Diversity of heart failure phenotypes in transthyretin amyloid cardiomyopathy. More than just heart failure with preserved ejection fraction

Ann Med. 2024 Dec;56(1):2418965. doi: 10.1080/07853890.2024.2418965. Epub 2024 Oct 26.

Abstract

Introduction: Current guidelines recommend suspecting transthyretin amyloid cardiomyopathy (ATTR-CM) in patients over 65 years of age with unexplained left ventricular (LV) hypertrophy in a non-dilated LV, heart failure (HF) and preserved ejection fraction (HFpEF), hypertrophic cardiomyopathy or severe aortic stenosis. However, there is evidence indicating a high prevalence of ATTR-CM in other HF phenotypes. As such, this study aimed to characterize the diversity of HF phenotypes of ATTR-CM by examining the LV ejection fraction and LV dilatation using echocardiography.

Methods: This multicentre, retrospective observational study included patients diagnosed with ATTR-CM between 2015-2023. The diagnosis was based on a positive cardiac biopsy or positive bone scintigraphy without monoclonal gammopathy. Echocardiographic measurements were categorized according to LV ejection fraction (LVEF) into HFpEF (LVEF ≥50%), HF with mildly reduced EF (HFmrEF, LVEF 40-49%), and HF with reduced EF (HFrEF, LVEF <40%). LV cavity size was categorized by LV end-diastolic diameter (LVEDD) and volume index (LVEDVi) as normal, moderately increased and severe dilatation.

Results: The study included 135 patients with ATTR-CM (mean age, 78 years; 89% male; 89% wild-type ATTR-CM). Most patients were screened for ATTR-CM because of unexplained HF and increased LV wall thickness (57%). Echocardiography showed LVEF <50% in 60% of the patients, with a significant portion presenting with HFrEF. Patients with LVEF <50% had higher NYHA class and elevated N-terminal pro-B-type natriuretic peptide levels than HFpEF patients. LV dilatation was observed in 43% of the patients, with 10% presenting with both LVEF <50% and severe LV dilatation.

Conclusion: This study revealed significant variability in HF phenotypes among patients with ATTR-CM, from HFpEF without LV dilatation to HFrEF with severe LV dilatation. Relying solely on HFpEF for screening may lead to under-diagnosis. These findings suggest the need for more comprehensive diagnostic criteria beyond echocardiographic measures to improve ATTR-CM detection and management.

Keywords: Echocardiography; Transthyretin cardiac amyloidosis; diagnostic guidelines; heart failure; left ventricular dilatation.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial* / complications
  • Amyloid Neuropathies, Familial* / diagnosis
  • Amyloid Neuropathies, Familial* / physiopathology
  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / diagnostic imaging
  • Cardiomyopathies* / physiopathology
  • Echocardiography*
  • Female
  • Heart Failure* / diagnosis
  • Heart Failure* / physiopathology
  • Humans
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / physiopathology
  • Male
  • Phenotype*
  • Retrospective Studies
  • Stroke Volume*
  • Ventricular Function, Left

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related

Grants and funding

Pfizer and Astra Zeneca provided an unrestricted research grant to Maastricht University Medical Centre. The provider of the research grant had no influence on the study design, data collection, analyses, interpretation of data, or writing of the report.