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

J Electrocardiol. 2024 May-Jun:84:104-108. doi: 10.1016/j.jelectrocard.2024.03.008. Epub 2024 Mar 26.

Abstract

Background: 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.

Aims: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients.

Methods: 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.

Results: 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).

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.

Keywords: Electrocardiography; Heart failure with reduced ejection fraction; Reverse cardiac remodeling; Sacubitril/valsartan.

MeSH terms

  • Aged
  • Aminobutyrates* / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds*
  • Drug Combinations*
  • Electrocardiography*
  • Female
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Registries
  • Retrospective Studies
  • Stroke Volume*
  • Tetrazoles / therapeutic use
  • Treatment Outcome
  • Valsartan* / therapeutic use

Substances

  • Valsartan
  • Aminobutyrates
  • Biphenyl Compounds
  • sacubitril and valsartan sodium hydrate drug combination
  • Drug Combinations
  • Angiotensin Receptor Antagonists
  • Tetrazoles