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

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
• cardiac amyloidosis
• transthyretin
• survival
• arrhythmia

Acknowledgments

Five investigators of this study (G. B-C., E. B-C., I. G-O., A. V-R., and M.G. C-L.) are members of the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV) of the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, Spanish Government.

Disclosure of financial/other conflicts of interest

G. B-C. received travel grants, speaker fees, and a research grant from Pfizer (not related to the present study). E. B-C. received speaker fees from Pfizer.

A reviewer of this manuscript has disclosed speaker fees from Pfizer, Alnylam. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplementary material

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Additional information

Funding

This study was founded by means of a competitive research grant from the Sociedad Gallega de Cardiología (SOGACAR) and an independent research grant from Pfizer (ID number 54963821).