Robert Lemery

Nonischemic ventricular tachycardia. Clinical course and long-term follow-up in patients without clinically overt heart disease.

This report describes the clinical, laboratory, and electrophysiologic features of 52 patients with ventricular tachycardia (VT) who had no clinical evidence of heart disease. The mean age of patients was 36 years, cardiovascular collapse occurred in 18 patients (35%), and exercise-related symptoms were present in 24 of 49 patients (49%). There were 20 patients with sustained monomorphic VT, 11 with incessant VT, and 21 with nonsustained VT. Abnormalities were present in 14 of 38 patients (37%) during echocardiography and in 21 of 47 patients (45%) who underwent cardiac catheterization. During baseline evaluation while patients were not receiving antiarrhythmic drugs, ambulatory monitoring and exercise testing showed an 88% and 57% incidence, respectively, of nonsustained or sustained monomorphic VT, whereas 31 of 50 patients (62%) had inducible VT (requiring an infusion of isoproterenol in 11 patients) during programmed electrical stimulation. The clinical VT (when a 12-lead electrocardiogram was available for analysis) had a left bundle branch block (LBBB) configuration in 20 of 33 patients (61%) and a right axis deviation in 17 of 33 patients (51%). The VT occurring during exercise testing and programmed electrical stimulation had the same configuration as the clinical VT in 22 of 22 patients. Three patients have received an antitachycardia pacemaker, and one patient underwent endocardial resection. Forty-eight patients (92%) were treated medically. One patient died of cancer; the remaining 47 patients were alive at a mean follow-up of 96 months after initial symptoms and 46 months after programmed electrical stimulation. We conclude that in patients without clinical evidence of heart disease, VT may be incessant, sustained, or nonsustained and that VT originates from the right ventricular outflow tract in more than 50% of patients. Although cardiac abnormalities may be found in more than 30% of patients, the exact significance of these abnormalities is unclear because of the absence of progressive changes and the excellent prognosis of this group of patients.

Paradigm of Genetic Mosaicism and Lone Atrial Fibrillation Physiological Characterization of a Connexin 43–Deletion Mutant Identified From Atrial Tissue

Background— Atrial fibrillation (AF) is the most common sustained arrhythmia observed in otherwise healthy individuals. Most lone AF cases are nonfamilial, leading to the assumption that a primary genetic origin is unlikely. In this study, we provide data supporting a novel paradigm that atrial tissue–specific genetic defects may be associated with sporadic cases of lone AF. Methods and Results— We sequenced the entire coding region of the connexin 43 (Cx43) gene (GJA1) from atrial tissue and lymphocytes of 10 unrelated subjects with nonfamilial, lone AF who had undergone surgical pulmonary vein isolation. In the atrial tissue of 1 patient, we identified a novel frameshift mutation caused by a single nucleotide deletion (c.932delC) that predicted 36 aberrant amino acids followed by a premature stop codon, leading to truncation of the C-terminal domain of Cx43. The mutation was absent from the lymphocyte DNA of the patient, indicating genetic mosaicism. Protein trafficking studies demonstrated intracellular retention of the mutant protein and a dominant-negative effect on gap junction formation of both wild-type Cx43 and Cx40. Electrophysiological studies revealed no electrical coupling of cells expressing the mutant protein alone and significant reductions in coupling when coexpressed with wild-type connexins. Conclusions— This study reports atrial tissue genetic mosaicism of a novel loss-of-function Cx43 mutation associated with lone AF. These findings implicate somatic genetic defects of Cx43 as a potential cause of AF and support the paradigm that sporadic, nonfamilial cases of lone AF may arise from genetic mosaicism that creates heterogeneous coupling patterns, predisposing the tissue to reentrant arrhythmias.

Reversibility of tachycardia-induced left ventricular dysfunction after closed-chest catheter ablation of the atrioventricular junction for intractable atrial fibrillation

Significant left ventricular (LV) dysfunction resulting from chronic uncontrolled tachycardia represents a diagnostic dilemma. In patients with a depressed LV function and tachycardia, the tachycardia may have developed as a consequence of a cardiomyopathy or may be the cause of the LV dysfunction [1-3]. In this report we demonstrate that intractable atrial fibrillation (AF) may be associated with LV dysfunction, and that closed-chest catheter ablation, by modifying conduction in the atrioventricular node, may be of therapeutic value.

Accelerating risk of Fidelis lead fracture

BACKGROUND Sprint Fidelis (Medtronic Inc., Minneapolis, Minnesota) is a 6.6-F implantable cardioverter-defibrillator lead. In October 2007 the manufacturer suspended distribution of Sprint Fidelis leads secondary to high early fracture rates. Reprogramming of lead impedance alerts was recommended to try to reduce inappropriate shocks. OBJECTIVE This study sought to assess how the hazard of Fidelis fracture varies with time, whether lead impedance alert thresholds programmed after recall have prevented inappropriate shocks, and predictors of lead fracture. METHODS We collected clinical and device interrogation data on all lead fractures and performed a Kaplan-Meier analysis. We performed a case control study to examine univariate and multivariate predictors of lead fracture. RESULTS There have been 17 lead fractures in our cohort of 480 Sprint Fidelis (model 6949) leads, median follow-up 19.8 months. The hazard of fracture increased significantly with time by a power of 2.74 (95% confidence interval: 2.57 to 2.91, P <.0001). Reprogrammed lead impedance thresholds prevented inappropriate shocks in only 1 of 6 patients. Independent predictors of lead fracture were greater left ventricular ejection fraction (P = .0011) and noncephalic venous access (P = .0224). CONCLUSION The risk of lead fracture increased with time by a power of 2.74. Reprogrammed lead impedance thresholds prevented inappropriate shocks in only 1 of 6 patients. Independent predictors of lead fracture were greater left ventricular ejection fraction and noncephalic access.

Human Study of Biatrial Electrical Coupling Determinants of Endocardial Septal Activation and Conduction Over Interatrial Connections

Background—The relative contribution of the atrial septum and interatrial connections to biatrial activation is a fundamental concept of human cardiac electrophysiology that has yet to be fully characterized. The purpose of the present study was to determine how both atria are coupled electrically. Methods and Results—Twenty patients (16 men; mean age 54±11years) with a history of symptomatic atrial fibrillation (AF) underwent simultaneous biatrial noncontact mapping before catheter ablation of AF. The multiple electrode array catheters were positioned, respectively, in the left atrium (LA; transseptally) and the right atrium (RA). In all but 2 patients, isopotential maps revealed that endocardial septal activations of the RA and LA were separate, independent, and asynchronous of each other. Interatrial conduction was related to the site of initial atrial depolarization, revealing conduction over Bachmanns bundle in all patients during sinus rhythm, high RA pacing, and pacing from the LA appendage. Pacing from the coronary sinus was associated with conduction over the interatrial connection at the level of the coronary sinus in all patients, and conduction over Bachmanns bundle also occurred in 5 (26%) of 19 patients. Interatrial conduction over the fossa ovalis occurred in only 2 (2%) of the 116 segments analyzed. Conclusions—Electrical coupling of the RA and LA in humans is predominantly provided by muscular connections at the level of Bachmanns bundle and the coronary sinus. The true septum (the fossa ovalis and its limbus) of the RA and LA is asynchronous and discordant, usually without contralateral conduction during sinus rhythm or atrial pacing.

Initial Experience With an Implantable Hemodynamic Monitor

BACKGROUND Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Normal Atrial Activation and Voltage During Sinus Rhythm in the Human Heart: An Endocardial and Epicardial Mapping Study in Patients with a History of Atrial Fibrillation

Background: The three‐dimensional contributions to human atrial activation in sinus rhythm have not been specifically characterized. We evaluated the sequence of endocardial and epicardial activation and voltage of the atria during normal sinus rhythm.

Nonischemic sustained ventricular tachycardia: Clinical outcome in 12 patients with arrhythmogenic right ventricular dysplasia

The clinical course and long-term follow-up of 12 patients with arrhythmogenic right ventricular dysplasia causing ventricular tachycardia are presented. No patient had a history of congestive heart failure and the cardiothoracic ratio measured less than or equal to 0.5 in all patients. All 12 patients were symptomatic during ventricular tachycardia; syncope occurred in 4. Exercise-related symptoms were present in 8 (73%) of 11 patients. The mean right ventricular ejection fraction was 31% (range 20% to 54%), and the mean left ventricular ejection fraction was 68% (range 44% to 88%). Signal averaging of the rest electrocardiogram (ECG) revealed late potentials in five of eight patients. During programmed electrical stimulation, sustained or nonsustained ventricular tachycardia showing a left bundle branch block configuration was induced in all patients. One patient underwent right ventricular disconnection and died 1 week after operation of low cardiac output failure. The remaining 11 patients were all treated medically and are alive at a mean follow-up time of 7.9 years after the onset of symptoms. Recurrence of symptomatic and documented sustained monomorphic ventricular tachycardia occurred in eight patients and could not be predicted by results of long-term ECG monitoring, treadmill exercise testing or programmed stimulation. In conclusion, despite recurrence of ventricular tachycardia, patients with arrhythmogenic right ventricular dysplasia have a favorable outcome when treated medically. Noninvasive studies (imaging techniques, ambulatory ECG monitoring and exercise testing) provide data that may be sufficient in diagnosing arrhythmogenic right ventricular dysplasia.

Initial Clinical Experience With Ambulatory Use of an Implantable Atrial Defibrillator for Conversion of Atrial Fibrillation

BackgroundA recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. Methods and ResultsAn atrial defibrillator was implanted in 105 patients (75 men; mean age, 59±12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented “not at all,” 10 represented “extremely”) after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6±1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2±2.4 for successful therapy and 4.2±2.2 for unsuccessful therapy (P >0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4±3.3 versus 8.7±1.3, P <0.05). There was no ventricular proarrhythmia observed throughout the course of this study. ConclusionsAmbulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Ventricular fibrillation in six adults without overt heart disease

Findings are described in six patients with no clinical evidence of heart disease who had documented ventricular fibrillation (five patients) or ventricular flutter (one patient). The mean age of the six patients, all men, was 34 years (range 26 to 43). Cardiovascular collapse occurred in all and was followed by successful cardioversion. No patient had electrolyte or QT abnormalities. One patient had slight right ventricular enlargement on M-mode echocardiography, and another had a left ventricular pressure gradient at rest of 30 mm Hg with a normal two-dimensional echocardiogram. Holter electrocardiographic monitoring revealed incessant ventricular tachycardia in one patient and nonsustained ventricular tachycardia in three others. Exercise testing revealed nonsustained ventricular tachycardia in one patient. Ventricular fibrillation was induced at the time of programmed electrical stimulation in four of the six patients. Documented recurrence of ventricular fibrillation or ventricular flutter occurred in three patients, but in only one patient receiving antiarrhythmic drugs. Four patients were treated with amiodarone and one received an automatic implantable cardioverter-defibrillator. All patients are alive after a mean follow-up period of 78 months after the first documentation of their arrhythmia and 37 months after programmed electrical stimulation. Ventricular fibrillation can occur in the apparently structurally normal human heart. Antiarrhythmic treatment can provide effective control of this malignant arrhythmia.