Sudden death in implantable cardioverter-defibrillator recipients: clinical context, arrhythmic events and device responses.

OBJECTIVES: We sought to investigate the nature of terminal events and potential contributory clinical and nonclinical (e.g., device-related) factors associated with sudden death (SD) in recipients of an implantable cardioverter-defibrillator (ICD). BACKGROUND: The ICD is very effective in terminating ventricular tachycardia (VT) or ventricular fibrillation (VF), but protection against SD is not absolute. Little is known about the nature and potential causes of SD in patients with ICDs. METHODS: We analyzed 25 cases of out-of-hospital SD among patients enrolled in the clinical investigation of the Cadence Tiered-Therapy Defibrillator System. RESULTS: All patients (24 men and 1 woman, mean age 62+/-10 years) received epicardial lead systems. The majority (92%) had coronary artery disease and a previous myocardial infarction (MI), with a mean left ventricular ejection fraction 0.25+/-0.07. At device implantation, the mean defibrillation threshold was 13+/-5 J. Sudden death occurred 13+/-11 months later. Twenty patients (80%) had received appropriate ICD therapies before death, and 18 (72%) were receiving > or = 1 antiarrhythmic drugs at the time of death. Sudden death was tachyarrhythmia-associated in 16 patients (64%), non-tachyarrhythmia-associated in 7 (28%) and indeterminate in 2 (8%). In the 16 patients with tachyarrhythmia-associated SD, the overall first therapy success rate in tachycardia and fibrillation zones was 60% and 67%, respectively. However, despite protracted therapies (> or = 2 shocks) in 7 (66%) of 12 patients who received fibrillation therapies, the final tachyarrhythmic episode was ultimately terminated by the ICD in 15 (94%) of the 16 patients, whereas 1 patient died after multiple (initially successful) internal and external shocks for intractable VT/VF during exercise. In 10 patients (40%) one or more, primarily clinical, factors potentially contributory to SD were identified: heart failure (n=8), angina (n=2), hypokalemia (n=1), adverse antiarrhythmic drug treatment (n=1) and acute MI (n=1). An additional 10 patients (40%) had experienced an increase in frequency of ICD shocks within 3 months of SD. Appropriate battery voltages and normal circuitry function were found in all devices interrogated and analyzed after death. CONCLUSIONS: In this select group of patients receiving a third-generation ICD, SD was associated with VT or VF events in nearly two-thirds of patients, and death occurred despite ultimately successful, although often protracted, device therapies. These observations, along with evidence of recent worsening clinical status, suggest acute cardiac mechanical dysfunction as a frequent terminal factor. In recipients with ICDs, SD directly attributable to device failure seems to be rare.

Maximal ascending and descending slopes of the T wave in men and women.

To investigate possible sex differences in the dynamics of T wave generation, the maximum instantaneous slope of the ascending and descending limbs of the T wave (max dV/dt and min dV/dt, respectively), were calculated. These rate of repolarization parameters, as well as more traditional repolarization duration parameters (QT, JT, Q to T wave peak [QTm] and J to T wave peak [JTm]), were measured by computer using digitized electrocardiograms (ECGs) from the V5 lead in 562 normal subjects (443 men and 119 women; mean age 37 years), whose heart rates (HRs) were confined to one of three narrow ranges, namely 60 +/- 1, 70 +/- 1, or 80 +/- 1 beats/min. In both men and women, for each HR range absolute values of min dV/dt exceeded those of max dV/dt (P < .0001). However, absolute values of both max dV/dt and min dV/dt were consistently greater in men than in women for each HR range (P < .0001 at HR 60 +/- 1; P < .02 at HR 70 +/- 1, or 80 +/- 1). By using correlation analysis, max dV/dt and min dV/dt were shown to be independent of the repolarization duration variables (r < .30). Thus, whereas in both men and women the descending limb of the T wave is steeper than the ascending limb, the maximum slope of each limb of the T wave is steeper in men than in women. These findings add to a growing body of data indicating fundamental sex differences in the physiology of cardiac repolarization and propensity to torsade de pointes.

Ventriculoatrial conduction capability and prevalence of 1:1 retrograde conduction during inducible sustained monomorphic ventricular tachycardia in 305 implantable cardioverter defibrillator recipients.

Despite the advent of dual chamber ICDs, differentiation of VT (SMVT) with 1:1 VA conduction will remain a challenge. In this study, VA conduction capability and prevalence of inducible sustained monomorphic (SM) VT with 1:1 VA conduction was assessed in 305 ICD recipients. SMVT with a mean cycle length (CL) of 304 +/- 61 ms was induced in 161 (53%) patients. Twenty-six percent of the patients maintained 1:1 VA conduction to CL < or = 400 ms during incremental ventricular pacing, regardless of presenting tachyarrhythmia or presence of inducible SMVT. Among ten patients who had inducible SMVT with possible 1:1 VA conduction (based on SMVT CL comparable to the shortest CL associated with 1:1 retrograde conduction during ventricular pacing), all seven with available intracardiac tracings had documented 1:1 VA conduction during the induced SMVT--representing 4.4% of the patients with inducible SMVT (95% CI 1.2%-7.6%), and 2.3% of the entire ICD cohort (95% CI 0.6%-4.0%). We conclude that about one-fifth of ICD recipients possess 1:1 VA conduction to CL < or = 400 ms and that inducible SMVT with 1:1 VA conduction can be demonstrated in a small but nonnegligible proportion of ICD recipients. These data are relevant to the design of tachyarrhythmia-discrimination algorithms for dual chamber ICDs.

Implantable cardioverter defibrillator utilization among device recipients presenting exclusively with syncope or near-syncope.

INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are occasionally used in presumed high-risk patients with electrocardiographically undocumented syncope, although the incidence of ventricular tachyarrhythmias in this population is not well defined. METHODS AND RESULTS: We studied 33 consecutive patients receiving an ICD (67% nonthoracotomy and 70% tiered therapy) after electrophysiologic testing for unmonitored "syncope" (n = 29) or "near-syncope" (n = 4). Atherosclerotic heart disease was present in 24 (73%); mean left ventricular ejection fraction (LVEF) was 0.39 +/- 0.15; and sustained monomorphic ventricular tachycardia (SMVT) was inducible in 18 (55%). Over a median follow-up of 17 months (range 4 to 61), 12 patients (36%) received > or = 1 appropriate ICD discharge triggered by SMVT (cycle length 230 to 375 msec) in 10 and ventricular flutter or fibrillation in 2--without concomitant antiarrhythmic medication in 8 of 12 cases. Inducible SMVT and LVEF < or = 0.35 were statistically significant, independent predictors of an appropriate ICD discharge (P < 0.02 and P < 0.03, respectively). Estimated 1-year cumulative survival free of appropriate discharge was 34% versus 87%, respectively, in patients with versus without inducible SMVT (P < 0.02), and 18% versus 56%, respectively, in patients with LVEF < or = 0.35 versus LVEF > 0.35 (P < 0.03). CONCLUSION: In this highly select, multicenter population of ICD recipients with electrocardiographically undocumented syncope, a substantial incidence of appropriate device discharges was observed, particularly in patients with inducible SMVT and LVEF < or = 0.35. These findings support the notion that, in patients with LV dysfunction and inducible SMVT, ventricular tachyarrhythmias are likely to account for episodes of syncope or near-syncope.

Does subclinical hypothyroidism explain the increased susceptibility of women to torsades de pointes?

Among 20 consecutive patients (65% women) with drug-associated torsades de pointes, chemical evidence for hypothyroidism was found in only 10% of both women and men. Subclinical hypothyroidism is therefore unlikely to account for the consistently observed sex difference in the propensity to torsades de pointes.

Unrecognized paroxysmal supraventricular tachycardia. Potential for misdiagnosis as panic disorder.

BACKGROUND: The diagnostic criteria for panic disorder include symptoms commonly experienced by patients with paroxysmal supraventricular tachycardia (PSVT). Since electrocardiographic documentation of PSVT can be elusive, symptoms may be ascribed to other conditions. OBJECTIVE: To systematically evaluate the potential for PSVT to simulate panic disorder. METHODS: A retrospective survey of 107 consecutive patients with reentrant PSVT was conducted. Objective and subjective assessments of PSVT symptomatology were made, including the application of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), panic disorder criteria. RESULTS: The criteria for panic disorder according to DSM-IV were fulfilled by 67% of patients. Paroxysmal supraventricular tachycardia was unrecognized after initial medical evaluation in 59 patients (55%), including 13 (41%) of 32 patients with ventricular preexcitation by electrocardiogram, and remained unrecognized for a median of 3.3 years. Prior to eventual identification of PSVT, physicians (nonpsychiatrists) attributed symptoms to panic, anxiety, or stress in 32 (54%) of the 59 patients. When PSVT was unrecognized, women were more likely than men to have symptoms ascribed to psychiatric origins (65% vs 32%, respectively; P < .04). Paroxysmal supraventricular tachycardia was detected in only 6 (9%) of 64 patients undergoing Holter monitoring vs 8 (47%) of 17 patients who wore an event monitor (P < .001). During a 20-month median follow-up, electrophysiologically guided therapy (ablation in 81% of patients) resolved symptoms in 86% of patients; only 4% continued to meet DSM-IV panic disorder criteria without evidence of PSVT recurrence. CONCLUSIONS: The clinical characteristics of patients with PSVT referred for electrophysiologically guided therapy can mimic panic disorder. Diagnosis of PSVT is often delayed by inappropriate rhythm detection techniques (Holter instead of event monitoring) and failure to recognize ventricular preexcitation on the sinus electrocardiogram; symptoms due to unrecognized PSVT are often ascribed to psychiatric conditions.

Torsade de pointes as a complication of subarachnoid hemorrhage: a critical reappraisal.

Subarachnoid hemorrhage is widely accepted as a potential cause of torsade de pointes (TdP), yet this putative etiologic relationship has never been systematically evaluated. We therefore undertook a MEDLINE search from 1966 through 1993, with relevant back referencing, and identified 20 cases of TdP in the setting of subarachnoid hemorrhage. It was impossible in any of these cases (usually because of insufficient data) to completely exclude one or more alternative explanations for TdP, including congenital long QT syndrome, hypokalemia, hypomagnesemia, or drug-induced QT prolongation. Furthermore, of a total of 1,139 patients in 16 prospective series of subarachnoid hemorrhage with electrographic analyses, there were only five reported cases of TdP, all in patients with hypokalemia. Thus, extremely limited scientific data exist to support the notion that subarachnoid hemorrhage can be a distinct cause of TdP. Until more definitive evidence is available, the development of TdP in patients with subarachnoid hemorrhage is probably better characterized as a multifactorial phenomenon occurring in an acute, typically intensive care, setting.

Probucol-associated tachyarrhythmic events and QT prolongation: importance of gender.

From published articles and adverse reactions reports filed with the FDA (available through the Freedom of Information Act), we analyzed occurrences of tachyarrhythmias and the magnitude of QTc prolongation associated with probucol therapy. Of 16 cases of tachyarrhythmic events reported in association with probucol, 15 (94%) occurred in women (p < 0.01 vs expected value of 58%). Tachyarrhythmias were specifically described as TdP in 11 (63%) cases, all women; additional potential contributory QT-prolonging factors (besides probucol) were not identifiable in 2 of the 11 cases. We also analyzed QTc responses in 359 probucol-treated patients, all having baseline QTc < or = 0.44 sec1/2. At doses of 500 to 1000 mg/day, probucol-associated prolongation of QTc to values > or = 0.45 sec1/2 was observed in 22% of women versus 7% of men (p < 0.001) and to values > or = 0.47 sec1/2 in 8% of women versus 2% of men (p < 0.03). Multivariate analysis identified baseline QTc (p < 0.0001) and female gender (p < 0.03), but neither age nor dose, as significant independent predictors of QTc prolongation to > or = 0.45 sec1/2 with probucol. These findings have relevance to the clinical use of probucol, provide further evidence that women have a relatively greater predisposition to development of acquired long QT syndrome, and carry implications for the design of trials involving QT-prolonging drugs.

Increased propensity of women to develop torsades de pointes during complete heart block.

INTRODUCTION: To determine whether an increased female gender susceptibility to torsades de pointes (TdP) may exist in a clinical model of bradycardia-induced long QT syndrome, we investigated reported cases of TdP associated with acquired complete heart block. METHODS AND RESULTS: Seventy-two cases reported in the medical literature dating from 1941 through 1993 were identified, all describing TdP or "transient ventricular tachycardia/fibrillation" (to include those cases reported prior to the use of TdP terminology) in the setting of acquired complete heart block unassociated with QT prolonging drugs. Expected female prevalence in complete heart block was estimated at 52%, based on projections derived from 206,016 hospital discharges in the National Inpatient Profile (Commission on Professional and Hospital Activities, Ann Arbor, MI), over the years 1985 through 1992. During complete heart block, mean heart rate was 37 beats/min in both sexes (combined n = 43), and absolute QT interval ranged from 0.52 to 0.88 seconds, with a mean of 0.68 seconds (n = 25). Female prevalence among patients with TdP during complete heart block was greater than expected: 72% for all studied cases (P < 0.001); 70% (P < 0.04) and 74% (P < 0.02) among those reported prior to (n = 35) and during or after (n = 37) 1980, respectively; 73% (P < 0.03) among those with documented normokalemia (n = 26); and 68% (P = 0.2) among those with a prolonged QT interval and known polymorphic VT (i.e., unequivocal TdP; n = 25). CONCLUSION: Despite inherent limitations of this retrospective study, the data are consistent in suggesting a greater than expected female prevalence among patients with TdP related to complete heart block. This finding lends support to a broadening concept of increased susceptibility of women to the development of TdP in various settings of QT prolongation.

Differentiation of sinus tachycardia from ventricular tachycardia with 1:1 ventriculoatrial conduction in dual chamber implantable cardioverter defibrillators: feasibility of a criterion based on the atrioventricular interval.

Tachycardia discrimination in future implantable cardioverter defibrillators (ICDs) is likely to be enhanced by the addition of an atrial sensing/pacing lead. However, differentiation of sinus tachycardia (ST) from ventricular tachycardia (VT) with 1:1 VA conduction will remain problematic. We assessed the use of the AV interval as a potential criterion for correctly differentiating ST from VT. Incremental V pacing at the right ventricular (RV) apex served as a "VT" model in each of 41 patients with 1:1 VA conduction to pacing cycle lengths < or = 450 msec. High right atrial and RV apical electrograms during normal sinus rhythm (NSR) and during incremental V pacing were digitized (simulating ICD sensing). From these signals, AV interval versus pacing cycle length plots were computer generated to identify crossover cycle lengths, each defined as the cycle length at which the AV interval during V pacing equals the AV interval during NSR. At cycle lengths longer than the crossover value, the AV interval during "VT" exceeds the AV interval during NSR. In contrast, the AV interval during ST is physiologically shorter than the AV interval during NSR. Thus, ST can be readily differentiated from "VT" over a range of cycle lengths greater than the crossover value. The overall mean calculated crossover cycle length was 371 +/- 52 msec. In 11 patients paced multiple times, each crossover cycle length was reproducible (mean coefficient of variation was 1.2% +/- 0.9% per patient). AV intervals measured at the RV apex were also analyzed with incremental V pacing during catecholamine stimulation (isoproterenol, n = 5) and during alternate site "VT" (RV outflow tract [n = 8] and left ventricle [n = 2]). In all these cases, the new "VT" plots of AV interval versus pacing cycle length coincided with or fell to the left of those obtained during control RV apical pacing and recording (i.e., these AV interval values crossed the NSR baseline at cycle lengths < or = the crossover cycle length). Thus, the cycle length range for recognizable differentiation of ST from "VT" remained valid. The data suggest that the described AV interval criterion relying on the crossover cycle length: (1) is a promising approach to improve differentiation of ST from relatively slow VTs with 1:1 VA conduction, and (2) can readily be automated in future dual chamber ICDs, given its computational simplicity.

Sudden death in recipients of first-generation implantable cardioverter defibrillators: analysis of terminal events. Participating investigators.

Clinical factors and terminal events associated with sudden death in 51 patients were analyzed from among a multicenter experience of 864 recipients of first generation automatic implantable cardioverter defibrillator (AICD) devices (single zone, committed, monophasic pulse with > or = 1 epicardial patch electrode) during the period May 1982-February 1988. For these 51 patients, mean age was 58 years and atherosclerotic heart disease was present in 84%, with a history of ventricular fibrillation (VF) in 61%, and inducible sustained ventricular tachycardia (VT) in 84%; mean left ventricular ejection fraction was 0.26. Nearly 80% experienced one or more appropriate AICD shocks during the median 9 month (range 0-46 months) period prior to death. Of 30 monitored deaths, the first documented terminal rhythm was VF in 12 (40%), VT in 8 (27%), and asystole or electromechanical dissociation in the remaining 10 (33%). Shocks were documented during terminal events in 21 (66%) of 32 witnessed cases of sudden death with activated devices. The proportion of monitored or witnessed sudden deaths that were known or presumed to be tachyarrhythmic (based on terminal VT, VF, or shocks) ranged from 69% (11/16 cases with activated/nondepleted devices and a defibrillation threshold [DFT] < or = 20 J) to 81% (29/36 cases on intention-to-treat basis). Of 27 patients with known or presumed sudden tachyarrhythmic death, the AICD had been deactivated prior to death in 4 (15%); activated, but depleted in 4 (15%); activated/nondepleted, but with DFT of 25 J in 4 (15%); and activated/nondepleted, but without DFT testing in 4 (15%). The remaining 11 (41%) known or presumed sudden tachyarrhythmic deaths occurred in patients with activated/nondepleted devices and DFT < or = 20 J; however, definite or suspected contributory factors (e.g., hematoma under epicardial patch, generator component failure, or drug-induced DFT rise) could be identified in 6 (55%) of 11 cases. Thus, in this first-generation AICD experience: 1) most sudden deaths occurred on the basis of a known or presumed tachyarrhythmia; and 2) an understanding of apparent "failure" of ICD therapy could often be gained through an integrated analysis of associated clinical factors and management practices, as well as device "hardware" function. These observations are likely to remain relevant, even with respect to newer generation ICDs.

T wave "humps" as a potential electrocardiographic marker of the long QT syndrome.

OBJECTIVES: This study attempted to determine the prevalence and electrocardiographic (ECG) lead distribution of T wave "humps" (T2, after an initial T wave peak, T1) among families with long QT syndrome and control subjects. BACKGROUND: T wave abnormalities have been suggested as another facet of familial long QT syndrome, in addition to prolongation of the rate-corrected QT interval (QTc), that might aid in the diagnosis of affected subjects. METHODS: The ECGs from 254 members of 13 families with long QT syndrome (each with two to four generations of affected members) and from 2,948 healthy control subjects (age > or = 16 years, QTc interval 0.39 to 0.46 s) were collected and analyzed. Tracings from families with long QT syndrome were read without knowledge of QTc interval or family member status (210 blood relatives and 44 spouses). RESULTS: We found that T2 was present in 53%, 27% and 5% of blood relatives with a "prolonged" (> or = 0.47 s, "borderline" (0.42 to 0.46 s) and "normal" (< or = 0.41 s) QTc interval, respectively (p < 0.0001), but in only 5% and 0% of spouses with a borderline and normal QTc interval, respectively (p = 0.06 vs. blood relatives). Among blood relatives with T2, the mean [+/- SD] maximal T1T2 interval was 0.10 +/- 0.03 s and correlated with the QTc interval (p < 0.01); a completely distinct U wave was seen in 23%. T2 was confined to leads V2 and V3 in 10%, whereas V4, V5, V6 or a limb lead was involved in 90% of blood relatives with T2. Among blood relatives with a borderline QTc interval, 50% of those with versus 20% of those without major symptoms manifested T2 in at least one left precordial or limb lead (p = 0.05). A T2 amplitude > 1 mm (grade III) was observed, respectively, in 19%, 6% and 0% of blood relatives with a prolonged, borderline and normal QTc interval with T2 in at least one left precordial or limb lead. Among the 2,948 control subjects, 0.6% exhibited T2 confined to leads V2 and V3, and 0.9% had T2 involving one or more left precordial lead (but none of the limb leads). Among 37 asymptomatic adult blood relatives with QTc intervals 0.42 to 0.46 s, T2 was found in left precordial or limb leads in 9 (24%; 5 with limb lead involvement) versus only 1.9% of control subjects with a borderline QTc interval (p < 0.0001). CONCLUSIONS: These findings are consistent with the hypothesis that in families with long QT syndrome, T wave humps involving left precordial or (especially) limb leads, even among asymptomatic blood relatives with a borderline QTc interval, suggest the presence of the long QT syndrome trait.

Implantable cardioverter-defibrillator therapy in 300 patients with coronary artery disease presenting exclusively with ventricular fibrillation.

To determine outcomes of implantable cardioverter-defibrillator (ICD) therapy in a uniform population of survivors of sudden cardiac death, we used epicardial defibrillation lead systems to study 300 patients with coronary artery disease (CAD) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Operative (30-day) mortality, 2.7% overall, was lower (0.6%) in patients with ejection fractions (EF) > or = 0.30. Over a median follow-up of 1.9 years, cumulative actuarial shock incidence was similar in patients who underwent concomitant coronary artery bypass graft (CABG) surgery (38%) and in those who did not. The 2-year cumulative actuarial incidences of any or appropriate shocks were 65% and 38%, respectively. Sudden death survival at 2 years was 92.5% and 99.3% for patients with EFs < or = 0.30 and > 0.30, respectively. The total mortality rate was similar in shocked and in unshocked patients. Multivariate analysis identified EF and female gender as significant predictors of any and appropriate shock occurrence (all p values < or = 0.05) and EF as a significant predictor of sudden, cardiac, and total mortality (all p values < 0.03). We conclude that in CAD patients presenting exclusively with VF unassociated with acute myocardial infarction and treated with thoracotomy-requiring ICD therapy: (1) operative (30-day) mortality is minimal for patients with an EF > or = 0.30; (2) device use is high and sudden death rates low regardless of concomitant CABG; (3) low EF is a significant predictor of cumulative shock occurrence and mortality (sudden, cardiac, and total); (4) female gender may be a predictor of shock occurrence; and (5) similar mortalities and low sudden-death rates in shocked and nonshocked ICD patients imply that ICD therapy improves survival in shocked patients to a level observed in comparable patients in whom ventricular tachyarrhythmia does not recur.

Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs.

OBJECTIVE: To test the hypothesis that female prevalence is greater than expected among reported cases of torsades de pointes associated with cardiovascular drugs that prolong cardiac repolarization. DATA SOURCES: A MEDLINE search of the English-language literature for the period of 1980 through 1992, using the terms torsade de pointes, polymorphic ventricular tachycardia, atypical ventricular tachycardia, proarrhythmia, and drug-induced ventricular tachycardia, supplemented by pertinent references (dating back to 1964) from the reviewed articles and by personal communications with researchers involved in this field. STUDY SELECTION: Ninety-three articles were identified describing at least one case of polymorphic ventricular tachycardia (with gender specified) associated with quinidine, procainamide hydrochloride, disopyramide, amiodarone, sotalol hydrochloride, bepridil hydrochloride, or prenylamine. A total of 332 patients were included in the analysis following application of prospectively defined criteria (eg, corrected QT [QTc] interval of 0.45 second or greater while receiving drug). DATA EXTRACTION: Clinical and electrocardiographic descriptors were extracted for analysis. Expected female prevalence for torsades de pointes associated with quinidine, procainamide, disopyramide, and aminodarone was conservatively estimated from gender-specific data reported for antiarrhythmic drug prescriptions in 1986, as derived from the National Disease and Therapeutic Index, a large pharmaceutical database; expected female prevalence for torsades de pointes associated with sotalol, bepridil, and prenylamine was assumed to be 50% or less since these agents are prescribed for male-predominant cardiovascular conditions. RESULTS: Women made up 70% (95% confidence interval, 64% to 75%) of the 332 reported cases of cardiovascular-drug-related torsades de pointes, and a female prevalence exceeding 50% was observed in 20 (83%) of 24 studies having at least four included cases. When analyzed according to various descriptors, women still constituted the majority (range, 51% to 94% of torsades de pointes cases), irrespective of the presence or absence of underlying coronary artery or rheumatic heart disease, left ventricular dysfunction, type of underlying arrhythmia, hypokalemia, hypomagnesemia, bradycardia, concomitant digoxin treatment, or level of QTc at baseline or while receiving drug. When cases of torsades de pointes were analyzed by individual drug, observed female prevalence was always greater than expected, representing a statistically significant difference (P < .05) for all agents except procainamide. CONCLUSIONS: These findings strongly suggest that women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization. The pathophysiological basis for, and therapeutic implications of, this gender disparity should be further investigated.

Effect of ibutilide, a new class III agent, on sustained atrial fibrillation in a canine model of acute ischemia and myocardial dysfunction induced by microembolization.

The effect of ibutilide, a new Class III antiarrhythmic agent, upon acute onset atrial fibrillation was investigated in a closed-chest canine model of acute left ventricular (LV) dysfunction. Twenty-four anesthetized mongrel dogs, mean weight 24.9 +/- 4 kg were subjected to coronary artery microsphere embolization and volume loading, followed by attempted induction of atrial fibrillation (AF) by rapid atrial pacing. Acute ischemic LV dysfunction was successfully induced by embolization in all dogs, and caused significant (P < 0.02) decreases in LV systolic pressure, peak + dp/dt (and -dp/dt), stroke volume, and RR interval; whereas LV end diastolic pressure and QTc significantly increased. Sustained AF (> or = 30 min) was successfully induced in 15 of 24 dogs (62%) and unsustained AF (< 30 min) was induced in the remainder (38%). At 30 minutes after induction of sustained AF, 15 dogs were randomized to intravenous ibutilide (0.15 mg/kg, given as a 0.075 mg/kg bolus, followed by 0.075 mg/kg infusion over 1 hour; n = 7) or placebo (saline; n = 8). There were no statistically significant differences between the ibutilide and the placebo groups with respect to mean LV systolic pressure, LV end diastolic pressure, LV dp/dt, RR interval, or QTc interval during AF prior to infusion. All seven dogs receiving ibutilide converted to sinus rhythm after a median of 3 minutes (range 0.5-26 min), while only three of eight placebo dogs (P < 0.03) converted to sinus rhythm after a median duration of 30 minutes (range 15-60 min) (P < 0.04 for difference in time to conversion).(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome with implantable cardioverter-defibrillator therapy for survivors of ventricular fibrillation secondary to idiopathic dilated cardiomyopathy or coronary artery disease without myocardial infarction.

Patients with idiopathic dilated cardiomyopathy (IDC) constitute a minority among implantable cardioverter-defibrillator (ICD) recipients; how these patients fare versus those with coronary artery disease (CAD) is not well defined, nor is the mechanism of cardiac arrest recurrence, which may involve a more significant role of bradyarrhythmias. A retrospective multicenter study regarding outcome of ICD therapy was conducted in 224 patients with either IDC (n = 69; 31%) or CAD (n = 155; 69%) presenting exclusively with ventricular fibrillation (VF) unassociated with acute myocardial infarction. Patients with IDC were significantly younger (mean age 57 vs 61 years in patients with CAD, p < 0.04) and less male predominant (64 vs 79% in patients with CAD, p < 0.02). There was no significant difference in mean left ventricular ejection fraction (0.27 in IDC patients vs 0.29 in CAD patients), but sustained ventricular tachycardia was induced less often in patients with IDC (21 vs 58% in CAD patients, p < 0.001). Bradycardia pacing, either by an ICD with bradycardia pacing ability or a separate bradycardia pacemaker, was available in only 15% of ICD implantees. During a median follow-up duration of 1.7 years for patients with IDC and 1.9 years for patients with CAD, estimated cumulative event rates were similar for any type shock (2-year incidence of 74% in IDC patients, 69% in CAD patients) as well as for appropriate shock (2-year incidence of 46% in IDC patients, 40% in CAD patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothyroid cardiac tamponade presenting with severe systemic hypertension.

Hemodynamic data are presented which not only depict typical tamponade physiology, but demonstrate that hypotension may not necessarily be present with slow accumulation of pericardial fluid in myxedema patients. This case is unique in that severe hypertension, as part of the presentation of hypothyroid tamponade, has never been reported.

Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter-defibrillator therapy.

OBJECTIVES: This study was undertaken to characterize the outcome of survivors of ventricular fibrillation with no or minimal structural heart disease who received an implantable cardioverter-defibrillator. BACKGROUND: The prognosis among survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities remains unclear. Since the advent of implantable cardioverter-defibrillators, this question takes on added importance. METHODS: This 10-center retrospective study provided information on 28 survivors of ventricular fibrillation (mean age 42 years) with minimal or no structural abnormalities who were treated with an implantable cardioverter-defibrillator. RESULTS: Ventricular tachyarrhythmias (polymorphic in all but one patient) were induced during baseline programmed stimulation in 39% of patients. During a median 30.6-month follow-up period after implantable cardioverter-defibrillator implantation, there were no cardiac deaths and two noncardiac deaths. Sixteen patients experienced 36 shock episodes (total 88 shocks). The majority of shocks were classified as "indeterminate"; one patient received 47 "spurious" shocks during one shock episode and each of four patients received one "appropriate" shock. Ventricular arrhythmias were not inducible in any of these latter four patients. CONCLUSIONS: Survivors of ventricular fibrillation with minimal or no structural cardiac abnormalities receiving an implantable cardioverter-defibrillator have an excellent 3-year survival rate. The occurrence, albeit infrequent, of appropriate implantable cardioverter-defibrillator shocks in this group suggests that these patients have a potential risk of recurrent cardiac arrest whose fatal outcome may be avoided by implantable cardioverter-defibrillator therapy.