUSION: The present systematic review and meta-analysis suggests that bariatric surgery is associated with reduced all-cause and CV mortality, and lowered incidence of several CV diseases in patients with obesity. Bariatric surgery should therefore be considered in these patients.

The value of echocardiographic measurement of epicardial adipose tissue in heart failure patients.

AIMS: Epicardial adipose tissue (EAT) is increasingly recognized as an important factor in the pathophysiology of heart failure (HF). Cardiac magnetic resonance (CMR) imaging is the gold-standard imaging modality to evaluate EAT size, but in contrast to echocardiography, CMR is costly and not widely available. We investigated EAT thickness on echocardiography in relation to EAT volume on CMR, and we assessed the agreement between observers for measuring echocardiographic EAT. METHODS AND RESULTS: Patients with HF and left ventricular ejection fraction >40% were enrolled. All patients underwent CMR imaging and transthoracic-echocardiography. EAT volume was quantified on CMR short-axis cine-stacks. Echocardiographic EAT thickness was measured on parasternal long-axis and short-axis views. Linear regression analyses were used to assess the association between EAT volume on CMR and EAT thickness on echocardiography. Intraclass correlation coefficient (ICC) was used to assess the interobserver agreement as well as the intraobserver agreement. EAT on CMR and echocardiography was evaluated in 117 patients (mean age 71 ± 10 years, 49% women and mean left ventricular ejection fraction 54 ± 7%). Mean EAT volume on CMR was 202 ± 64 mL and ranged from 80 to 373 mL. Mean EAT thickness on echocardiography was 3.8 ± 1.5 mm and ranged from 1.7 to 10.2 mm. EAT volume on CMR and EAT thickness on echocardiography were significantly correlated (junior-observer: r = 0.62, P < 0.001, senior-observer: r = 0.33, P < 0.001), and up to one-third of the variance in EAT volume was explained by EAT thickness (R2  = 0.38, P < 0.001). The interobserver agreement between junior and senior observers for measuring echocardiographic EAT was modest [ICC, 0.65 (95% confidence interval (CI) 0.47-0.77], whereas the intraobserver agreement was good (ICC 0.98, 95% CI 0.84-0.99). CONCLUSIONS: There was a modest correlation between EAT volume on CMR and EAT thickness on echocardiography. Limited agreement between junior and senior observers for measuring echocardiographic EAT was observed. EAT thickness on echocardiography is limited in estimating EAT volume.

Preoperative cardiac screening using NT-proBNP in obese patients 50 years and older undergoing bariatric surgery: a study of 310 consecutive patients.

BACKGROUND: Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists. OBJECTIVES: We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool. SETTING: High-volume bariatric center. METHODS: Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography. RESULTS: We included 310 consecutive patients (median age, 56 years; 79% female; body mass index = 43±6.5 kg/m2). A history of CV disease was present in 21% of patients, mainly atrial fibrillation (7%) and coronary artery disease (10%). A total of 72 patients (23%) had elevated NT-proBNP levels, and 67 of them underwent further cardiac workup. Of these 67 patients, electrocardiography (ECG) showed atrial fibrillation in 7 patients (10%). On echocardiography, 3 patients had left ventricular ejection fraction (LVEF) <40%, 9 patients had LVEF 40%-49%, and 13 patients had LVEF ≥50% with structural and/or functional remodeling. In 2 patients, elevated NT-proBNP prompted workup leading to a diagnosis of coronary artery disease and consequent percutaneous coronary intervention in 1 patient. CONCLUSIONS: Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery.