Department of Cardiology, Heart Failure Research Center, Academic Medical Center, Amsterdam, the Netherlands.
J Am Coll Cardiol. 2012 Jan 31;59(5):493-500. doi: 10.1016/j.jacc.2011.08.078.
The purpose of this study was to determine risk factors that predict malignant ventricular arrhythmias (MVA) in Lamin A/C (LMNA) mutation carriers.
LMNA mutations cause a variety of clinical phenotypes, including dilated cardiomyopathy and conduction disease. Many LMNA mutation carriers have a poor prognosis, because of a high frequency of MVA and progression to end-stage heart failure. However, it is unclear how to identify mutation carriers that are at risk for MVA.
In this multicenter cohort of 269 LMNA mutation carriers, we evaluated risk factors for MVA, defined as sudden cardiac death, resuscitation, and appropriate implantable cardioverter-defibrillator (ICD) treatment.
In a median follow-up period of 43 months (interquartile range: 17 to 101 months), 48 (18%) persons experienced a first episode of MVA: 11 persons received successful cardiopulmonary resuscitation, 25 received appropriate ICD treatment, and 12 persons died suddenly. Independent risk factors for MVA were nonsustained ventricular tachycardia, left ventricular ejection fraction <45% at the first clinical contact, male sex, and non-missense mutations (ins-del/truncating or mutations affecting splicing). MVA occurred only in persons with at least 2 of these risk factors. There was a cumulative risk for MVA per additional risk factor.
Carriers of LMNA mutations with a high risk of MVA can be identified using these risk factors. This facilitates selection of LMNA mutation carriers who are most likely to benefit from an ICD.
本研究旨在确定预测 lamin A/C（LMNA）突变携带者恶性室性心律失常（MVA）的危险因素。
LMNA 突变导致多种临床表型，包括扩张型心肌病和传导疾病。许多 LMNA 突变携带者预后不良，因为 MVA 发生率高且进展为终末期心力衰竭。然而，尚不清楚如何识别有发生 MVA 风险的突变携带者。
在这项由 269 名 LMNA 突变携带者组成的多中心队列中，我们评估了 MVA 的危险因素，定义为心源性猝死、复苏和适当的植入式心脏复律除颤器（ICD）治疗。
在中位数为 43 个月（四分位间距：17 至 101 个月）的随访期间，48 名（18%）患者发生了首次 MVA 事件：11 名患者接受了成功的心肺复苏，25 名患者接受了适当的 ICD 治疗，12 名患者猝死。MVA 的独立危险因素是非持续性室性心动过速、首次临床接触时左心室射血分数<45%、男性和非同义突变（插入缺失/截断或影响剪接的突变）。仅在具有至少 2 个这些危险因素的患者中发生 MVA。每增加一个危险因素，MVA 的累积风险就会增加。
可以使用这些危险因素来识别 LMNA 突变携带者中发生 MVA 的高风险者。这有助于选择最有可能从 ICD 中获益的 LMNA 突变携带者。
