Abstract
Introduction: Sacubitril/valsartan (SV) therapy is currently recommended as first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. Hypothesis: Certain electrocardiographic (ECG) parameters may predict response to SV therapy in HFrEF patients. Methods: Retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (NHYA class II - III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. For P-wave duration (PWD), the reference level was set to <100ms; for the remaining variables, reference levels were set as: (a) the normal range for ECG variables; (b) absence for bundle branch blocks; and (c) the other category for binary variables. Calibration and discriminative performance of the models were also assessed. Results: In the 102 patients studied, PWD 100 - 120ms, PWD >120ms, and QTc >460ms were independently associated with response to SV therapy: OR 18.00 (4.45 - 122.90), 5.00 (1.47 - 20.42), and 3.10 (1.18 - 9.22) respectively. A multivariate logistic regression model including these predictors, and adjusting for pre-therapy LVEF, was both highly selective (area under the ROC curve = .840) and well-calibrated (Hosmer-Lemeshow p = .973). Conclusions: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.
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