Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial

Abstract

Background: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive.

Methods: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband.

Results: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90).

Conclusions: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT03037632.

Keywords: cardiomyopathy; dilated; health communication; randomized controlled trial.

Figure 1.

Study flow diagram.

Figure 2.. Effectiveness of Family Heart Talk overall and by race-ethnicity group.

Odds ratios comparing the Family Heart Talk arm to the control arm given proband site-race-ethnicity randomization stratum, sex, and enrollment age quartile were obtained from a GEE-type GLMM with the logit link fit to binary outcome data from eligible first-degree relatives (enrolled and unenrolled) using residual subject-specific pseudolikelihood. The linear predictor included a two-level normal random effects structure (proband site and self-identified race-ethnicity stratum within site) and fixed effects for self-identified race-ethnicity stratum to account for stratified randomization. Fixed effects for proband sex and enrollment age quartile, which were expected a priori to affect the outcome, were also pre-specified in the statistical analysis plan to improve power. Residual correlation between outcomes of first-degree relatives of each proband was addressed by assuming a compound symmetric conditional variance matrix for the outcomes among first-degree relatives of the same proband and no conditional correlation between the outcomes of first-degree relatives of different probands. Bias-corrected robust standard errors were obtained using the Morel-Bokossa-Neerchal correction with sites as independent units, and one-sided Wald 95% confidence intervals were calculated using the standard normal distribution. Except for the overall effects, confidence intervals have not been adjusted for multiplicity and should not be used to infer statistical significance. P-values calculated from this model included a one-sided Wald test for the null hypothesis that the odds ratio between the Family Heart Talk and control arms was ≤1 and a two-sided Wald p-value for the null hypothesis of no interaction between race-ethnicity stratum and the intervention effect. Detailed information on the model fits contributing to this figure is provided in Tables S2 – S5.