背景:马凡氏综合征与室性心律失常相关,但包括FBN1突变特征在内的危险因素需要阐明。
结果:我们进行了一项连续80名成年人的观察性队列研究(30名男性,50名42±15岁的女性)患有由FBN1突变引起的马凡氏综合征。我们在基线动态心电图上评估室性心律失常为每小时>10个室性早搏(>10PVC/h),作为心室对联(对联),或作为非持续性室性心动过速(nsVT),在31±18个月的随访期间,室性心动过速(VT)事件(VTE),如心源性猝死(SCD),持续室性心动过速(sVT)。我们在28(35%)中发现>10PVC/h,耦合/nsVT在32(40%),6例患者(8%)和VTE,包括3例SCD(4%)。PVC>10/h,耦合/nsVT,和VTE显示血清N末端脑钠肽前体水平升高(P<0.001)。所有心律失常均与NT-proBNP升高相关(P<.001),其中PVC>10/h和Couplet/nsVT也与增加的指数收缩末期LV直径有关(P=.024和P=.020),中度二尖瓣反流(P=0.018和P=0.003),以及延长的QTc间隔(P=.001和P=.006),分别。此外,VTE与外显子24-32中的突变相关(P=.021)。Kaplan-Meier分析证实了VTE与NT-proBNP增加(P<.001)和外显子24-32突变(P<.001)的相关性。
结论:具有致病性FBN1突变的马凡氏综合征与心律失常风险增加相关,和受影响的人可能需要终身监测。心电图上的室性心律失常,心肌功能障碍和外显子24-32突变可能是VTE的危险因素.
BACKGROUND: Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.
RESULTS: We performed an observational cohort
study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro-brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24-32 (P = .021). Kaplan-Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24-32 (P<.001).
CONCLUSIONS: Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24-32 may be risk factors of VTE.