Clinical, genetic, and prognostic implications of illicit drug use in dilated cardiomyopathy
S Stroeks, M Venner, I Cortenraad, N Beelen, S Van Der Crabben, J Ellenbroek, M Hazebroek, S Heymans, J A J VerdonschotAbstract
Background
Dilated cardiomyopathy (DCM) is a major cause of heart failure and heart transplantation, yet its etiology remains heterogeneous. Although illicit drug use has been implicated in myocardial injury, its contribution to disease severity and long-term outcomes in DCM have not been systematically evaluated.
Objectives
To characterize the clinical phenotype, genetic background, and outcomes of patients with illicit drug use an to compare them with DCM patients with no drug use.
Methods
We performed a retrospective analysis of patients with DCM enrolled in our local registry. Illicit drug use prior to or at the time of DCM diagnosis was identified using a combination of manual chart review and automated text mining of electronic medical records with CTcue software, yielding 407 patients with documented drug use status. Baseline clinical, echocardiographic, and genetic data were collected. Outcomes included all-cause mortality, heart failure hospitalization, life-threatening arrhythmia, and heart transplantation, which together constituted the composite major adverse event endpoint. Survival analyses were performed using Kaplan–Meier methods and Cox proportional hazards models adjusted for age and sex.
Results
Illicit drug use was documented in 64 patients with DCM (15.7%). Among these patients, 24 reported use of multiple substances, while single-substance use included marijuana (n=13), cocaine (n=12), amphetamines (n=5), heroin (n=2), and other drugs (n=8). The age of DCM diagnosis was different dependent on the drug substance (p<0.001), with amphetamine users being youngest (30 years [IQR 24–33]). Compared to DCM patients without drug use (n=343), patients with drug use were younger at the age of diagnosis (42 years [IQR 30-52 years] vs. 56 years [IQR 46-66 years], p<0.001), while there were no differences in baseline LVEF and LVEDDi. Genetic testing was performed in 76% of drug use patients and 85% of patients without drug use (p=0.11), where a (likely) pathogenic variant was detected in 18% and 26%, respectively (p=0.29). A significant improvement of LVEF occurred at similar rates in both groups (56% vs. 57%; p=1.0). Drug use was associated with an increased risk of the major adverse events (adjusted HR 3.28, 95% CI 1.88–5.72; p<0.001). In analyses of individual outcomes, drug use was associated with higher risks of all-cause mortality (adjusted HR 3.10, 95% CI 1.67–5.75; p<0.001) and life-threatening arrhythmia (adjusted HR 2.77, 95% CI 1.04–7.35; p=0.041).
Conclusions
Illicit drug use defines a unique subgroup of DCM patients who are younger at presentation and have a genetic yield comparable to other DCM populations. Despite a similar and generally good response to guideline-directed medical therapy, these patients experience a markedly higher risk of mortality and malignant arrhythmias. This study provides novel insights and highlights illicit drug use as an important modifier of disease trajectory.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Hazard ratioFor image description, please refer to the figure legend and surrounding text.