Efficacy and safety of implantable cardioverter-defibrillator implantation in the elderly-The I-70 Study: A randomized clinical trial.

Background: There is conflicting evidence on the efficacy of primary prevention implantable cardioverter-defibrillator (ICD) implantation in the elderly. Objective: The purpose of this study was to determine the efficacy and safety of ICD implantation in patients 70 years and older. Methods: Patients (n = 167) aged 70 years or older and eligible for ICD implantation were randomly assigned (1:1) to receive either optimal medical therapy (OMT) (n = 85) or OMT plus ICD (n = 82). Results: Of the 167 participants (mean age 76.4 years; 165 men), 144 completed the study protocol according to their assigned treatment. Average participant follow-up was 31.5 months. Mortality was similar between the 2 groups: 27 deaths in OMT vs 26 death in ICD (unadjusted hazard ratio 0.92; 95% confidence interval 0.53-1.57), but there was a trend favoring the ICD over the first 36 months of follow-up. Rates of sudden death (7 vs 5; P = .81) and all-cause hospitalization (2.65 events per participant in OMT vs 3.09 in ICD; P = .31) were not statistically significantly different. Eleven participants randomized to ICD received appropriate therapy. Five participants received an inappropriate therapy that included at least 1 ICD shock. Conclusion: The study did not recruit to target sample size, and accumulated data did not show benefit of ICD therapy in patients 70 years or older. Future studies similar in design might be feasible but will need to contend with patient treatment preference given the large number of patients who do not want an ICD implanted. Further research is needed to determine whether the ICD is effective in prolonging life among elderly device candidates.

Health-Related Quality of Life in the Spironolactone to Reduce ICD Therapy (SPIRIT) Trial.

To describe health related quality of life (HRQOL) and symptoms in the SPIRIT trial and determine effects of implantable cardioverter defibrillator (ICD) shocks on HRQOL over 24 months. Ninety participants aged 66 ± 10 years, 96% men, 75% with NYHA class II, with an ICD were randomized to spironolactone 25 mg (N = 44) or placebo (N = 46). HRQOL was measured every 6 months for 24 months using: Patient Concerns Assessment (PCA), Short Form Health Survey-Veterans Version (SF-36V), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Linear mixed modeling compared changes in HRQOL over-time and ANCOVA compared HRQOL between those getting an ICD shock or not. Over 24-months, there were no differences in HRQOL between the spironolactone versus placebo groups. Those with at least one ICD shock reported significantly lower HRQOL and more symptoms at 6- and 24-months. Patients receiving one or more ICD shocks reported significant reductions in HRQOL and higher symptoms.

Adaptive Cardiac Resynchronization Therapy Effect on Electrical Dyssynchrony (aCRT-ELSYNC): A randomized controlled trial.

BACKGROUND: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear. OBJECTIVE: Compare effects of aCRT and conventional CRT on electrical dyssynchrony. METHODS: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times. RESULTS: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V5-V6, conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups. CONCLUSION: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling.

Dexmedetomidine Sedation for Paroxysmal Supraventricular Tachycardia Ablation Is Not Associated With Alteration of Arrhythmia Inducibility.

BACKGROUND: Dexmedetomidine (Dex) is an attractive agent for procedural sedation due to its unique pharmacodynamic profile, specifically affording predictable sedation without concurrent respiratory depression. However, Dex has previously been reported to prevent or terminate arrhythmias. The purpose of this study was to investigate paroxysmal supraventricular tachycardia (PSVT) inducibility and homeostatic stability during electrophysiology studies (EPSs) and ablation when a standardized Dex protocol was used as the primary sedation agent. METHODS: We performed a retrospective review of 163 consecutive procedures for PSVT ablation that received Dex as the primary sedative with adjunct fentanyl and midazolam boluses (DEX-FENT-MIDAZ). This cohort was compared to 163 consecutive control procedures wherein strictly fentanyl and midazolam were used for sedation. The primary outcome reviewed was PSVT inducibility assessed before ablation. Reviewed secondary outcomes included level of sedation and intraprocedure hemodynamics and oxygenation. RESULTS: The arrhythmia profiles of the DEX-FENT-MIDAZ and control cohorts were very similar. The overall incidence of a "negative" EPSs in which arrhythmia was not induced was 24% in the DEX-FENT-MIDAZ group and 26% in the control group (P = .7). Unintended deep sedation was significantly less with DEX-FENT-MIDAZ (4.3% vs 27%; P ≤ .0001). However, DEX-FENT-MIDAZ use was associated with a higher incidence of intraprocedure hypotension. CONCLUSIONS: Dex sedation during EPSs is not associated with a reduction in PSVT inducibility. The therapeutic utility of Dex during EPS arises from the predictable sedation Dex affords but is associated with an increased incidence of intraprocedure hypotension.

Effectiveness of dual external direct current cardioversion for initial cardioversion in atrial fibrillation.

INTRODUCTION: Dual external direct current cardioversion (dual-DCCV) is a rhythm control strategy for persistent atrial fibrillation (AF), involving simultaneous delivery of two shocks from two defibrillators. The long-term effectiveness of this approach has not been studied in the biphasic cardioversion era. METHODS: Seventy-seven consecutive patients at a single center were identified to receive dual-DCCV at the time of their initial cardioversion for AF, when maximum output standard external direct current cardioversion failed in two vectors. Logistic regression was used to analyze risk factors for dual-DCCV in a historical control group of 77 patients undergoing standard cardioversion and Cox proportional hazard models were used to compare time to AF recurrence. RESULTS: The dual-DCCV group had a significantly larger body mass index (BMI), but similar AF duration and left atrial size as controls. Multivariable logistic regression revealed that BMI and absence of prior paroxysmal AF were risk factors for dual-DCCV (P < 0.05). There was no difference observed between dual-DCCV and control groups (adjusted hazard ratio = 0.57; P = .12) after adjusting for number of shocks and age. Transient hypoxia was the only acute complication in either group (P > .999). CONCLUSION: Dual-DCCV appears to be a safe and effective cardioversion strategy for patients with AF. The need for dual-DCCV in the treatment of AF appears to be influenced more by body habitus than atrial substrate.

Outcomes of Telemedicine Video-Conferencing Clinic Versus In-Person Clinic Follow-Up for Implantable Cardioverter-Defibrillator Recipients.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) recipients require close follow-up that can be difficult for patients who have to travel long distances for clinic follow-up. We aimed to compare clinical outcomes between ICD patients followed-up in a telemedicine video-conferencing clinic (TMVC) and a conventional in-person clinic (CIC). We hypothesized that outcomes of patients followed in the TMVC are noninferior to the CIC. METHODS AND RESULTS: This retrospective study compares time to first appropriate ICD therapy, time to first inappropriate ICD therapy, time to first shock, and overall survival in patients followed in TMVC compared with CIC between 2001 and 2016. Two hundred and eighty-seven patients were followed in the TMVC group and 236 patients in the CIC. The average age of the TMVC and CIC groups was 64.13±9.38 and 65.23±8.57 years, respectively (P=0.164). There was no difference in the modified Seattle heart failure model score between the 2 groups (-0.12±1.0 versus -0.21±0.99; P=0.287). The Charlson comorbidity index score was higher in the CIC group compared with the TMVC group (7.0 versus 6.0; P=0.01). Mean duration of follow-up was 4.8 years. Adjusted and unadjusted tests of noninferiority found TMVC was not inferior to in-person follow-up for the prespecified outcomes. CONCLUSIONS: Video-conferencing ICD follow-up for patients in areas where electrophysiology subspecialty care is not available leads to outcomes that are noninferior to CIC follow-up.

The effect of spironolactone on ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators.

BACKGROUND: Previous studies have suggested that aldosterone blockade can reduce the incidence of ventricular tachycardia (VT) or ventricular fibrillation (VF) in patients with heart failure. The SPIronolactone to Reduce ICD Therapy (SPIRIT) trial was designed to test the hypothesis that spironolactone reduces the incidence of VT/VF in patients with implantable cardioverter-defibrillators (ICDs) who are at moderately high risk for recurrent VT/VF. METHODS AND RESULTS: Ninety patients who had ICDs who were at moderately high risk for recurrent VT/VF and who were not candidates for spironolactone by current heart failure guidelines were randomized to receive spironolactone 25 mg daily or placebo in a double-blind fashion. All patients had previously received ICD therapy (shock or antitachycardia pacing) for VT/VF within 2 years of randomization or an ICD for secondary prevention of VT/VF within 6 months of randomization. The primary end point was time to first recurrence of VT/VF requiring ICD therapy. After a median follow-up of 35 months, the Kaplan-Meier probability estimates for VT/VF requiring ICD therapy were 68.7% in the placebo group and 84.7% in the spironolactone group. Compared with placebo, spironolactone was associated with a similar risk of VT/VF (hazard ratio, 1.01; 95% CI, 0.64-1.83; P=0.71). There was no significant difference between the median times to first VT/VF recurrence requiring ICD therapy in the 2 groups. CONCLUSIONS: In patients with ICDs who were at moderately high risk for recurrent VT/VF on account of a recent VT/VF event that was either sustained or treated by the ICD and who were not candidates for spironolactone by current heart failure guidelines, spironolactone did not delay the first recurrence of VT/VF or reduce the risk of recurrent VT/VF.

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial.

CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. PATIENTS: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. INTERVENTION: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.

Enhanced detection of arrhythmia vulnerability using T wave alternans, left ventricular ejection fraction, and programmed ventricular stimulation: a prospective study in subjects with chronic ischemic heart disease.

INTRODUCTION: In previous studies, the prognostic value of T wave alternans (TWA) was similar to that of programmed ventricular stimulation (PVS). However, presently it is unclear if TWA and PVS identify the same patients or provide complementary risk stratification information. In addition, the effects of left ventricular ejection fraction (LVEF) on the prognostic value of TWA are unknown. The aim of this study was to determine if combined assessment of TWA, LVEF, and PVS improves arrhythmia risk stratification. METHODS AND RESULTS: This was a prospective study of 144 patients with coronary artery disease and LVEF < or =40% who were referred for PVS for standard clinical indications. The endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator (ICD) therapy. TWA (hazard ratio 2.2, P = 0.03) and PVS (hazard ratio 1.9, P = 0.05) both were significant predictors of endpoint events, and TWA was the only independent predictor. LVEF markedly influenced the prognostic value of TWA, which was a potent predictor of events in subjects with LVEF between 30% and 40% (event rates: TWA+ 36%, TWA- 0%, P = 0.001) but did not predict events in subjects with LVEF <30% (hazard ratio 1.1, P > 0.5). PVS successfully identified additional low-risk patients within the cohort with negative or indeterminate TWA results (hazard ratio 4.7, P = 0.015) but did not provide incremental prognostic information for TWA+ patients (hazard ratio 0.9, P > 0.5). CONCLUSION: The combined use of TWA, LVEF, and PVS is a promising new approach to arrhythmia risk stratification that permits identification of high-risk and very-low-risk patients.

Exercise is superior to pacing for T wave alternans measurement in subjects with chronic coronary artery disease and left ventricular dysfunction.

INTRODUCTION: T wave alternans (TWA) is a heart rate-dependent marker of vulnerability to ventricular arrhythmias. Atrial pacing and exercise both are used as provocative stimuli to elicit TWA. However, the prognostic value of the two testing methods has not been compared. The aim of this prospective study was to compare the prognostic value of TWA measured during bicycle exercise and atrial pacing in a large cohort of high-risk patients with ischemic heart disease and left ventricular dysfunction. METHODS AND RESULTS: This was a prospective study of 251 patients with coronary artery disease and left ventricular dysfunction who were referred for electrophysiologic studies (EPS) for standard clinical indications. Patients underwent TWA testing using bicycle ergometry (exercise TWA, n = 144) and/or atrial pacing (pacing TWA, n = 178). The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The predictive value of exercise and pacing TWA for EPS results and for endpoint events was determined. Exercise and pacing TWA both were significant predictors of EPS results (odds ratios 3.0 and 2.9 respectively, P < 0.02). Kaplan-Meier survival analysis of the primary endpoint revealed that exercise TWA was a significant predictor of events (hazard ratio 2.2, P = 0.03). In contrast, pacing TWA had no prognostic value for endpoint events (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA should be measured during exercise when it is used for clinical risk stratification. EPS results may not be an adequate surrogate for spontaneous events when evaluating new risk stratification tests.

Influence of QRS duration on the prognostic value of T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising new noninvasive marker of arrhythmia vulnerability that quantifies beat-to-beat changes in ventricular repolarization. Secondary repolarization abnormalities are common in subjects with wide QRS complexes. However, the relationship between TWA and QRS prolongation has not been evaluated. The goal of this study was to determine if QRS prolongation influences the prevalence or prognostic value of TWA. METHODS AND RESULTS: The study consisted of 108 consecutive patients with coronary artery disease and left ventricular ejection fraction < or = 40% who were referred for electrophysiologic studies. Patients underwent TWA testing using bicycle ergometry in the absence of beta-blockers or antiarrhythmic drugs. The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The prognostic value of TWA was assessed in the entire cohort and in two subgroups: QRS < 120 msec (normal, n = 62) and QRS > or = 120 msec (prolonged, n = 46). TWA (hazard ratio 2.2, P = 0.03) and QRS prolongation (hazard ratio 2.2, P = 0.01) were both significant and independent predictors of arrhythmic events. QRS prolongation had no effect on the prevalence of positive TWA tests (QRS < 120 msec: 48%, QRS > or = 120 msec: 50%, P = NS). TWA was a highly significant predictor of events in patients with a normal QRS (hazard ratio 5.8, P = 0.02). In contrast, TWA was not useful for risk stratification in subjects with QRS prolongation (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA is useful only for risk stratification in the absence of QRS prolongation. The presence of QRS prolongation and left ventricular ejection fraction < or = 40% may be sufficient evidence of an adverse prognosis that additional risk stratification is not useful or necessary.

Effects of selective autonomic blockade on T-wave alternans in humans.

BACKGROUND: T-wave alternans (TWA) is an important noninvasive measure of ventricular arrhythmia vulnerability. This study tested the hypothesis that the autonomic nervous system influences TWA measurement in high-risk subjects with coronary artery disease. METHODS AND RESULTS: T-wave alternans was measured in 60 patients with coronary artery disease, left ventricular dysfunction, and inducible sustained ventricular tachycardia during electrophysiological studies. All patients had TWA measured at baseline with atrial pacing at 100 bpm (600 ms), 109 bpm (550 ms), and 120 bpm (500 ms). After a 10-minute recovery period, TWA was measured again after sympathetic blockade (esmolol, n=20), parasympathetic blockade (atropine, n=20), or no intervention (control subjects, n=20). The prevalence of significant TWA was unchanged compared with baseline after atropine infusion and in the control group. In contrast, the amplitude of TWA in the vector magnitude lead was significantly reduced after esmolol infusion (P<0.001), and the number of positive TWA tests was reduced by 50% (70% versus 35%, P<0.05). CONCLUSIONS: Our findings have important implications for the use of TWA to risk-stratify patients for life-threatening ventricular arrhythmias and provide a new potential mechanism for the reduction in sudden cardiac death conferred by beta-blockers among patients with coronary artery disease and congestive heart failure.

Effect of shock polarity on the efficacy of transthoracic atrial defibrillation.

BACKGROUND: The energy requirement for internal ventricular defibrillation is reduced by reversal of shock polarity. The influence of shock polarity on the efficacy of transthoracic atrial defibrillation is unknown. METHODS: This prospective, randomized study enrolled 110 consecutive patients who were referred for elective cardioversion of persistent atrial fibrillation (AF). The electrodes were placed in the anteroposterior position. The patients were randomized to receive either standard (anterior pad = cathode) or reversed polarity (anterior pad = anode) shocks with a damped sinusoidal monophasic waveform. A step-up protocol was used to estimate the cardioversion threshold. The initial shock energy was 50 J, with subsequent increments to 100, 200, 300, and 360 J in the event of cardioversion failure. RESULTS: Sixty-four percent of the patient population were men, with a mean age of 66 +/- 13 years and a mean duration of AF of 242 +/- 556 days. The overall success rates of cardioversion were 84% for standard polarity and 78% for reversed polarity (P not significant). Among the patients who were successfully cardioverted, the mean atrial defibrillation threshold was 198 +/- 103 J for standard polarity and 212 +/- 107 J for reversed polarity (P not significant). CONCLUSIONS: Reversal of shock polarity does not improve transthoracic cardioversion efficacy with a standard damped sinusoidal monophasic waveform. Alternate strategies should be considered for patients who fail external cardioversion, such as adjunctive pharmacologic treatment, use of a biphasic shock waveform, or internal cardioversion.