Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT.

OBJECTIVE: The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality. METHODS: Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up. RESULTS: The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks. CONCLUSION: In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy. Clinical trials.gov identifier: NCT00180271.

The prognostic impact of pre-implantation hyponatremia on morbidity and mortality among patients with left ventricular dysfunction and implantable cardioverter-defibrillators.

AIMS: Hyponatremia is commonly observed among patients with left ventricular (LV) dysfunction and is a marker for adverse outcomes. We aimed to determine the prognostic significance of pre-implant hyponatremia on the outcomes of death, acute decompensated heart failure (ADHF) and appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmias among patients with ICDs. METHODS AND RESULTS: The study population consisted of patients with an ejection fraction ≤40% undergoing ICD implantation (n = 911) for the primary or secondary prevention of sudden cardiac death from 1997 to 2007. The predictive value of the severity of pre-implantation hyponatremia stratified into mild hyponatremia (n = 268, sodium 134-136 mmol/L), moderate hyponatremia (n = 105, sodium 131-133 mmol/L), and severe hyponatremia (n = 31, sodium ≤130 mmol/L) on the risk of death, ADHF, and appropriate ICD therapy for ventricular arrhythmias as compared with patients a normal serum sodium (n = 507, sodium ≥ 137 mmol/L), was calculated using multivariable Cox proportional hazards analyses. During a mean follow-up of 775 ± 750 days as the severity of hyponatremia (from a normal sodium to severe hyponatremia) increased an incremental incidence of death (25% to 61%, P < 0.001) and ADHF (11% to 26%, P = 0.004) was observed with a reduced incidence of ICD therapy for ventricular tachycardia/ventricular fibrillation (37-29%, P = 0.037). Compared with the normal sodium cohort, patients with severe hyponatremia demonstrated an increased risk of death [adjusted hazard ratio (AHR) 2.69 (95% confidence interval, CI 1.57-4.59), P = 0.004] and ADHF [AHR 2.98 (95% CI 1.41-6.30), P = 0.004], with a lower probability of appropriate ICD therapy [AHR 0.68 (95% CI 0.27-0.88), P = 0.031]. CONCLUSION: Hyponatremia is commonly observed among ICD recipients with LV dysfunction. Patients with an increasing severity of hyponatremia are at increased risk of death and HF related morbidity with a reduced incidence of appropriate ICD therapy particularly among patients with severe hyponatremia.

Prognostic impact of thyroid stimulating hormone levels in patients with cardiomyopathy.

BACKGROUND: Thyroid stimulating hormone (TSH) abnormalities have been associated with various cardiac arrhythmias. Effect of TSH abnormalities on mortality and implantable cardioverter defibrillators (ICD) behavior in patients with cardiomyopathy has not been investigated. METHODS: Our ICD database includes 1,445 patients between December 1997 and January 2008. TSH levels using the ultra sensitive assay were available in 371 patients. Patients were classified based on TSH levels as: High TSH (N = 102, TSH > 5) and Low TSH (N = 26, TSH < 0.4). TSH groups were compared for mortality, appropriate and inappropriate ICD therapies. RESULTS: A high or low TSH was an independent predictor of all-cause mortality: Hazard ratio (HR) 1.46 (95% CI 1.03-2.08), P = 0.033 and HR 1.76 (95% confidence interval 1.02-3.03), P = 0.043 respectively. TSH abnormalities were not associated with an increased incidence in appropriate or inappropriate ICD therapy. CONCLUSION: A low or high TSH was associated with a higher mortality; however, neither were associated with appropriate or inappropriate ICD therapy after multivariate analysis. Univariate analysis demonstrated an association of high TSH and appropriate ICD therapy. However, multivariate analysis did not show this association. Therefore, we are concluding that TSH levels are predictors of all-cause mortality but not ICD therapy.

Evaluation of the Charlson comorbidity index to predict early mortality in implantable cardioverter defibrillator patients.

BACKGROUND: Current guidelines consider the implantation of an implantable cardioverter defibrillator (ICD) a class III indication in patients with a life expectancy of <1 year. An evaluation of concomitant noncardiac conditions may identify patients whom may not derive benefit with ICD therapy. We sought to evaluate the association of the Charlson comorbidity index (CCI) on the prediction of early mortality (EM), death <1 year after ICD implant. METHODS: The study population consisted of patients (n = 1062) undergoing ICD implantation for the primary or secondary prevention of sudden cardiac death from 1997 to 2007. The predictive value of the CCI on the risk of EM and appropriate shock therapy for ventricular arrhythmias as compared to patients without EM after ICD implant was calculated using multivariable Cox proportional hazards and receiver operator analyses. RESULTS: Patients experiencing EM (n = 110) demonstrated higher CCI scores (mean 2.8 ± 1.3 vs 1.5 ± 1.2, P < 0.001) as compared to individuals without EM (n = 963). Among patients with a CCI of 0, 1, 2, 3, 4, and ≥5, the incidence of EM increased from 5% to 78%. The CCI was an independent predictor of EM (AHR 1.4 [95% CI 1.2-1.6], P < 0.001, per single score increase). Patients who experienced EM demonstrated a decreased incidence of appropriate ICD therapy when compared to patients without EM (AHR 0.4 [95% CI 0.2-0.7], P = 0.001). CONCLUSION: Noncardiac conditions are commonly observed among patients undergoing ICD implantation. Guidelines must incorporate a comprehensive assessment of concomitant comorbidities to minimize the risk of EM and to maximize the survival benefit with ICD therapy.

Predictors of pacemaker dependence and pacemaker dependence as a predictor of mortality in patients with implantable cardioverter defibrillator.

BACKGROUND: The prevalence, predictors, and survival for the development of pacemaker dependence (PD) in patients implanted with an implantable cardioverter defibrillator (ICD) are unknown. METHODS: This was a retrospective analysis of 1,550 consecutive patients with ICD implantation at a single center from 1996 to 2008 with a mean of 4.2 ± 3.4 years. Patients with implant intrinsic heart rates less than 40 beats/min (n = 48) and cardiac resynchronization therapy (n = 444) were excluded leaving 1,058 patients in this study. PD was defined as an intrinsic rhythm <40 beats/min after inhibiting the pacemaker, <50 beats/min with transient symptoms of dizziness relieved by resumption of pacing and right ventricle pacing despite algorithms to promote intrinsic conduction at the 3 monthly follow-up ICD clinic visits. Multivariate regression and Cox proportional hazard models were used for analysis. RESULTS: The mean age was 64 ± 13 years; 79% were male with a primary indication for the ICD in 57%. PD occurred in 142 (13.4%) of patients, with a mean time to PD of 2.6 ± 1.9 years. PD was associated with a 48% increased odds for mortality versus non-PD ICD patients during the mean follow-up time of 4.2 ± 3.4 years (adjusted odds ratio = 1.48 [95% confidence interval 1.080-2.042]; P = 0.015). Older age, a history of atrial fibrillation, amiodarone use, and secondary prevention were the strongest predictors for the development of PD. CONCLUSIONS: In this single-center ICD cohort, the development of PD was not uncommon and was associated with decreased survival.

The gender-paradox among patients with implantable cardioverter-defibrillators: a propensity-matched study.

BACKGROUND: Several meta-analyses of the implantable cardioverter-defibrillator (ICD) clinical trials have demonstrated that while men derived a mortality reduction with prophylactic ICD implantation, women did not. These trials also observed that women receive less appropriate ICD shock therapy compared to men. We aimed to investigate this "gender-paradox" among a heterogeneous community cohort of patients receiving ICDs. METHODS: We identified 1,445 consecutive patients undergoing ICD implantation from 1997 to 2007. The study population consisted of 582 patients, of whom 291 were women who could be propensity matched to 291 men, based on age, ejection fraction, implantation indication (primary or secondary), etiology of cardiomyopathy (ischemic or nonischemic), and the presence of a cardiac resynchronization therapy-defibrillator (CRT-D) device. The impact of gender difference on the probability of death and appropriate ICD shocks for ventricular arrhythmias was calculated using multivariable Cox proportional hazards analyses. RESULTS: During a mean follow-up of 909 ± 901 days, compared to men, women demonstrated a similar risk of death (25% vs 25%, adjusted hazard ratio [AHR] 1.05 [95% confidence interval (CI) 0.81-1.35], P = 0.74). In contrast, women demonstrated a decreased probability of appropriate ICD-shock therapy (14% vs 19%, AHR 0.80 [95% CI 0.59-0.88], P = 0.03) compared to men, and among cohorts with a nonischemic cardiomyopathy (10% vs 20%, P < 0.001) and CRT-D devices (7% vs 19%, P = 0.01). CONCLUSION: Among a community cohort with ICDs, women have a similar mortality compared to men while experiencing less appropriate ICD therapy. These results support the findings of a lower arrhythmic mortality among women.

Frequency of inappropriate therapy in patients implanted with dual- versus single-chamber ICD devices in the ICD arm of MADIT-CRT.

BACKGROUND: The majority of implantable cardioverter defibrillators (ICDs) are dual-chamber devices, but studies on the frequency of inappropriate therapy in dual- versus single-chamber devices have shown conflicting results. The aim of this study is to determine whether implantation of dual-chamber ICD devices decrease the incidence of inappropriate therapy without an unacceptable increase in complications. METHODS: In the ICD arm of the MADIT-CRT study (N = 704), comparisons of single- versus dual-chamber ICD devices were investigated on the endpoints of inappropriate therapy (antitachycardia pacing [ATP] and shocks) and device- and procedure-related complications by use of multivariate Cox proportional hazard regression analysis (hazard ratio dual:single chamber) adjusting for relevant covariates. RESULTS: The frequency of inappropriate therapies in single- and dual-chamber recipients was 41/294 (14%) and 50/410 (12%), respectively. There was no significant difference in overall inappropriate therapy (hazard ratio [HR] = 0.95 [CI: 0.63-1.45], P = 0.95) or inappropriate ATP (HR = 0.98 [CI: 0.61-1.58], P = 0.94), between single- and dual-chamber devices, using single-chamber as a reference (Dual:Single). However, there was a trend toward a decrease in inappropriate shocks (HR = 0.60 [CI: 0.34-1.08], P = 0.09) in the dual-chamber group. The same was evident when only analyzing inappropriate therapy for atrial tachyarrhythmias (HR = 0.88 [CI: 0.56-1.38], P = 0.58). There was no significant difference between the groups in device- or procedure-related complications (HR = 1.54 [CI: 0.82-2.90], P = 0.18). CONCLUSION: No significant difference was found in inappropriate therapy or complications in patients treated with single- versus dual-chamber ICD devices.

Bidirectional ventricular tachycardia due to coronary allograft vasculopathy a unique presentation.

Bidirectional ventricular tachycardia (BVT) is an uncommon type of polymorphic ventricular tachycardia (PVT) with alternating polarity of the QRS complex most commonly described digitalis toxicity. Recent data has demonstrated the possible molecular basis of this electrocardiographic phenomenon. To our knowledge this is the first reported case of BVT in a patient with orthotopic cardiac transplantation and coronary allograft vasculopathy.

CRT-D Therapy in Patients with Decompensated NYHA Class-Four CHF.

Background. ACC-HRS Guidelines for Cardiac Resynchronization Therapy ICD implantation (CRT-D) do not include patients with advanced nonambulatory NYHA class-four CHF due to an expectation of limited survival. There is little data available from these large multicenter randomized studies to support or refute this claim. Purpose. We evaluated the outcomes of patients with advanced nonambulatory NYHA class-four CHF who received CRT-D devices as an attempt to improve the clinical status and promote hospital discharge. Methods. Sixteen (of our six hundred and seventy CRT-D patients) were classified as advanced nonambulatory NYHA Class four inotrope/vasodilator/diuretic-dependent patients. These patients were analyzed retrospectively for weaning success to oral medications, hospital discharge, hemodynamic stability, and survival over eighteen months. Results. Thirteen of sixteen patients were discharged to home within two weeks of implantation. The survival to hospital discharge, as well as at six, twelve, and eighteen months was positive (ninety-four percent, seventy-five percent, sixty-nine percent, sixty-nine percent, resp.). The groups showed significant improvements in systolic blood pressure, renal function, left ventricular ejection fraction, and CHF class. Conclusion. CRT-D in advanced nonambulatory NYHA four patients proved feasible and beneficial. These findings suggest that the strategy merits further study.

Pharmacologic and nonpharmacologic thromboprophylactic strategies in atrial fibrillation.

Stroke prevention in atrial fibrillation (SPAF) has traditionally been confined to aspirin and warfarin therapy. Based on CHADS2 scoring it was clearly delineated when aspirin and warfarin would be used in individual patients, but many patients had to forgo recommended therapy due to contraindications or adverse events. There has recently been a paradigm shift in SPAF, with new and promising options on the horizon. These emerging strategies include dual antiplatelet therapy, direct thrombin inhibition, factor Xa inhibition and mechanical prophylaxis therapy. With each of these aforementioned approaches there are moderate to large clinical trials that assess the comparative effectiveness of these approaches in direct comparative trials. From an Ovid MEDLINE search from 1950 to present, we systematically identified 15 randomized trials comparing two thromboprophylactic drugs, devices or procedures for SPAF. Specific mechanical, pharmacologic and pharmacokinetic advantages and disadvantages are also reviewed.

IntravenousCorticosteroid Use Is Associated With Reduced Early Recurrence of Atrial Fibrillation Immediately Following Radiofrequency Catheter Ablation.

Background: Early recurrence of atrial fibrillation (ERAF) occurs in up to 40% of patients after radiofrequency catheter ablation for atrial fibrillation (RFCA), increasing hospital stay, need for anti-arrhythmic medications (AADs) and cardioversion, and, possibly, the risk of future AF. It has been postulated that inflammation plays a key role in developing ERAF. Short term postoperative use of corticosteroids to reduce ERAF post-RFCA has not been vigorously studied. Methods: This was a case-control study of consecutive patients undergoing RFCA for the management of AF at a single-institution. RFCA was performed by a single operator from October 2005 through July 2009. Patients receiving intravenous corticosteroids immediately following the ablation and for 48 hours (6 doses) constituted the treatment group. Controls received no intravenous corticosteroids during their hospitalization. All other management strategies were similar between the 2 groups, including the administration of AADs post- operatively. All patients had continuous electrocardiographic monitoring throughout their hospitalization. Multivariable logistic regression analysis was used to determine the impact of intravenous corticosteroids on ERAF defined as any AF>10 minutes during hospitalization. Results: A total of 68 patients undergoing RFCA for the management of AF were included in this analysis. The overall ERAF rate, irrespective of intravenous corticosteroid use, was 23.5%. The administration of intravenous corticosteroids (n=37; mean±SD dexamethasone mean dose 11.9±4.6 mg/day; range 4-16 mg/day) was associated with an 82% reduction in patients' odds of ERAF (adjusted odds ratio; 0.18, 95% confidence interval [CI] 0.04 to 0.78) compared with those who did not receive corticosteroids (n=31). A dose-response effect was also observed, with a 17% reduction in ERAF odds for each dexamethasone mg-equivalent administered (adjusted odds ratio; 0.83, 95%CI 0.73 to 0.96). Conclusions: The use of intravenous corticosteroids was associated with a dose-dependent reduction in the odds of developing ERAF after RFCA for the management of AF.

The prognostic impact of shocks for clinical and induced arrhythmias on morbidity and mortality among patients with implantable cardioverter-defibrillators.

BACKGROUND: Recent investigations have demonstrated that the occurrence of implantable cardioverter-defibrillator (ICD) shocks is associated with adverse long-term outcomes. These studies have emphasized that the risk is most reasonably due to arrhythmias rather than to the shock itself. We sought to compare the impact of shock delivery for induced ventricular arrhythmias during implantation defibrillation threshold testing and noninvasive electrophysiology study (NIPS) to clinical shocks on long-term outcomes among patients with ICDs. METHODS: This was a cohort evaluation of 1,372 patients undergoing ICD implantation at a tertiary hospital from December 1997 to January 2007. The probability of all-cause mortality and hospitalization for acute decompensated heart failure (ADHF) was evaluated based upon the type of ICD shock received using multivariable Cox proportional analyses. The four shock types analyzed were implantation shocks only (n = 694), additional NIPS shocks only (n = 319), additional appropriate shocks only (n = 128), or additional inappropriate shocks only (n = 104). RESULTS: The risk of death (adjusted hazard ratio [AHR] 0.91 [95% confidence interval (CI) 0.69-1.20]; P = .491) or ADHF (AHR 0.71 [95% CI 0.46-1.16]; P = .277) were similar between recipients of NIPS shocks and recipients of implantation shocks. Receiving an appropriate ICD shock increased the risk of death (AHR 2.09 [95% CI 1.38-2.69]; P <.001) and ADHF (AHR 2.40 [95% CI 1.51-3.81]; P <.002) as compared with implantation shocks and also increased the risk of death (AHR 2.61 [95% CI 1.86-3.67]; P <.001) and ADHF (AHR 2.29 [95% CI 1.33-3.97]; P = .003) as compared with NIPS shocks. CONCLUSIONS: ICD shocks delivered during induced ventricular arrhythmias at the time of NIPS testing does not increase the risk of death or ADHF as compared with recipients of appropriate ICD shocks. The occurrence of spontaneous arrhythmias in vulnerable substrates may explain the increased risk.

Coronary sinus shocking lead as salvage in patients with advanced CHF and high defibrillation thresholds.

BACKGROUND: We report a series of three patients whose implantable cardioverter-defibrillators (ICD) implants were unsuccessful due to inability to achieve defibrillation thresholds (DFT) at maximum available energy after failure of standard modification and enhancement procedures. All patients had advanced cardiomyopathy. METHODS: Use of the coronary sinus (CS) for left ventricular (LV) shocking electrode placement resulted in acceptable DFTs in each patient. The position of the shocking coil in all three patients was posterior, and in two patients alongside a left ventricular CS pacing lead. The best shocking configuration tested was LV (CS) + CAN (Anode) to RV (cathode) in each patient. The short- and long-term outcomes of these patients is presented and discussed. CONCLUSION: This approach is suggested as a salvage option for those problematic patients who have unacceptable DFT results at implantation of an endovascular ICD system.

Comparison of single and double vein approaches for His bundle ablation and pacemaker placement for symptomatic rapid atrial fibrillation.

BACKGROUND: His Bundle ablation (HBA) with permanent pacemaker (PPM) implantation is an effective strategy for controlling heart rate in symptomatic patients with rapid atrial fibrillation (AF), resistant to pharmacologic therapy. The standard double vein (DV) approach involves mapping and HBA from a femoral approach to achieve complete heart block (CHB), while single chamber (SC), dual chamber (DC), or biventricular (BiV) PPM is then placed via a subclavian approach. METHODS: We compared 7 patients with drug-resistant rapid AF who underwent the standard DV approach to 8 patients who underwent a single vein (SV) approach, in which HBA and PPM implantation were performed through the subclavian vein. The two groups were compared for acute success in creating CHB, total procedure and fluoroscopy times and patient discomfort. Results are expressed as mean +/- standard error (SEM). RESULTS: The procedure times for the SV versus DV were 70.4 +/- 11.4 v 100.0 +/- 19.2 min, and the fluoroscopy times, 13.9 +/- 3.1 (SV) v 13.0 +/- 2.9 (DV). All patients were discharged in stable condition with CHB and SC, DC pacemaker or BiV/Implantable Cardioverter Defibrillator (ICD). CHB with symptomatic improvement was maintained in all patients over a mean follow-up period of 22.6 months (SV), and 9.6 months (DV). CONCLUSION: The SV approach for HBA combined with PPM implantation was at least as effective and may be more efficient than the classic DV approach, and should be considered as an alternative to DV technique to reduce procedural time and patient discomfort.

Impact of magnesium sulfate on serum magnesium concentrations and intracellular electrolyte concentrations among patients undergoing radio frequency catheter ablation.

BACKGROUND: We evaluated the impact of intravenous magnesium on intracellular magnesium (iMg) and serum magnesium (sMg) in patients undergoing radio frequency catheter ablation (RFCA) for atrial fibrillation (AF). METHOD: Patients with AF received 4g intravenous magnesium sulfate or normal saline in a randomized, double-blinded fashion. Venous blood and buccal cells were collected for evaluation of sMg and iMg at baseline, postinfusion, at the end of ablation procedure and six-hours posttherapy. RESULTS: All subjects (n = 18) had baseline sMg within normal range but iMg concentrations below normal in 89% of subjects. Baseline sMg and iMg concentrations were similar between groups. After infusion, the magnesium group had significantly higher sMg concentration than the placebo group over the six hours. In contrast, iMg concentrations were significantly higher than placebo immediately after the infusion (P = 0.007) but not at the end of RFCA or six-hours postinfusion (P = 0.187 and P = 0.267). CONCLUSION: iMg deficiencies exist despite normal sMg concentrations in patients undergoing RFCA. Intravenous magnesium sulfate corrects iMg deficiencies immediately postinfusion.

A comparison of outcomes for patients receiving implantable cardioverter defibrillators for primary vs secondary-prevention.

OBJECTIVE: Compare characteristics and outcomes of patients receiving implantable cardioverter defibrillators (ICDs) for primary vs secondary cardiac arrest prevention. METHODS: Patients in this cohort study were identified from a prospectively collected ICD database from June 1999 to August 2003 and divided into groups based on whether they received their ICD for primary or secondary-prevention of cardiac arrest. Patient follow-up continued until August of 2006 and the occurrence of appropriate ICD shocks, inappropriate ICD shocks, and mortality were compared between groups. RESULTS: Of the 437 patients, 80.8% were male, 70.3% had coronary disease, and the mean age was 65.7+/-13.1 years. At baseline, primary-prevention patients had lower left ventricular ejection fraction (LVEF), use of a single chamber device and utilization of beta blockers and antiarrhythmics while having a greater use of biventricular pacing as compared to secondary-prevention patients. Over the first 12 months after implantation, the primary-prevention group was 43.0% less likely to receive an appropriate shock for ventricular arrhythmias (P=0.002) and 34.2% less likely to have an appropriate shock over the entire follow-up period (P=0.018). The incidence of inappropriate ICD shocks over the first 12 months after implantation and over the entire follow-up period was similar between groups (P=0.900 and P=0.217, respectively) as was mortality (P=0.228 and P=0.757, respectively). CONCLUSIONS: Primary-prevention patients are characteristically different in numerous ways from secondary-prevention patients, but despite having a greater risk of experiencing appropriate shocks, exhibit a similar risk of inappropriate shocks and mortality over an average follow-up time exceeding 41 months.

Association between statin therapy and reductions in atrial fibrillation or flutter and inappropriate shock therapy.

AIMS: In patients without implantable cardioverter defibrillators (ICDs), statins have been shown to reduce the incidence of atrial fibrillation and atrial flutter (AF/AFL). We sought to determine if statin therapy could reduce the occurrence of AF/AFL with rapid ventricular rates with and without inappropriate shock therapy among a large heterogeneous ICD cohort. METHODS AND RESULTS: We prospectively followed 1445 consecutive patients receiving an ICD for the primary (n = 833) or secondary (n = 612) prevention from December 1997 through January 2007. Outcome measures include incidence of AF/AFL that initiated ICD therapy or was detected during ICD interrogation. Cox hazard regression analyses were conducted to determine the predictors of AF/AFL with and without inappropriate shock delivery and did not include inappropriate shocks resulting from lead dysfunction or other exogenous factors. Patients in this study (n = 1445) were followed over a mean follow-up period of (mean +/- SD) 874 +/- 805 days. There were 563 episodes of AF/AFL detected, with 200 episodes resulting in inappropriate shock therapy. Overall, 745 patients received statin therapy and 700 did not. The use of statin therapy was associated with an adjusted hazard ratio of 0.472 [95% confidence interval (CI), 0.349-0.638, P < 0.001] for the development of AF/AFL with shock therapy and 0.613 (95% CI, 0.496-0.758, P < 0.001) without shock therapy when compared with the group without statin use. CONCLUSION: Among a cohort with ICDs at high risk for cardiac arrhythmias, statin therapy was associated with a reduction in AF/AFL tachyarrhythmia detection and inappropriate shock therapy.

Association between statin use and mortality in patients with implantable cardioverter-defibrillators and left ventricular systolic dysfunction.

BACKGROUND: A few previous nested cohort trials have evaluated the use of statins on survival and the occurrence of ventricular tachycardia or fibrillation (VT/VF). While the studies generally agreed on the survival effects, they disagreed on the magnitude of the mortality benefit and on the effect on VT/VF. OBJECTIVE: The purpose of this study was to determine in a large, long-term follow-up cohort whether statin therapy could reduce mortality and the occurrence of VT/VF in a mixed population receiving an implantable cardioverter-defibrillator (ICD) for primary or secondary prevention and either ischemic or nonischemic cardiomyopathy. METHODS: Cohort evaluation of all patients undergoing implantation of an ICD with a left ventricular ejection fraction <40% at an urban U.S. teaching hospital from December 1997 through January 2007. Multivariable analysis of predictors of mortality and VT/VF were conducted. RESULTS: There were 314 deaths among the 1204 patients (26.1%). The use of statin therapy (n = 642) was associated with an adjusted hazard ratio of 0.67 (95% confidence interval [CI] 0.53-0.85; P<.001) for mortality as compared with the no-statin group (n = 562). The use of statin therapy was not associated with a reduction in the adjusted hazard ratio for VT/VF (0.85; 95% CI 0.68-1.06; P = .14). CONCLUSIONS: Statin therapy is associated with a reduction in overall mortality in patients with ischemic or nonischemic cardiomyopathy with an ICD implanted for either primary or secondary prevention. The magnitude of survival benefit might have been underestimated given our inability to use statin as a time-dependent covariate.

The impact of carvedilol on the defibrillation threshold.

BACKGROUND: Defibrillation threshold (DFT) is the minimum energy required to successfully terminate ventricular fibrillation. Epinephrine has been shown to increase the DFT in the beta-blocker naïve, but using cardioselective beta-blockers leads to a reduction in the DFT on infusion of epinephrine and norepinephrine. We sought to determine the impact of carvedilol therapy on the DFT after infusion of epinephrine and norepinephrine. METHODS: DFT was determined in patients receiving carvedilol by the step-down method (baseline DFT), and then patients (n = 27, 67.3 years, 70.0% were male, average left ventricular ejection fraction = 19%) were randomized to a 7-minute infusion of norepinephrine, epinephrine, or placebo in a double-blind manner. After the study drug infusion, DFT testing was repeated (experimental DFT) and results were compared between groups. RESULTS: No differences in intragroup DFTs were observed among carvedilol-treated patients receiving norepinephrine (9.4 +/- 4.6 J vs 11.1 +/- 7.8 J; P = .589), epinephrine (10.6 +/- 5.3 J vs 9.8 +/- 6.3 J; P = .779), or placebo (11.1 +/- 7.0 vs 8.5 +/- 4.2; P = .349). CONCLUSIONS: Carvedilol prevents alterations in DFT produced by stress levels of catecholamines.