Platelet glycoprotein Ia gene dimorphism alpha2-807 in malignant arrhythmia in coronary artery disease.

It has been shown recently that the variable expression of the platelet collagen receptor integrin alpha2beta1 predisposes to thrombotic risk on the one hand and hemorrhagic risk on the other hand. The level of expression of the integrin alpha2beta1 is genetically controlled and associated with the alpha2-807 dimorphism. The expression level of this platelet collagen receptor may play a central role in the rapidly evolving coronary artery lesions that lead to malignant arrhythmia and sudden cardiac death. We studied allelic frequencies of the alpha2-807 dimorphism for their relation as a risk factor for malignant arrhythmia in a well-defined subgroup of patients with coronary artery disease. We compared allelic frequencies (by sequence specific primer polymerase chain reaction) of the dimorphism that is associated with integrin alpha2beta1 levels in 94 Caucasoid survivors of sudden cardiac death with a matched group of 106 patients with coronary artery disease without sudden cardiac death. Gene frequencies in the patient groups did not differ and were similar to those in the general population represented by 217 healthy individuals. There was no overrepresentation of an allele in any group. The inherited dimorphism that is associated with the levels of platelet integrin alpha2beta1 is not associated with malignant arrhythmia in coronary artery disease patients.

Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphism in coronary disease and malignant ventricular arrhythmias.

OBJECTIVES: It has been reported that patients carrying the angiotensin-converting enzyme (ACE) deletion DD genotype with the angiotensin II type 1 (AT1) C allele are at increased risk for myocardial infarction. The frequency distribution of the ACE and AT1 receptor gene polymorphism and their possible relation regarding malignant ventricular arrhythmias in patients with coronary artery disease (CAD) and left ventricular dysfunction was determined. METHODS: The ACE I/D and AT1 A/C polymorphisms (using polymerase chain reaction) in 100 Caucasian patients suffering from CAD with a history of malignant ventricular arrhythmias treated with an implantable cardioverter defibrillator (ICD group) was compared to 127 age-matched Caucasian patients with CAD and no history of malignant ventricular arrhythmias (control group). All patients had reduced left ventricular ejection fraction of < 40% and were comparable regarding sex distribution, body mass index, ACE-inhibitor treatment, lipid status and duration of CAD. RESULTS: The prevalence of DD/CC in the ICD group was significantly higher (19% versus 10%, p < 0.0001). The risk for malignant ventricular arrhythmias was associated with the combination of ACE D and AT1 C alleles (odds-ratio: 2.4, 95% confidence interval 1.41 to 3.94, p < 0.001). The distribution of ACE and AT1 genotypes was not different between the two group. CONCLUSIONS: Patients with coronary artery disease and left ventricular dysfunction carrying ACE D and AT1 C alleles are at increased risk for development of malignant ventricular arrhythmias. Because of available pharmacological inhibitors, these results may have clinical implications for the prevention of sudden cardiac death.

Predictors of outcome in patients with implantable cardioverter defibrillators.

UNLABELLED: This study determined the impact of clinical characteristics on shock occurrence and survival in patients with implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: During a follow-up of 27 +/- 18 months, the actuarial incidence of appropriate shocks in 200 consecutive patients was 18, 36 and 72% at 1, 3, and 5 years, respectively. Coronary artery disease was the only significant predictor for shock occurrence (relative risk 1.32, p = 0.03). The actuarial incidence of total mortality was 10, 17 and 33% at 1, 3, and 5 years, respectively. The most powerful predictors for total mortality were: New York Heart Association functional class (NYHA) III (relative risk 4.8, p = 0.001) and a history of congestive cardiac failure (relative risk 3.6, p = 0.01). CONCLUSION: During long-term follow-up, the majority of patients receive appropriate shocks. No strong predictors for shock occurrence can be identified from the data analyzed. A history of congestive cardiac failure and the NYHA III are the most powerful predictors for total mortality. These clinical factors may provide valuable criteria to identify patients who will benefit from the implantation of ICD.

Comparison of three cardioverter defibrillator implantation techniques: initial results with transvenous pectoral implantation.

A total of 121 patients underwent epicardial (n = 32), transvenous abdominal (n = 30), and transvenous pectoral (n = 59) ICD implants. Perioperative complications were defined as those occurring within 30 days after surgery. Hospital costs were calculated with $750 per day as a fixed charge. Duration of surgery was the time between the first skin incision and the last skin suture. Severe perioperative complications that were life-threatening or required surgical intervention occurred in the epicardial (6%) and transvenous (10%) abdominal groups, but not in the pectoral group. Perioperative mortality occurred only in the epicardial abdominal group, predominantly in patients with concomitant surgery (18%), and in 5% of patients without concomitant surgery. The duration of surgery was significantly shorter for transvenous pectoral implantation (58 +/- 15 min, P < 0.05) compared to transvenous abdominal implantation (115 +/- 38 min). Epicardial abdominal ICD implantation had the longest procedure time (154 +/- 31 min). The postimplant hospital length of stay was significantly shorter for pectoral implantation (5 +/- 3 days, P < 0.05) compared to transvenous (13 +/- 5) and epicardial (19 +/- 5) abdominal implantation. Total hospitalization costs significantly decreased in the pectoral implantation group ($4,068 +/- $2,099 for the pectoral group vs $14,887 +/- $4,415 and $9,975 +/- $3,657 for the epicardial and the transvenous abdominal group, respectively, P < 0.05). These initial results demonstrate the advantage of transvenous pectoral ICD implantation in terms of perioperative complications, procedure time, hospital length of stay, and hospitalization costs.

Implantation of a unipolar cardioverter/defibrillator system under local anaesthesia.

OBJECTIVE: To evaluate prospectively the safety and feasibility of the implantation of cardioverter/defibrillator systems under local anaesthesia. Conventionally, cardioverter/defibrillator systems are implanted under general anaesthesia. With the development of single-lead transvenous unipolar cardioverter/defibrillator systems for subpectoral implantation a pacemaker-like approach for device implantation appears applicable. METHODS: Implantation of a single-lead transvenous unipolar cardioverter/defibrillator under local anaesthesia with sedation for defibrillation threshold testing was performed in 37 consecutive patients. The presenting arrhythmia was ventricular fibrillation in 13 patients, and monomorphic ventricular tachycardia in 24 patients. A 1% lidocaine solution was used for local anaesthesia, and midazolam was applied for sedation to perform defibrillation threshold testing. Arterial blood pressure, arterial oxygen saturation and heart rate were monitored throughout the procedure. The patient's tolerance of the implantation procedure was evaluated with a standardized questionnaire. RESULTS: The unipolar transvenous cardioverter/defibrillator system was implanted successfully in all patients under local anaesthesia. During defibrillation threshold testing, sufficient sedation was achieved with 12.5 +/- 3.7 mg midazolam. For determination of the defibrillation threshold 5.9 +/- 1.4 episodes of ventricular fibrillation were induced. The mean defibrillation threshold was 13.1 +/- 5.5 J, and the mean duration of the implantation procedure was 68 +/- 30 min. Mean heart rate, mean arterial blood pressure and arterial oxygen saturation were not significantly different before and after defibrillation threshold testing. Twenty-six patients (70%) were symptom-free throughout the implantation procedure; most of the remaining patients reported minor symptoms. There were no complications, and patients were discharged 2.2 +/- 0.7 days after implantation. In 12 patients, post-implant testing of the implantable cardioverter/defibrillators was performed successfully, without sedation, 2.8 +/- 1.4 days after as an outpatient procedure. CONCLUSION: Single-lead unipolar transvenous implantable cardioverter/defibrillator systems can be safely implanted under local anaesthesia with mild sedation for defibrillation threshold testing. The procedure is well tolerated.