4792Late gadolinium enhancement and arrhythmic risk prediction in patients with LMNA-related cardiomyopathy: results from a long-term follow-up multicenter study

Abstract

Background: Cardiomyopathy (CMP) in carriers of LMNA gene mutations is associated with risk of malignant ventricular arrhythmias (MVA). Small studies have shown that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) may predict an adverse outcome. However, long‐term follow‐up (FU) studies are lacking, so that arrhythmic risk prediction is still a challenge in these patients. Purpose: We conducted a multicenter study to prospectively analyse a cohort of patients with LMNA‐CMP, to assess CMR role in predicting occurrence of MVA at 9y FU. Methods: We analysed 41 LMNA+ patients (mean age 43+/‐17 y; 51% males) from three centers of the Italian Network of Laminopathies (NIL). All of the patients underwent baseline CMR with LGE sequences. When indicated, an ICD was implanted. Patients were followed for 9+/‐4 years by 2/y ECG, 24h‐Holter monitoring and (when applicable) ICD interrogation. MVA were defined including sustained ventricular tachycardia, ventricular fibrillation or appropriate ICD shock. Results: Biventricular end‐diastolic volumes and ejection fraction at baseline CMR were: LVEDV 137+/‐45 mL, LVEF 55+/‐9%, RVEDV 115+/‐32 mL, RVEF 56+/‐8%. Overall, LGE was present in 25/41 patients (61%), with dominant septal/inferior distribution (74%) and midwall pattern (92%). An ICD was implanted in 23 patients (56%). By 9y FU, 2 patients only died, both LGE+ (p=n.s.), 1 from electrical storm. During FU, MVA occurrence in LGE+ vs. LGE‐ patients was 8/25 vs. 0/16 (p=0.01). Also non‐sustained VTs were more common in patients with LGE (19/25 vs. 7/16, p=0.05). In patients with ICD, non‐significant difference in appropriate shocks incidence was seen (6/17 LGE+ vs. 0/5 LGE‐, p=n.s.). However, since mean ndegreeof shocks in LGE+ patients was 6+/‐5, absolute ndegreeof shocks was significantly different between groups (p<0.001). Inappropriate shocks from atrial fibrillation occurred in 1 LGE+ vs. 1 LGE‐ patient (p=n.s.). Non‐significant differences were found between LGE+ and LGE‐ groups in terms of: age (45+/‐18 vs. 29+/‐16 y), gender (M=14/25 vs. 7/16), missense mutations (17/25 vs. 7/16), LVEDV, RVEDV, RVEF and any degree atrioventricular block (all p=n.s). Baseline LVEF only was slightly different between groups (53+/‐11% LGE+ vs. 59+/‐6% LGE‐, p=0.05). Conclusion: In patients with LMNA‐related CMP, the presence of LGE at CMR is associated with a significantly higher occurrence of MVA, non‐sustained VTs and ndegree of shocks at long‐term FU. Significantly, LGE+ patients have also a mild but significant impairment in baseline LVEF.