Biventricular Arrhythmogenic Cardiomyopathy Mimicking Cardiac Sarcoidosis.

Noninvasive imaging is crucial for diagnosing and managing arrhythmogenic cardiomyopathy. Despite advanced multimodality imaging tools, challenges persist in differentiating it from other arrhythmogenic diseases (eg, cardiac sarcoidosis). We present a case of arrhythmogenic cardiomyopathy with an FLNC variant of uncertain significance exhibiting a phenocopy of cardiac sarcoidosis.

Seasonal Variation in the Incidence of In-Hospital Cardiac Arrest.

BACKGROUND: Seasonal variation in cardiovascular outcomes, including out-of-hospital cardiac arrest, has been described. OBJECTIVES: This study aimed to investigate seasonal differences in the incidence of in-hospital cardiac arrest (IHCA) and associated mortality. METHODS: Using National Inpatient Sample data from 2005 to 2019, we determined the incidence of IHCA in 4 seasons. The primary objective was to evaluate overall seasonal trends in the incidence of IHCA and trends stratified by sex, age, and region. The secondary aim was to determine common causes of admission that led to IHCA, differences in those with shockable vs nonshockable IHCA, independent predictors of IHCA, and seasonal variation in IHCA-related in-hospital mortality and length of stay. RESULTS: A consistent winter peak was observed in the incidence of IHCA in both male and female patients over the years in all age groups except young (<45 years) and in all regions. In 2019, both unadjusted and risk-adjusted odds of IHCA were higher (OR: 1.13; P < 0.001; adjusted OR: 1.08; P = 0.033) in winter than in summer. Patients with shockable IHCA were mainly admitted for cardiac and those with nonshockable IHCA for noncardiac conditions. No seasonal variation was observed in in-hospital mortality after IHCA. Therefore, seasonal variation exists, with a higher IHCA event rate in winter than summer. CONCLUSIONS: Improving insights into factors that influence the higher IHCA event rate during winter may help with proper resource allocation, development of strategies for early recognition of patients vulnerable to IHCA, and closer monitoring and optimization of care to prevent IHCA and improve outcomes.

Risk of Atrial Fibrillation and Stroke After Bariatric Surgery in Patients With Morbid Obesity With or Without Obstructive Sleep Apnea.

Background and Purpose: Weight loss in morbidly obese patients reduces atrial fibrillation (AF); however, it is unknown whether similar benefits are maintained in patients with obstructive sleep apnea (OSA). We sought to determine whether incident AF and stroke rates are affected by OSA after weight loss and to identify predictors of AF and stroke. Methods: Differences in laparoscopic adjustable gastric banding­induced weight loss on incident AF and stroke events in those with and without OSA in the entire and in propensity-matched cohorts were determined longitudinally, and independent predictors of AF and stroke were identified. Results: Of 827 morbidly obese patients who underwent laparoscopic adjustable gastric banding (mean age, 44±11 years; mean body mass index, 49±8 kg/m2), incident AF was documented in 4.96% and stroke in 5.44% of patients during a mean 6.0±3.2-year follow-up. Despite a similar reduction in body weight (19.6% and 21% in 3 years), new-onset AF was significantly higher in patients with OSA than without OSA in the entire (1.7% versus 0.5% per year; P<0.001) and propensity-matched cohorts. Incident stroke was higher in the OSA than in the non-OSA group (2.10% versus 0.47% per year; P<0.001), but only 20% of patients with stroke had documented AF. On multivariate analysis, OSA (hazard ratio, 2.88 [95% CI, 1.45­5.73]), age, and hypertension were independent predictors of new-onset AF, and OSA (hazard ratio, 5.84 [95% CI, 3.02­11.30]), depression, and body mass index were for stroke events. Conclusions: In morbidly obese patients who underwent laparoscopic adjustable gastric banding, despite similar weight loss, patients with OSA had a higher incidence of AF and stroke than patients without OSA. Both non-AF and AF-related factors were involved in increasing stroke risk. Further investigation is warranted into whether OSA treatment helps reduce AF or stroke events in this population.

A Tale of Fits and Faint: A Case of Hypervagotonic Nerve Stimulation.

Vagal nerve stimulators are devices used to treat medically refractory epilepsy. Here, we present a rare, unique, and life-threatening side effect of vagal nerve stimulator placement. (Level of Difficulty: Advanced.).

Preexcitation Syndromes.

The classic electrocardiogram in Wolff-Parkinson-White (WPW) syndrome is characterized by a short PR interval and prolonged QRS duration in the presence of sinus rhythm with initial slurring. The clinical syndrome associated with above electrocardiogram finding and the history of paroxysmal supraventricular tachycardia is referred to as Wolff-Parkinson-White syndrome. Various eponyms describing accessory or anomalous conduction pathways in addition to the normal pathway are collectively referred to as preexcitation syndromes. The latter form and associated eponyms are frequently used in literature despite controversy and disagreements over their actual anatomical existence and electrophysiological significance. This communication highlights inherent deficiencies in the knowledge that has existed since the use of such eponyms began. With the advent of curative ablation, initially surgical, and then catheter based, the knowledge gaps have been mostly filled with better delineation of the anatomic and electrophysiological properties of anomalous atrioventricular pathways. It seems reasonable, therefore, to revisit the clinical and electrophysiologic role of preexcitation syndromes in current practice.

Guiding the management of ventricular arrhythmias in patients with left ventricular noncompaction cardiomyopathy: a knowledge gap.

Left ventricular noncompaction (LVNC) is a cardiomyopathy that occurs due to an arrest of myocardial maturation during embryogenesis. The diagnostic echocardiographic features in individuals with LVNC include a thick, bilayered myocardium, prominent ventricular trabeculations, and deep intertrabecular recesses. Clinical features associated with LVNC vary in asymptomatic and symptomatic patients, and include the potential for heart failure, conduction defects (eg, left bundle branch block), supraventricular and ventricular arrhythmias, thromboembolic events, and sudden cardiac death. The authors report five cases that emphasize asymptomatic and apparently benign symptoms in patients with LVNC; despite normal physical examination and 12-lead electrocardiogram results, all of these cases unveiled potentially serious clinical consequences. These cases highlight the concern that LVNC patients with mild to moderate left ventricular systolic dysfunction, particularly in the presence of ventricular arrhythmias or a family history of sudden cardiac death, may need consideration for an implantable cardioverter defibrillator (ICD). All potential benefits of an ICD need to be balanced by the risk of device infection, lead and device malfunction, and potential for inappropriate shocks.

Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome.

BACKGROUND: BrS is an inherited sudden cardiac death syndrome. Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A, a neuronal sodium channel gene encoding Nav1.8, in the electrical function of the heart. OBJECTIVES: The purpose of this study was to test the hypothesis that SCN10A variants contribute to the development of Brugada syndrome (BrS). METHODS: Clinical analysis and direct sequencing of BrS susceptibility genes were performed for 150 probands and family members as well as >200 healthy controls. Expression and coimmunoprecipitation studies were performed to functionally characterize the putative pathogenic mutations. RESULTS: We identified 17 SCN10A mutations in 25 probands (20 male and 5 female); 23 of the 25 probands (92.0%) displayed overlapping phenotypes. SCN10A mutations were found in 16.7% of BrS probands, approaching our yield for SCN5A mutations (20.1%). Patients with BrS who had SCN10A mutations were more symptomatic and displayed significantly longer PR and QRS intervals compared with SCN10A-negative BrS probands. The majority of mutations localized to the transmembrane-spanning regions. Heterologous coexpression of wild-type (WT) SCN10A with WT-SCN5A in HEK cells caused a near doubling of sodium channel current compared with WT-SCN5A alone. In contrast, coexpression of SCN10A mutants (R14L and R1268Q) with WT-SCN5A caused a 79.4% and 84.4% reduction in sodium channel current, respectively. The coimmunoprecipitation studies provided evidence for the coassociation of Nav1.8 and Nav1.5 in the plasma membrane. CONCLUSIONS: Our study identified SCN10A as a major susceptibility gene for BrS, thus greatly enhancing our ability to genotype and risk stratify probands and family members.

Repolarization syndromes.

Repolarization syndromes, including early repolarization, Brugada, and short and long QT, have been implicated increasingly as causes of sudden cardiac death (SCD) despite no obvious mechanical cardiac abnormalities. So-called idiopathic ventricular fibrillation is now often reassigned to one of the aforementioned entities. Underlying causes are diverse; genetic mutation has been proven in many but not all cases. Although high-risk individuals generally can be identified, most of the potential victim pool is still unknown and cannot be discovered at this time. Awareness of these entities' existence, knowledge of family history, and 12-lead electrocardiography are the initial steps toward preventing SCD in this population. Underlying mechanisms for ventricular tachycardia/fibrillation in such individuals include phase 2 reentry, early after depolarization, and vortex reentry. For the time-being, although most forms of long QT syndrome can be treated with ß-blockers, an implantable cardioverter-defibrillator remains the only definitive therapy for the prevention of arrhythmic death among high-risk populations.

Cardiac Image Registration: Rotational Error Correction and Gated Stabilization for Cardiac Motion.

Background: Dynamic motion of the heart due to cardiac and respiratory cycles, and rotation from varying patient positions between imaging modalities, can cause errors during cardiac image registration. This study used phantom, patient and animal models to assess and correct these errors. Methods and Results: Rotational errors were identified and corrected using different phantom orientations. ECG-gated fluoro images were aligned with similarly gated CT images in 9 patients, and accuracy assessed during atrial fibrillation (AF) and sinus rhythm. A tracking algorithm corrected errors due to respiration; 4 independent observers compared 25 respiration sequences to an automated method. Following correction of these errors, target registration error was assessed. At 20 mm and 30 mm from the phantom model's center point with an in-plane rotation of 8 degrees, measured error was 2.94 mm and 5.60 mm, respectively, and the main error identified. A priori method accurately predicted ECG location in only 38% (p=0.0003) of 313 R-R intervals in AF. A posteriori method accurately gated the ECG during AF and sinus rhythm in 97% and 98% of 375 beats evaluated, respectively (p=NS). Tracking algorithm for ECG-gated motion compensation was identified as good or fair 96% of the time, with no difference between observers and automated method (chi-square=25; p=NS). Target registration error in phantom and animal models was 1.75±1.03 mm and 0 to 0.5 mm, respectively. Conclusions: Errors during cardiac image registration can be identified and corrected. Cardiac image stabilization can be achieved using ECG gating and respiration.

Periprocedural anticoagulation for atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) can increase risk of left atrial (LA) thrombi and stroke. Optimal periprocedural anticoagulation has not been determined. OBJECTIVE: We report the role of administering warfarin and aspirin without low molecular weight heparin in patients undergoing AF ablation. METHODS: A total of 207 patients underwent ablation for AF. Transesophageal echocardiography (TEE) guided transseptal puncture and ruled out clot in the LA. After first puncture, the sheath was flushed with heparin (5,000 Units/mL). After second puncture, a bolus of 80 units/kg of heparin was given, followed by an infusion to maintain activated clotting time (ACT) around 300-350 seconds. Warfarin was stopped and aspirin was started (325 mg/day) 3 days preprocedure. Warfarin was restarted on the day of the procedure. Both medications were continued for 6 weeks postablation. Warfarin was continued for 6 months in patients with prior history of persistent or recurrent AF. Thirty-seven patients who showed smoke in the LA on TEE were given low molecular weight heparin postprocedure until international normalized ratio (INR) was therapeutic. RESULTS: Thirty-two patients had persistent and 175 had paroxysmal AF; 87 were cardioverted during ablation. Two patients had transient ischemic attack (TIA) on the sixth and eighth days, respectively, following ablation, with complete recovery. Both had subtherapeutic INRs. CONCLUSION: In patients without demonstrable clot or smoke in the LA, starting aspirin 3 days prior and warfarin immediately post-radiofrequency ablation, without low molecular weight heparin, with meticulous anticoagulation during the procedure, appears to be a safe mode of anticoagulation.

Biventricular pacing and QT interval prolongation.

INTRODUCTION: The purpose of this study was to examine BiV pacing-dependent changes in QT interval and the related potential for proarrhythmia. Biventricular (BiV) pacing has emerged as a promising therapy for patients with advanced congestive heart failure (CHF) and bundle branch block (BBB). METHODS AND RESULTS: One hundred and seventy-six consecutive patients (123 men and 53 women; mean age 67 +/- 16 years) with ischemic (n = 128) or nonischemic (n = 48) cardiomyopathy in New York Heart Association Class II (8%) or III (92%) CHF (ejection fraction 24 +/- 9%) underwent atrial synchronous BiV pacing. The QRS, QT, and JT intervals were measured at 30 minutes after initiation of BiV pacing, at 24 hours, and at 1 month postimplant. QT interval was defined as the time interval between the initial deflection of the QRS complex and the point at which the T wave crossed the isoelectric line. At baseline, the average QRS duration was 178 +/- 10 ms, attributable to left BBB (n = 158) or intraventricular conduction delay (n = 18). BiV pacing resulted in a small but statistically significant reduction in QRS duration (148 +/- 9 ms during BiV pacing vs 178 +/- 10 ms at baseline [P < 0.0001]), yet the QT increased to 470 +/- 34 ms with BiV pacing versus 445 +/- 32 ms at baseline [P < 0.0001]). The JTc interval during BiV pacing was significantly shorter than during LV pacing (290 +/- 9 ms vs 320 +/- 20 ms, P < 0.0001). During a mean follow-up of 24 +/- 6 months, one patient developed recurrent torsade de pointes. That was eliminated once left ventricular pacing was discontinued. CONCLUSION: Biventricular pacing prolongs QT interval. However, the occurrence of torsade de pointes is uncommon.

Computed tomography-fluoroscopy image integration-guided catheter ablation of atrial fibrillation.

INTRODUCTION: This study examines the feasibility of atrial fibrillation (AF) ablation using registered three-dimensional computed tomography (CT) images of the left atrium with fluoroscopy. METHODS AND RESULTS: A total of 50 consecutive patients with symptomatic AF refractory to medical therapy (32 paroxysmal, 18 persistent, age 55 +/- 10 years) were randomized to undergo a catheter-based AF ablation procedure with or without the CT-fluoroscopy guidance system. All patients underwent preprocedural contrast-enhanced CT imaging and segmentation of the left atrium. For the CT-fluoroscopy group, circumferential lesions encompassing the pulmonary vein (PV) antrum and linear lesions along the roof of the left atrium between the superior PVs and the mitral isthmus were created on the CT image, which was registered with real-time fluoroscopy. The registered images were then used to navigate the ablation catheters to the sites of planned ablation. After the ablation sites were completed, any remaining PV potentials were isolated with electrophysiological guidance. In the control patients, the same technique was performed without using the CT-fluoro guidance system. CT scans were accurately registered to fluoroscopic images with minimal manual correction. Operators could navigate catheters on the registered images to preplanned, extraostial sites for ablation. CT-fluoroscopy guidance decreased procedure duration and fluoro times (P < 0.05). At a mean follow-up of 9 +/- 2 months, 21 patients (84%) in the CT-fluoro guidance group and 16 patients (64%) in the control group have had no recurrence of AF. CONCLUSION: CT-fluoroscopic-guided left atrial ablation is feasible and allows appropriate catheter manipulation in the left atrium.

Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS: This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.

Posterior left atrial-esophageal relationship throughout the cardiac cycle.

BACKGROUND: Radiofrequency energy delivered throughout the cardiac cycle has the potential to cause thermal injury to the esophagus if the anatomical relationship between the posterior left atrium and the esophagus changes during cardiac motion. OBJECTIVE: To assess the posterior left atrial-esophageal relationship throughout the cardiac cycle. METHODS: In this study, the anatomical relationship between the posterior left atrium and the esophagus was assessed throughout the cardiac cycle in 10 consecutive patients. All patients underwent contrast-enhanced, ECG-gated CT scanning. Left atrial volumes and the esophageal structure were generated from the reconstructed data at 10 phases of the cardiac cycle from 5% to 95% of the R-R interval. The posterior left atrial-esophageal anatomical relationship was measured at four levels, the superior pulmonary vein ostial site, and the upper, mid and lower left atrium. RESULTS: There were significant variations in the left atrial-esophageal relationship in the 10 patients. The relative movement between the esophagus and the posterior left atrium throughout the cardiac cycle in the anteroposterior and right-to-left orientations was 0.55 +/- 0.99 mm and 0.60 +/- 1.02 mm (95% confidence interval, 2.03 and 1.98 respectively). CONCLUSIONS: Under normal conditions, there is little change in the anatomical relationship between the posterior left atrium and the esophagus during the entire cardiac cycle. However, due to the interpatient variability at the esophageal location, identification of esophageal location may help prevent complications during catheter ablation procedures involving the left atrium.

Pulmonary vein isolation and linear lesions in atrial fibrillation ablation.

BACKGROUND: Various strategies have been used for atrial fibrillation (AF) ablation. It is unclear whether adding linear lesions to pulmonary vein (PV) isolation has significant advantages. OBJECTIVES: We assessed the clinical benefit of adding linear lesions in patients undergoing PV isolation for AF. METHODS: One hundred patients (63 male and 37 female; mean age of 59 +/- 11 years) with documented paroxysmal AF were included in the study. Patients were randomized into two groups. The first group underwent PV isolation alone. The second group underwent PV isolation and had two linear lesions created; one line between the superior PVs, and a second line from the left inferior PV to the mitral valve annulus. Patients' clinical progress after the ablation was evaluated and compared at 1, 3, and 9 months after their respective ablation procedures. RESULTS: The linear lesions group maintained sinus rhythm and had fewer symptoms than the lone PV isolation group (86 vs. 58%, respectively) (p < 0.05) at 1 month. At 9 months, when patients who reverted to AF underwent additional management to regain sinus rhythm (90 vs. 82%, respectively) (p = NS), there was no statistical difference between the groups regarding the use of antiarrhythmics, the need for electrical cardioversion, and subjective improvement. CONCLUSION: The addition of linear lesions to PV isolation more effectively achieved sinus rhythm initially and fewer patients required additional management to maintain their rhythm when compared to patients who underwent lone PV isolation. However, at 9 months, the overall results were similar in both groups.

The implantable cardioverter defibrillator: technology, indications, and impact on cardiovascular survival.

Since the introduction of the implantable cardioverter defibrillator (ICD) for the management of patients with high risk of arrhythmic SCD, there has been increasing use of this device. Its basic promise to effectively terminate ventricular tachycardia (VT)-ventricular fibrillation (VF) has been repeatedly met. In several randomized trials, the ICD has been shown to be superior to conventional anti-arrhythmic therapy, both in patients with documented VT-VF (secondary prevention) and those with high risk such as left ventricular ejection fraction and no prior sustained VT-VF (primary prevention). In both groups, the ICD showed overall and cardiac mortality reduction. The device now can more accurately detect VT-VF and differentiate these from other arrhythmias through a series of algorithms and direct-chamber sensing. Therapy options include painless antitachycardia pacing, low-energy cardioversion, and high-energy defibrillation. The technique implant is now simple as a pacemaker with one lead attached to an active (hot) can functioning as the other electrode. Among other improvements is its weight, volume, multiprogrammability, and storage of information,dual-chamber pacing and sensing, dual-chamber defibrillation, and addition of biventricular pacing for cardiac synchronization. It is anticipated that further improvement in ICD technology will take place and the list of indications will grow.

Pharmacotherapy of atrial fibrillation.

Atrial fibrillation is the most common sustained arrhythmia of clinical significance. Its prevalence rises with age. It is a significant cause of thromboembolic phenomena. We describe briefly the etiology and classification of atrial fibrillation, the risk factors for thromboembolism and stroke associated with it, the indications for hospitalization, and the therapeutic goal. We discuss in depth the management strategies for such patients and compare the impact of rate versus rhythm control in reducing morbidity and mortality attributed to arrhythmia, in light of past and present trials. A brief overview of the drugs used in the management of atrial fibrillation, their pharmacology and dosage, their effects and use in rhythm versus rate control with important side effects are also included. Finally, the prevention and treatment of thromboembolism in patients with atrial fibrillation, an important aspect of therapy, is revisited in light of recent advances.