Jacques Mansourati

Influence of Omeprazole on the Antiplatelet Action of Clopidogrel Associated With Aspirin: The Randomized, Double-Blind OCLA (Omeprazole CLopidogrel Aspirin) Study

OBJECTIVES This trial sought to assess the influence of omeprazole on clopidogrel efficacy. BACKGROUND Clopidogrel has proved its benefit in the treatment of atherothrombotic diseases. In a previous observational study, we found clopidogrel activity on platelets, tested by vasodilator-stimulated phosphoprotein (VASP) phosphorylation, to be diminished in patients receiving proton pump inhibitor (PPI) treatment. METHODS In this double-blind placebo-controlled trial, all consecutive patients undergoing coronary artery stent implantation received aspirin (75 mg/day) and clopidogrel (loading dose, followed by 75 mg/day) and were randomized to receive either associated omeprazole (20 mg/day) or placebo for 7 days. Clopidogrel effect was tested on days 1 and 7 in both groups by measuring platelet phosphorylated-VASP expressed as a platelet reactivity index (PRI). Our main end point compared PRI value at the 7-day treatment period in the 2 groups. RESULTS Data for 124 patients were analyzed. On day 1, mean PRI was 83.2% (standard deviation [SD] 5.6) and 83.9% (SD 4.6), respectively, in the placebo and omeprazole groups (p = NS), and on day 7, 39.8% (SD 15.4) and 51.4% (SD 16.4), respectively (p < 0.0001). RESULTS Omeprazole significantly decreased clopidogrel inhibitory effect on platelet P2Y12 as assessed by VASP phosphorylation test. Aspirin-clopidogrel antiplatelet dual therapy is widely prescribed worldwide, with PPIs frequently associated to prevent gastrointestinal bleeding. The clinical impact of these results remains uncertain but merits further investigation.

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.

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.

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

Background— Brugada syndrome is an arrhythmogenic disease characterized by an increased risk of sudden cardiac death (SCD) by ventricular fibrillation. At present, an implantable cardioverter-defibrillator (ICD) is the recommended therapy in high-risk patients. This multicenter study reports the outcome of a large series of patients implanted with an ICD for Brugada syndrome. Methods and Results— All patients (n=220, 46±12 years, 183 male) with a type 1 Brugada ECG pattern implanted with an ICD in 14 centers between 1993 and 2005 were investigated. ICD indication was based on resuscitated SCD (18 patients, 8%), syncope (88 patients, 40%), or positive electrophysiological study in asymptomatic patients (99 patients, 45%). The remaining 15 patients received an ICD because of a family history of SCD or nonsustained ventricular arrhythmia. During a mean follow-up of 38±27 months, no patient died and 18 patients (8%) had appropriate device therapy (10±15 shocks/patient, 26±33 months after implantation). The complication rate was 28%, including inappropriate shocks, which occurred in 45 patients (20%, 4±3 shocks/patient, 21±20 months after implantation). The reasons for inappropriate therapy were lead failure (19 patients), T-wave oversensing (10 patients), sinus tachycardia (10 patients), and supraventricular tachycardia (9 patients). Among implantation parameters, high defibrillation threshold, high pacing threshold, and low R-wave amplitude occurred, respectively, in 12%, 27%, and 15% of cases. Conclusion— In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of >3 years, in addition to a significant risk of device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones.

SCN5A mutations and the role of genetic background in the pathophysiology of Brugada syndrome

Background— Mutations in SCN5A are identified in ≈20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families. Methods and Results— Families were included if at least 5 family members were carriers of the SCN5A mutation, which was identified in the proband. Thirteen large families composed of 115 mutation carriers were studied. The signature type I ECG was present in 54 mutation carriers (BrS-ECG+; 47%). In 5 families, we found 8 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG+). Among these 8 mutation-negative BrS-ECG+ individuals, 3, belonging to 3 different families, had a spontaneous type I ECG, whereas 5 had a type I ECG only after the administration of sodium channel blockers. One of these 8 individuals had also experienced syncope. Mutation carriers had, on average, longer PR and QRS intervals than noncarriers, demonstrating that these mutations exerted functional effects. Conclusions— Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG+ and that genetic background may play a powerful role in the pathophysiology of BrS. These findings add further complexity to concepts regarding the causes of BrS, and are consistent with the emerging notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels.

Long-term left ventricular pacing: assessment and comparison with biventricular pacing in patients with severe congestive heart failure.

OBJECTIVE The purpose of this study is to report prospectively the results of six-month follow-up of permanent left ventricular (LV) based pacing in patients with severe congestive heart failure (CHF) and left bundle branch block (LBBB). BACKGROUND Left ventricular pacing alone has been demonstrated to result in identical improvement compared to biventricular pacing (BiV) during acute hemodynamic evaluation in patients with advanced CHF and LBBB. However, to our knowledge, the clinical outcome during permanent LV pacing alone versus BiV pacing mode has not been evaluated. METHODS Pacing configuration (LV or BiV) was selected according to the physicians preference. Patient evaluation was performed at baseline and at six months. RESULTS Thirty-three patients with advanced CHF and LBBB were included. Baseline characteristics of LV (18 patients) and BiV (15 patients) pacing groups were similar. During the six-month follow-up period, seven patients died three BiV and four LV). In the surviving patients at 6 months, 8 of 14 patients in the LV group and 9 of 12 in the BiV group were in New York Heart Association class I or II (p = 0.39). No significant difference was observed between the two groups in terms of objective parameters except for LV end-diastolic diameter decrease (-4.4 mm in BiV group vs. -0.7 mm in LV group; p = 0.04). CONCLUSION At six-month follow-up, a trend toward improvement was observed in objective parameters in patients with severe CHF and LBBB following LV-based pacing. The two pacing modes (LV and BiV) were associated with almost equivalent improvement of subjective and objective parameters.

Evaluation of left ventricular based pacing in patients with congestive heart failure and atrial fibrillation

Acute hemodynamic data of left ventricular based pacing were assessed in 2 groups of patients with severe cardiac failure: 11 patients with atrial fibrillation and 17 patients with sinus rhythm. Both biventricular and left ventricular pacing significantly improved acute hemodynamic findings to a similar degree in both groups, suggesting that left ventricular based pacing may be beneficial in patients with severe cardiac failure regardless of whether or not they are in sinus rhythm.

Angiographic Anatomy of the Coronary Sinus and Its Tributaries

Permanent left ventricular pacing has been shown to imporve the hemodynamic and clinical status of patients with severe heart failure. To pace the left ventricle, the electrode is implanted in tributaries of the coronary sinus (CS). However, the anatomy of cardiac veins with this purpose in mind has not been described in detail. Methods: One hundred consecutive patients admitted for coronary angiography had a simultaneous coronary venography performed after the injection of 8 to 10 mL of contrast material into the left coronary artery. Cardiac veins were analyzed in antero‐posterior, left anterior oblique 60±, and right anterior oblique 30± views by three different observers. The number, dimension, angulation, and position of the coronary sinus and of its tributaries were studied. Results: Two veins are consistently present: the middle cardiac vein (mean diameter 2.62 ± 1.26 mm) and the great cardiac vein (mean diameter 3.55 ± 1.24 mm). The left posterior vein(s) (LPV) (mean diameter 2.25 ± 1.2 mm) is (are) variable in number (ranging from 0 to 3), size, and angulation. The absence of LPV limits the ability to pace the left ventricle endovenously. The diameter of the vein (< 2 mm) and its angulation may also complicate the insertion of the lead. Conclusion: Angiographic analysis of dimensions, tortuosity, number, and angulation of venous tributaries of the CS seems to allow the insertion of commercially available pacing leads in approximately 85% of cases. An increase in this percentage hinges on the development of new, dedicated leads.

Outcome After Implantation of a Cardioverter-Defibrillator in Patients With Brugada SyndromeClinical Perspective: A Multicenter Study–Part 2

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.

Same-Day Combined Percutaneous Coronary Intervention and Coronary Artery Surgery

BACKGROUND Either percutaneous coronary intervention (PCI) or coronary artery bypass grafting can be chosen for the treatment of multiple-vessel coronary artery disease. We report the results of a hybrid procedure performed on the same day, combining PCI of the right coronary artery and internal mammary artery bypass grafting of the left coronary artery, for the treatment of diffuse extensive lesions. METHODS AND RESULTS Since January 2000, 70 patients (53 male, mean age 68.5 +/- 10 years) underwent this hybrid revascularization combining primary right coronary artery PCI and, within the next 16 h, left coronary artery grafting with left and/or right internal mammary artery. Thirty-one patients (98%) were treated on the same day. At a mean follow-up of 33 months (range: 2-70 months), 68 patients (97%) were asymptomatic at the time of writing. Three adverse events were reported: 2 were PCI-related, due to failure to take ticlopidine, and 1 was surgery-related, resulting in the patients death during hospitalization. CONCLUSION These preliminary results for a same-day combined procedure in patients with diffuse multivessel coronary artery disease are encouraging. This strategy optimizes revascularization when patients are unstable or present very severe coronary lesions, which requiring rapid treatment and are not ideally suitable for PCI management alone.