Pre-transplant clinical and post-transplant outcomes of patients with a novel mutation in the emerin gene

Abstract

Introduction Different that cardiac pathologies may exhibit different progression towards advanced heart failure (HF).

Recently, a novel mutation c.77T>C (p.Val26Ala) in the gene coding for emerin (a member of the nuclear lamina-associated protein family) has been published. This gene variation has been catalogued as a pathogenic variant for the development of dilated cardiomyopathy, major cardiac events and cardiac transplant (CT).

Aims To explore the prevalence, characteristics and clinical outcomes of CT recipients with familial dilated cardiomyopathy due to the pathogenic variant c.77T>C (p.Val26Ala) in the emerin gene in chromosome Xq28, in a transplant program that receives patients referred from a region with a possible founder effect for that mutation, compared to other cardiomyopathies.

Methods We performed a retrospective, single center, and observational study of all adult patients who underwent CT between November 2019 and December 2023. Patients were classified in three groups: Isquemic cardiomyopathy (ICM), emerin mutation (EME) and other forms of Familiar Cardiomyopathy (FCM).

Results Of 76 patients transplanted, we identified 16 patients (21%) with the EMD gene mutation, 27 patients (45%) with ICM and 17 patients (28%) with FCM.

Compared to patients with ICM and FCM , the EMD group were younger at the time of CT (EMD 50.31± 6.65 vs ICM 57.74 ± 6.61 vs FCM 58.94 ± 8.45 years old, p = 0 002), had lower body mass index (EMD 22.9± 2.87 vs ICM 25.67 ± 3.83 vs FCM 27.5 ± 8.44.285, p = 0 004), were less comorbid, had higher creatin levels (EMD 1.59± 0.42 vs ICM 1.35 ± 0.45 vs FCM 1.18 ± 0.44 mg/dL, p = 0 011), had worse right ventricular function by TAPSE (EMD 11.53. ± 2.64 vs ICM 16.53 ± 4.33 vs FCM 16.81 ± 4.86 mm, p = 0 001), tricuspid s´ (EMD 6.21 ± 1.9 vs ICM 9.11 ± 3.23 vs FCM 9.17 ± 3.39 cm/s´, p = 0 041), and right atrium pressure (EMD 12.75 vs ICM 8.23 vs EMD 12.75 vs FCM 9.76 mmHg, p = 0.042); and had higher grades of tricuspid regurgitation (EMD 2.44 vs ICM 1.38 vs FCM 1.71, p = 0.009).

However, there were no differences in post-CT outcomes in terms of primary graft failure, intubation, acute renal function or renal replacement therapy, intensive care unit and total hospitalization stay, or survival.

Conclusion Patients with p.Val26Ala mutation in the emerin gene was very prevalent in the Canarian CT program. Our data highlights the early onset of disease, disease severity with biventricular dysfunction and worse renal function in these patients. However, after transplantation, outcomes are similar. Future research should focus on larger cohorts and prospective studies to further validate these findings and enhance our understanding of this rare yet impactful condition.