Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure

Study Questions:

Does cardiac resynchronization therapy (CRT) benefit patients with less severe systolic heart failure (HF)?

Methods:

This was a secondary analysis of the REVERSE trial, which evaluated the effect of CRT in patients with New York Heart Association (NYHA) class I/II HF, a left ventricular ejection fraction (LVEF) ≤40%, and QRS ≥120 ms. Patients were subgrouped into moderate (LVEF 30-40%) and severe (LVEF <30%) systolic HF categories. CRT was programed as either CRT-on versus CRT-off. The primary outcome was the percentage of patients at 12 months with a worsened HF composite score (improved, worsened, or unchanged) based on LVEF and CRT on/off.

Results:

Patients with an LVEF >30% (n = 177, 24%) were older, had higher serum creatinines, were more likely NYHA class I, and had shorter QRS durations (147 ± 20 vs. 156 ± 22 ms) than those (n = 254, 76%) with an LVEF ≤30%. At 12 months, there was a nonsignificant trend toward improvement in clinical HF composite score (p = 0.06, trend p = 0.13) in patients with an LVEF >30% with CRT-on versus CRT-off. This difference was significant (p = 0.02) in those with an LVEF ≤30% receiving CRT therapy versus CRT-off. While events (death/heart failure hospitalization) were more common in those with an LVEF ≤30%, time to HF hospitalization or death was reduced with CRT-on in both the LVEF ≤30% (hazard ratio [HR], 0.58; p = 0.047) and LVEF >30% (HR, 0.26; p = 0.012) groups compared to CRT-off. In adjusted analyses of the whole cohort, CRT assignment (on vs. off) was independently associated with improved outcomes (HR, 0.54; p = 0.035). The interaction between CRT and LVEF was not significant (p = 0.27).

Conclusions:

The author concluded that CRT reduces adverse outcomes in both severe and moderate systolic HF.

Perspective:

This secondary analysis of the REVERSE trial suggests that systolic HF patients who are NYHA class I/II with an LVEF <40% benefit from CRT therapy regardless of the severity of LVEF reduction. While significant gains were not made in the clinical composite score (worsening/unchanged), more patients with an LVEF >30% were class I. Thus, there was ‘less to gain’ in this subgroup. Importantly, time to death or HF hospitalization was reduced greatly in the moderate LV dysfunction group. It makes sense that patients who are less ill with wide QRS’s (dyssynchrony) are more likely to gain from CRT. An unanswered question remains: When are patients just too ill to benefit from a trial of CRT? Will a patient who is NYHA class III with an LV internal dimension-diastole (LViDd) of 80 mm benefit?

Keywords: Ventricular Dysfunction, Heart Failure, Hospitalization, Cardiac Resynchronization Therapy


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