目的:未描述LMNA基因型阳性患者在首次室性心律失常(VA)之前的心脏病进展。
结果:我们进行了一级预防队列研究,包括我们中心连续的LMNA基因型阳性患者。患者经历了反复的临床,心电图,和超声心动图检查。通过广义估计方程分析评估了心电图和超声心动图疾病进展作为首次VA的预测指标。通过阈值回归分析评估过渡到心律失常表型的阈值。我们纳入了94例LMNA基因型阳性患者,既往无VA(年龄38±15岁,32%先证者,53%女性)。19例(20%)患者在4.6年(四分位距2.1-7.3年)随访期间经历了VA,平均年龄50±11岁。我们分析了536次超声心动图和261次心电图检查。个体患者疾病进展与VA[左心室射血分数(LVEF)比值比(OR)1.4,95%置信区间(CI)1.2-1.6每降低5%,左心室舒张末期容积指数(LVEDVi)或1.2(95%CI1.1-1.3)每增加5mL/m2,每10ms增加PR间期OR1.2(95%CI1.1-1.4)]。向心律失常表型过渡的阈值为LVEF44%,LVEDVi77mL/m2,PR间隔280ms。
结论:在4.6年随访期间,LMNA基因型阳性患者的首次VA发生率为20%。通过ECG和超声心动图检查的个体患者疾病进展是VA的强预测因子,表明在考虑一级预防ICD时,疾病进展率可能比绝对测量值具有额外价值。LVEF的阈值<44%,LVEDVi>77mL/m2,PR间期>280ms表明转变为更多的致心律失常表型。
Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype-positive patients is not described.
We performed a primary prevention cohort
study, including consecutive LMNA genotype-positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype-positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1-7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2-1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1-1.3) per 5 mL/m2 increase, PR interval OR 1.2 (95% CI 1.1-1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m2, and PR interval 280 ms.
Incidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype-positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype.