Follow-up of patients with unexplained syncope and inducible ventricular tachyarrhythmias: analysis of the AVID registry and an AVID substudy. Antiarrhythmics Versus Implantable Defibrillators.

INTRODUCTION: A prospective registry and substudy were conducted in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the prognosis and recurrent event rate, risk factors, and impact of implantable cardioverter defibrillator (ICD) therapy in patients with unexplained syncope, structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND RESULTS: Included in the AVID registry were patients from all participating sites who had "out of hospital syncope with structural heart disease and EP-inducible VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth clinical and electrophysiologic data as part of a formal prospective substudy. Patients in the substudy were followed by local investigators for recurrent arrhythmic events and mortality. Registry patients were tracked for fatal outcomes by the National Death Index. A total of 429 patients with syncope were entered in the AVID registry, of whom 80 participated in the substudy. Of the substudy patients, 21 patients (26%) had inducible polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59% of the syncope registry patients. Survival rates at 1 and 3 years were 93% and 74% for the substudy patients and 90% and 74% for the registry patients, respectively. Survival of the syncope substudy patients (predominantly treated by ICD) was similar to the VT patients treated by ICD and superior to the VT patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main trial. Mortality events in the substudy were marginally predicted by ejection fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The significant predictor of increased mortality in the registry was age (P = 0.003) and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The results of these analyses support the role of the ICD as primary antiarrhythmic therapy in patients with unexplained syncope, structural heart disease, and inducible VT/VF at electrophysiologic study.

Shock reduction using antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients with coronary artery disease.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) can terminate some ventricular tachycardias (VTs) painlessly with antitachycardia pacing (ATP). ATP has not routinely been applied for VT >188 bpm because of concerns about efficacy, risk of acceleration, and delay of definitive shock therapy. This prospective, multicenter study evaluated the efficacy of empirical ATP to terminate fast VT (FVT; >188 bpm). METHODS AND RESULTS: Two hundred twenty coronary artery disease patients received ICDs for standard indications. Empirical, standardized therapy was programmed so that all FVT episodes (average cycle length [CL] 240 to 320 ms, 250 to 188 bpm) were treated with 2 ATP sequences (8-pulse burst pacing train at 88% of the FVT CL) before shock delivery. A total of 1100 episodes of spontaneous ventricular tachyarrhythmias occurred during a mean of 6.9+/-3.6 months of follow-up. Fifty-seven percent were classified as slow VT (CL>/=320 ms), 40% as FVT (240 ms

K+ currents and K+ channel mRNA in cultured atrial cardiac myocytes (AT-1 cells).

Atrial tumor myocytes derived from transgenic mice (AT-1 cells) maintain a well-differentiated cardiac biochemical and histological phenotype. In addition, they beat spontaneously in culture and exhibit long action potentials whose repolarization resembles that observed in native mammalian myocytes. In this study, we identified the major depolarization-activated outward currents in AT-1 cells; also, the presence of mRNAs that encode outwardly conducting ion channels was determined by cloning from an AT-1 cDNA library or by Northern hybridization. Among K+ channel isoforms, Kv2.1, minK, and Kv1.4 were readily detected in tumors and at 1 day in culture. Their abundance remained relatively stable (twofold or less change) after 14 days. The major outward current in AT-1 cells is a delayed rectifier that displays prominent inward rectification, activates rapidly (eg, 182 +/- 27 milliseconds [mean +/- SEM] at + 20 mV, n = 12), exhibits biexponential deactivation kinetics, and is extremely sensitive to the methanesulfonanilide dofetilide (IC50, 12 nmol/L). These characteristics identify this current as IKr, a delayed rectifier observed only in cardiac cells. IKr in AT-1 cells displayed slow inactivation: dofetilide-sensitive deactivating tails were greater after 1-second than after 5-second pulses. When IKr was blocked by > or = 0.5 mumol/L dofetilide, time-independent current was usually recorded (50 of 65 experiments); rapidly inactivating (6 of 65) or slowly inactivating (9 of 65) outward currents were occasionally observed. We conclude that AT-1 cells express mRNAs encoding cardiac K+ channels and display a cardiac electrophysiological phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Classification and terminology of supraventricular tachycardia. Diagnosis and management of the atrial tachycardias.

This article describes some of the historical approaches to classifying supraventricular tachycardias and the evolution of the nomenclature as the knowledge of tachycardias improved. A classification scheme that is mechanistically based and favored by the authors, diagnostic criteria, clinical presentation, and therapy of the atrial tachycardias is also presented.

Dihydropyridine receptor gene expression is regulated by inhibitors of myogenesis and is relatively insensitive to denervation.

To evaluate developmental and physiological signals that may influence expression of the dihydropyridine-sensitive "slow" Ca2+ channel, we analyzed dihydropyridine receptor (DHPR) mRNA abundance in mouse skeletal muscle. Using synthetic oligonucleotide probes corresponding to the rabbit skeletal muscle DHPR, a 6.5 kb DHPR transcript was identified in postnatal skeletal muscle and differentiated C2 or BC3H1 myocytes, but not cardiac muscle or brain. DHPR gene expression was reversibly suppressed by 0.4 nM transforming growth factor beta-1 or by transfection with a mutant c-H-ras allele, nominal inhibitors of myogenesis that block the appearance of slow channels and DHPR. In contrast, both BC3H1 and C2 myocytes containing the activated ras vector expressed the gene encoding the nicotinic acetylcholine receptor delta subunit, demonstrating that not all muscle-specific genes are extinguished by ras. Denervation stimulated DHPR gene expression less than 0.6-fold, despite 8-fold upregulation of delta-subunit mRNA and reciprocal effects on the skeletal and cardiac alpha-actin genes. Thus, DHPR gene induction is prevented by inhibitors of other muscle-specific genes, whereas, at most, relatively small changes in DHPR mRNA abundance occur during adaptation to denervation.

Hyperthyroid-induced atrial flutter-fibrillation with profound sinoatrial nodal pauses due to small doses of digoxin, verapamil, and propranolol.

Atrial fibrillation due to hyperthyroidism is characterized by a rapid ventricular response which is typically resistant to digoxin therapy. We report a patient with atrial flutter-fibrillation who developed cyclic sinus node dysfunction with profound ventricular pauses in response to small doses of digoxin, verapamil, and propranolol, which resolved with discontinuation of the medications. Caution is necessary to avoid paradoxical ventricular slowing when treating hyperthyroid-induced atrial fibrillation.