Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives
- Cardiovascular screening (history, exam, ECG, TTE) of first-degree relatives of patients with dilated cardiomyopathy (familial and nonfamilial) results in over 14% of relatives being diagnosed with LV enlargement and/or LV systolic dysfunction.
- This finding was consistent across racial/ethnic groups and sex.
- Most new diagnoses occur when the proband had positive genetic results, though a small number of cases occurred when proband genetic testing was benign.
What is the value of clinical screening among reportedly unaffected first-degree relatives (FDRs) of patients (probands) with dilated cardiomyopathy (DCM)?
The DCM Precision Medicine Study was conducted at 25 sites between 2016 and 2021. The study enrolled 1,223 patients with DCM (probands) and 1,781 FDRs of the probands. Enrollment of Black and Hispanic probands was emphasized. Enrollment included probands with nonfamilial DCM as well as their FDRs to assess the value of clinical screening in reportedly unaffected FDRs. Clinical screening included a history and examination, transthoracic echocardiogram (TTE), and electrocardiogram (ECG).
In this analysis of the DCM Precision Medicine Study, adult probands and their adult FDRs without known DCM (left ventricular systolic dysfunction [LVSD] defined by an ejection fraction <50% and left ventricular enlargement [LVE] defined an internal diastolic dimension >95th percentile for age and sex) or a DCM partial phenotype (LVSD only or LVE only) at time of enrollment were included.
The group analyzed included 735 probands and 1,365 FDRs. The probands were 45.9% female sex, 34.1% non-Hispanic Black, and 8.8% Hispanic. Probands carried a pathogenic (P)/likely pathogenic (LP) variant in 143 (19.5%) of cases and a variant of uncertain significance (VUS) in 309 (42.2%) cases. The FDRs were a mean age of 44.8 years (standard deviation = 16.9), 61.7% female sex, 27.5% non-Hispanic Black, and 9.8% Hispanic.
Of the 1,365 FDRs undergoing clinical screening, 193 (14.1%) had a new diagnosis of DCM or a partial DCM phenotype. Of these, there were 29 FDRs with DCM (2.1%), 115 with LVE only (8.4%), and 49 with LVSD only (3.6%). Few ECG abnormalities were noted. A new diagnosis was more likely in the 45- to 64-year-old age group (3.6%) than 18- to 44-year-old group (1.4%). After adjusting for age, a new diagnosis was more likely among FDRs with hypertension (HTN 20.0% vs. no HTN 11.8%; 95% confidence interval [CI], 3.3%-13.3% for difference) and obesity (obesity 18.3% vs. no obesity 10.5%; 95% CI, 4.4%-11.2% for difference). No differences in new diagnoses were noted between racial and ethnic groups (16.2% Hispanic, 15.2% non-Hispanic Black, 13.1% non-Hispanic White) or by sex (14.6% female, 12.8% male). New DCM diagnoses were more likely when probands of the FDRs had a P/LP/VUS genetic variant for DCM rather than benign genetic results. Three FDRs were diagnosed with DCM when the proband’s genetic testing was benign.
Cardiovascular screening among FDRs of patients with DCM identified new cases of DCM or partial DCM phenotypes in over 14% of cases.
Understanding the risk for FDRs of patients with DCM in developing future cardiomyopathy or detecting asymptomatic disease is important. Prior studies assessing clinical screening in FDRs have been limited by smaller study size, single-center designs, limited representation of diverse patient populations, and limited data on screen in nonfamilial DCM patients. This study helps to address some of these limitations and provide reassurance of the value of clinical screening, even when genetic data may not be available. Higher rates of new DCM or DCM phenotype diagnoses were seen in patients with HTN and obesity, suggesting that traditional cardiovascular risk factors may play an important role in those with a possible genetic predisposition. Also important to note is that rates of new DCM diagnoses were not different by sex or racial and ethnic groups studied. While this study was limited to advanced heart failure centers and not all FDRs were enrolled in the screening process, these findings were largely consistent with prior work. Overall, the results here add to our understanding of best strategies for DCM clinically and demonstrate value across many populations.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Genetic Arrhythmic Conditions, Acute Heart Failure, Echocardiography/Ultrasound, Hypertension
Keywords: Cardiomyopathy, Dilated, Diagnostic Imaging, Echocardiography, Electrocardiography, Genetics, Heart Failure, Hypertension, Hypertrophy, Left Ventricular, Obesity, Phenotype, Physical Examination, Secondary Prevention, Stroke Volume, Ventricular Dysfunction, Left
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