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After implantation of a permanent pacemaker, patients may experience severe symptoms of dyspnea, palpitations, malaise, and syncope resulting from pacemaker syndrome. Although pacemaker syndrome is most often ascribed to the loss of atrioventricular (A-V) synchrony, more recent data may also implicate left ventricular dysynchrony caused by right ventricular pacing. Previous studies have not shown reductions in mortality or stroke with rate-modulated dual-chamber (DDDR) pacing as compared to ventricular-based (VVI) pacing. The benefits in A-V sequential pacing with the DDDR mode are likely mitigated by the interventricular (V-V) dysynchrony imposed by the high percentage of ventricular pacing commonly seen in the DDDR mode. Programming DDDR pacemakers to encourage intrinsic A-V conduction and reduce right ventricular pacing will likely decrease heart failure and pacemaker syndrome. Studies are currently ongoing to address these questions.

Introduction: Cooled radiofrequency ablation has been developed clinically for the treatment of ventricular tachycardia. Although clinical studies employ a constant saline flow rate for cooling, we hypothesized that varying the flow rates might optimize the temperature profile at depth.Methods: In excised ovine left ventricle, we compared the temperature profile from a catheter tip electrode thermocouple to those placed at depths of 0.0 mm, 1.0 mm, and 2.0 mm. We compared the following settings: 20 Watts without flow, 20 Watts with 0.3 cc/sec flow, 20 Watts with 0.5 cc/sec flow, and 70 degrees C surface temperature without flow (temperature control).Results: The temperatures decreased from 77.5+/-10.5 degrees C, 91.7+/-6.3 degrees C, 65.5+/-11.8 degrees C, and 52. 5+/-11.8 degrees C at 20 W without saline irrigation at the tip, 0.0 mm, 1.0 mm, and 2.0 mm, respectively, to 33.0+/-1.4 degrees C*, 63. 4+/-7.0 degrees C*, 57.1+/-5.8 degrees C*, 49.9+/-5.8 degrees C+ at 20 W with 0.5 ml/sec flow (*P

Over this last decade of the 20th century revolutionary developments in cardiovascular biology have resulted in critically important insights into the genetic and molecular mechanism of many cardiac arrhythmias [1–25]. During this same time, these observations about the molecular and genetic basis of arrhythmias have come to in_uence the clincial electrophysiologists’ approach to prediction, prevention, and therapy. As the science of molecular biology matures and focuses on cardiovascular conditions associated with arrhythmias and suddendeath, there will be a larger impact on the clinical approaches taken with an emphasis on prediction, prevention, and cure. Molecular biological approaches have led to an understanding of the genetic basis for the congenital long QT syndromes (LQTS) [7–15], arrhythmogenic right ventricular dysplasia (ARVD) and the closely related Naxis disease [16–21], idiopathic ventricular ~brillation (IVF) [22,23], and familial atrial ~brillation [24,25]. As the multiple genetic defects causing other cardiovascular conditions associated with cardiac arrhythymias such as hypertrophic cardiomyopathy, familial dilated cardiomyopathy, and myotonic dystrophy are elucidated the approach to arrhythmia and sudden death prediction and prevention will continue to evolve and have clinical implications [26–41]. With the exponential increase in transgenic strains of mice, genetically-engineered animals have become important as models for human cardiovascular disease [1–6]. For many conditions, genotype analysis has the potential to provide a screening tool in individuals at risk for the condition and con~rmation of the presymptomatic diagnosis. For some diseases, genotype analysis can predict the severity of the condition, determine the risk status of the patients’ relatives and establish the basis for genetic counseling and treatment [6]. As we approach the new millenium it is appropriate to consider the clinical implications of these basic developments, as they could fundamentally change our approach to many common arrhythmias. The important messages sent to the clinician from the molecular cardiologist regarding long QT syndrome will likely be extended to a range of other conditions such as familial atrial ~brillation, hypertrophic cardiomyopathy, familial right and left ventricular myopathies and other cardiovascular conditions associated with arrhythmias and sudden cardiac death. Elucidation of the genetic and ion channel abnormalities underlying the long-QT syndrome have had a profound impact on the clinicial approach to this condition [4,7–15]. These syndromes originally were categorized into an autosomal dominant form with variable penetrance (Romano-Ward Syndrome) and an autosomal recessive from with congenital neural deafness (Jervell-Lange-Neilsen Syndrome). It is now appreciated that the familial long-QT syndromes arise from multiple distinct mutations that result in a common phenotype [4,7–15]. Five distinct genetic abnormalities recently have been identi~ed for the long-QT syndrome (LQT1-LQT5), arising from speci~c mutations in ion channel genes located on chromosomes 3, 7, 11, and 4 [4,7–15]. The two most common mutations, LQT1 and LQT2, are due to potassium channel mutations leading to prolonged repolarization and polymorphic ventricular tachycardia. LQT1 and LQT2 are associated with mutations in KvLQT1 (chromsome 11) and HERG (chromosome 7) that result in defects in the channels responsible for IKs and IKr, respectively [7–15]. LQT3 is associated with mutations in a gene on chromosome 3 that results in inactivation of the sodium channel. Clinically sodium channel blockade with mexiletine is more effective in shortening the long QT interval in LQT3 patients who manifest this sodium channel defect than in LQT1 or LQT2 patients who have potassium channel defects [15]. Predictably, these latter patients have been shown to correct their repolarization abnormality with exogenous potassium [13]. Cardiac events such as torsades de pointes and sudden death are more likely to be associated with adrenergic stress in LQTS1 than either LQTS2 or LQTS3. Accordingly b-blockers are more likely to reduce these events in LQTS1. Recently murine models of LQTS have been developed by designing targeted disruption of speci~c potassium chan

Reversible cryothermal mapping of cardiac arrhythmias has beenperformed intraoperatively. However, a steerable cooling catheter forreversible mapping has not yet been developed. We therefore developed andtested a cooling system consisting of a +15°C hypertonic salinereservoir and a 7F steerable catheter also capable of radiofrequency (RF)ablation. Using excised ovine hearts placed in a 37°C circulating salinebath, we measured the temperatures at depths of 0 mm, 1 mm, and 2 mm. Thetemperature after 90 seconds of cooling was 16.5 ± 2.1°C at 0 mmcompared to 23.9 ± 4.1°C at 1 mm and 31.1 ± 3.9°C at 2mm depth (p < 0.01). These data suggest that a 7F steerable combined RFablation–cooling catheter may achieve temperatures suitable formapping arrhythmias such as atrial tachycardias and right ventricularoutflow tract tachycardias. Further enhancements to achieve lowertemperatures at depth may be needed to reversibly map other arrhythmiassuch as left ventricular tachycardias.

Athletes, although the healthiest segment of society, can develop cardiac arrhythmias. Benign bradycardias and atrial and ventricular premature contractions are common and seldom require treatment. Supraventricular tachycardias are less common and are usually not life-threatening, but do require treatment. Ventricular arrhythmias, although uncommon, are life-threatening and require treatment. Most athletes with ventricular arrhythmias have structural cardiac abnormalities, and further competitive play is usually prohibited. Commotio cordis, which is a recently described syndrome of sudden death caused by low-energy chest wall impact, may account for a significant percentage of the sudden deaths in athletes.

BackgroundStandard clinical practice permits the use of either single-chamber ventricular pacemakers or dual-chamber pacemakers for most patients who require cardiac pacing. Ventricular pacemakers are less expensive, but dual-chamber pacemakers are believed to be more physiologic. However, it is not known whether either type of pacemaker results in superior clinical outcomes.MethodsThe Pacemaker Selection in the Elderly study was a 30-month, single-blind, randomized, controlled comparison of ventricular pacing and dual-chamber pacing in 407 patients 65 years of age or older in 29 centers. Patients received a dual-chamber pacemaker that had been randomly programmed to either ventricular pacing or dual-chamber pacing. The primary end point was health-related quality of life as measured by the 36-item Medical Outcomes Study Short-Form General Health Survey.ResultThe average age of the patients was 76 years (range, 65 to 96), and 60 percent were men. Quality of life improved significantly after pacemaker implantation (P

The formation of γ-glutamylhydroxamate by homogenates under optimum assay condition showed an inconstancy in the ratios of the enzyme activities utilizing l-glutamate and ATP (γ-glutamylhydroxamate synthetase) and l-glutamine and ADP (l-glutamine–hydroxylamine glutamyltransferase) in a number of normal and neoplastic rat tissues. Although γ-glutamylhydroxamate synthetase activities in adult livers and kidneys were identical in males and females, l-glutamine–hydroxylamine glutamyltransferase activities in the organs of females were significantly lower. The developmental formations of the two activities in liver, kidney, brain and muscle were not simultaneous. The l-glutamine–hydroxylamine glutamyltransferase activity in foetal liver or neonatal kidney could be prematurely evoked by thyroxine, but the γ-glutamylhydroxamate synthetase activity remained unchanged. Injections of cortisol also had dissimilar effects on the two activities in thymus and hepatomas. The discrepant tissue distribution, asynchronous developmental formation and differential response to several hormonal stimuli provide evidence in vivo that the two activities are not catalysed by the same protein.

Context Recently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved. Objective To study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM. Design, Setting, and Patients Multicenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope. Main OutcomeMeasure Appropriate ICD intervention terminating ventricular tachycardia or fibrillation. Results The 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P=.77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%). Conclusions In a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) studies in patients with coronary artery disease report higher risk of ventricular tachycardia/fibrillation (VT/VF) early post-implant, potentially related to local proarrhythmic effects of ICD leads. OBJECTIVE: To characterize early and long-term risk of ICD discharge for VT/VF in a large hypertrophic cardiomyopathy (HCM) cohort. METHODS: By using HCM multicenter registry data, we compared long-term risk of VT/VF subsequent to an early post-implant period (a priori defined as within 3 months of implant) between patients with or without VT/VF within 3 months after ICD implantation. RESULTS: Over a median follow-up of 4.3 years, 109 of 506 (22%) patients with HCM who received ICDs received at least 1 ICD discharge for VT/VF. Risk of first ICD discharge for VT/VF was highest in the first year post-implant (10.8% per person-year; 95% confidence interval 7.9-13.8) and particularly in the first 3 months (17.0% per person-year; 95% confidence interval 9.8-24.3). Patients with early VT/VF (≤3 months post-implant) were older, and more commonly had secondary prevention ICDs following cardiac arrest or systolic dysfunction (end-stage HCM with ejection fraction