Patrick Yong

Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias

OBJECTIVES This study was conducted to assess the safety and effectiveness of cardiac resynchronization therapy (CRT) when combined with an implantable cardioverter defibrillator (ICD). BACKGROUND Long-term outcome of CRT was measured in patients with symptomatic heart failure (HF), intraventricular conduction delay, and malignant ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) requiring therapy from an ICD. METHODS Patients (n = 490) were implanted with a device capable of providing both CRT and ICD therapy and randomized to CRT (n = 245) or control (no CRT, n = 245) for up to six months. The primary end point was progression of HF, defined as all-cause mortality, hospitalization for HF, and VT/VF requiring device intervention. Secondary end points included peak oxygen consumption (VO(2)), 6-min walk (6 MW), New York Heart Association (NYHA) class, quality of life (QOL), and echocardiographic analysis. RESULTS A 15% reduction in HF progression was observed, but this was statistically insignificant (p = 0.35). The CRT, however, significantly improved peak VO(2) (0.8 ml/kg/min vs. 0.0 ml/kg/min, p = 0.030) and 6 MW (35 m vs. 15 m, p = 0.043). Changes in NYHA class (p = 0.10) and QOL (p = 0.40) were not statistically significant. The CRT demonstrated significant reductions in ventricular dimensions (left ventricular internal diameter in diastole = -3.4 mm vs. -0.3 mm, p < 0.001 and left ventricular internal diameter in systole = -4.0 mm vs. -0.7 mm, p < 0.001) and improvement in left ventricular ejection fraction (5.1% vs. 2.8%, p = 0.020). A subgroup of patients with advanced HF (NYHA class III/IV) consistently demonstrated improvement across all functional status end points. CONCLUSIONS The CRT improved functional status in patients indicated for an ICD who also have symptomatic HF and intraventricular conduction delay.

Effects of Cardiac Resynchronization Therapy With or Without a Defibrillator on Survival and Hospitalizations in Patients With New York Heart Association Class IV Heart Failure

Background— Cardiac resynchronization therapy (CRT) alone or combined with an implantable defibrillator (CRT-D) has been shown to improve exercise capacity and quality of life and to reduce heart failure (HF) hospitalizations and mortality in patients with New York Heart Association (NYHA) class III and IV HF. There is concern that the device procedure may destabilize these very ill class IV patients. We sought to examine the outcomes of NYHA class IV patients enrolled in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial to assess the potential benefits of CRT and CRT-D. Methods and Results— The COMPANION trial randomized 1520 patients with NYHA class III and IV HF to optimal medical therapy, CRT, or CRT-D. In the class IV patients (n=217), the primary end point of time to death or hospitalization for any cause was significantly improved by both CRT (hazard ratio [HR], 0.64; 95% CI, 0.43 to 0.94; P=0.02) and CRT-D (HR, 0.62; 95% CI, 0.42 to 0.90; P=0.01). Time to all-cause death and HF hospitalization was also significantly improved in both CRT (HR, 0.57; 95% CI, 0.37 to 0.87; P=0.01) and CRT-D (HR, 0.49; 95% CI, 0.32 to 0.75; P=0.001) Time to all-cause death trended to an improvement in both CRT (HR, 0.67; 95% CI, 0.41 to 1.10; P=0.11) and CRT-D (HR, 0.63; 95% CI, 0.39 to 1.03; P=0.06). Time to sudden death appeared to be significantly reduced in the CRT-D group (HR, 0.27; 95% CI, 0.08 to 0.90; P=0.03). There was a nonsignificant reduction in time to HF deaths for both CRT (HR, 0.68; 95% CI, 0.34 to 1.37; P=0.28) and CRT-D (HR, 0.79; 95% CI, 0.41 to 1.52; P=0.48). Conclusions— CRT and CRT-D significantly improve time to all-cause mortality and hospitalizations in NYHA class IV patients, with a trend for improved mortality. These devices should be considered in ambulatory NYHA class IV HF patients similar to those enrolled in COMPANION.

Cardiac Resynchronization Therapy Reduces the Risk of Hospitalizations in Patients With Advanced Heart Failure Results From the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) Trial

Background— In the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial, 1520 patients with advanced heart failure were assigned in a 1:2:2 ratio to optimal pharmacological therapy or optimal pharmacological therapy plus cardiac resynchronization therapy (CRT-P) or CRT with defibrillator (CRT-D). Use of CRT-P and CRT-D was associated with a significant reduction in combined risk of death or all-cause hospitalizations. Because mortality also was significantly reduced (optimal pharmacological therapy versus CRT-D only), an assessment of the true reduction in hospitalization rates must consider the competing risk of death and varying follow-up times. Methods and Results— To overcome the challenges of comparing treatment groups, we used a nonparametric test of right-censored recurrent events that accounts for multiple hospital admissions, differential follow-up time between treatment groups, and death as a competing risk. An end-point committee adjudicated and classified all hospitalizations. Compared with optimal pharmacological therapy, CRT-P and CRT-D were associated with a 21% and 25% reduction in all-cause, 34% and 37% reduction in cardiac, and 44% and 41% reduction in heart failure hospital admissions per patient-year of follow-up, respectively. Similar reductions were seen in hospitalization days per patient-year. The reduction in hospitalization rate for heart failure in the CRT groups appeared within days of randomization and remained sustained. Noncardiac hospitalization rates were not different between groups. Conclusion— Use of CRT with or without a defibrillator in advanced heart failure patients was associated with marked reductions in all-cause, cardiac, and heart failure hospitalization rates in an analysis that accounted for the competing risk of mortality and unequal follow-up time.

Influence of Left Ventricular Lead Location on Outcomes in the COMPANION Study

Introduction: There are no randomized controlled trial data that evaluate mortality and hospitalization rates in cardiac resynchronization therapy (CRT) recipients based on left ventricular (LV) lead location. We analyzed the event‐driven outcomes of mortality and hospitalization as well as functional outcomes including Functional Class, Quality‐of‐Life, and 6‐minute walk distance in 1,520 patients enrolled in the COMPANION study of CRT versus optimal medical therapy.

Impact of Biventricular Pacing on Mortality in a Randomized Crossover Study of Patients with Heart Failure and Ventricular Arrhythmias

Biventricular (BV) pacing is under clinical investigation for the treatment of heart failure. Its impact on mortality is unknown. Patients with heart failure and ventricular tachyarrhythmias received an implantable cardioverter defibrillator with BV pacing capability. Patients were randomized 1:1 to BV pacing or no pacing, then crossed over to the alternate mode after 3 months. All‐cause mortality was measured in each arm up to the point of crossover. Fifteen of 222 patients died between implant and crossover. Five patients died while programmed to BV pacing and 19 died while programmed to no pacing. Survival in the BV pacing arm was 93 ± 4% versus 86 ± 6% in the no pacing arm (P = 0.18). In a patient population with symptomatic heart failure and ventricular arrhythmias, BV pacing does not appear to be associated with excess mortality. Larger and longer studies will be needed to determine if BV pacing confers a survival benefit.

Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study.

BACKGROUND A total of 405 participants in the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were prospectively enrolled in an exercise sub-study designed to study the influence of cardiac resynchronization therapy (CRT) on measures of exercise capacity, functional capacity, and quality of life (QOL). METHODS AND RESULTS Substudy eligibility included New York Heart Association (NYHA) functional Class III or IV heart failure, left ventricular ejection fraction < or =0.35, QRS interval of > or =120 ms, normal sinus rhythm, a heart failure hospitalization (or equivalent) within 1 year, a peak VO2 < or =22 mL x kg x min, the ability to walk 150 to 425 meters in 6 minutes, forced expiratory volume in 1 second/forced vital capacity > or =50%, and no clinical indication for a pacemaker or implantable cardioverter-defibrillator. Patients were randomized in a 1:4 ratio to optimal medical therapy (OPT) or to OPT plus CRT. Cardiopulmonary exercise testing (peak VO2 and 6-minute walk distance [6MWD]) and assessment of NYHA functional class and QOL were assessed at baseline and at 3 and 6 months of assigned therapy. There was no significant improvement in peak VO2 at 6 months in the CRT group compared with the OPT group (+0.63 mL x kg x min) by unadjusted analysis (P = .05) or by analyses adjusted for missing data. Thus the primary end point of the study was not met. There was significantly greater improvement in the 6MWD in the CRT group compared with the OPT group at both 3 and 6 months by both statistical methods (P < or = .045). Likewise, a greater proportion of CRT patients improved by 1 or more NYHA functional classes (P < .01) at 3 months and had better QOL scores (P < .01) at 3 and 6 months compared with the OPT patients. Baseline peak VO2 predicted clinical events (time to death, time to death or first hospitalization, or time to death and first heart failure hospitalization: P < .05) in CRT participants. CONCLUSION CRT patients with moderate to advanced symptoms of systolic heart failure and prolonged QRS intervals benefit from the addition of CRT to OPT in terms of exercise capacity, functional status, and QOL. CRT should be considered standard therapy in this select group of heart failure patients.

Defibrillation Energy Requirements in an ICD Population Receiving Cardiac Resynchronization Therapy

Objectives: While defibrillation energy requirements (DERs) have been extensively studied in patients receiving conventional defibrillators, the DERs of patients receiving cardiac resynchronization therapy with defibrillation capability (CRT‐D) devices have not been well described. The purpose of this analysis was to characterize DERs (defined as true threshold or the presence of appropriate safety margins) in patients undergoing implant of a CRT‐D and to determine whether DERs in this population were similar to those reported for patients undergoing implantation of conventional defibrillators.

Does cardiac resynchronization therapy provide unrecognized benefit in patients with prolonged PR intervals? The impact of restoring atrioventricular synchrony: An analysis from the COMPANION Trial

BACKGROUND The influence of PR prolongation on outcomes after cardiac resynchronization therapy (CRT) is uncertain. OBJECTIVE To determine whether PR prolongation predicts outcomes in potential CRT candidates and whether CRT benefits these candidates regardless of baseline PR interval. METHODS A database of 1520 patients fulfilling criteria for CRT implant (the COMPANION Trial) was examined. Patients assigned to normal (PR < 200 ms) or prolonged (PR ≥ 200 ms) cohorts were compared within the optimal pharmacologic therapy (OPT) and CRT groups regarding an endpoint of all-cause mortality or heart failure hospitalization. CRT was compared with OPT in normal and prolonged PR interval groups. An interaction test was performed to determine whether CRT influenced outcome as a function of PR interval. RESULTS PR prolongation was present in 52% of COMPANION subjects. Randomization to CRT was associated with a reduction in the endpoint, but the strength of the association was greater for those with prolonged PR (hazard ratio = 0.54; P <.01) versus normal PR (hazard ratio = 0.71; P = .02) intervals. CRT (vs OPT) was associated with reduction in the endpoint for subjects with normal or prolonged PR intervals. Reduction in relative risk (CRT vs OPT) was 29% (P = .02) for those with normal PR intervals but was 46% (P <.01) for those with PR prolongation. No interaction was detected between PR interval cohort and treatment (P = .17). CONCLUSIONS PR prolongation may affect mortality and heart failure hospitalizations in patients with systolic dysfunction, heart failure, and wide QRS complexes. The effect of PR prolongation may be attenuated by CRT.

Predictors of Appropriate Defibrillator Therapy Among Patients with an Implantable Defibrillator That Delivers Cardiac Resynchronization Therapy

Introduction: The purpose of this study was to determine predictors of appropriate implantable defibrillator (ICD) therapy among patients with heart failure who are treated with a cardiac resynchronization therapy‐defibrillator (CRT‐D).

Performance of a new steroid-eluting coronary sinus lead designed for left ventricular pacing.

The Ventak CHF/CONTAK CD Biventricular Pacing Study is a prospective randomized trial to examine the safety and efficacy of biventricular (BV) pacing in patients with standard indications for an ICD, symptomatic heart failure, a LVEF ≤ 0.35, and a QRS ≥ 120 ms. Patients underwent implantation of a BV pacing and sensing system with backup defibrillation capability, which includes a steroideluting coronary venous lead that is advanced into the coronary venous vasculature by over‐the‐wire techniques. LV pacing threshold, BV impedance, and BV R wave amplitude were measured in 58 consecutive patients. Using a percutaneous over‐the‐wire insertion technique, steroid‐eluting coronary venous leads were associated with satisfactory mean LV pacing threshold, BV impedance, and BV R wave amplitude acutely up to 4 months after implantation. Pacing threshold stabilized 2 weeks after lead implantation and sensing threshold remained stable from the time of implant.