Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON-HF study

Eur J Heart Fail. 2024 Apr;26(4):871-881. doi: 10.1002/ejhf.3167. Epub 2024 Feb 18.

Abstract

Aims: Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population.

Methods and results: We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS <16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02-1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction >0.1).

Conclusions: In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF.

Keywords: Heart failure with preserved ejection fraction; Prognosis; Strain.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminobutyrates / therapeutic use
  • Angiotensin Receptor Antagonists / therapeutic use
  • Biphenyl Compounds
  • Drug Combinations
  • Echocardiography* / methods
  • Female
  • Heart Failure* / complications
  • Heart Failure* / physiopathology
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology
  • Hospitalization* / statistics & numerical data
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prognosis
  • Stroke Volume* / physiology
  • Tetrazoles / therapeutic use
  • Valsartan* / therapeutic use
  • Ventricular Dysfunction, Left* / physiopathology

Substances

  • Valsartan
  • Aminobutyrates
  • Biphenyl Compounds
  • sacubitril and valsartan sodium hydrate drug combination
  • Tetrazoles
  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • Angiotensin Receptor Antagonists
  • pro-brain natriuretic peptide (1-76)
  • Drug Combinations