Females with DSP variants had higher right ventricular LGE (30% vs 8.3%; p=0.042) and heart failure occurrence (21% vs 6.7%; p=0.041), but pregnancy and autoimmune disease did not affect diagnosis.
Do pregnancy and autoimmune disease impact the diagnosis of cardiomyopathy in individuals carrying desmoplakin (DSP) likely pathogenic/pathogenic variants?
In individuals with DSP-related cardiomyopathy, female sex is associated with a higher occurrence of heart failure and RV LGE, but pregnancy and autoimmune disease do not appear to trigger or impact the diagnosis of DCM/ARVC.
Absolute Event Rate: 0% vs 0%
Abstract Introduction Desmoplakin (DSP)-related cardiomyopathy is characterized by a high risk for heart failure (HF) and sustained ventricular arrhythmias (VA), which are predisposed by ‘hot-like’ phases resembling myocarditis(1). Although the disease has an autosomal dominant inheritance pattern, recent literature reports a female predominance in DSP (likely) pathogenic (LP/P) variant carriership (1.7:1)(1) with female sex also being a risk factor for developing VA(1). We hypothesize that this female predominance is caused by pregnancies and/or concomitant autoimmune disease as triggers for diagnosis. Purpose To determine clinical differences in presentation between female and male carriers with LP/P variants, and to assess the impact of pregnancies and auto-immune disease on development of cardiomyopathy and adverse outcomes. Methods We retrospectively collected clinical data of individuals with LP/P DSP variants from two centers. ECG, Holter monitoring, and imaging studies including cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) were reviewed to assess cardiac phenotype. Diagnosis was defined as dilated cardiomyopathy (DCM) per 2023 ESC cardiomyopathy guidelines(2) and arrhythmogenic right ventricular cardiomyopathy (ARVC) as per 2010 Task Force Criteria(3). In addition, information on the number of pregnancies and presence of auto-immune disease was collected. HF was defined as NYHA=2; VA was defined as sustained ventricular arrhythmia with hemodynamic compromise and/or requiring cardioversion. Impact of pregnancy and autoimmune diseases on diagnosis was analysed through a Kaplan-Meier curve with log rank-rank test. Results We included 112 individuals (56% female, female-male 1.29:1, 44.9 ±20.9 years,n=36 probands) with a LP/P DSP variant. LV LGE was comparable between females and males (LV LGE n=16(53.3%) vs n=12(50.0%); p=0.694, respectively), whereas RV LGE was higher in females (n=9 (30.0%) vs n=2(8.3%); p=0.042). Occurrence of VA (n=10(16.1%) vs n=11(24.4%); p=0.312) and hot-like myocarditis episodes (n=4(6.5%) vs n=3(6.7%); p=1.000) were comparable between sexes. Nonetheless, females had a significantly higher occurrence of HF compared to males (n=13(21.0%) vs n=3(6.7%);p=0.041). Fulfillment of diagnosis at follow-up was comparable between females and males (n=31(50.0%) vs n=18 (40%)). There were no females with auto-immune disease compared to two males(4.1%). Information on childbearing history was available for 47 females (74.6%) of which 37(78.7%) experienced pregnancy (median 2 pregnancies per female). Pregnancies and auto-immune disease had no significant impact on diagnosis in life-time survival analysis (p=0.542;p=0.261 respectively). Conclusion Female predominance in DSP-cardiomyopathy is observed at a 1.29:1 ratio. Presence of RV LGE and occurrence of HF is higher in females. Pregnancy and auto-immune disease do not seem to impact DCM/ARVC diagnosis in individuals carrying DSP LP/P variants.Table 1:clinical presentation of DSP Figure 1:KM curve pregnancy-diagnosis
Salavati et al. (Sat,) reported a other. Females with DSP variants had higher right ventricular LGE (30% vs 8.3%; p=0.042) and heart failure occurrence (21% vs 6.7%; p=0.041), but pregnancy and autoimmune disease did not affect diagnosis.