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.

Peritricuspid annular prostate pellet.

A 75-year-old was treated for prostate adenocarcinoma with brachytherapy in September 2018. A routine follow-up chest radiograph 3 months later revealed a metallic object of the same dimensions as a brachytherapy pellet located in the right ventricle. Further imaging showed the brachtherapy pellet was located in the anterobasal right ventricular endocardium close to the tricuspid valve. Frequent asymptomatic premature ventricular contractions were observed with likely origin from the left ventricular outflow tract, an area remote from the site of the pellet. The patient remains asymptomatic and subsequent imaging shows that the position of the pellet has not changed.

Long-Term Follow-Up of Idiopathic Ventricular Fibrillation in a Pediatric Population: Clinical Characteristics, Management, and Complications.

Background The natural history and long-term outcome in pediatric patients with idiopathic ventricular fibrillation ( IVF ) are poorly characterized. We sought to define the clinical characteristics and long-term outcomes of a pediatric cohort with an initial diagnosis of IVF . Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty-six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow-up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF . Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow-up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device-related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF , a minority develop a definite clinical phenotype during long-term follow-up. Recurrent VF is common in this patient group.

Ibutilide-induced cardioversion of atrial fibrillation during pregnancy.

We present two cases of successful cardioversion of atrial fibrillation using intravenous ibutilide during pregnancy. One patient had atrial fibrillation, complicating the Wolff-Parkinson-White syndrome and the other had a history of nonobstructive hypertrophic cardiomyopathy. No adverse maternal or fetal effects were observed during or after pregnancy in either case.

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.

Failure of Listeria monocytogenes keratitis to respond to topical ofloxacin.

PURPOSE: The purpose of this case report is to demonstrate the need for identification of the offending pathogen in bacterial keratitis to guide appropriate treatment. METHODS: Case report. RESULTS: We report a case of Listeria monocytogenes keratitis in a young healthy adult that failed to respond to standard empirical therapy for bacterial keratitis but was treated successfully with topical ampicillin, chloramphenicol, and systemic amoxicillin. CONCLUSION: This case demonstrates the need for identification of the offending pathogen to guide appropriate treatment. It also demonstrates discrepancy between in vitro sensitivity and clinical response.

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.

Achieving sufficient safety margins with fixed duration waveforms and the use of multiple time constants.

INTRODUCTION: There are several options to achieve a sufficient safety margin in a patient with a high defibrillation threshold (DFT), with varying and typically modest success. Programming fixed (millisecond) durations of both phases of a biphasic waveform in an implantable cardioverter defibrillator (ICD) has demonstrated utility. METHODS: We established an informal multisite registry of ICD implanting facilities. Each facility agreed to attempt the use of fixed duration waveforms whenever there was an inadequate safety margin with tilt-based waveforms. A 3.5-ms-based fixed duration shock was tried first. If that failed to achieve a 10-J safety margin then a 2-ms-based shock was used. We also tabulated an HEDFT (high estimate DFT) as precise DFTs were not determined. RESULTS: Sixteen patients (15 M, 1 F) were entered into the registry (age 58.2 +/- 17.9 years) with ejection fractions of .30 +/-.11. Superior vena cava coils were used in 7 patients according to physician preference. The tilt-based HEDFTs were 35.4 +/- 3.2 J delivered and 35.8 +/- 3.3 J stored energy. The 3.5-ms based shocks were evaluated on 14 patients and the HEDFT fell to 23.4 +/- 6.3 J delivered (P < 0.0001) and 26.2 +/- 6.9 J stored energy (P < 0.0001). The 2-ms-based fixed duration shocks were then evaluated on 6 patients and the delivered energy HEDFT was 22.2 +/- 5.8 J (P = 0.001 vs. tilt-based shocks) while the stored energy HEDFT was 27.9 +/- 6.4 J (P = 0.01 vs. tilt-based shocks). Using the better of the two fixed duration waveforms, the mean safety margin was improved from -1.2 +/- 1.9 J to 9.5 +/- 5.9 J (P < 0.00001). Multivariate predictors of the safety margin improvement were the absence of the Superior Vena Cava (SVC) coil and absence of Ventricular fibrillation (VF) presentation. Four patients still required lead repositioning after the use of the fixed duration waveforms. No additional leads were implanted. CONCLUSION: The use of a selection of directly programmed fixed duration biphasic shocks had a striking impact on the HEDFT for these difficult patients. Adequate safety margins were obtained for 12 of 16 patients with no lead manipulation or other approaches.