Pregnancy and Progression of Cardiomyopathy in Women With LMNA Genotype-Positive.

Background We aimed to assess the association between number of pregnancies and long-term progression of cardiac dysfunction, arrhythmias, and event-free survival in women with pathogenic or likely pathogenic variants of gene encoding for Lamin A/C proteins ( LMNA+). Methods and Results We retrospectively included consecutive women with LMNA+ and recorded pregnancy data. We collected echocardiographic data, occurrence of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, and implantation of cardiac electronic devices (implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator). We analyzed retrospectively complications during pregnancy and the peripartum period. We included 89 women with LMNA+ (28% probands, age 41±16 years), of which 60 had experienced pregnancy. Follow-up time was 5 [interquartile range, 3-9] years. We analyzed 452 repeated echocardiographic examinations. Number of pregnancies was not associated with increased long-term risk of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, or implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator implantation. Women with previous pregnancy and nulliparous women had a similar annual deterioration of left ventricular ejection fraction (-0.5/year versus -0.3/year, P=0.37) and similar increase of left ventricular end-diastolic diameter (0.1/year versus 0.2/year, P=0.09). Number of pregnancies did not decrease survival free from death, left ventricular assist device, or need for cardiac transplantation. Arrhythmias occurred during 9% of pregnancies. No increase in maternal and fetal complications was observed. Conclusions In our cohort of women with LMNA+, pregnancy did not seem associated with long-term adverse disease progression or event-free survival. Likewise, women with LMNA+ generally well-tolerated pregnancy, with a small proportion of patients experiencing arrhythmias.

Ventricular tachycardia in cardiolaminopathy: Characteristics and considerations for device programming.

BACKGROUND: Mutations in LMNA cause an arrhythmogenic cardiomyopathy (cardiolaminopathy) with high risk of ventricular tachycardia (VT). The natural history of VT among patients with cardiolaminopathy is incompletely understood. OBJECTIVE: The purpose of this study was to determine the longitudinal burden and progression of VT, including change in tachycardia cycle length (TCL), response to antitachycardia pacing (ATP), and prognostic significance of high-burden VT (>5 episodes of VT at any device interrogation) in cardiolaminopathy patients. METHODS: Patients with cardiolaminopathy and an implantable cardioverter-defibrillator (ICD) were identified from a single-center database. Serial device interrogations and medical records were used to collect data on VT burden, TCL, and response to ATP. RESULTS: Cardiolaminopathy patients with primary (n = 27) or secondary prevention (n = 16) ICDs were followed for 2 years (interquartile range [IQR] 1-5). VT burden was substantially higher in patients receiving secondary prevention ICDs (28 ± 40.9 vs 3.6 ± 7.3 episodes per 100 patient-years; P <.001). ATP was highly effective (94%) at terminating VT except for short TCL (<250 ms), for which ATP failed in 60%. Among patients with recurrent VT, TCL increased by 112 ± 93.6 ms during follow-up. Inappropriate shocks were rare (0.4% of all therapies). Median time to transplantation, ventricular assist device, or death was 18 months (IQR 0.7-27.1) in patients with high-burden VT. CONCLUSION: In patients with cardiolaminopathy, VT is recurrent and highly responsive to ATP, which supports the use of transvenous ICDs iteratively programmed to manage VT of various TCLs. Onset of high-burden VT indicates poor prognosis and should warrant referral to a heart failure specialist.