Adaptive versus conventional cardiac resynchronization therapy in asian heart failure patients with moderately wide QRS: primary results from the Mid-Q Response randomized trial

Heart failure (HF) patients with reduced ejection fraction (HFrEF), normal atrioventricular (AV) conduction and left bundle branch block (LBBB) respond well to cardiac resynchronization therapy (CRT). While guidelines give the strongest recommendation for patients with a QRS≥150 ms, evidence suggests that those with moderately wide QRS (120-149 ms) may also benefit from CRT. In select patients, including those with moderately wide QRS, adaptive CRT might offer better outcomes than conventional biventricular CRT. Asian HF patients often have moderately wide QRS, but the clinical benefit of adaptive versus conventional CRT in this population is not well-established.

To test the hypothesis that adaptive CRT would increase the proportion of patients with an improved Clinical Composite Score (CCS) at 6 months compared to conventional CRT in Asian HFrEF patients with normal AV conduction, LBBB and moderately wide QRS.

This randomized, multi-center, single-blinded trial enrolled Asian HF patients (between January 2020 and March 2023) receiving optimal medical therapy that had NYHA class II-IV HF symptoms, left ventricular EF ≤35%, PR interval ≤200ms, LBBB, and QRS 120-149 ms. Patients were implanted with a CRT device and 1:1 randomized to receive adaptive CRT or conventional CRT and followed for 12 months. The primary outcome was the proportion of patients with an improved CCS at 6-months. Secondary outcomes were change in NYHA class, hospitalization for worsening HF, and all-cause and cardiovascular (CV) mortality.

A total of 171 Asian HFrEF patients from 8 countries were randomized to adaptive CRT (n=86) or conventional CRT (n=85). Baseline characteristics and medications were similar across therapy arms (Table 1). Mean follow-up was 11.8 and 12.1 months in the adaptive CRT and conventional CRT arms, respectively. The proportion of patients with an improved CCS at 6 months was 77% in the adaptive CRT arm and 80% in the conventional CRT arm (Figure 1; p=0.61). With both CRT therapy arms combined, the CCS at 6 months improved in 78.4% and was unchanged in 12.3%. At 6 months, 67.9% of adaptive CRT and 72.0% of conventional CRT patients had an improved NYHA class relative to baseline (p=0.47), while at 12 months, 79.8% of adaptive CRT and 72.3% of conventional CRT patients had improved (p=0.30). Compared to the conventional CRT arm, at 12 months the adaptive CRT arm had similar rates of HF hospitalization (9.4% v. 11.8%; p=0.64), all-cause mortality (7.1% vs. 5.9%; p=0.78) and CV mortality (3.5% vs. 2.3%; p=0.98).

While adaptive CRT was not superior to conventional CRT, 90.6% of patients across both therapy arms benefited from CRT based on the CCS at 6 months. These findings indicate benefit of CRT in Asian HFrEF patients with normal AV conduction, LBBB, and QRS 120-149ms. A stronger level of recommendation for CRT may be warranted in this patient population.