Syncope in patients with transthyretin amyloid cardiomyopathy: clinical features and outcomes

Postgrad Med. 2022 May;134(4):420-428. doi: 10.1080/00325481.2022.2054174. Epub 2022 Mar 23.

Abstract

Background: We aimed to describe the clinical characteristics, underlying causes and outcomes of syncope in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

Methods: The clinical profile and underlying causes of syncopal episodes were reviewed in a cohort of 128 patients with ATTR-CM enrolled from January 2018 to June 2020 in a prospective multicentre registry in 7 hospitals of Galicia (Spain). After enrollment, patients were followed during a median period of 520 days. The effect of syncope on all-cause mortality was assessed by means of multivariate Cox´s regression.

Results: Thirty (23.4%) patients had a history of previous syncope as a clinical antecedent before being enrolled in the prospective phase of the registry, and 4 (3.1%) experienced a first episode of syncope thereafter. The estimated incidence density rate of syncope during the prospective follow-up period after registry enrollment was 71.9 episodes per 1000 patients-year (95% Confidence Interval (CI) 32.8-111.1). The estimated overall prevalence of syncope was 26.6% (95% CI 18.9%-34.2%). Cardiac arrhythmias (n = 11, 32.3%), structural diseases of the heart or great vessels (n = 5, 14.7%), a neurally mediated reflex (n = 6, 17.6%), and orthostatic hypotension (n = 4, 11.8%) were identified as probable underlying causes of syncope; in 8 (23.6%) patients, syncope remained unexplained. Patients with syncope had increased non-adjusted all-cause mortality than patients without it (univariate hazard-ratio 3.37; 95% CI 1.43-7.94). When other independent predictors of survival were added to the survival model, this association was no longer statistically significant (multivariate hazard-ratio 1.81, 95% CI 0.67-4.84).

Conclusions: Syncope is frequent in patients with ATTR-CM. This study could not demonstrate an independent association between syncope and mortality in those individuals.Abbreviations: ATTR-CM: Transthyretin amyloid cardiomyopathy; CI: Confidence Interval; HF: Heart Failure; HR: Hazard Ratio; IQR: Interquartile rank; LVEF: Left Ventricular Ejection Fraction; NTproBNP: N-terminal pro-brain natriuretic peptide; SD: Standard Deviation; 99mTc-DPD: technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid.

Keywords: Syncope; arrhythmia; cardiac amyloidosis; survival; transthyretin.

MeSH terms

  • Amyloid Neuropathies, Familial* / complications
  • Cardiomyopathies* / complications
  • Humans
  • Prealbumin
  • Prospective Studies
  • Stroke Volume
  • Syncope* / diagnosis
  • Syncope* / drug therapy
  • Syncope* / etiology
  • Ventricular Function, Left

Substances

  • Prealbumin

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related