Sutton, Martin St. John

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 Re synchronization 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: NCT 00271154.

Background The utility of longitudinal, circumferential, and radial strain and strain rate in determining prognosis in chronic heart failure is not well established. Methods and Results In 416 patients with chronic systolic heart failure, we performed speckle‐tracking analyses of left ventricular longitudinal, circumferential, and radial strain and strain rate on archived echocardiography images (30 frames per second). Cox regression models were used to determine the associations between strain and strain rate and risk of all‐cause mortality, cardiac transplantation, and ventricular‐assist device placement. The area under the time‐dependent ROC curve ( AUC ) was also calculated at 1 year and 5 years. Over a maximum follow‐up of 8.9 years, there were 138 events (33.2%). In unadjusted models, all strain and strain rate parameters were associated with adverse outcomes ( P <0.001). In multivariable models, all parameters with the exception of radial strain rate ( P =0.11) remained independently associated, with patients in the lowest tertile of strain or strain rate parameter having a ≈2‐fold increased risk of adverse outcomes compared with the reference group ( P <0.05). Addition of strain to ejection fraction ( EF ) led to a significantly improved AUC at 1 year (0.697 versus 0.633, P =0.032) and 5 years (0.700 versus 0.638, P =0.001). In contrast, strain rate did not provide incremental prognostic value to EF alone. Conclusions Longitudinal and circumferential strain and strain rate, and radial strain are associated with chronic heart failure prognosis. Strain provides incremental value to EF in the prediction of adverse outcomes, and with additional study may be a clinically relevant prognostic tool.

Background— β-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF. Methods and Results— Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol ( r =−0.72, P <0.0001) and was the most significant multivariate predictor of change in LVEF ( P =0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687±333 versus 420±246 pg/mL, P <0.05) and greater decrease in plasma norepinephrine in response to bucindolol (−249±171 versus −35±277 pg/mL, P <0.05). Conclusions— This study suggests a direct relationship between contractile reserve and improvement in LVEF with β-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol.