In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Electric shock is the only effective therapy against ventricular fibrillation. However, shocks are also known to cause electroporation of cell membranes. We sought to determine the impact of electroporation on ventricular conduction and defibrillation. We optically mapped electrical activity in coronary-perfused rabbit hearts during electric shocks (50 to 500 V). Electroporation was evident from transient depolarization, reduction of action potential amplitude, and upstroke dV/dt. Electroporation was voltage dependent and significantly more pronounced at the endocardium versus the epicardium, with thresholds of 229+/-81 versus 318+/-84 V, respectively (P=0.01, n=10), both being above the defibrillation threshold of 181.3+/-45.8 V. Epicardial electroporation was localized to a small area near the electrode, whereas endocardial electroporation was observed at the bundles and trabeculas throughout the entire endocardium. Higher-resolution imaging revealed that papillary muscles (n=10) were most affected. Electroporation and conduction block thresholds in papillary muscles were 281+/-64 V and 380+/-79 V, respectively. We observed no arrhythmia in association with electroporation. Further, preconditioning with high-energy shocks prevented reinduction of fibrillation by 50-V shocks, which were otherwise proarrhythmic. Endocardial bundles are the most susceptible to electroporation and the resulting conduction impairment. Electroporation is not associated with proarrhythmic effects and is associated with a reduction of vulnerability.

The safety of pacemaker and defibrillator implantations in orally anticoagulated patients using standard techniques has not been thoroughly evaluated. This article describes a prospectively collected experience in such patients. Patients presenting for device implantation who were treated with warfarin were allowed to continue therapy provided that the INR was < 3.5. Implantations involved cannulation of the left axillary vein. Except for defibrillator leads, 7 Fr introducers were used, and all were leads actively fixated. The study included 47 patients who underwent implantation of permanent pacemakers (n = 39), defibrillators (n = 5), or biventricular pacemakers (n = 3). The mean INR was 2.3. The primary indication for anticoagulation was a mechanical cardiac prosthesis in 11 (24%) patients. Atrial fibrillation was present in 33 patients. There were no instances of major bleeding or hematomas requiring evacuation. One patient had a small soft hematoma, which resolved spontaneously. At 6 weeks, all patients had well-healed scars with satisfactory pacing and sensing thresholds. In experienced centers, patients requiring treatment with warfarin may undergo implantation of pacemakers or defibrillators with minimal risk despite continuation of anticoagulation.

Romano-Ward syndrome (RWs) and Jervell and Lange-Nielsen Syndrome (JLNs) are two inherited arrhythmia disorders caused by monoallelic or bi-allelic mutations, respectively, in the KCNQ1 or KCNE1 genes. Both disorders could cause Long QT syndrome either without deafness (RWs), or with deafness (JLNs). We have performed clinical, molecular and functional investigation in two consanguineous Arabian families with history of sudden death of several children. Importantly, none of the affected individuals had (or have) any hearing impairment. Homozygosity mapping followed by molecular analysis identified a novel splice acceptor site mutation (homozygously) in intron-1 of the KCNQ1 gene (c.387 -5T>A), in these two apparently unlinked families. RNA analysis revealed that this splice site mutation causes incomplete transcriptional aberration of the KCNQ1 gene, leaving 10% of the normal allele transcript intact, which restores the hearing function. Our molecular and functional data provide the first evidence that small amount (as low as 10%) of normal KCNQ1 current can effectively maintain the hearing function but fails to maintain cardiac repolarization characteristics within normal limits. Additionally, we have revealed four extra low frequency aberrant isoforms emphasizing the importance of intronic and other non-coding sequences in maintaining cellular homeostasis as pathologic changes in a single nucleotide can affect splicing events at distant sites. The novel KCNQ1 mutation found in this study is very likely a founder mutation in the southern province of Saudi Arabia emphasizing its screening in the LQT population in this region.

A proactive multifactorial risk factor intervention strategy that simultaneously treated both BP and cholesterol regardless of individual risk factors per se, is more effective in reducing calculated Framingham 10-year CHD risk than UC in patients with hypertension and additional risk factors.

Extraction of pacemaker leads has been demonstrated to be successful and safe in experienced hands using current tools. Whether application of such techniques and tools yield similar results among patients undergoing extraction of nonthoracotomy implantable defibrillator leads is unknown. This report describes a retrospective analysis of indications, techniques used, and outcome of patients who had a single ventricular nonthoracotomy implantable defibrillator lead extracted at The Cleveland Clinic Foundation. Results were compared to a matched population of patients undergoing extraction of ventricular pacemaker leads from a national registry and to the experience with pacemaker lead extraction at The Cleveland Clinic Foundation. Successful complete extraction of ventricular nonthoracotomy implantable defibrillator leads, in the absence of major complications, was achieved in 96.9% of attempts to extract leads from 161 patients. Clinical success was achieved in 98.1% of patients. Failure occurred in three patients. Two patients had major complications, including one death. The most common indication for extraction was infection (46.6%), followed by lead failure (34.2%). Procedure (140.8 vs 171.2 minutes, P<0.01) and fluoroscopy (9.9 vs 11.0 minutes, P<0.01) times compared favorably with those obtained from the pacemaker lead extraction database. Use of LASER did not influence the safety of the procedure or fluoroscopy times. Extraction of ventricular nonthoracotomy implantable defibrillator leads using currently available tools is a complex but effective procedure. In experienced hands, excellent success rates should be achieved with a low incidence of complications.

Congenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder characterized by prolongation of the QT interval; patients are predisposed to ventricular tachyarrhythmias and fibrillation leading to recurrent syncope or sudden cardiac death. We performed clinical and genetic studies in six Saudi Arabian families with a history of sudden unexplained death of children. Clinical symptoms, ECG phenotypes, and genetic findings led to the diagnosis of LQT1 in two families (recessive) and LQT2 in four families (three recessive and one dominant). Onset of arrhythmia was more severe in the recessive carriers and occurred during early childhood in all recessive LQT1 patients. Arrhythmia originated at the intrauterine stages of life in the recessive LQT2 patients. LQT1, causing mutation c.387-5 T > A in the KCNQ1 gene, and LQT2, causing mutation c.3208 C > T in the KCNH2 gene, are presumably founder mutations in the Assir province of Saudi Arabia. Further, all LQTS causing mutations detected in this study are novel and have not been reported in other populations.

In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.