Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction

• Published in: Journal of electrocardiology 2024-05, Vol.84, p.104-108
• Main Authors: Shpigelman, Jonathan, Blaine, Ciara, Nugent, Carol-Ann, Kiernan, Louise, Cahir, Caitriona, Curtain, Benjamin Mac, Bachari, Amir, Irfan, Wadeed, O'Boyle, Patrick, O'Neill, James, Daly, Michael
• Format: Article
• Language: English
• Subjects: Electrocardiography; Heart failure with reduced ejection fraction; Reverse cardiac remodeling; Sacubitril/valsartan
• ISSN: 0022-0736; 1532-8430; 1532-8430
• DOI: 10.1016/j.jelectrocard.2024.03.008

Sacubitril/valsartan (SV) is currently recommended as a 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. To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association 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-maximal-dose 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. Backward stepwise regression was employed to develop a parsimonious model. P-wave duration (PWD) 100–120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45–122.90), 5.00 (1.47–20.42), and 3.10 (1.18–9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). 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. SV can reverse cardiac remodeling in HFrEF patients; however, not all patients respond to therapy. In our retrospective study of 102 consecutive HFrEF patients, response to SV, i.e., 10% relative improvement in LVEF at 3-months post-maximal-dose therapy, was predicted by indicators of early atrial and ventricular remodeling (prolonged PWD and QTc interval) on the baseline ECG and not by indicators of terminal remodeling (PAF, LBBB, and RBBB). AUROC = area under the receiver operating characteristic curve; BBB = bundle branch block; HFrEF = heart failure with reduced ejection fraction; LAS = left atrial size; LBBB = left bundle branch block; LVEF = left ventricular ejection fraction; LVS = left ventricular size; PAF = permanent atrial fibrillation; PWD = P-wave duration; RBBB = right bundle branch block; SV = sacu