Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE)

Abstract

Background: Cardiac resynchronization therapy results in improved ejection fraction in patients with heart failure. We sought to determine whether these effects were mediated by changes in contractility, afterload, or volumes.

Methods and results: In 610 patients with New York Heart Association class I/II heart failure from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study, we performed detailed quantitative echocardiography assessment prior to and following cardiac resynchronization therapy. We derived measures of contractility (the slope [end-systolic elastance] and the volume intercept of the end-systolic pressure-volume relationship, stroke work, and preload recruitable stroke work), measures of arterial load and ventricular-arterial coupling, and measures of chamber size (volume intercept, end-systolic and end-diastolic volumes). At 6 and 12 months, cardiac resynchronization therapy was associated with a reduction in the volume intercept and end-systolic and end-diastolic volumes (P<0.01). There were no consistent effects on end-systolic elastance, stroke work, preload recruitable stroke work, or ventricular-arterial coupling. In the active cardiac resynchronization therapy population, baseline measures of arterial load were associated with the clinical composite score (odds ratio 1.30, 95% CI 1.04 to 1.63, P=0.02). The volume intercept was associated with mortality (hazard ratio 1.90, 95% CI 1.01 to 3.59, P=0.047) and more modestly with the combined end point of mortality or heart failure hospitalization (hazard ratio 1.48, 95% CI 0.8 to 2.25, P=0.06). In contrast, end-systolic elastance, stroke work, preload recruitable stroke work, and ventricular-arterial coupling were not associated with any outcomes.

Conclusion: In patients with NYHA Class I/II heart failure, cardiac resynchronization therapy exerts favorable changes in left ventricular end-systolic and end-diastolic volumes and the volume intercept. The volume intercept may be useful to gain insight into prognosis in heart failure.

Clinical trial registration: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00271154.

Keywords: cardiac resynchronization; echocardiography; heart failure.

Figure 1

Schematic description of these measures of myocardial mechanics. The purple line denotes the end systolic pressure volume relationship (ESPVR), and the Ees represents the slope of the ESPVR. ESP denotes end-systolic pressure, and Ees_sb represents the noninvasively derived single-beat estimation of Ees. LVEDV is the end-diastolic volume, and LVESV is the end-systolic volume. V₀ is the volume intercept of the ESPVR at an end-systolic pressure of 0 mm Hg. Ea represents the negative slope joining the end-systolic pressure-volume point to the point on the volume axis at end-diastole with this line denoted in orange. Stroke work is represented by the gray shaded region of the pressure-volume area. The dashed line within this region is the stroke volume (SV), or the difference between the LVEDV and LVESV. Ea indicates effective arterial elastance; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; SV, stroke volume; V₀, volume intercept.

Figure 2

Changes in echocardiography parameters over 6 and 12 months. Mean values along with 95% CIs are presented according to CRT ON or CRT OFF for Ea, Ees_sb, Ea/Ees_sb, and V₀. The numbers below each figure represent the number of participants in each subgroup (CRT OFF or CRT ON). The most pronounced changes were observed in V₀. CRT indicates cardiac resynchronization therapy; CRT OFF, control group; CRT ON, active group; Ea, effective arterial elastance; Ees_sb, single beat–derived end-systolic elastance; V₀, volume intercept.

Figure 3

Relationship between baseline V₀ and time to first HF hospitalization or death in CRT ON. Kaplan–Meier plots (inverted) describing the relationship between V₀ and time to first heart failure hospitalization or death in CRT ON alone. V₀ expressed as quartiles. Q1 represents V₀<−1.5 mL, Q2 represents −1.5 to 38 ml, Q3 represents 38 to 80.5 mL, and Q4 represents >80.5 mL. CRT indicates cardiac resynchronization therapy; CRT ON, active group; HF, heart failure; Q, quartile; V₀, volume intercept.