非缺血性扩张型心肌病患者左心室逆重构的临床研究

【作者】 邹长虹；

【导师】 张健；

【作者基本信息】 北京协和医学院 ， 内科学， 2014， 博士

【摘要】 背景：尽管在非缺血性扩张型心肌病(NIDCM)患者中左心室收缩功能显著改善的报道逐渐增多,但目前有关左心室射血分数(LVEF)恢复正常的研究还较少。本研究的目的是在一组大样本量的中国NIDCM患者中,评价LVEF恢复正常的发生率、预测因素、预后判断价值及LVEF恢复正常后的复发风险。方法：连续入选2008年10月至2012年10月之间住院治疗且首次超声心动图检查LVEF≤40%的NIDCM患者,给予当前指南推荐的标准抗心衰治疗,根据出院后随访复查超声心动图LVEF≥50%来定义’LVEF恢复正常”,分析随访早期(1年)及随访结束时LVEF恢复正常的发生率。收集患者基线时可能与LVEF恢复相关的临床和超声心动图指标,采用多变量logistic回归分析方法评价与早期LVEF恢复正常相关的预测因素。以心血管原因死亡和心脏移植为临床复合事件,采用Kaplan-Meier法进行生存分析,早期LVEF恢复正常与未恢复患者生存率比较采用log-rank检验。利用Cox比例风险模型,建立包含基线指标的生存预测模型,再通过“受试者工作特征(ROC)”曲线分析,评价早期随访LVEF恢复正常能否提高基线指标的预后判断价值。以LVEF≤45%且较恢复时至少减低10%为标准定义收缩功能障碍“复发”,分析LVEF恢复正常患者长期随访时的复发风险。结果：共有490名NIDCM患者纳入该研究。随访1年时,114名(占23.3%)患者LVEF恢复正常,其LVEF从基线的30.4±5.8%明显升高至1年随访时的54.7±4.0%。随访结束时(27±15个月),LVEF恢复正常的发生率为31.2%。多变量logistic回归分析结果表明,高血压病史(OR=2.529,p=0.017)、心衰症状病史(OR=0.979,p<0.001)、入院收缩压水平(OR=1.064,p<0.001)及超声心动图测量左心室舒张末期内径(OR=0.902,p<0.001)这四个基线指标是早期LVEF恢复正常的独立预测因素。Kaplan-Meier生存分析表明,早期LVEF恢复正常与长期无心脏移植存活显著相关。以1年随访时存活且完成早期LVEF评估的患者(n=260)为研究对象,多变量Cox回归分析结果显示,超声心动图测量的右心室前后径、入院血清钠浓度及出院带药含β受体阻滞剂三个基线指标是临床复合事件的独立预测因素。在此基础上,增加早期LVEF恢复正常这一随访结果,可以明显提高基线指标的预后判断价值,曲线下面积(AUC)从0.694明显提高至0.840(p=0.002)。然而,153名LVEF恢复正常患者,恢复后继续随访26±12个月,有15名(占9.8%)患者收缩功能障碍复发,其LVEF从恢复时56.5±3.8%降低至36.1±7.6%。结论：大约1/4-1/3的NIDCM患者经当前标准抗心衰治疗后1-2年时间内LVEF可以恢复正常。既往高血压病史、心衰症状病史、入院收缩压水平以及超声心动图测量的LVEDD四个基线指标是早期(1年)随访时LVEF恢复正常的独立预测因素。早期LVEF恢复正常与患者长期无心脏移植存活显著相关,可以提高基线指标对长期预后的判断价值。部分LVEF恢复正常患者存在收缩功能障碍的复发风险,强调了长期密切随访的必要性。背景：近年来不断有研究报道部分新发心肌病(ROCM)患者的左心室收缩功能在抗心衰治疗后发生显著改善,并确定了一些有预测价值的临床及影像学指标。本研究的目的是在一组中国ROCM患者中,评价当前标准抗心衰药物治疗下左心室射血分数(LVEF)恢复正常的发生率及其预测因素。方法：连续入选了2008年10月至2012年12月之间住院治疗且首次超声心动图检查LVEF≤40%的ROCM患者,给予当前指南推荐的标准抗心衰药物治疗。患者出院后至少随访1年,以随访时复查超声心动图LVEF≥50%为标准来定义“LVEF恢复正常”,调查ROCM患者不同随访时间内LVEF恢复正常的发生率。另外,根据恢复时间将恢复分成“早期恢复(恢复时间≤1年)”和“晚期恢复(恢复时间大于1年)”。详细收集患者基线时可能与LVEF恢复相关的临床和超声心动图指标,采用多变量logistic逐步回归分析方法确定有预测价值的基线指标,据此建立一个预测模型,并评价该模型预测LVEF恢复正常的校准能力和鉴别能力。结果：共有128名ROCM患者纳入本研究,平均随访31±13个月后,有62名患者(占48%)LVEF恢复正常,其LVEF从基线的32±6%显著升高至末次随访时的58±5%(p<0.001),平均升高了26±8%；伴有左心室舒张末期内径(LVEDD)从基线63±5mm显著缩小至末次随访时52±4mm(p<0.001)。62名LVEF恢复正常患者的平均恢复时间为10±9个月,在随访6个月、1年及2年内LVEF恢复正常的发生率分别为24%(n=31)、33%(n=42)和45%(n=58)。另外,在62名LVEF恢复患者中,“早期恢复”患者占68%。多变量logistic逐步回归分析结果表明,既往高血压病史(OR=3.278,p=0.030)、入院收缩压水平(OR=1.041,p=0.002)、QRS波群宽度(OR=0.975,p=0.019)、超声心动图测量的LVEDD (OR=0.914,p=0.001)及LVEF(OR=1.123,p=0.005)这五个基线指标是随访时LVEF恢复正常的独立预测因素,包含这些变量的模型预测ROCM患者LVEF恢复正常具有良好的校准能力(Hosmer-Lemeshow检验p=0.132)和鉴别能力(曲线下面积AUC=0.860,p<0.001)。结论：经当前标准抗心衰药物治疗,平均随访3年左右时间,约有一半ROCM患者LVEF恢复正常,其中2/3发生在随访1年时间内。既往有高血压病史、入院收缩压水平高、QRS间期短、超声测量的LVEDD小及LVEF高这五个基线指标是随访时LVEF恢复正常的独立预测因素。背景：尽管在非缺血性扩张型心肌病(NIDCM)患者中左心室逆重构(LVRR)的报道逐渐增多,但目前有关特发性扩张型心肌病(IDCM)患者LVRR的研究还较少。本研究的目的是在一组较大样本量的中国IDCM患者中,评价当前标准抗心衰药物治疗情况下LVRR的发生率及其预测因素。方法：连续入选了2008年10月至2012年10月之间住院且首次超声心动图检查左心室射血分数(LVEF)≤40%且左心室舒张末期内径(LVEDD)>55mm (男)或50mm(女)的IDCM患者,出院后至少随访12个月,以随访时复查超声心动图LVEF≥50%且LVEDD≤55mm(男)或50mm(女)为标准来定义LVRR,调查IDCM患者在当前标准抗心衰治疗情况下LVRR的发生率。详细收集患者基线时可能与LVRR发生相关的临床和超声心动图指标,采用多变量logistic逐步回归分析方法确定与LVRR有关的预测因素。结果：共有240名接受标准抗心衰药物治疗的IDCM患者纳入本研究,平均随访30±14个月后,有45名患者(占18.8%)发生LVRR,其LVEF从基线时的32.4±5.9%显著升高至末次随访时的57.4±4.9%,平均增加了25.0±6.9%。同时,其LVEDD从基线时的62.7±4.1mm显著缩小至末次随访时的50.7±3.5mm,平均缩小了12.0±4.5mm。45名发生LVRR患者的平均恢复时间为14±10个月,中位时间为12.5个月。亚组分析显示,新发IDCM患者(心衰症状病史≤6个月)患者LVRR发生率(31.1%)明显高于慢性IDCM(病史>6个月)患者的9.0%(p<0.01),但两者发生LVRR的平均恢复时间相似。多变量logistic逐步回归分析结果表明,心衰症状病史(OR=0.977,95%CI：0.961-0.993；p=0.005)、入院收缩压水平(OR=1.033,95%CI：1.007-1.060；p=0.013)、超声心动图测量的LVEDD (OR=0.895,95%CI:0.858-0.933；p<0.001)及LVEF (OR=1.091,95%CI:1.015-1.173; p=0.018)这四个基线指标是发生LVRR的独立预测因素。结论：在当前标准抗心衰药物治疗情况下,部分IDCM患者的LVEF及LVEDD均可以发现显著改善,即发生了LVRR。心衰症状病史短、基线收缩压水平高、基线超声心动图测量的LVEDD较小及LVEF较高的患者发生LVRR的可能性大。更多还原

【Abstract】 Background:Although marked improvement in left ventricular systolic function has been increasingly reported in non-ischemic dilated cardiomyopathy (NIDCM), data on recovery of normal left ventricular ejection fraction (LVEF) is rare to date. The present study was designed to determine the frequency of recovery of normal LVEF in a cohort of Chinese patients with NIDCM, to identify predictors of early (after1year follow-up) recovery, to evaluate the prognostic value of early recovery on long-term prognosis, and finally, to evaluate the risk of recurrence after recovery.Methods:A consecutive series of patients admitted between October2008and October2012with clinical diagnosis of NIDCM and LVEF of40%or less by echocardiography at presentation were followed up to identify those with recovery of normal LVEF, defined as an increase in LVEF to a final level of50%or greater. An array of variables at baseline regarded as potentially relevant to recovery was evaluated to identify predictors of early recovery using multivariate logistic regression analysis. Survival data based on the combined clinical events of cardiovascular death and heart transplantation were analyzed using the Kaplan-Meier method and compared using the log-rank test between patients with and those without early recovery. A prognostic survival model was established by using the Cox hazard proportional analysis from baseline parameters and the possible additive prognostic role of the presence of early recovery with respect to baseline variables was evaluated by means of receiver-operating characteristic (ROC) analysis. The risk of recurrence of systolic dysfunction after recovery, defined as a decrease in LVEF at least10%from recovery to a level of≤45%, was also evaluated.Results:A total of490patients with NIDCM were enrolled in this analysis. At1year follow-up,114patients (23.3%) had a recovery of normal LVEF, showing a significant increase in LVEF from30.4±5.8%at baseline to54.7±4.0%at1year follow-up. At last follow-up of27±15months, the frequency of recovery was31.2%(n=153). Multivariate logistic analysis showed that history of hypertension (OR=2.529, p=0.017), shorter symptom duration (OR=0.979, p<0.001), higher systolic blood pressure at presentation (OR=1.064, p<0.001) and smaller left ventricular end-diastolic diameter (OR=0.902, p<0.001) on echocardiogram at baseline were independent predictors of early recovery. Kaplan-Meier method survival analysis showed that early recovery was associated with better long-term prognosis in terms of transplant-free survival. Multivariate Cox regression analysis showed that baseline independent predictors for combined clinical events after evaluation of early recovery for surviving patients at1year were right ventricular diameter on echocardiogram, serum sodium and the use of a P-blocker on discharge, and incorporating the presence of early recovery added the prognostic power with a significant increase in area under the curve of ROC from0.694to0.840(p=0.002). However, among the153patients with recovery,15patients (9.8%) suffered from recurrence of systolic dysfunction at26±12months after recovery with a decrease in LVEF from56.5±3.8%to36.1±7.6%.Conclusion:Around one fourth to one third of a cohort of Chinese patients with NIDCM has shown a recovery of normal LVEF after a mean follow-up of1to2years on current optimal therapy, which was associated with some baseline clinical and echocardiographic variables. Early recovery was associated with better long-term prognosis in terms of transplant-free survival, and added the prognostic power of baseline parameters for combined clinical events. However, some recovered patients may experience recurrence of systolic dysfunction, highlighting the necessity of close long-term follow-up. Background:Emerging evidences have shown the potential of marked improvement in left ventricular ejection fraction (LVEF) in patients with recent onset cardiomyopathy (ROCM) on medical therapy. This study was designed to determine the frequency and to identify some predictors of recovery of normal LVEF in a cohort of Chinese patients with ROCM on contemporary optimal medical therapy.Methods:A consecutive series of patients hospitalized in a single tertiary for heart failure management between October2008and December2012with the clinical diagnosis of ROCM and LVEF of40%or less by echocardiography at presentation were followed up for at least12months to identify those with recovery of normal LVEF, defined as an increase in LVEF to a final level of50%or greater. Early recovery was defined as recovery of normal LVEF at1year after initial evaluation and late recovery referred to those beyond1year. An array of clinical and echocardiographic variables at baseline regarded as potentially relevant to the recovery was evaluated to identify some predictors using multivariate stepwise logistic regression analysis, and consequently to establish a predictive model which consisted of some simple baseline parameters.Results:A total of128patients with ROCM were enrolled in this study. After a mean follow-up period of31±13months,62patients (48%) had a recovery of normal LVEF, who showed a significant increase in LVEF from32±6%at baseline to58±5%at last follow-up (p<0.001), with a mean increase of26±8%. This increase in LVEF was associated with a marked decrease in left ventricular end-diastolic diameter (LVEDD) from63±5mm to52±4mm (p<0.001). For the62patients with recovery, the length of time required for recovery was10±9months, and the frequency of recovery of normal LVEF at6months,1year and2years after initial evaluation was24%(n=32),33%(n=42) and45%(n=58), respectively. Moreover, early recovery occurred in68%patients with recovery of normal LVEF. Multivariate analysis showed that recovery of normal LVEF was significantly associated with previous history of hypertension (OR=3.278, p=0.030), higher systolic blood pressure at presentation (OR=1.041, p=0.002), shorter QRS interval on electrocardiogram (OR=0.975, p=0.019), smaller LVEDD (OR=0.914, p=0.001) and greater LVEF by echocardiography (OR=1.123, p=0.005) at baseline. The model composed of such variables was shown to be of excellent calibration by Hosmer-Lemeshow test (p=0.132) and discriminatory capacity tested by the area under the curve (AUC) of Receiver Operative Characteristics (ROC) of0.860(95%CI:0.795-0.925; p<0.001). Conclusion:Nearly half of a cohort of Chinese patients with ROCM has shown a remarkable recovery of normal LVEF on current optimal medical therapy after a mean follow-up of about3years, and two thirds of them occurred early at1year after initial evaluation, which was associated with some history of hypertension, systolic blood pressure at presentation, electrocardiographic QRS interval, echocardiographic LVEDD and LVEF at baseline. Background:Although emerging evidences have shown the potential of left ventricular reverse remodeling (LVRR) on current medical therapy, neither the likelihood nor the clinical variables associated with its occurrence in idiopathic dilated cardiomyopathy (IDCM) is well delineated so far. This study was designed to determine the frequency and to identify some predictors of LVRR in a cohort of Chinese patients with IDCM on contemporary optimal medical therapy.Methods:A consecutive series of patients hospitalized in a single tertiary for heart failure management between October2008and October2012with the clinical diagnosis of IDCM, and left ventricular ejection fraction (LVEF) of40%or less, as well as left ventricular end-diastolic diameter (LVEDD) of>55mm for male or50mm for female by echocardiography at presentation were followed for at least12months to identify those with LVRR, defined as an increase in LVEF to a final level of50%or greater and a decrease in LVEDD to a final level of55mm or less for male or50mm or less for female. An array of clinical and echocardiographic variables at baseline regarded as potentially relevant to the LVRR was evaluated to identify some predictors using multivariate stepwise logistic regression analysis.Results:A total of240patients with IDCM on current medical therapy were enrolled in this study. After a mean follow-up period of30±14months,45patients (18.8%) had a LVRR, showing a significant increase in LVEF from32.4±5.9%at baseline to57.4±4.9%at last follow-up, with a mean increase of25.0±6.9%. This increase in LVEF was associated with a marked decrease in LVEDD from62.7±4.1mm to50.7±3.5mm, with a mean decrease of12.0±4.5mm. For the45patients with LVRR, the length of time required for LVRR was14±10months. Subgroup analysis showed that the frequency of LVRR in recent onset IDCM (symptom duration≤6months)(31.1%) was significantly higher than that (9.0%) of in chronic IDCM (symptom duration>6months)(p<0.01). Multivariate analysis demonstrated that LVRR was significantly associated with shorter symptom duration (OR=0.977,95%CI:0.961-0.993; p=0.005), higher systolic blood pressure at presentation (OR=1.033,95%CI:1.007-1.060; p=0.013), smaller LVEDD (OR=0.895,95%CI:0.858-0.933; p<0.001) and greater LVEF (OR=1.091,95%CI:1.015-1.173; p=0.018) by echocardiography at baseline.Conclusion:On current optimal medical therapy, some patients with IDCM may have a remarkable recovery of LVEF and LVEDD. namely LVRR, which was associated with symptom duration, systolic blood pressure at presentation, echocardiographic LVEDD and LVEF at baseline.更多还原