Low voltage-guided ablation of posterior wall improves 5-year arrhythmia-free survival in persistent atrial fibrillation.

INTRODUCTION: The posterior wall (PW) has been proposed as a standard target for ablation beyond pulmonary vein antral isolation (PVI) in patients with persistent atrial fibrillation (AF). However, studies have shown inconsistent outcomes with the addition of PW ablation. The presence or absence of low voltage on the PW may explain these inconsistencies. We evaluated whether PW ablation based on the presence or absence of low voltage improves long-term arrhythmia-free outcomes. METHODS: We retrospectively reviewed 5-year follow-up in 152 consecutive patients who received either standard ablation (SA) with PVI alone or PVI + PW ablation (PWA) based on physician discretion (n = 77) or voltage-guided ablation (VGA) with PVI and addition of PWA only if low voltage was present on the PW (n = 75). RESULTS: The two groups were well matched for baseline characteristics. At 5-year follow-up, 64% of patients receiving VGA were atrial tachyarrhythmia (AT)/AF free compared to 34% receiving SA (HR 0.358 p < .005). PWA had similar AF recurrence in SA and VGA groups (0.30 vs. 0.27 p = .96) but higher AT recurrence when comparing SA and VGA groups (0.39 vs. 0.15 p = .03). In multivariate analysis, both VGA and PWA predicted AF arrhythmia-free survival (HR 0.33, p = .001 and HR 0.20, p = .008, respectively). For AT, VGA predicted arrhythmia-free survival (HR 0.22, p = .028), while PWA predicted AT recurrence (HR 4.704, p = .0219). CONCLUSION: VGA of the posterior wall ablation beyond PVI in persistent AF significantly improves long-term arrhythmia-free survival when compared with non-voltage-guided ablation. PW ablation without voltage-guidance reduced AF recurrence but at the cost of a higher incidence of AT.

Idiopathic Ventricular Fibrillation: Diagnosis, Ablation of Triggers, Gaps in Knowledge, and Future Directions.

Idiopathic ventricular fibrillation (IVF) is a diagnosis of exclusion made when no underlying cause is identified in a cardiac arrest survivor. Although the frequency of this diagnosis has declined over time due to advances in diagnostic techniques, it remains a substantial cause of sudden cardiac arrest. Further, IVF tends to recur. This article reviews the criteria for diagnosis, patient characteristics, the two primary arrhythmic phenotypes-short-coupled variant of torsades de pointes and recurrent paroxysmal IVF-and the electrophysiologic features, treatment, and ablation of premature ventricular complexes that can trigger IVF.

Ventricular Arrhythmias.

Ventricular tachycardia is commonly seen in medical practice. It may be completely benign or portend high risk for sudden cardiac death. Therefore, it is important that clinicians be familiar with and able to promptly recognize and manage ventricular tachycardia when confronted with it clinically. In many cases, curative therapy for a given ventricular arrhythmia may be provided after a thorough understanding of the underlying substrate and mechanism. In this article, the authors broadly review the current classification of the different ventricular arrhythmias encountered in medical practice, provide brief background regarding the different mechanisms, and discuss practical diagnosis and management scenarios.

Ventricular Tachycardia Triggered by Loperamide and Famotidine Abuse.

A 32-year-old male developed recurrent ventricular tachycardia after taking mega doses of loperamide and famotidine in order to experience an opiate-like euphoric effect. He was taking up to 200 mg of loperamide and multiple doses of famotidine each day. He developed palpitations and syncope. Electrocardiography demonstrated ventricular tachycardia and QT interval prolongation (corrected QT interval was 597 ms). He was diagnosed with loperamide-induced QT prolongation resulting in incessant ventricular tachycardia. Loperamide was discontinued, and he was treated with electrolyte replacement, supportive care, and monitoring. After 5 days, his electrocardiogram (ECG) normalized and he had no more ventricular tachycardia. A Naranjo assessment score of 8 was obtained, indicating a probable relationship between QT prolongation and his use of loperamide. Large doses of loperamide can cause QT interval prolongation and life-threatening arrhythmias. These effects may be accentuated when histamine-2 receptor blockers are also abused.

Whole-exome sequencing reveals microsatellite DNA markers for response to dofetilide initiation in patients with persistent atrial fibrillation: A pilot study.

BACKGROUND: Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associates with corrected QT interval (QTc) prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associated with congenital and acquired health conditions. HYPOTHESIS: DNA microsatellite polymorphism may associate with QTc response to dofetilide initiation in patients with persistent AF. METHODS: We performed whole-exome sequencing in a cohort of patients with persistent AF undergoing DI. Electrocardiographic variables and clinical data were assessed. We defined patients as eligible for DI when no significant QTc prolongation (>20% compared with baseline) was seen with a 500-µg dose. We defined patients as ineligible for DI when significant QTc prolongation was seen during DI with 500 µg. We investigated polymorphisms for 11 919 DNA microsatellite loci in relation to QTc response to DI. RESULTS: During the study, 14 consecutive patients with persistent AF presenting for DI were enrolled. Whole-exome sequencing revealed 14 different microsatellite loci in the 2 groups. All genes or proximal genes that harbor these loci are known to have expression in the human heart. Two genes, MYH6 and TRAK2, are known to have expression in the atria. TRAK2 is known to interact with KCNJ2, the inward-rectifier potassium channel 1. CONCLUSIONS: Microsatellite DNA polymorphisms seem to associate with QTc response to DI therapy in patients with persistent AF who are deemed otherwise eligible for dofetilide therapy.

Intercalated Disk Extracellular Nanodomain Expansion in Patients With Atrial Fibrillation.

Aims: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous evidence in animal models suggests that the gap junction (GJ) adjacent nanodomain - perinexus - is a site capable of independent intercellular communication via ephaptic transmission. Perinexal expansion is associated with slowed conduction and increased ventricular arrhythmias in animal models, but has not been studied in human tissue. The purpose of this study was to characterize the perinexus in humans and determine if perinexal expansion associates with AF. Methods: Atrial appendages from 39 patients (pts) undergoing cardiac surgery were fixed for immunofluorescence and transmission electron microscopy (TEM). Intercalated disk distribution of the cardiac sodium channel Nav1.5, its ß1 subunit, and connexin43 (C×43) was determined by confocal immunofluorescence. Perinexal width (Wp) from TEM was manually segmented by two blinded observers using ImageJ software. Results: Nav1.5, ß1, and C×43 are co-adjacent within intercalated disks of human atria, consistent with perinexal protein distributions in ventricular tissue of other species. TEM revealed that the GJ adjacent intermembrane separation in an individual perinexus does not change at distances greater than 30 nm from the GJ edge. Importantly, Wp is significantly wider in patients with a history of AF than in patients with no history of AF by approximately 3 nm, and Wp correlates with age (R = 0.7, p < 0.05). Conclusion: Human atrial myocytes have voltage-gated sodium channels in a dynamic intercellular cleft adjacent to GJs that is consistent with previous descriptions of the perinexus. Further, perinexal width is greater in patients with AF undergoing cardiac surgery than in those without.

Left atrial appendage exclusion and the risk of thromboembolic events following mitral valve surgery.

OBJECTIVES: We aimed to evaluate left atrial appendage (LAA) exclusion in patients undergoing mitral valve surgery with respect to thromboembolic events. BACKGROUND: LAA is the predominant source of emboli in patients with atrial fibrillation. Prophylactic LAA exclusion at the time of heart surgery has been recommended to reduce the risk of future thromboembolism. METHODS: An observational cohort of 136 patients undergoing LAA exclusion during mitral valve surgery was identified between May 1993 and November 1998 at our institution. RESULTS: During a mean follow-up of 3.6 +/- 1.3 years, there were 14 (12.3%) thromboembolic events. Compared with patients who received warfarin upon hospital discharge, there were more thromboembolic events in patients not prescribed warfarin upon hospital discharge (n = 7/67, 10% vs n = 6/40, 15%, respectively). The warfarin status was not known for one patient. The majority of thromboembolic events (n = 10/14, 71%) occurred in those who underwent mitral valve repair. CONCLUSION: In this observational study, patients who undergo LAA exclusion during mitral valve surgery to reduce the risk of thromboembolism have a significant incidence of thromboembolic events, especially when warfarin therapy is not prescribed upon hospital discharge.

New criteria during right ventricular pacing to determine the mechanism of supraventricular tachycardia.

BACKGROUND: Right ventricular pacing (RVP) during supraventricular tachycardia produces progressive QRS fusion before the QRS morphology becomes stable. This transition zone (TZ) may provide useful information for differentiating orthodromic reciprocating tachycardia (ORT) from atrioventricular nodal reentrant tachycardia and atrial tachycardia independent of entrainment success. METHODS AND RESULTS: We studied the effect of properly timed RVP on atrial timing during the TZ in 92 patients with supraventricular tachycardia who had RVP within 40 ms of the tachycardia cycle length. The TZ during RVP includes progressively fused QRS complexes and the first paced complex with a stable QRS morphology based on analysis of the 12-lead ECG. We also measured the stimulus-atrial interval from the end of the TZ and with each QRS complex thereafter until pacing was terminated or ventriculo-atrial block occurred. A fixed stimulus-atrial interval was defined as variation <10 ms during RVP. Atrial preexcitation, postexcitation, or supraventricular tachycardia termination with abrupt ventriculo-atrial block was observed within the TZ in 32 of 34 patients with ORT. A fixed stimulus-atrial interval was established within the TZ in 33 of 34 patients with ORT. At least 1 of these 2 responses was observed in all patients with ORT. None of the patients with atrioventricular nodal reentrant tachycardia or atrial tachycardia had atrial timing perturbed or a fixed stimulus-atrial interval established within the TZ. CONCLUSIONS: During RVP within 40 ms of the tachycardia cycle length, ORT is the likely mechanism when atrial timing is perturbed or a fixed stimulus-atrial interval is established within the TZ.

Predictive value of high sensitivity C-reactive protein in the diagnosis and outcomes of acute aortic syndromes.

OBJECTIVE: The purpose of this study was to determine whether high-sensitivity C-reactive protein (hsCRP) levels differ among patients with acute aortic syndromes (AAS) and if hsCRP could predict their long-term outcomes. DESIGN: Retrospective observational study. SETTING: Cleveland Clinic Hospital, Cleveland, Ohio. PATIENTS: 115 consecutive patients with AAS admitted to the cardiac intensive care unit. INTERVENTIONS: HsCRP and other laboratory data were measured within 24 h of admission. Demographic, imaging and laboratory data were obtained at the time of presentation. For the long-term survival analysis, the social security death index was used to determine all-cause mortality. MAIN OUTCOME MEASURES: HsCRP levels among AAS patients. RESULTS: Hospital mortality was 4.3% for AAS patients. HsCRP levels differed significantly among AAS; the median hsCRP was higher in the aortic dissection group (49 mg/l) than in those with penetrating aortic ulcer (28 mg/l), symptomatic aortic aneurysm (14 mg/l), and intramural haematoma (10 mg/l); (p=0.02). In multivariable analysis, aortic dissection patients had higher hsCRP levels than intramural haematoma (p=0.03) and symptomatic aortic aneurysm (p=0.04) patients, after adjusting for age and gender. Multivariable Cox regression analyses showed that elevated hsCRP levels at presentation were associated with a higher long-term mortality (p=0.007). CONCLUSIONS: Among patients with AAS, those with aortic dissection have the highest hsCRP levels at presentation. Elevated hsCRP independently predicted a higher long-term mortality in AAS patients.