Philippe Mabo

Sudden Cardiac Arrest Associated with Early Repolarization

BACKGROUND Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest. METHODS We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects. RESULTS Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). CONCLUSIONS Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.

Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome Results From the FINGER Brugada Syndrome Registry

Background— Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. Methods and Results— Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. Conclusions— In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

Multisite Pacing as a Supplemental Treatment of Congestive Heart Failure: Preliminary Results of the Medtronic Inc. InSync Study

This report describes the initial results of the “InSync” study, a European and Canadian multicenter trial that examines the safety and efficacy of a multisite pacemaker (Medtronic InSync) and of left ventricular pacing leads (Medtronic 2187 and 2188) implanted via a cardiac vein as a supplemental treatment of refractory congestive heart failure. Over a 10‐month period, the system was implanted successfully in 68 of the 81 (84%) patients who had been enrolled in the study. The 68 patients were, on average, 66 ± 10 years old, had a mean left ventricular ejection fraction (LVEF) = 21 %± 9%, and 63% were in NYHA functional Class III and 37% were in Class IV. No system implant related complication occurred. During follow‐up, 7 of 10 patients who exited the study had died, 4 suddenly. There was a clinical benefit among surviving patients, which was corroborated by a significant improvement in NYHA functional class and in the Minnesota Living with Heart Failure Quality of Life Questionnaire Score (MLS) and by a longer distance covered during a 6‐minute walk test. This clinical improvement was associated with a significant narrowing of the paced QRS complex during biventricular pacing, a significant decrease in the interventricular mechanical delay, and a trend towards an increase in the duration of ventricular filling. These encouraging preliminary results confirm the feasibility and reliability of this new multisite pacing system in the management of dilated cardiomyopathy and support the continuation of further evaluations of this complementary treatment of refractory congestive heart failure.

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada Syndrome A Multicenter Study

Background— Implantable cardioverter-defibrillator indications in Brugada syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small numbers of patients or short follow-up durations. We report the outcome of patients with Brugada syndrome implanted with an implantable cardioverter-defibrillator in a large multicenter registry. Methods and Results— A total of 378 patients (310 male; age, 46±13 years) with a type 1 Brugada ECG pattern implanted with an implantable cardioverter-defibrillator (31 for aborted sudden cardiac arrest, 181 for syncope, and 166 asymptomatic) were included. Fifteen patients (4%) were lost to follow-up. During a mean follow-up of 77±42 months, 7 patients (2%) died (1 as a result of an inappropriate shock), and 46 patients (12%) had appropriate device therapy (5±5 shocks per patient). Appropriate device therapy rates at 10 years were 48% for patients whose implantable cardioverter-defibrillator indication was aborted sudden cardiac arrest, 19% for those whose indication was syncope, and 12% for the patients who were asymptomatic at implantation. At 10 years, rates of inappropriate shock and lead failure were 37% and 29%, respectively. Inappropriate shock occurred in 91 patients (24%; 4±4 shocks per patient) because of lead failure (n=38), supraventricular tachycardia (n=20), T-wave oversensing (n=14), or sinus tachycardia (n=12). Importantly, introduction of remote monitoring, programming a high single ventricular fibrillation zone (>210–220 bpm), and a long detection time were associated with a reduced risk of inappropriate shock. Conclusions— Appropriate therapies are more prevalent in symptomatic Brugada syndrome patients but are not insignificant in asymptomatic patients (1%/y). Optimal implantable cardioverter-defibrillator programming and follow-up dramatically reduce inappropriate shock. However, lead failure remains a major problem in this population.

Permanent Left Ventricular Pacing With Transvenous Leads Inserted Into The Coronary Veins

This paper describes a preliminary experiment ‐ conducted jointly by 2 centers ‐ of permanent left ventricular pacing using leads inserted by the transvenous route and through the coronary sinus into the cardiac veins of the left ventricle free wall. The aim was to obtain permanent biventricular pacing in a totally endocavitary configuration in pattents with severe LV dysfunction and drug‐refractory heart failure. Two types of leads were used: nonspecific unipolar leads at the beginning of the experiment, followed by leads specifically designed to be used in the coronary sinus in a second step. The electrode could be fitted in an adequate location in 35 of the 47 patients (75.4%), with a 1.15±0.7 V acute pactng threshold and 11.8±5.7 mV R wave amplitude. The success rate was significantly higher with the specific electrodes (81.8% vs 53,3%, p < 0.001). The pacing and sensing thresholds upon implantation were not influenced by the type of lead or by the localization of the cardiac vein that was catheterized (great cardiac vein, lateral vein, postero‐lateral or posterior vein, mid cardiac vein). In contrast, the pacing threshold was significantly lower (0.8 ± 0.2 vs L8 ± 0.8 V; p = 0.002) and the R wave amplitude tended to be greater (13.1 ± 4.5 mV vs 9.3 ± 6.5 mV; p = 0.07) when the tip electrode could be inserted distally into the vein, by comparison with a proximal site near the ostium. At the end of follow‐up (10.2 ± 8.7 months), 34 out of the 35 leads were still fully functional, with a chronic pacing threshold of 1.8 ± 0.7 V and a R wave amplitude of 10.7 ± 6 mV. To conclude, permanent LV pacing via the transvenous route is possible in most patients, with excellent safety and long‐term results.

Electrocardiographic predictive factors of long-term clinical improvement with multisite biventricular pacing in advanced heart failure

Biventricular pacing has recently been proposed for treating patients with drug refractory heart failure and intraventricular conduction delay. The purpose is to restore ventricular relaxation and contraction sequences as homogeneously as possible. The aim of this study was to determine if some factors could predict the long-term clinical effectiveness of that new treatment. This study included 26 patients, aged 66 +/- 7 years, with drug refractory heart failure and wide QRS. Patients were implanted with a biventricular pacemaker. The left ventricle was paced through a coronary sinus tributary. New York Heart Association functional class, exercise tolerance, and left ventricular (LV) ejection fraction were collected at baseline and after pacemaker implantation. Patients were divided into 2 groups: group I = responders; group II = nonresponders. QRS duration and axis at baseline and during biventricular pacing, interventricular conduction time, and LV and right ventricular lead positions were compared between the 2 groups. Group I patients (n = 19) had a mean reduction of 1.3 in functional class and an increase in peak oxygen consumption rate by a mean of 50%. The only parameter that differed between the 2 groups was the QRS duration during biventricular pacing, with a significantly shorter value in group I than in group II (154 +/- 17 vs 177 +/- 26 ms; p = 0.016). Thus, a positive response to biventricular pacing is correlated with the quality of electrical resynchronization. The optimal positions of the right and LV leads would be those that could induce the greatest shortening of QRS duration.

Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing

Pacing the right ventricle in the apex profoundly modifies the sequence of activation and thus the sequence of contraction and relaxation of the left ventricle. To evaluate the relative importance of preserving normal ventricular activation sequence and optimal atrioventricular (AV) synchrony in permanent pacing, we compared the effects of three pacing modes: AAI, preserving both normal AV synchrony and normal activation sequence; DDD, with complete ventricular capture that preserves only AV synchrony; and VVI, disrupting both, at rest and during exercise. Hemodynamic and radionuclide studies were performed in 11 patients who had normal intrinsic conduction and who were implanted on a long-term basis with a DDDR pacemaker for isolated sinus node dysfunction. AAI versus DDD and VVI significantly increased cardiac output at rest (6.6 +/- 1.3 L/min vs 6 +/- 0.9 L/min vs 5 +/- 1 L/min; p < 0.01) and during exercise (13.5 +/- 2 L/min vs 12.1 +/- 2.2 L/min vs 14.4 +/- 2.1 L/min; p < 0.01). Pulmonary capillary wedge pressure was lowest with AAI (15.4 +/- 4.5 mm Hg), with an average reduction of 17% compared with DDD (19.6 +/- 5 mm Hg; p < 0.01) and of 30% compared with VVI (25.8 +/- 7 mm Hg; p < 0.01) during exercise. Identical benefits were observed for all other hemodynamic parameters: right atrial pressure, pulmonary artery pressure, left ventricular (LV) stroke work index, and systemic vascular resistances. LV ejection fraction was significantly higher in AAI than in DDD at rest (61% vs 58%, respectively; p < 0.05) and during exercise (65% vs 60%, respectively; p < 0.05). This improvement in LV systolic function resulted principally from the increase in septal ejection fraction. LV filling also was improved in AAI as demonstrated by a significant increase in peak filling rate at rest and during exercise. These data show the importance of preserving, whenever possible, not only normal AV synchrony but also normal ventricular activation sequence in permanent cardiac pacing.

Six year experience of transvenous left ventricular lead implantation for permanent biventricular pacing in patients with advanced heart failure: technical aspects

BACKGROUND Biventricular pacing has been proposed as an adjuvant to optimal medical treatment in patients with drug refractory heart failure caused by chronic left ventricular systolic dysfunction and intraventricular conduction delay. OBJECTIVE To assess the technical feasibility and long term results (over six years) of transverse left ventricular pacing with the lead inserted into a tributary vein of the coronary sinus. SUBJECTS From August 1994 to February 2000, left ventricular lead implantation was attempted in 116 patients who were eligible for biventricular pacing (mean (SD) age 67 (9) years, New York Heart Association (NYHA) functional class III/IV, left ventricular ejection fraction 22 (6)%, QRS duration 185 (26) ms). RESULTS The overall implantation success rate was 88% (n = 102). A learning curve was indicated by a progressive increase in success from 61% early on to 98% in the last year. The mean pacing threshold was 1.1 (0.7) V/0.5 ms at the time of implantation and increased slightly up to 1.9 (0.9) V/0.5 ms at the end of the follow up period (15 (13) months). The rate of acute and delayed left ventricular lead dislodgement decreased from 30% in the early years to 11% after 1999. During follow up, 19 patients required reoperation for delayed lead dislodgement or increase in left ventricular pacing threshold (n = 15), phrenic nerve stimulation (n = 3), or infection (n = 3). CONCLUSIONS Transverse left ventricular pacing through the coronary sinus is feasible and safe. The rate of implantation failure and of lead related problems has decreased greatly with increasing experience and with improvements in the equipment.

Clinical Aspects and Prognosis of Brugada Syndrome in Children

Background— Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and augmented risk of sudden cardiac death. Little is known about the clinical presentation and prognosis of this disease in children. Methods and Results— Thirty children affected by Brugada syndrome who were <16 years of age (mean, 8±4 years) were included. All patients displayed a type I ECG pattern before or after drug provocation challenge. Diagnosis of Brugada syndrome was made under the following circumstances: aborted sudden death (n=1), syncope of unexplained origin (n=10), symptomatic supraventricular tachycardia (n=1), suspicious ECG (n=1), and family screening for Brugada syndrome (n=17). Syncope was precipitated by fever in 5 cases. Ten of 11 symptomatic patients displayed a spontaneous type I ECG. An implantable cardioverter-defibrillator was implanted in 5 children; 4 children were treated with hydroquinidine; and 1 child received a pacemaker because of symptomatic sick sinus syndrome. During a mean follow-up of 37±23 months, 1 child experienced sudden cardiac death, and 2 children received an appropriate implantable cardioverter-defibrillator shock; all of them were symptomatic and had manifested a type I ECG spontaneously. One child had a cardioverter-defibrillator infection that required explantation of the defibrillator. Conclusions— In the largest population of children affected by Brugada syndrome described to date, fever represented the most important precipitating factor for arrhythmic events, and as in the adult population, the risk of arrhythmic events was higher in previously symptomatic patients and in those displaying a spontaneous type I ECG.