Clinical response with adaptive CRT algorithm compared with CRT with echocardiography-optimized atrioventricular delay: a retrospective analysis of multicentre trials.

AIMS: Adaptive cardiac resynchronization therapy (aCRT) is a novel algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular (LV) or bi-ventricular (BiV) pacing and optimization of atrioventricular (AV) and inter-ventricular (VV) delays based on periodic measurement of intrinsic conduction. We aimed to compare the clinical response between aCRT and standard CRT in historical trials. METHODS AND RESULTS: The treatment arm of the aCRT trial was compared with a pooled historical control (HC) derived from the CRT arms of four clinical trials (MIRACLE, MIRACLE ICD, PROSPECT, and InSync III Marquis) with respect to the proportion of patients who had an improved clinical composite score (CCS) at the 6-month follow-up. Patients in the HC underwent echocardiography-guided AV optimization after the implant. A propensity score model was used to adjust for 22 potential baseline confounders of the effect of CRT. Patients were stratified into quintiles according to the propensity score and the adjusted absolute treatment effect was obtained by averaging estimates across these quintiles. The propensity score model included 751 patients (aCRT: 266, historical trials: 485). The adjusted absolute difference in percent improved in CCS between the aCRT and HC arms was 11.9% [95% confidence interval (CI): 2.7-19.2%] favouring aCRT. The patients in the aCRT group were significantly more likely to have an improved CCS than the patients in the HC (odds ratio = 1.65, 95% CI: 1.1-2.5). CONCLUSION: The aCRT algorithm may be associated with additional improvement in clinical response compared with historical CRT with echocardiographic AV optimization.

A novel algorithm for individualized cardiac resynchronization therapy: rationale and design of the adaptive cardiac resynchronization therapy trial.

BACKGROUND: The magnitude of benefit of cardiac resynchronization therapy (CRT) varies significantly among its recipients; approximately 30% of CRT patients do not report clinical improvement. Optimization of CRT pacing parameters can further improve cardiac function, both acutely and chronically. Echocardiographic optimization is used in clinical practice, but it is time and resource consuming. In addition, optimal settings at rest may change later with activity or cardiac remodeling. The adaptive CRT (aCRT) algorithm was designed to provide automatic ambulatory adjustment of CRT pacing configuration (left ventricular or biventricular pacing) and device delays based on periodic measurement of electrical conduction intervals. METHODS: The aCRT algorithm is currently undergoing evaluation in a prospective, randomized, double-blinded, worldwide clinical trial. The trial enrolled 522 patients, who satisfied standard clinical indications for a CRT device. Within 2 weeks after the implant, the patients were randomized to aCRT versus echo-optimized biventricular pacing (Echo) settings in 2:1 ratio and followed up at 1-, 3-, 6-, and 12-month postrandomization. The noninferiority primary trial objectives at 6-month postrandomization are to demonstrate that (a) the percentage of aCRT patients who improved in their clinical composite score is at least as high as the percentage of Echo patients; (b) cardiac performance as assessed by echocardiography is similar when using aCRT settings versus echo-optimized settings; and (c) aCRT does not result in inappropriate device settings. First and last patient enrollments occurred in November 2009 and December 2010, respectively. CONCLUSIONS: The safety and efficacy of the aCRT algorithm will be evaluated in this ongoing clinical trial.

Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT trial.

BACKGROUND: Acute studies have suggested that left ventricular pacing (LVP) may have benefits over biventricular pacing (BVP). The adaptive cardiac resynchronization therapy (aCRT) algorithm provides LVP synchronized to produce fusion with the intrinsic activation when the intrinsic atrioventricular (AV) interval is normal. The randomized double-blind adaptive cardiac resynchronization therapy trial demonstrated noninferiority of the aCRT algorithm compared to echocardiography-optimized BVP (control). OBJECTIVE: To examine whether synchronized LVP (sLVP) resulted in better clinical outcomes. METHODS: First, stratification by percent sLVP (%sLVP) and multivariate Cox proportional hazards model was used to assess the relationship between %sLVP and clinical outcomes. Second, outcomes were compared between patients in the aCRT arm (n = 318) and control patients (n = 160) stratified by intrinsic AV interval at randomization. RESULTS: In the aCRT arm, %sLVP ≥50% (n = 142) was independently associated with a decreased risk of death or heart failure hospitalization (hazard ratio 0.49; 95% confidence interval 0.28-0.85; P = .012) compared with %sLVP <50% (n = 172). A greater proportion of patients with %sLVP ≥50% improved in Packer's clinical composite score at 6-month (82% vs. 68%; P = .002) and 12-month (80% vs. 62%; P = .0006) follow-ups compared to controls. In the subgroup with normal AV (n = 241), there was a lower risk of death or heart failure hospitalization (hazard ratio 0.52; 95% confidence interval 0.27-0.98; P = .044) with the aCRT algorithm. A greater proportion of patients in the aCRT arm improved in the clinical composite score at 6-month (81% vs. 69%; P = .041) and 12-month (77% vs. 66%; P = .076) follow-ups compared to controls. CONCLUSIONS: Higher %sLVP was independently associated with superior clinical outcomes. In patients with normal AV conduction, the aCRT algorithm provided mostly sLVP and demonstrated better clinical outcomes compared to echocardiography-optimized BVP.

Investigation of a novel algorithm for synchronized left-ventricular pacing and ambulatory optimization of cardiac resynchronization therapy: results of the adaptive CRT trial.

BACKGROUND: In patients with sinus rhythm and normal atrioventricular conduction, pacing only the left ventricle with appropriate atrioventricular delays can result in superior left ventricular and right ventricular function compared with standard biventricular (BiV) pacing. OBJECTIVE: To evaluate a novel adaptive cardiac resynchronization therapy ((aCRT) algorithm for CRT pacing that provides automatic ambulatory selection between synchronized left ventricular or BiV pacing with dynamic optimization of atrioventricular and interventricular delays. METHODS: Patients (n = 522) indicated for a CRT-defibrillator were randomized to aCRT vs echo-optimized BiV pacing (Echo) in a 2:1 ratio and followed at 1-, 3-, and 6-month postrandomization. RESULTS: The study met all 3 noninferiority primary objectives: (1) the percentage of aCRT patients who improved in their clinical composite score at 6 months was at least as high in the aCRT arm as in the Echo arm (73.6% vs 72.5%, with a noninferiority margin of 12%; P = .0007); (2) aCRT and echo-optimized settings resulted in similar cardiac performance, as demonstrated by a high concordance correlation coefficient between aortic velocity time integrals at aCRT and Echo settings at randomization (concordance correlation coefficient = 0.93; 95% confidence interval 0.91-0.94) and at 6-month postrandomization (concordance correlation coefficient = 0.90; 95% confidence interval 0.87-0.92); and (3) aCRT did not result in inappropriate device settings. There were no significant differences between the arms with respect to heart failure events or ventricular arrhythmia episodes. Secondary end points showed similar benefit, and right-ventricular pacing was reduced by 44% in the aCRT arm. CONCLUSIONS: The aCRT algorithm is safe and at least as effective as BiV pacing with comprehensive echocardiographic optimization.