Christopher A. Clyne

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.

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.

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.

Electromagnetic Interference (EMI) and Arrhythmic Events in ICD Patients Undergoing Gastrointestinal Procedures

Background: The objective was to determine the effect of electromagnetic interference (EMI) in patients undergoing gastrointestinal endoscopy. The implantable cardioverter‐defibrillator (ICD) is the primary therapeutic modality for patients at risk for sudden cardiac death. One potential problem with ICDs is interactions with electrical devices and medical procedures causing EMI or triggering arrhythmic events. Endoscopy frequently employs electrocautery (EC) for diagnosis and treatment of gastrointestinal diseases. Current guidelines advise inactivating ICDs before any surgical procedure. There is limited information on management of ICDs during endoscopy with or without EC. We prospectively evaluated patients with ICDs undergoing endoscopic procedures at our institution.

The Gender-Paradox among Patients with Implantable Cardioverter-Defibrillators: A Propensity-Matched Study

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.

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.

Evaluation of the Charlson Comorbidity Index to Predict Early Mortality in Implantable Cardioverter Defibrillator Patients

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.

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.

Thermal mapping of right ventricular outflow tract tachycardia.

Background: Acute and long‐term success of catheter ablation of right ventricular outflow tract tachycardia (RVOT VT) may be limited by the inability to reproduce the arrhythmia at the time of activation (AM) and pace mapping (PM). We have observed early initiation of the clinical VT when subtherapeutic radiofrequency (RF) energy was applied to the target area (TA), defined as a 2‐cm2 area around a pace match. We describe a novel approach using thermal mapping (TM) to guide the ablation of RVOT VT.

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.