Prognostic effect and modulation of cardiac sympathetic function in heart failure patients treated with cardiac resynchronization therapy.

BACKGROUND: Cardiac autonomic dysfunction as assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy is associated with poor prognosis in heart failure (HF) patients. Although cardiac resynchronization therapy (CRT) has emerged as an effective therapy in improving outcomes on HF patients, its effect on cardiac sympathetic nervous function is still not fully understood. We aimed to study the value of pre-implantation 123I-mIBG late heart-to-mediastinum ratio (HMR) as a predictor of response and outcomes after CRT and to correlate modification in this parameter with CRT response and functional improvement. METHODS AND RESULTS: BETTER-HF (Benefit of exercise training therapy and cardiac resynchronization in HF patients) is a prospective randomized clinical trial including HF patients submitted CRT (mean LVEF 24 ± 8%, 74% NYHA class ≥ III) who underwent a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. One-hundred and twenty-one patients were included. Echocardiographic response was observed in 54% and composite outcome of cardiac mortality, cardiac transplant or heart failure hospitalization in 24% of patients. Baseline late HMR was an independent predictor of CRT response (regression coefficient 2.906, 95% CI 0.293-3.903, P .029) and outcomes (HR 0.066 95% CI 0.005-0.880, P .040). At follow-up, 123I-mIBG imaging showed positive changes in cardiac sympathetic nerve activity only in responders to CRT (1.36 ± 0.14 prior vs. 1.42 ± 0.16 after CRT, P .039). There was a significant correlation between improvement in late HMR and improvement in peak oxygen consumption (r 0.547, P < .001). CONCLUSION: In our study, baseline cardiac denervation predicted response and clinical outcomes after CRT implantation. Cardiac sympathetic function was improved only in patients who responded to CRT and these positive changes were correlated with improvement in functional capacity.

Impact on long-term cardiovascular outcomes of different cardiac resynchronization therapy response criteria.

INTRODUCTION: There is a lack of consensus on the definition of response to cardiac resynchronization therapy (CRT), and it is not clear which response criteria have most influence on cardiac event-free survival. OBJECTIVES: To assess the predictive value of various response criteria in patients undergoing CRT and the agreement between them. METHODS: We performed a secondary analysis of the BETTER-HF trial. Patient response was classified at six months after CRT according to eleven criteria used in previous trials. The predictive value of response criteria for survival free from mortality, cardiac transplantation and heart failure hospitalization was assessed by Cox regression analysis. Agreement between the different response criteria was assessed using Cohen's kappa (κ). RESULTS: A total of 115 patients were followed for a mean of 25 months. During follow-up, 15 deaths occurred (13%) and 29 patients had at least one adverse cardiac event (25%). Only five of the eleven response criteria were predictors of event-free survival. The most powerful isolated clinical and echocardiographic predictors were a reduction of ≥1 NYHA functional class (HR 0.39 for responders; 95% CI 0.18-0.83, p=0.014) and an increase of at least 15% in left ventricular ejection fraction (HR 0.43, 95% CI 0.20-0.90, p=0.024), respectively. Agreement between the different response criteria was poor. CONCLUSIONS: Most currently used response criteria do not predict clinical outcomes and have poor agreement. It is essential to establish a consensus on the definition of CRT response in order to standardize studies.