Atrial cardiomyopathy by strain predicts atrial fibrillation in young Lamin A/C patients

Abstract Introduction Cardiac laminopathy is a malignant and highly arrhythmogenic form of dilated cardiomyopathy caused by variants in the lamin A/C (LMNA) gene. Atrial fibrillation (AF) is common during disease progression and often occurs at a young age, before evident structural cardiac changes and therefore, decision making on anticoagulation for AF is challenging. Whether atrial cardiomyopathy is present at this early stage of LMNA disease has not yet been explored. Purpose We aimed to evaluate for atrial cardiomyopathy in LMNA genotype positive subjects without prior atrial arrhythmias and assess whether atrial cardiomyopathy would be associated with the occurrence of AF during follow-up. Methods We prospectively recruited LMNA genotype-positive patients in a cohort study. Patients without prior documented atrial arrhythmias were evaluated for atrial cardiomyopathy by echocardiography. Atrial cardiomyopathy was evaluated by left atrial (LA) volume index (LAVI) and LA strain (peak reservoir strain and peak conduit strain). LA strain was assessed by 2D speckle-tracking echocardiography, averaged from apical four- and two-chamber views using a LA strain dedicated software with R-wave at end diastole as zero-reference point. Results We evaluated 129 LMNA genotype positive patients (51% women, age 40±15 years), of whom 57 patients (44%) had previous AF. Hence, we included 72 patients (32±14 years old, 49% female, left ventricular ejection fraction 53±11%) for assessment of atrial cardiomyopathy. The mean LA reservoir strain was 35±14%, conduit strain 25±13% and LAVI 38±23 ml/m2. During 7.7±5.0 years of follow-up, 28 (39%) patients developed AF after a median of 2.2 years. Patients with AF during follow-up had larger LAVI (47±30 vs. 32±10ml/m2, p=0.01) and worse LA reservoir strain (29±12% vs. 38±14%, p=0.02) at baseline than those who did not develop AF. LA reservoir strain and LAVI at baseline were both predictors of AF during short-term follow-up (HR 0.95 [CI 0.90-0.99], p=0.025 and HR 1.02 [CI 1.01-1.03], p=0.009, respectively), whereas LA conduit strain was not (HR 0.98 [CI 0.94-1.03], p=0.45). ROC analysis identified LA reservoir strain better than 32.5% as the best discriminating value for survival free of AF (log rank p=0.05) (Figure). Conclusion Atrial cardiomyopathy was common in LMNA genotype positive patients without previous atrial arrhythmias. LA volume and and LA reservoir strain predicted new onset AF during follow-up and may be used as markers for detecting short term risk of AF and potentially guide anticoagulation treatment in LMNA disease.LA reservoir strain and AF in LaminA/C