Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort.

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high-risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co-infected. SVR among those with HCV mono-infection was 64% by intention to treat; SVR was 68% among HCV/HIV co-infection. Independent predictors of SVR in HCV mono-infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85-0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13-4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03-4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31-6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype-1 infection. Interferon-based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision-making.

The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

The individual and combined influence of HIV and hepatitis C virus on dyslipidaemia in a high-risk Hispanic population.

OBJECTIVES: To assess the effects of chronic hepatitis C (HCV) and HIV infection on dyslipidaemia in a Hispanic population at high risk of insulin resistance. METHODS: We compared serum lipids and C-reactive protein (CRP) in 257 Hispanic adults including 47 HIV- mono-infected, 43 HCV-mono-infected and 59 HIV/HCV-co-infected individuals as well as 108 healthy controls. We also assessed the effect of HCV on lipid alterations associated with antiretroviral therapy (ART), and the impact of HCV and HIV on the associations among insulin resistance, triglycerides and cholesterol. RESULTS: HCV infection was associated with lower total and low-density lipoprotein (LDL) cholesterol, but not high-density lipoprotein (HDL) cholesterol or triglycerides compared with healthy controls. HIV infection was associated with higher triglycerides and lower HDL, but not total or LDL cholesterol. HCV mitigated the elevation of triglycerides associated with ART. In healthy Hispanic adults, insulin resistance was significantly correlated with higher triglycerides, CRP and lower HDL. HIV infection nullified the association of insulin resistance with triglycerides and HDL, and the association of triglycerides with LDL. HCV infection nullified the association of insulin resistance with triglycerides, HDL and CRP. CONCLUSIONS: HCV co-infection alters the profile of HIV-associated dyslipidaemia. The clinical significance of these findings for cardiovascular complications in HIV merits further study.

Analysis of the initiation of spontaneous monomorphic ventricular tachycardia by stored intracardiac electrograms.

OBJECTIVES: This study was designed to analyze stored intracardiac electrograms generated during spontaneous monomorphic ventricular tachycardia to examine the possible mechanisms responsible for the initiation of ventricular tachycardia in a group of postinfarction patients. BACKGROUND: Implantable cardioverter-defibrillators capable of storing electrograms during an arrhythmic event provide an intracardiac electrogram analog to Holter ambulatory electrocardiographic monitoring. Such electrograms are of value in arrhythmia diagnosis and in determining the appropriateness of implantable cardioverter-defibrillator therapy and may aid in understanding the initiation of ventricular arrhythmias. METHODS: We studied 73 stored electrograms in 22 postinfarction patients with spontaneous monomorphic ventricular tachycardia. Premature depolarizations before tachycardia were classified by morphology and number. Electrogram morphology was compared with the morphology of the baseline rhythm and ventricular tachycardia. Prematurity was assessed by the coupling interval and a calculated prematurity ratio. RESULTS: During baseline rhythm, ectopic activity was present in 30 (41%) of 73 stored episodes. Ventricular tachycardia was preceded by a short-long-short sequence in 14% of episodes and by a rapid ventricular rhythm in 5.5% of episodes. The onset of ventricular tachycardia was marked by single premature depolarizations in 33 episodes (45%), by pairs in 16 (22%) and by multiple complexes in 24 (33%). Morphology was similar to that of the ensuing tachycardia in 35 episodes (48%). The mean coupling interval was 364 ms, and the mean prematurity ratio was 0.56. In all 10 episodes (14%) where the prematurity ratio was < 0.40, a short-long-short sequence was responsible. When classified by morphology, the mean prematurity ratio of depolarizations dissimilar to ventricular tachycardia (0.53) was significantly less than that of the morphologically similar group (0.60, p = 0.035). CONCLUSIONS: In this select group of postinfarction patients with recurrent sustained monomorphic ventricular tachycardia treated with implantable cardioverter-defibrillators, ventricular tachycardia was most often preceded by late-coupled premature depolarizations. Not infrequently, a short-long-short sequence occurred before tachycardia. Premature depolarizations with a morphology different from that of the tachycardia occurred earlier in the cardiac cycle than did those with a morphology similar to that of the tachycardia. These findings may reflect different mechanisms of ventricular tachycardia initiation.

Perioperative and long-term results after electrophysiologically directed ventricular surgery for recurrent ventricular tachycardia.

Thirty-six patients underwent ventricular aneurysmectomy and electrophysiologically directed endocardial resection for treatment of recurrent ventricular tachycardia refractory to antiarrhythmic drug therapy. The surgical mortality rate was 17% and all 30 patients discharged from the hospital were alive at the end of the follow-up period (range 6 to 54 months), yielding a cumulative projected survival rate of 83% by actuarial analysis. Poor systolic function of the nonaneurysmal ventricular segments was the strongest and the only independent predictor of operative mortality among the clinical, hemodynamic, angiographic and electrophysiologic variables analyzed by stepwise logistic regression. Ventricular tachycardia recurred early in four of the six patients in whom the endocardial resection was limited to a small area for technical reasons. Twelve patients, including 10 with sustained ventricular tachycardia still inducible by postsurgical programmed electrical stimulation, were discharged receiving antiarrhythmic drugs that had been tried unsuccessfully before surgery. During a mean follow-up period of 25 +/- 15 months, nonfatal sustained ventricular tachycardia recurred in two patients after discharge. Inadequate endocardial resection was a significant predictor of arrhythmia recurrence.

Serial analysis of electrically induced ventricular arrhythmias in a canine model of myocardial infarction.

To determine the rate of induction, specificity and evolution of electrically induced postmyocardial infarction ventricular arrhythmias, 10 dogs that underwent a sham operation and 20 dogs with experimental transmural apical myocardial infarction underwent serial closed chest electrophysiologic studies with programmed ventricular stimulation under light anesthesia 1, 2, 4 and 6 weeks after the operation. The reproducibility of the electrically induced ventricular arrhythmias was at a maximum when three extrastimuli were used during ventricular pacing for induction. The reproducibility of the arrhythmias was also a function of the age of the infarct. Electrically induced sustained monomorphic ventricular tachycardia, observed in 45 to 50% of the animals, was a highly specific postinfarction finding (0% specificity in control animals, regardless of the mode or timing of programmed cardiac stimulation), whereas nonsustained polymorphic ventricular tachycardia was not. The specificity of induced ventricular fibrillation was a function of the mode and timing of programmed stimulation. The rate of induction of the electrically induced ventricular arrhythmias did not change significantly during the 6 week period after myocardial infarction. A large infarct size (determined by postmortem examination) and a low left ventricular ejection fraction (determined during premortem cardiac catheterization) were the only variables identified that predisposed the animals to electrically induced sustained monomorphic ventricular tachycardia. These factors, however, did not correlate with the presence of electrically induced ventricular fibrillation or nonsustained ventricular tachycardia.

Electrophysiologic effects of d-sotalol in humans.

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.

Low energy conversion of atrial fibrillation in the sheep.

OBJECTIVES: In this study, the feasibility, efficacy and safety of low energy internal atrial cardioversion were investigated in a sheep model. The relation between the level of energy used for atrial defibrillation and the probability of successful cardioversion was examined. BACKGROUND: Atrial fibrillation is a common clinical arrhythmia that frequently recurs after termination with high energy external cardioversion. In some patients with drug-refractory and poorly tolerated atrial fibrillation, an automatic implantable cardioverter may prove useful by providing rapid restoration of sinus rhythm. METHODS: In 16 pentobarbital-anesthetized sheep, a right atrial spring electrode was implanted percutaneously and a left thoracic cutaneous patch electrode was placed on the thorax. Sustained atrial fibrillation was induced by rapid atrial pacing and terminated by biphasic cathodal shocks synchronized to the R wave of the surface electrocardiogram (ECG). RESULTS: During 768 defibrillation attempts in 16 sheep, the percent of successful cardioversion attempts increased in a dose-response manner, reaching a plateau at the average energy level of 5 J. With greater than or equal to 1.5 and greater than or equal to 2.5 J energy levels, cardioversion was achieved, respectively, in greater than 50% and greater than 80% of attempts. Ventricular fibrillation occurred in 18 (2.4%) of 768 cardioversion attempts; in all 18 cases, the shock was poorly synchronized with the ECG R wave. CONCLUSIONS: Low energy cardioversion of atrial fibrillation to sinus rhythm is feasible with use of a right atrial spring/cutaneous patch electrode configuration. The percent of successful cardioversion attempts depends on the level of energy output, and there is a risk of ventricular fibrillation if cardioversion is poorly synchronized with ventricular depolarization.

Determinants of the outcome of electrophysiologic study in patients with ventricular tachyarrhythmias.

To determine those factors predictive of the ability to both initiate and suppress ventricular tachyarrhythmias during electrophysiologic study, the results of programmed cardiac stimulation were evaluated in 261 patients: 66 presenting with nonsustained ventricular tachycardia, 91 with sustained ventricular tachycardia and 104 with ventricular fibrillation. Multivariate logistic regression analysis revealed that the presenting arrhythmia was a potent and independent predictor of the ability to provoke ventricular arrhythmias at electrophysiologic study; a history of myocardial infarction and male sex were also significant independent predictors. Of patients presenting with sustained ventricular tachycardia, 89% (81 of 91) had inducible ventricular arrhythmias compared with 61 (40 of 66) and 66% (69 of 104) of patients with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Complete suppression of inducible arrhythmias could be achieved in only 52% (34 of 66) of patients with sustained ventricular tachycardia, compared with 73 (24 of 33) and 75% (46 of 61) of patients presenting with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Multivariate analysis showed that the major independent determinants of the ability to suppress inducible arrhythmias were the number of drug trials performed before electrophysiologic study (inversely correlated) and the nature of the induced arrhythmia. The nature of the presenting clinical arrhythmia is, therefore, a highly significant and independent predictor of the ability to induce ventricular arrhythmias during electrophysiologic testing and an important determinant of the ability to suppress induced arrhythmias in patients with spontaneous ventricular tachyarrhythmias.

Successful implantation of cardioverter-defibrillator systems in patients with elevated defibrillation thresholds.

OBJECTIVES: . The purpose of this study was to conduct a retrospective analysis of 16 patients with high initial defibrillation thresholds in whom a three-electrode system was used to lower defibrillation thresholds and permit implantation of a cardioverter-defibrillator system. BACKGROUND: Patients with high defibrillation thresholds (> 25 J) are uncommon but may be problematic to physicians implanting cardioverter-defibrillator systems. Most conventional systems use two defibrillating electrodes, most commonly two epicardial patches. When defibrillation thresholds remain elevated despite extensive testing of a two-electrode system, a third electrode can be incorporated and tested. However, few published data exist on the use of a three-electrode system in patients with high defibrillation thresholds. METHODS: After failure to achieve satisfactory defibrillation thresholds < 25 J with a two-patch electrode system, a third electrode was incorporated and tested. In all cases, two electrodes were joined to form a common cathode or anode, while a single electrode was used as the opposite polarity electrode. Various three-electrode configurations were then tested. RESULTS: In all 16 patients, satisfactory defibrillation thresholds were achieved and a cardioverter-defibrillator was implanted (95% confidence interval [CI] = 0% to 21%). The mean final defibrillation threshold using the revised three-electrode system was 19.5 +/- 3.7 J (p < 0.0001). A mean of 6 +/- 3 electrode configurations/patient were tested before the final configuration was selected. A total of nine different electrode configurations were used in the 16 study patients; the most common of these incorporated left and right ventricular patches as combined cathode and a superior vena cava coil (n = 5) or right atrial patch electrode (n = 3) as single anode. CONCLUSION: Patients with high initial defibrillation thresholds can generally undergo successful cardioverter-defibrillator implantation with a three-electrode system if enough electrode configurations are tested after a third electrode is incorporated.

Determinants of successful nonthoracotomy cardioverter-defibrillator implantation: experience in 101 patients using two different lead systems.

OBJECTIVES: This study was conducted to identify the determinants of successful nonthoracotomy cardioverter-defibrillator implantation. BACKGROUND: Until recently, either median sternotomy or thoracotomy was necessary to implant the electrodes used for internal cardioverter-defibrillator systems. A number of manufacturers have developed nonthoracotomy lead systems comprising two transvenous coil electrodes and a subcutaneous patch electrode. At present, the factors associated with the success or failure of a nonthoracotomy approach are unknown. METHODS: A total of 101 consecutive patients requiring a cardioverter-defibrillator underwent an initial nonthoracotomy approach. Factors associated with successful nonthoracotomy implantation were prospectively determined. RESULTS: A nonthoracotomy system was implanted in 72 (71%) of 101 patients. Twenty-nine patients (29%) required thoracotomy. Univariate predictors of successful nonthoracotomy implantation included smaller cardiac size (p < 0.0001), smaller cardiothoracic ratio (p < 0.0002), QRS duration < 120 ms (p = 0.003), female gender (p = 0.006), ventricular fibrillation as the presenting arrhythmia (p = 0.03) and smaller echocardiographic left ventricular size (p = 0.04). Multivariate predictors included smaller cardiac size (p < 0.002) and female gender (p < 0.007). Total actuarial survival over a mean (+/- SD) follow-up interval of 12 +/- 7 months was 91 +/- 0.03% and was not different in the thoracotomy and nonthoracotomy groups. CONCLUSIONS: A nonthoracotomy cardioverter-defibrillator system can be implanted in a majority of patients. Smaller cardiac size and female gender are associated with a high probability of successful implantation.

Quality of life, continence and frequency of pouchitis following laparoscopic versus open colectomy and ileal pouch-anal anastomosis: an Irish perspective.

BACKGROUND: This study aims to assess quality of life outcomes, continence, rates of pouchitis and predictors of pouchitis for patients undergoing laparoscopic versus open three-stage ileal pouch-anal anastomosis (IPAA) surgery in our institution. METHODS: Forty-two patients having had three-stage (IPAA) surgery were identified. One was excluded as they had undergone pouchectomy. A postal questionnaire followed by telephone contact was undertaken. The questionnaire was based on The Gastrointestinal Quality of Life Index (GIQLI) and Wexner/Cleveland Clinic Faecal Incontinence Symptom Severity Scoring Systems. AIMS: Our aim was to assess morbidity, quality of life, incidence of pouchitis and continence following restorative panproctocolectomy and IPAA. RESULTS: Thirty-five patients completed the response. The median age at colectomy of our patient population was 32 years. 57 % were male and 43 % were female. 54.3 % of cases were carried out laparoscopically. 8/19 patients who had laparoscopic surgery had pouchitis (42.1 %) versus 9/16 patients who had open surgery (56.3 %). The median Wexner score was 0. Nine patients (25.7 %) had a GIQLI score that was within or above the range reported for healthy controls. The rate of complications was 31.7 % for emergency cases and 25.7 % for elective cases. The rate of pouchitis in this group was 48.5 %. Overall pelvic sepsis rate was 12.8 %. CONCLUSIONS: Ileal pouch-anal anastomosis is a successful and well-tolerated procedure with 94 % of patients opting to have the surgery again. Preliminary results do not show any significant difference in the incidence of pouchitis following laparoscopic surgery.

Adenosine and the treatment of supraventricular tachycardia.

Adenosine has recently become widely available for the treatment of paroxysmal supraventricular tachycardia. In order to evaluate its role in the management of arrhythmias, we have reviewed the literature on the cellular mechanisms, metabolism, potential for adverse effects, and clinical experience of the efficacy and safety of intravenous adenosine. Adenosine produces transient atrioventricular nodal block when injected as an intravenous bolus. This is of therapeutic value in the conversion to sinus rhythm of the majority of paroxysmal supraventricular tachycardias, which involve the atrioventricular node in a re-entrant circuit. The mean success rate was 93% from over 600 reported episodes. Compared with other antiarrhythmic agents, adenosine is remarkable for its rapid metabolism and brevity of action, with a half-life of a few seconds. It commonly produces subjective symptoms, particularly chest discomfort, dyspnea, and flushing, which are of short duration only. No serious adverse effect has been reported. Arrhythmias may recur within minutes in a minority of patients. Comparative studies have shown that adenosine is as effective as verapamil in the treatment of supraventricular tachycardia, and has less potential for adverse effects. Patients with supraventricular tachycardia should initially be treated using vagotonic physical maneuvers. Immediate electrical cardioversion is indicated if the arrhythmia is associated with hemodynamic collapse. Adenosine is the preferred drug in those patients in whom verapamil has failed or may cause adverse effects, such as those with heart failure or wide-complex tachycardia. The safety profile of adenosine suggests that it should be the drug of first choice for the treatment of supraventricular tachycardia, but only limited comparative data to support this view are available at present.

Antiarrhythmic drug therapy in pregnancy and lactation.

Antiarrhythmic agents commonly used in clinical practice are reviewed with respect to their potential for teratogenic or other adverse fetal effects. Although most experience with antiarrhythmic drug therapy during pregnancy has accrued with digoxin, quinidine, and propranolol, other antiarrhythmic agents may also be used in the pregnant patient if indicated. The choice of antiarrhythmic drug depends on the specific arrhythmia being treated, the cardiac condition of the patient or fetus, and the known or anticipated actions of the antiarrhythmic drug being considered. The management of specific arrhythmias encountered in pregnant women are also discussed. For benign arrhythmias, a conservative approach starting first with preventive measures is appropriate. For more severe or symptomatic arrhythmias, pharmacologic therapy should be instituted using drugs with proven safety to the fetus, if possible. Electrical cardioversion of the patient may be performed with relative safety in more emergent situations.

Evolving role of sotalol in the management of ventricular tachyarrhythmias.

Sotalol is a unique compound with several potential antiarrhythmic mechanisms, including beta blockade (class II activity), action potential duration prolongation (class III activity), and possibly reduction of QT dispersion. In recent years, trials such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial reported disappointing results with the use of class I agents in the management of ventricular arrhythmias in patients with coronary artery disease. These results have led to increased interest in class III antiarrhythmic agents, including sotalol. Sotalol is effective in suppressing ventricular premature complexes as well as nonsustained and sustained ventricular tachyarrhythmias. The interaction between sotalol and implantable cardioverter-defibrillators (ICDs) is generally favorable. As is the case with other antiarrhythmic drugs, there is no placebo-controlled trial assessing the effect of sotalol on mortality. It is not known if sotalol is more effective than placebo, conventional beta blockade, amiodarone, or ICDs in reducing mortality from life-threatening ventricular arrhythmias. In addition, the optimal method of selecting patients for sotalol therapy has yet to be determined. The safety profile of sotalol has been well established in > 3,000 patients worldwide. Proarrhythmia occurs in approximately 4% of patients, and torsades de pointes occurs in approximately 2.5%. The majority of episodes of torsades de pointes occurs within 3 days of commencing sotalol therapy, and the risk of torsades de pointes increases sharply at dosages > 320 mg daily. It is recommended that initiation of sotalol therapy or dosage increases be performed in a monitored setting. Overall, only 1% of patients enrolled in clinical trials of sotalol discontinued therapy as a result of drug-related congestive heart failure. However, these trials have excluded patients with poor left ventricular systolic function and/or overt heart failure. The optimal management of these patients, who are at greatest risk of sudden cardiac death, and of patients with substrates other than coronary artery disease remains to be elucidated.

Long-term reproducibility of responses to programmed cardiac stimulation in spontaneous ventricular tachyarrhythmias.

Programmed electrical stimulation (PES) of the heart has been used to initiate and terminate ventricular tachyarrhythmias under controlled conditions in patients in whom these arrhythmias have occurred spontaneously. The long-term reproducibility of the response to programmed cardiac stimulation in patients with ventricular arrhythmias is unknown. Seventeen patients with previously documented spontaneously occurring ventricular tachyarrhythmias were evaluated: 5 with nonsustained ventricular tachycardia (VT), 10 with sustained VT and 2 with ventricular fibrillation. The underlying cardiac diagnosis was atherosclerotic coronary heart disease (CAD) in 11 patients, dilated cardiomyopathy in 2 patients, congenital heart disease in 1 patient and no structural heart disease in 3. All patients underwent PES in the absence of antiarrhythmic drug treatment, and patients with inducible VT underwent serial electrophysiologic-pharmacologic testing in an attempt to suppress the arrhythmia. All 17 patients were reexamined with PES at a mean of 18 months (range 2 to 42) after their initial electrophysiologic study, during which time none had a myocardial infarction or intervening cardiac surgery. Repeat electrophysiologic studies, performed in the absence of antiarrhythmic agents, were undertaken because of drug intolerance, availability of new drugs, recurrent arrhythmia or preoperative reevaluation. All 11 patients with CAD had inducible VT on both the first and second electrophysiologic evaluation. Of the 6 patients with no CAD, only 1 had inducible VT on both occasions. Thus, long-term reproducibility of PES-induced VT in patients with stable CAD appears to be high.

Influence of drive cycle length during programmed stimulation on induction of ventricular arrhythmias: analysis of 403 patients.

The drive cycle length at which programmed ventricular stimulation is performed is a fundamental variable in all stimulation protocols, but the influence of this variable on the ability to induce ventricular arrhythmias has not been systematically analyzed. This study, which included 403 patients with prior ventricular tachycardia (VT) or ventricular fibrillation undergoing programmed ventricular stimulation with a uniform protocol that incorporated 3 basic drive cycle lengths from the right ventricular apex, was performed to examine the influence of drive cycle length on the induction of ventricular arrhythmias. The sensitivity of the protocol was 62% for nonsustained VT, 73% for ventricular fibrillation and 89% for sustained VT. Fifty-four percent (217 patients) had an arrhythmia induced with programmed ventricular stimulation during ventricular pacing. No arrhythmia was induced in 96 patients (24%), whereas induction was accomplished during sinus rhythm in 61 patients (15%) and rapid ventricular pacing in 29 patients (7%). With this protocol, the sensitivity for single and double extrastimuli during ventricular pacing increases using decremental drive cycle lengths. Although only 2 patients had induction of a ventricular arrhythmia at a drive cycle length of 700 to 650 ms using a single extrastimulus, 14, 8 and 3 patients had ventricular arrhythmias induced by single extrastimuli at drive cycle lengths of 600 to 550, 500 to 450 and 400 ms, respectively. Of 163 patients with arrhythmias induced with double extrastimuli, only 6 had an arrhythmia induced at drive cycle lengths of 700 to 650 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Management of refractory supraventricular tachyarrhythmias using low-energy transcatheter shocks.

Alteration of atrioventricular (AV) conduction was attempted in 7 consecutive patients with severely symptomatic, drug-refractory supraventricular tachyarrhythmias using low-energy, direct-current transcatheter shocks of between 20 and 50 J. A single shock of 50 J or less delivered at the AV junction resulted immediately in complete AV block in 6 of the patients. Complete AV block has persisted in 3 patients, and in another who received a second shock 24 hours after the first. AV conduction was altered in the 3 patients in whom conduction either persisted or returned in such a way that supraventricular arrhythmias no longer occurred or were associated with a much slower ventricular response. After a follow-up of 20 to 37 months (mean 27 +/- 8), all 7 patients have improved symptomatically and 6 are taking no antiarrhythmic drugs. Thus, single low-energy transcatheter shocks can be used to ablate AV conduction. Such shocks may also modify AV conduction without production of complete AV block, but with changes in anterograde or retrograde conduction that may favorably influence recurrent symptomatic supraventricular tachyarrhythmias.

Reproducibility of ventricular tachycardia suppression by antiarrhythmic drug therapy during serial electrophysiologic testing in coronary artery disease.

The short-term reproducibility of pharmacologic suppression of ventricular tachycardia (VT) induced by programmed cardiac stimulation was tested in patients with coronary artery disease presenting with documented recurrent VT or ventricular fibrillation. Sixty-three consecutive patients in whom sustained VT (30 patients) or nonsustained VT (33 patients) was induced by programmed cardiac stimulation without antiarrhythmic drug treatment, and in whom at least 1 oral antiarrhythmic drug regimen suppressed the induced VT during serial electrophysiologic testing, were entered into the study. Programmed cardiac stimulation was repeated after a mean of 37 +/- 14 hours during the same antiarrhythmic drug regimen. No VT was induced in 59 of the 63 patients during the second study, resulting in a rate of 94% for short-term reproducibility of pharmacologic suppression of induced VT. Of the remaining 4 patients, programmed cardiac stimulation during the second drug study induced sustained VT in 1 patient and nonsustained VT in 3 patients. There was no significant difference in mean right ventricular effective refractory period and QT interval between the first and second drug study. Thus, in this selected population of patients, pharmacologic suppression of electrically induced VT is a reproducible phenomenon.