Peter Geelen

Improvement of Left Ventricular Function After Cardiac Resynchronization Therapy Is Predicted by Tissue Doppler Imaging Echocardiography

Background—Cardiac resynchronization therapy was shown to reverse left ventricular (LV) remodeling in patients with congestive heart failure (CHF). However, the prediction of benefit is controversial. We aimed to investigate predictive factors of LV functional recovery and reversed remodeling after biventricular pacing. Methods and Results—Forty-nine consecutive patients with CHF and a wide QRS complex (182±32 ms) were studied by echocardiography before resynchronization. Intraventricular and interventricular asynchrony and their combination were assessed by pulsed-wave tissue Doppler imaging from measurements of regional electromechanical coupling times in basal segments of the right and left ventricle. At 6-month follow-up, responders were defined by a relative increase in LV ejection fraction ≥25% compared with baseline (n=27). Receiver operating curve analysis revealed the degree of intraventricular asynchrony (area under the curve=0.77), interventricular asynchrony (area under the curve=0.69), and their combination (area under the curve=0.84) as the best predictors of functional recovery after resynchronization. In addition, the degree of intraventricular and interventricular asynchrony correlated significantly with the improvement of LV ejection fraction (r =0.73, P <0.0001), end-diastolic diameter (r =−0.59, P <0.0001), and end-systolic diameter (r =−0.48, P <0.001) at follow-up. QRS duration and conventional echo-Doppler indices were not predictive of reversed LV remodeling. Conclusions—In patients with CHF, the degree of intraventricular and interventricular asynchrony and their combination are the best predictive factors of LV functional recovery and reversed remodeling after cardiac resynchronization therapy.

Natural History of Brugada Syndrome

Introduction: The prognostic value of electrophysiologic studies in individuals with the syndrome of right bundle branch block and ST segment elevation in precordial leads V1 to V3 (Brugada syndrome) remains controversial. Our previous data from 252 individuals with the syndrome suggested that programmed ventricular stimulation had a good overall accuracy to predict events. However, studies from independent investigators questioned our results. We report here the largest population with Brugada syndrome ever studied by programmed electrical stimulation of the heart.

Ventricular Fibrillation and Sudden Death After Radiofrequency Catheter Ablation of the Atrioventricular Junction

Two hundred thirty‐five patients underwent RF catheter abhtion of AV conduction for symptomatic drug refractoiy AF (84%), atrial flutter (9%), and atrial tachycardia (7%). In the first 100 patients, postahlation pacing was not prospectively set at any specific rate and was always ≤ 70 beats/min. In the next 135 patients, postabiotion pacing was prospectively set at 90 beats/min for 1–3 months. Six of the first 100 patients (6%) had VF or sudden death after the RF procedure and none (0%) of the next 135 patients did (P < 0.05). One of the six patients had recurrent VF 4 days after the ablation. Five patients were successfully resuscitated and one patient died. There were no statistically significant differences between patients with and without (aborted) sudden death or between the first 100 and the next 135 patients with respect to age, sex, underlying heart disease, EF, number of RF applications, or leftor right‐sided approach of the procedure. VF mostly occurred during episodes of slow ventricular escape rhythms or during slow ventricular pacing. We conclude that malignant ventricular arrhythmias and sudden death are possible complications of RF ablation of the AV junction. The mechanism of these complications could have a bradycardia dependent nature and it seems that the occurrence of malignant arrhythmias can be prevented by temporarily pacing the heart at relatively fast rates immediately after ablation.

Prognostic Value of Electrophysiologic Investigations in Brugada Syndrome

Brugada Syndrome. Introduction: The prognostic value of electrophysiologic investigations in individuals with Brugada syndrome is unclear. Previous studies failed to determine its value because of a limited number of patients or lack of events during follow‐up. We present data on the prognostic value of electrophysiologic studies in the largest cohort ever collected of patients with Brugada syndrome.

Myocardial Gene Expression in Heart Failure Patients Treated With Cardiac Resynchronization Therapy: Responders Versus Nonresponders

OBJECTIVES We studied whether functional improvement after cardiac resynchronization therapy (CRT) is associated with reversal of the heart failure (HF) gene program. BACKGROUND Cardiac resynchronization therapy improves exercise tolerance and survival in patients with advanced congestive HF and dyssynchrony. METHODS Twenty-four patients referred for CRT underwent left ventricular (LV) endomyocardial biopsies immediately before CRT implantation (baseline). In addition, 17 of them underwent LV endomyocardial biopsy procurement 4 months later (follow-up). In 6 control patients with normal LV function, LV biopsies were obtained at the time of coronary artery bypass grafting. The LV messenger ribonucleic acid (mRNA) levels of contractile and calcium regulatory genes were measured by quantitative real time polymerase chain reaction and normalized for glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The HF patients showing an improvement in New York Heart Association (NYHA) functional class by >1 score and a relative increase in LV ejection fraction > or =25% at 4 months after CRT were considered as responders. RESULTS The HF patients were characterized by lower LV mRNA levels of alpha-myosin heavy chain (alpha-MHC), beta-myosin heavy chain (beta-MHC), sarcoplasmic reticulum calcium ATPase 2alpha (SERCA), phospholamban (PLN), and higher brain natriuretic peptide (BNP) mRNA levels as compared with control subjects. Responders to CRT (n = 11) showed an increase in LVEF (p < 0.001), a decrease in left ventricular end-diastolic diameter (p = 0.003), and NYHA functional class (p = 0.002), and a reduction in N-terminal proBNP levels (p = 0.032) as compared with baseline. This was associated with an increase in mRNA levels of alpha-MHC (p = 0.035), SERCA (p = 0.032), a decrease in BNP mRNA levels (p = 0.002), and an increase in the ratio of alpha-/beta-MHC (p = 0.018) and SERCA/PLN (p = 0.012). No significant changes in molecular profile were observed in nonresponders. CONCLUSIONS In HF patients with electromechanical cardiac dyssynchrony, functional improvement related to CRT is associated with favorable changes in established molecular markers of HF, including genes that regulate contractile function and pathologic hypertrophy.

Sildenafil (Viagra) Prolongs Cardiac Repolarization by Blocking the Rapid Component of the Delayed Rectifier Potassium Current

BACKGROUND-Several cases of unexpected death have been reported with sildenafil in patients predisposed to ischemic cardiac events. Although acute episodes of ischemia could account for some of these deaths, we hypothesized that sildenafil may have unsuspected electrophysiological effects predisposing some patients to proarrhythmia. METHODS AND RESULTS-Studies were undertaken in 10 isolated guinea pig hearts that demonstrated prolongation of cardiac repolarization in a reverse use-dependent manner by sildenafil 30 mcmol/L. Action potential duration increased 15% from baseline 117+/-3 to 134+/-2 ms with sildenafil during pacing at 250 ms cycle length, whereas a 6% increase from 99+/-2 to 105+/-2 ms was seen with pacing at 150 ms cycle length. Experiments in human ether-a-go-go-related gene (HERG)-transfected HEK293 cells (n=30) demonstrated concentration-dependent block of the rapid component (I(Kr)) of the delayed rectifier potassium current: activating current was 50% decreased at 100 mcmol/L. This effect was confirmed using HERG-transfected Chinese hamster ovary (CHO) cells, which exhibit no endogenous I(K)-like current. CONCLUSIONS-Sildenafil possesses direct cardiac electrophysiological effects similar to class III antiarrhythmic drugs. These effects are observed at concentrations that may be found in conditions of impaired drug elimination such as renal or hepatic insufficiency, during coadministration of another CYP3A substrate/inhibitor, or after drug overdose and offer a new potential explanation for sudden death during sildenafil treatment.

Use of the prophylactic implantable cardioverter defibrillator for patients with normal hearts.

About 10-20% of patients dying suddenly and unexpectedly do not have structural heart disease. The major causes of sudden death in this population are acute ischemia, the syndrome of right bundle branch block, and ST-elevation from V1 to V3, the long QT-syndrome, and the Wolff-Parkinson-While syndrome. In some patients, none of these syndromes can be recognized and ventricular fibrillation is classified as idiopathic. There are good preventive and therapeutic methods against acute ischemia and there are also curative treatments for the Wolff-Parkinson-White syndrome. Patients with idiopathic ventricular fibrillation cannot be recognized beforehand. However, there are electrocardiographic and genetic markers for the Brugada syndrome and the long QT syndrome. It is, therefore, justified to discuss the possible role of the prophylactic defibrillator to prevent sudden death in these 2 syndromes for which no effective treatment exists. Patients with Brugada syndrome have a high incidence of sudden death, and prophylactic defibrillators are indicated in patients with inducible arrhythmias at electrophysiologic study, irrespective of symptoms. On the contrary, the incidence of sudden death in the long QT syndrome is very low, making prophylactic defibrillator implantation not cost-effective.

A Randomized Prospective Study of Single Coil Versus Dual Coil Defibrillation in Patients with Ventricular Arrhythmias Undergoing Implantable Cardioverter Defibrillator Therapy

ICD implantation is standard therapy for malignant ventricular arrhythmias. The advantage of dual and single coil defibrillator leads in the successful conversion of arrhythmias is unclear. This study compared the effectiveness of dual versus single coil defibrillation leads. The study was a prospective, multicenter, randomized study comparing a dual with a single coil defibrillation system as part of an ICD using an active pectoral electrode. Seventy‐six patients (64 men, 12 women; age 61 ± 11 years ) were implanted with a dual (group 1, n = 38) or single coil lead system (group 2, n = 38 ). The patients represented a typical ICD cohort: 60% presented with ischemic cardiomyopathy as their primary cardiac disease, the mean left ventricular ejection fraction was 0.406 ± 0.158 . The primary tachyarrhythmia was monomorphic ventricular tachyarrhythmia in 52.6% patients and ventricular fibrillation in 38.4%. There was no significant difference in terms of P and R wave amplitudes, pacing thresholds, and lead impedance at implantation and follow‐up in the two groups. There was similarly no difference in terms of defibrillation thresholds (DFT) at implantation. Patients in group 1 had an average DFT of 10.2 ± 5.2 J compared to 10.3 ± 4.1 J in Group 2, P = NS. This study demonstrates no significant advantage of a dual coil lead system over a single coil system in terms of lead values and defibrillation thresholds. This may have important bearing on the choice of lead systems when implanting ICDs. (PACE 2003; 26:1684–1690)

Recurrent cardiac events in patients with idiopathic ventricular fibrillation, excluding patients with the Brugada syndrome

BackgroundThe recurrence of cardiac events in patients with idiopathic ventricular fibrillation (VF) excluding patients with the Brugada syndrome is unclear since this entity remains present in previous studies.MethodsSince 1992, 18 patients (72% male) with idiopathic VF out of 455 ICD implants were treated with an implantable cardioverter defibrillator (ICD). The mean age at first ICD implantation was 42 ± 14 years. Brugada syndrome, as well as other primary electrical diseases (e.g. long QT), were systematically excluded in all patients by the absence of the typical electrocardiogram (ST elevation in the right precordial leads) at rest and/or after pharmacological tests (ajmaline, flecainide, or procainamide). Recurrence of cardiac events was prospectively assessed.ResultsDuring a mean follow-up period of 41 ± 27 months, VF recurrence with appropriate shock occurred in 7 patients (39%) covering a total of 27 shocks. The median time to first appropriate shock was 12 ± 9 months. There were no deaths. In the electrophysiological study, 39% of patients were inducible, but inducibility failed to predict subsequent arrhythmic events. Forty-four percent of patients suffered 21 inappropriate shocks, which were caused by sinus tachycardia, atrial arrhythmias or lead malfunction.ConclusionIdiopathic ventricular fibrillation patients have a high recurrence rate of potentially fatal ventricular arrhythmias, excluding patients with the Brugada syndrome or other known causes. ICD prevents sudden cardiac death but inappropriate shocks remained a major issue in this young and active population.

Hypertrophic Cardiomyopathy: Role of the Implantable Cardioverter-Defibrillator

OBJECTIVES We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation. BACKGROUND The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem. METHODS We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II). RESULTS After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred. CONCLUSIONS Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.