Implantable Cardioverter-Defibrillator (ICD) Therapy: Initial Clinical Experience in 6 Patients

Sudden cardiac death accounts for approximately half of all cardiovascular mortality in the industrialized countries and ventricular tachyarrhythmia is the most common mechanism for this event. Implantable cardioverter-defibrillator (ICD) has been effectively used for prevention of sudden cardiac death in patients with life-threatening ventricular tachyarrhythmias since 1980. Clinical experience with ICD device now exceeds 100,000 implants worldwide and the number of implantation is increasing. In Korea, there is also increasing trend of ICD implantation. The authors report the initial experience of of ICD implantation in 6 patients who had high risk of sudden cardiac death.ope

A Case of Torsades de Pointes Induced by Cisapride

Torsades de pointes, a polymorphic ventricular tachycardia associated with prolonged QT interval, is a well-known life-threatening arrhythmia, which has been found to be induced by various causes such as drugs, electrolyte imbalances, and severe bradycardia. Cisapride is a gastrointestinal prokinetic drug, which is widely used to treat gastroesophageal reflux disease or other functional gastrointestinal disorders. Cisapride can cause torsades de pointes and cases of torsedes de pointes induced by cisapride have been reported in other countries. Cases of torsades de pointes associated with antihistamine drugs have been reported in Korea, however, cisapride-induced torsades de pointes case has not been reported. We report a case of 31 year-old female patient who experienced repeated loss of consciousness due to cisapride-induced torsades de pointes.ope

Physical Activity and Risk of Atrial Fibrillation: A Nationwide Cohort Study in General Population

Although exercise prevents cardiovascular disease and mortality, vigorous exercise and endurance athletics can cause atrial fibrillation (AF). However, no large cohort study has assessed the relationship between physical activity and AF in the general population. We assessed the effect of physical activity at different energy expenditures on the incidence of AF. We studied 501,690 individuals without pre-existing AF (mean age, 47.6 ± 14.3 years; 250,664 women [50.0%]) included in the Korean National Health Insurance Service database. The physical activity level was assessed using a standardized self-reported questionnaire at baseline. During a median follow-up of 4 years, 3,443 participants (1,432 women [41.6%]) developed AF. The overall incidence of AF at follow-up was 1.79 per 1,000 person-years. The subjects who met the recommended physical activity level (500-1,000 metabolic equivalent task [MET] minutes/week) had a 12% decreased AF risk (adjusted hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.80-0.97), but not the insufficiently (1-500 MET-minutes/week; HR: 0.94, 95% CI: 0.86-1.03) and highly active subjects (≥1,000 MET-minutes/week; HR: 0.93, 95% CI: 0.85-1.03). The recommended minimum key target range of physical activity level was associated with the maximum benefit for reduced AF risk in the general population. The dose-response relationship between physical activity level and AF risk showed a U-shaped pattern. Although exceeding the key target range attenuated this benefit, it did not increase the AF risk beyond that during inactivity.ope

Conduit Puncture for Electrophysiological Procedures in Patients with Fontan Circulation

Background: Electrophysiological procedures are challenging in patients who have undergone lateral tunnel or extracardiac conduit Fontan operation because the caval veins are not connected to the cardiac atria and ventricles. This study describes our experience in managing a series of patients with Fontan circulation requiring catheter ablation for arrhythmias. Methods: This study included eight consecutive patients with Fontan circulation who underwent catheter ablation or pacemaker implantation via Fontan conduit puncture [median age (interquartile range), 21.5 (16.0-25.8) years; 5 men]. Lateral tunnel and extracardiac conduit were equally distributed among the eight patients. A standard technique for conduit puncture and subsequent electrophysiologic procedure was used. The time taken for conduit puncture was compared for different types of conduits. Results: The median age of patients in this series was 21.5 years (interquartile range: 16.0-25.8 years). Fontan conduit puncture via right femoral vein under intracardiac echocardiographic guidance was successfully performed without complications in seven of the eight patients. Conduit puncture failed in one patient with extracardiac conduit made of the pericardium due to interruption of both femoral veins. In three patients with Fontan conduit made of pericardium, a Bronckenbrough transseptal needle or a radiofrequency transseptal needle with a snare was used. In four patients with Fontan conduit made of Gore-tex, a radiofrequency transseptal needle with a snare, and percutaneous transluminal angioplasty balloon were used. Fontan conduit puncture time was significantly longer in patients with conduit made of Gore-tex (median time, 91 min; interquartile range, 59.8-130.5 min) than in patients with conduit made of the pericardium (median time, 11.5 min; interquartile range, 10.0-18.3 min), respectively (p=0.020). Conclusions: Conduit puncture is feasible and safe in patients with lateral tunnel and extracardiac Fontan circulation. Puncture of the Gore-tex conduit is more difficult and time consuming than puncture of the pericardium conduit.ope

Preventing ventricular fibrillation by flattening cardiac restitution

Ventricular fibrillation is the leading cause of sudden cardiac death. In fibrillation, fragmented electrical waves meander erratically through the heart muscle, creating disordered and ineffective contraction. Theoretical and computer studies, as well as recent experimental evidence, have suggested that fibrillation is created and sustained by the property of restitution of the cardiac action potential duration (that is, its dependence on the previous diastolic interval). The restitution hypothesis states that steeply sloped restitution curves create unstable wave propagation that results in wave break, the event that is necessary for fibrillation. Here we present experimental evidence supporting this idea. In particular, we identify the action of the drug bretylium as a prototype for the future development of effective restitution-based antifibrillatory agents. We show that bretylium acts in accord with the restitution hypothesis: by flattening restitution curves, it prevents wave break and thus prevents fibrillation. It even converts existing fibrillation, either to a periodic state (ventricular tachycardia, which is much more easily controlled) or to quiescent healthy tissue.ope

Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol

We hypothesized that partial cellular uncoupling produced by low concentrations of heptanol increases the vulnerability to inducible atrial fibrillation (AF). The epicardial surface of 12 isolated-perfused canine left atria was optically mapped before and after 1–50 μM heptanol infusion. At baseline, no sustained (>30 s) AF could be induced in any of the 12 tissues. However, after 2 μM heptanol infusion, sustained AF was induced in 9 of 12 tissues (P 5 μM caused loss of 1:1 capture during rapid pacing, causing no AF to be induced. AF was initiated by conduction block across the fiber leading to reentry, which broke up after one to two rotations into two to four independent wavelets that sustained the AF. Heptanol at 2 μM had no effect on the cellular action potential duration restitution or on the maximal velocity rate over time of the upstroke. The effects of heptanol were reversible. We conclude that partial cellular uncoupling by heptanol without changing atrial active membrane properties promotes wavebreak, reentry, and AF during rapid pacing.ope

Effects of amiodarone on wave front dynamics during ventricular fibrillation in isolated swine right ventricle

The effects of acute amiodarone infusion on dynamics of ventricular fibrillation (VF) are unclear. Six isolated swine right ventricles (RVs) were studied in vitro. Activation patterns during VF were mapped optically, whereas action potentials were recorded with a glass microelectrode. At baseline, VF was associated with frequent spontaneous wave breaks. Amiodarone (2.5 μg/ml) reduced spontaneous wave breaks and increased the cycle length (CL) of VF from 83.3 ± 17.8 ms at baseline to 118.4 ± 25.8 ms during infusion (P < 0.05). Amiodarone increased the reentrant wave front CL (114.4 ± 15.5 vs. 78.2 ± 19.0 ms, P < 0.05) and central core area (4.1 ± 3.8 vs. 0.9 ± 0.3 mm2, P < 0.05). Within 30 min of infusion, VF terminated (n = 1), converted to ventricular tachycardia (VT) (n = 1) or continued at a slower rate (n = 4). Amiodarone flattened the APD restitution curves. We conclude that amiodarone reduced spontaneous wave breaks. It might terminate VF or convert VF to VT. These effects were associated with the flattening of APD restitution slope and increased core size of reentrant wave fronts.ope

Wavebreak Mechanism During Ventricular Fibrillation in Isolated Swine Right Ventricle

Background：Several different patterns of wavebreak have been described by mapping of the tissue surface during fibrillation. However, it is not clear whether these surface patterns are caused by multiple distinct mechanisms or by a single mechanism. Method：To determine the mechanism by which wavebreaks are gener-ated during ventricular fibrillation, we conducted optical mapping studies and single cell transmembrane potential recording in 6 isolated swine right ventricles. Results：Among 763 episodes of wavebreak (0.75 times/sec/cm2), optical maps showed 3 patterns：80% due to a wavefront encountering the refractory waveback of another wave, 11.5% due to wavefronts passing perpendicularly each other and 8.5% due to a new (target) wave arising just beyond the refractory tail of a previous wave. Computer simulations of scroll waves in 3-D tissue showed that these surface patterns could be attributed to two fundamental mechanisms：head-to-tail interactions and filament break. Conclusion：We conclude that during sustained ventricular fibrillation in swine RV, surface patterns of wavebreak are produced by two fundamental mechanisms：head-to-tail interaction between waves and filament break. (Korean Circulation J 2000;30(11):1404-1416)ope

Catheter Ablation of Atrial Fibrillation Raises the Plasma Level of NGF-β Which Is Associated with Sympathetic Nerve Activity

PURPOSE: The expression of nerve growth factor-β (NGF-β) is related to cardiac nerve sprouting and sympathetic hyper innervation. We investigated the changes of plasma levels of NGF-β and the relationship to follow-up heart rate variability (HRV) after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). MATERIALS AND METHODS: This study included 147 patients with AF (117 men, 55.8±11.5 years, 106 paroxysmal AF) who underwent RFCA. The plasma levels of NGF-β were quantified using double sandwich enzyme linked immunosorbent assay method before (NGF-β(pre)) and 1 hour after RFCA (NGF-β(post-1hr)). HRV at pre-procedure (HRV(pre)), 3 months (HRV(post-3mo)), and 1 year post-procedure (HRV(post-1yr)) were analyzed and compared with plasma levels of NGF-β. RESULTS: 1) The plasma levels of NGF-β significantly increased after RFCA (20.05±11.09 pg/mL vs. 29.60±19.43 pg/mL, p18 pg/mL, low frequency components (LF)/high-frequency components (HF) (p=0.003) and the number of atrial premature contractions (APCs, p=0.045) in HRV(post-3mo) were significantly higher than those with ≤18 pg/mL. 3) The LF/HF at HRV(post-3mo) was linearly associated with the NGF-β(pre) (B=4.240, 95% CI 1.114-7.336, p=0.008) and the NGF-β(post-1hr) (B=7.617, 95% CI 2.106-13.127, p=0.007). 4) Both NGF-β(pre) (OR=1.159, 95% CI 1.045-1.286, p=0.005) and NGF-β(post-1hr) (OR=1.098, 95% CI 1.030-1.170, p=0.004) were independent predictors for the increase of LF/HF at HRV(post-3mo). CONCLUSION: AF catheter ablation increases plasma level of NGF-β, and high plasma levels of NGF-β(pre) was associated with higher sympathetic nerve activity and higher frequency of APCs in HRV(post-3mo).ope

Intracellular Ca dynamics in ventricular fibrillation

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Cai transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and ventricular tachycardia (VT; 1.13 +/- 0.21 and 1.69 +/- 0.18, respectively) but fell dramatically during VF (0.28 +/- 0.06, P < 0.001). Cai at sites 4-6 mm apart also showed decreased MI during VF (0.63 +/- 0.13) compared with pacing (1.59 +/- 0.34, P < 0.001) or VT (2.05 +/- 0.67, P < 0.001). Spatially, Cai waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Cai is closely associated with Vm closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Cai release events occur and may influence wavebreak by altering Vm and APD locally.ope