Syncope in patients with diagnosed with hypertrophic cardiomyopathy: risk of ventricular tachycardia, cardiac arrest and death
Authors: Zoerner C R , Pallisgaard J P , Schjerning A M , Jensen M K , Toennesen J , Riis-Vestergaard L D , Middelfart C , Rasmussen P V , Gislason G , Hansen M L 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disorder; however, detection rates remain low. While most patients are only mildly symptomatic, some develop serious complications such as heart failure (HF), atrial fibrillation (AF), and sudden cardiac death (SCD). Given the possibility of severe outcome, a large focus is put on early detection and prevention of possible HCM related complications. Syncope has long been one of these factors associated with increased risk of SCD, however little concrete data on the impact and consequences of prior syncope in a large HCM population exist.

Objectives
To determine the risk of ventricular tachycardia (VT), cardiac arrest (CA) and death in patients with HCM and prior history of syncope compared to HCM patients without syncope.

Methods
All patients aged ≥16 years diagnosed with HCM from 2005 - 2018 were identified in the Danish National Registers and included at first time diagnosis. All admissions or prior presentation of syncope were registered and analyzed for the outcome of a combined endpoint comprising occurrence of VT, CA or death. The association between HCM, syncope and the combined endpoint were investigated using multivariable cox proportional-hazard analysis adjusted for gender, age, and comorbidities. Cumulative incidence of the combined endpoint was calculated using the Aalen-Johansen estimator.

Results
In this study 3,856 HCM patients were included (median age 68 years [IQR 56-78]) with near equal gender distribution (males 53%, females 47%). Overall 361 (9%) of patients had a registered contact for syncope prior to HCM diagnosis. A total of 1356 patients (35%) reached the combined endpoint. Of those patients with prior syncope 163 patients (45%) reached the endpoint, compared to 1193 patients (34%) who had no registered syncope prior to HCM diagnosis. Univariate analysis showed a significantly increased risk (HR 1.5 (CI 1.3-1.8) p = &lt;0.001) of patients in the syncope group of VT, CA and death, however in multivariate analysis adjusted for gender, age and comorbidities this difference did not prove significant (HR 1.1 (CI 0.9-1.3) p = 0.35) (Figure 1). Subgroup analysis revealed a striking disparity between male and female HCM patients with prior syncope in their risk of reaching the combined endpoint. Adjusted for age and comorbidities, males were at a significantly increased risk of ventricular tachycardia, cardiac arrest and death (HR 1.6 (CI 1.1-2.2) p = 0.008) (Figure 2).

Conclusion
Although there was a significant increased rate of HCM patients with prior syncope reaching the combined endpoint of ventricular tachycardia, cardiac arrest and death, multivariate analysis showed this association to be mainly driven by comorbidity and age. In this cohort males with prior syncope were at a significantly higher risk of reaching the combined endpoint. More research will be needed to explore this disparity.