Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families.

BACKGROUND: The genetic basis for dilated cardiomyopathy (DCM) can be difficult to determine, particularly in familial cases with complex phenotypes. Next generation sequencing may be useful in the management of such cases. METHODS: We report two large families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes included atrial and ventricular septal defects, cardiac arrhythmia and sudden death. Probands underwent whole exome sequencing to identify potentially causative variants. RESULTS: Each whole exome sequence yielded over 18,000 variants. We identified distinct mutations affecting a common amino acid in NKX2.5. Segregation analysis of the families support the pathogenic role of these variants. CONCLUSION: Our study emphasizes the utility of next generation sequencing in identifying causative mutations in complex inherited cardiac disease. We also report a novel pathogenic NKX2.5 mutation.

The therapeutic benefit of upgrade to cardiac resynchronization therapy in patients with pacing-induced cardiomyopathy.

Background: Pacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients with a right ventricular pacing burden. Recent evidence suggests that an upgrade to cardiac resynchronization therapy (CRT) may confer benefit in PICM. Objective: To assess the extent and identify predictors of improvement following upgrade to CRT in patients with PICM. Methods: We retrospectively analyzed 43 patients undergoing CRT upgrade for PICM over the 10-year period of 2011 to 2021 at our center. All patients with PICM who underwent device upgrade from a dual- or single-chamber ventricular pacemaker to CRT were included. PICM was defined as a decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in an LVEF <50% among patients with ≥20% Right ventricular pacing burden without an alternative cause for cardiomyopathy. Results: LVEF significantly improved from 28.7% preupgrade to 44.3% post-CRT upgrade (P < .01). Of 37 patients with severe LV dysfunction, 34 (91.9%) improved to an LVEF >35% and 13 (35.1%) improved to an LVEF >50%. The LV end-diastolic diameter decreased from 5.9 cm preupgrade to 5.4 cm postupgrade (P < .01). Using linear regression, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with significant LVEF improvement (+7.21%, P = .05). We observed a low rate of complications, and 1 in 4 CRT upgrades required venoplasty (n = 10 of 43, 23.3%). Conclusion: We provide further evidence for the benefit of CRT upgrade in the management of patients with PICM.

Characterization of the right ventricular substrate participating in postinfarction ventricular tachycardia.

BACKGROUND: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined. OBJECTIVES: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT. METHODS: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified. RESULTS: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died. CONCLUSION: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.

A Smartwatch Heart Rate Monitor Prompts an Unusual Diagnosis.

We report the case of a 54-year-old woman who presented for cardiological evaluation having noted a decline in her heart rate on her wearable heart rate monitor. She was found to be in 2:1 atrioventricular block. Subsequent evaluation revealed cardiac and pulmonary sarcoidosis, treated with steroids and implantable cardioverter-defibrillator placement. (Level of Difficulty: Beginner.).

Ablation of Ventricular Arrhythmias From the Left Ventricular Apex in Patients Without Ischemic Heart Disease.

OBJECTIVES: This study aimed to characterize the incidence, clinical characteristics, and electrocardiographic and electrophysiologic features of LVA VA in the absence of CAD and to describe the experience with catheter ablation (CA) in this group. BACKGROUND: The left ventricular apex (LVA) is a well-described source of ventricular arrhythmias (VAs) in patients with coronary artery disease (CAD) and history of apical infarction but is a rare source of VA in the absence of CAD. METHODS: Patients referred for CA of VA at our institution were retrospectively reviewed, and those with LVA VA in the absence of CAD were identified. RESULTS: Of 3,710 consecutive patients undergoing VA ablation, CA of LVA VA was performed in 24 patients (20 with monomorphic ventricular tachycardia, 4 with premature ventricular contractions or nonsustained ventricular tachycardia; 18 men; mean age: 54 ± 15 years). These cases comprised 10 of 35 (29%) hypertrophic cardiomyopathy, 9 of 789 (1.2%) nonischemic cardiomyopathy, and 5 of 1,432 (0.4%) idiopathic VA ablation procedures. VA QRS morphology was predominantly right bundle with slurred upstroke and right superior frontal plane axis with precordial transition ≤V3. Epicardial ablation was performed in 14 of 24 (58%). After a median of 1 procedure (range 1 to 4) at this institution and median follow-up of 47 months (range 0-176), VA recurred in 1 patient (4%). CONCLUSIONS: LVA VA in the absence of CAD is unusual and may occur in patients with hypertrophic cardiomyopathy or nonischemic cardiomyopathy or, rarely, in the absence of structural heart disease. It can be recognized by characteristic ECG features. CA of LVA VA is challenging; multiple procedures, including epicardial approaches, may be required to achieve VA control over long-term follow-up.

First experience with zero-fluoroscopic ablation for supraventricular tachycardias using a novel impedance and magnetic-field-based mapping system.

AIMS: Zero- and near-zero-fluoroscopic ablation techniques reduce the harmful effects of ionizing radiation during invasive electrophysiology procedures. We aimed to test the feasibility and safety of a zero-fluoroscopic strategy using a novel integrated magnetic and impedance-based electroanatomical mapping system for radiofrequency ablation (RFA) of supraventricular tachycardias (SVTs). METHODS: We retrospectively studied 92 consecutive patients undergoing electrophysiology studies with/without RFA for supraventricular tachycardia (SVT) performed by a single operator at a single center. The first 42 (Group 1) underwent a conventional fluoroscopic-guided approach and the second 50 (Group 2) underwent a zero-fluoroscopic approach using the Ensite Precision™ 3-D magnetic and impedance-based mapping system (Abbott Inc). RESULTS: Group 1 comprised 14 AV-nodal re-entrant tachycardia (AVNRT), 12 typical atrial flutter, 4 accessory pathway (AP), 2 atrial tachycardia (AT), and 9 diagnostic EP studies (EPS). Group 2 comprised 16 AVNRT, 17 atrial flutter, 6 AP, 3 AT, 2 AV-nodal ablations, and 7 EPS. A complete zero-fluoroscopic approach was achieved in 94% of Group 2 patients. All procedures were acutely successful, and no complications occurred. There was a significant reduction in fluoroscopy dose, dose area product, and time (p < 0.0001, for all), with no difference in procedure times. Ablation time for typical atrial flutter was shorter in Group 2 (p = 0.006). CONCLUSIONS: A zero-fluoroscopic strategy for diagnosis and treatment of SVTs using this novel 3D-electroanatomical mapping system is feasible in majority of patients, is safe, reduces ionizing radiation exposure, and does not compromise procedural times, success rates, or complication rates.

Relationship of the lungs to the left atrium of particular relevance for ablation of atrial fibrillation.

BACKGROUND: Symptoms of possible lung and pleural injury such as chest pain and hemoptysis occur during and after radiofrequency ablation (RFA) and cryoablation (CA) of the left atrium (LA) for treatment of atrial fibrillation (AF). We determined the anatomical relationship of the lungs to the LA with particular reference to areas commonly targeted during AF ablation. METHODS: Distances from the LA endocardium to the lungs were measured from pre-procedure CT angiograms of 100 consecutive patients (71 males, age 60 ± 8 years) who underwent AF ablation. RESULTS: In 97% of the patients, the posterior right pulmonary vein antrum was <5 mm from the lower lobe of the right lung (RLL) over a supero-inferior distance of 3.6 ± 1.5 cm (minimum distance 1.2 ± 0.7 mm). The right inferior pulmonary vein (RIPV) ostium was <5 mm from the RLL in 94% (mean 2.7 ± 1.9 mm). The right superior pulmonary vein ostium was <5 mm from the RLL in 29% (mean 7.1 ± 3.8 mm). The medial segment of the right middle lobe was <5 mm from the carina between right pulmonary veins in 83% (mean 3.6 ± 1.9 mm). The mitral isthmus was <5 mm from the lingula in 5% (mean 9.4 ± 3.6 mm). The inferior lobe of the left lung was <5 mm from the posterior aspect of the ostia of the left inferior and superior pulmonary veins in 9 and 0%, respectively. The bronchi were <5 mm from the LA in 5%. CONCLUSIONS: The lungs are intimately related to sites of the LA commonly targeted during AF RFA. Whether this anatomical proximity translates into clinically significant potential for collateral lung damage during RFA merits further study.

Anatomy of the left main coronary artery of particular relevance to ablation of left atrial and outflow tract arrhythmias.

BACKGROUND: Left main coronary artery (LMCA) damage is a rare but catastrophic complication of cardiac ablation procedures. OBJECTIVE: The purpose of this study was to describe the anatomic relationships of the LMCA to its adjacent structures using analysis of computed tomographic coronary angiograms (CTCA). METHODS: We studied 100 patients (55 males, age 51 ± 10 years) who were investigated for chest pain with CTCA. The relationships between the LMCA and adjacent structures were described by analysis of 2-dimensional images and 3-dimensional reconstructions. RESULTS: The LMCA coursed within 5 mm of the anterior left atrial endocardium and/or base of left atrial appendage in 49% (within 2 mm in 17%) and from the pulmonary artery in 90% (within 2 mm in 43%). The LMCA was within 5 mm of the right ventricular outflow tract in 1%. In 4% the LMCA coursed inferiorly, remaining within 5 mm of the left aortic sinus of Valsalva at a vertical distance >5 mm from the inferior margin of the LMCA ostium. CONCLUSION: The LMCA is often intimately related to the anterior left atrium, left atrial appendage base, and pulmonary artery and occasionally to the inferior part of the left aortic sinus of Valsalva and thus is exposed to the risk of injury during ablation in these areas. The LMCA is rarely close to the right ventricular outflow tract.

Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats.

Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ± 7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the K(ATP) channel opener pinacidil was attenuated in SHROB (E(Max) = 77 ± 7%), compared with WKY (E(Max) = 115 ± 19) and SHR (E(Max) = 93 ± 12%). Vasodilation to pinacidil was improved by rosiglitazone (E(Max) = 92 ± 14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ± 20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ± 9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome.