可溶性ST2和半乳糖凝集素-3水平与室间隔心肌切除术后肥厚型梗阻性心肌病患者预后的相关性分析
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摘要
目的:探讨可溶性ST2(s ST2)和半乳糖凝集素-3(Gal-3)水平与室间隔心肌切除术后肥厚型梗阻性心肌病(HOCM)患者临床预后的相关性。方法:纳入2011-03至2016-02期间在中国医学科学院阜外医院行改良Morrow手术的HOCM患者200例,采用酶联免疫吸附法(ELISA)检测其血浆s ST2与Gal-3水平。根据血浆s ST2水平进行三分位数分组:低s ST2组(<9.05 ng/ml)、中s ST2组(9.05~16.74 ng/ml)及高s ST2组(>16.74 ng/ml);根据血浆Gal-3水平进行三分位数分组:低Gal-3组(<6.19 ng/ml)、中Gal-3组(6.19~8.22 ng/ml)、高Gal-3组(>8.22 ng/ml)。另外收集了42例无心脏疾病的志愿者血液样本作为正常对照,并按照性别和年龄匹配了42例HOCM患者,比较两者血浆中sS T2与Gal-3水平的差异。使用Cox回归模型评估血浆sS T2和Gal-3水平对主要终点事件(全因死亡或心血管住院)的预测价值。结果:ELISA分析结果表明,与正常对照者相比,HOCM患者的血浆s ST2和Gal-3水平显著升高(P均<0.01)。中位随访26个月时,Kaplan-Meier生存分析显示,血浆s ST2及Gal-3不同水平组的复合终点事件发生率均无明显差异(log-rank P分别为0.06和0.68)。Cox回归分析表明,血浆sS T2和Gal-3水平都不能独立预测终点事件(P均>0.05),而年龄是复合终点事件的独立危险因素(HR=1.06,95%CI:1.02~1.11,P<0.01)。结论:尽管HOCM患者的血浆sS T2与Gal-3水平升高,但血浆sS T2和Gal-3水平与心肌切除术后HOCM患者临床预后无关。年龄增长是室间隔心肌切除术后HOCM患者全因死亡及心血管事件住院的复合终点事件的独立预测因子。
Objective: To explore the relationship between plasma levels of soluble ST2(sS T2), galectin-3(Gal-3) and clinical prognosis of ventricular septal myectomy in patients with obstructive hypertrophic cardiomyopathy(HOCM).Methods: A total of 200 consecutive HOCM patients received modified Morrow surgery in our hospital from 2011-03 to 2016-02 were studied. According to plasma levels of sS T2, patients were divided into 3 groups: Low sS T2 group(sS T2<9.05 ng/ml), Middle sS T2 group(sS T2 9.05-16.74 ng/ml) and High sS T2 group(sS T2>16.74 ng/ml); based on plasma levels of Gal-3, patients were divided into another 3 groups: Low Gal-3 group(Gal-3<6.19 ng/ml), Middle group(Gal-3 6.19-8.22 ng/ml) and High Gal-3 group(Gal-3>8.22 ng/ml); in addition, Control group, n=42 volunteers without heart disease. Plasma levels of sS T2 and Gal-3 were measured by ELISA, compared between Control group and HOCM group(n=42 patients with matched gender and age to Control group). The predictive value of sS T2 and Gal-3 on major endpoint events including all cause death or cardiovascular hospitalization were assessed by Cox regression analysis.Results: Compared with Control group, plasma levels of sS T2 and Gal-3 were increased in HOCM patients, P<0.01. The patients were followed-up for the average of 26 months, Kaplan-meier survival analysis showed that the incidences of composite endpoint event were similar at different levels of sS T2 and Gal-3(log-rank P=0.06 and P=0.68). Cox regression analysis indicated that either sS T2 or Gal-3 could not independently predict the endpoint events, both P>0.05, while age was an independent risk factor for composite endpoint event occurrence(HR=1.06, 95% CI 1.02-1.11, P<0.01).Conclusion: Plasma levels of sS T2 and Gal-3 were not related to clinical prognosis of ventricular septal myectomy in HOCM patients even they had increased sS T2 and Gal-3; while advanced age was the independent predictor for endpoint event occurrence.
Objective: To explore the relationship between plasma levels of soluble ST2(sS T2), galectin-3(Gal-3) and clinical prognosis of ventricular septal myectomy in patients with obstructive hypertrophic cardiomyopathy(HOCM).Methods: A total of 200 consecutive HOCM patients received modified Morrow surgery in our hospital from 2011-03 to 2016-02 were studied. According to plasma levels of sS T2, patients were divided into 3 groups: Low sS T2 group(sS T2<9.05 ng/ml), Middle sS T2 group(sS T2 9.05-16.74 ng/ml) and High sS T2 group(sS T2>16.74 ng/ml); based on plasma levels of Gal-3, patients were divided into another 3 groups: Low Gal-3 group(Gal-3<6.19 ng/ml), Middle group(Gal-3 6.19-8.22 ng/ml) and High Gal-3 group(Gal-3>8.22 ng/ml); in addition, Control group, n=42 volunteers without heart disease. Plasma levels of sS T2 and Gal-3 were measured by ELISA, compared between Control group and HOCM group(n=42 patients with matched gender and age to Control group). The predictive value of sS T2 and Gal-3 on major endpoint events including all cause death or cardiovascular hospitalization were assessed by Cox regression analysis.Results: Compared with Control group, plasma levels of sS T2 and Gal-3 were increased in HOCM patients, P<0.01. The patients were followed-up for the average of 26 months, Kaplan-meier survival analysis showed that the incidences of composite endpoint event were similar at different levels of sS T2 and Gal-3(log-rank P=0.06 and P=0.68). Cox regression analysis indicated that either sS T2 or Gal-3 could not independently predict the endpoint events, both P>0.05, while age was an independent risk factor for composite endpoint event occurrence(HR=1.06, 95% CI 1.02-1.11, P<0.01).Conclusion: Plasma levels of sS T2 and Gal-3 were not related to clinical prognosis of ventricular septal myectomy in HOCM patients even they had increased sS T2 and Gal-3; while advanced age was the independent predictor for endpoint event occurrence.
引文
[1]Pascual-Figal DA,Januzzi JL.The biology of ST2:the International ST2 Consensus Panel[J].Am J Cardiol,2015,115(7 Suppl):3B-7B.DOI:10.1016/j.amjcard.2015.01.034.
[2]Ahmad T,Fiuzat M,Felker GM,et al.Novel biomarkers in chronic heart failure[J].Nat Rev Cardiol,2012,9(6):347-359.DOI:10.1038/nrcardio.2012.37.
[3]Broch K,Ueland T,Nymo SH,et al.Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology[J].Eur J Heart Fail,2012,14(3):268-277.DOI:10.1093/eurjhf/hfs006.
[4]Manzano-Fernández S,Mueller T,Pascual-Figal D,et al.Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction[J].Am J Cardiol,2011,107(2):259-267.DOI:10.1016/j.amjcard.2010.09.011.
[5]Dumic J,Dabelic S,Flogel M.Galectin-3:an open-ended story[J].Biochem Biophys Acta,2006,1760:616-635.
[6]de Boer RA,Voors AA,Muntendam P,et al.Galectin-3:a novel mediator of heart failure development and progression[J].Eur J Heart Fail,2009,11(9):811-817.DOI:10.1093/eurjhf/hfp097.
[7]de Boer RA,Lok DJ,Jaarsma T,et al.Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction[J].Ann Med,2011,43(1):60-68.DOI:10.3109/07853890.2010.538080.
[8]Edelmann F,Holzendorf V,Wachter R,et al.Galectin-3 in patients with heart failure with preserved ejection fraction:results from the Aldo-DHF trial[J].Eur J Heart Fail,2015,17(2):214-223.DOI:10.1002/ejhf.203.
[9]Elliott PM,Anastasakis A,Borger MA,et al.2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy:the Task Force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology(ESC)[J].Eur Heart J,2014,35(39):2733-2779.DOI:10.1093/eurheartj/ehu284.
[10]Roncarati R,Viviani AC,Losi MA,et al.Circulating mi R-29a,among other up-regulated micro RNAs,is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2014,63(9):920-927.DOI:10.1016/j.jacc.2013.09.041.
[11]D'Amato R,Tomberli B,Castelli G,et al.Prognostic value of N-terminal pro-brain natriuretic peptide in outpatients with hypertrophic cardiomyopathy[J].Am J Cardiol,2013,112(8):1190-1196.DOI:10.1016/j.amjcard.2013.06.018.
[12]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines[J].Circulation,2011,124(24):e783-e831.DOI:10.1161/CIR.0b013e318223e230.
[13]Wang S,Cui H,Yu Q,et al.Excision of anomalous muscle bundles as an important addition to extended septal myectomy for treatment of left ventricular outflow tract obstruction[J].J Thorac Cardiovasc Surg,2016,152(2):461-468.DOI:10.1016/j.jtcvs.2016.01.051.
[14]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.急性心力衰竭诊断和治疗指南[J].中华心血管病学杂志,2010,38(3):195-208.DOI:10.3760/cma.j.issn.0253-3758.2010.03.002.
[15]Lang RM,Bierig M,Devereux RB,et al.Recommendations for chamber quantification:a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group,developed in conjunction with the European Association of Echocardiography,a branch of the European Society of Cardiology[J].J Am Soc Echocardiogr,2005,18(12):1440-1463.DOI:10.1016/j.echo.2005.10.005.
[16]Robbins RC,Stinson EB.Long-term results of left ventricular myotomy and myectomy for obstructive hypertrophic cardiomyopathy[J].J Thorac Cardiovasc Surg,1996,111(3):586-594.
[17]O'Hanlon R,Grasso A,Roughton M,et al.Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2010,56(11):867-874.DOI:10.1016/j.jacc.2010.05.010.
[18]Gaggin HK,Szymonifka J,Bhardwaj A,et al.Head-to-head comparison of serial soluble ST2,growth differentiation factor-15,and highly-sensitive troponin T measurements in patients with chronic heart failure[J].JACC:Heart Failure,2014,2(1):65-72.DOI:10.1016/j.jchf.2013.10.005.
[19]Meijers WC,Januzzi JL,Defilippi C,et al.Elevated plasma galectin-3is associated with near-term rehospitalization in heart failure:a pooled analysis of 3 clinical trials[J].Am Heart J,2014,167(6):853-860.DOI:10.1016/j.ahj.2014.02.011.
[20]Srivatsan V,George M,Shanmugam E.Utility of galectin-3 as a prognostic biomarker in heart failure:where do we stand?[J].Eur J Prev Cardiol,2015,22(9):1096-1110.DOI:10.1177/2047487314552797.
[21]van der Velde AR,Gullestad L,Ueland T,et al.Prognostic value of changes in galectin-3 levels over time in patients with heart failure:data from CORONA and COACH[J].Circ Heart Fail,2013,6(2):219-226.DOI:10.1161/CIRCHEARTFAILURE.112.000129.
[22]Nishimura RA,Seggewiss H,Schaff HV.Hypertrophic obstructive cardiomyopathy:surgical myectomy and septal ablation[J].Circ Res,2017,121(7):771-783.DOI:10.1161/CIRCRESAHA.116.309348.
[23]Frioes F,Lourenco P,Laszczynska O,et al.Prognostic value of s ST2added to BNP in acute heart failure with preserved or reduced ejection fraction[J].Clin Res Cardiol,2015,104(6):491-499.DOI:10.1007/s00392-015-0811-x.
[24]López B,González A,Ravassa S,et al.Circulating biomarkers of myocardial fibrosis:the need for a reappraisal[J].J Am Coll Cardiol,2015,65(22):2449-2456.DOI:10.1016/j.jacc.2015.04.026.
[2]Ahmad T,Fiuzat M,Felker GM,et al.Novel biomarkers in chronic heart failure[J].Nat Rev Cardiol,2012,9(6):347-359.DOI:10.1038/nrcardio.2012.37.
[3]Broch K,Ueland T,Nymo SH,et al.Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology[J].Eur J Heart Fail,2012,14(3):268-277.DOI:10.1093/eurjhf/hfs006.
[4]Manzano-Fernández S,Mueller T,Pascual-Figal D,et al.Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction[J].Am J Cardiol,2011,107(2):259-267.DOI:10.1016/j.amjcard.2010.09.011.
[5]Dumic J,Dabelic S,Flogel M.Galectin-3:an open-ended story[J].Biochem Biophys Acta,2006,1760:616-635.
[6]de Boer RA,Voors AA,Muntendam P,et al.Galectin-3:a novel mediator of heart failure development and progression[J].Eur J Heart Fail,2009,11(9):811-817.DOI:10.1093/eurjhf/hfp097.
[7]de Boer RA,Lok DJ,Jaarsma T,et al.Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction[J].Ann Med,2011,43(1):60-68.DOI:10.3109/07853890.2010.538080.
[8]Edelmann F,Holzendorf V,Wachter R,et al.Galectin-3 in patients with heart failure with preserved ejection fraction:results from the Aldo-DHF trial[J].Eur J Heart Fail,2015,17(2):214-223.DOI:10.1002/ejhf.203.
[9]Elliott PM,Anastasakis A,Borger MA,et al.2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy:the Task Force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology(ESC)[J].Eur Heart J,2014,35(39):2733-2779.DOI:10.1093/eurheartj/ehu284.
[10]Roncarati R,Viviani AC,Losi MA,et al.Circulating mi R-29a,among other up-regulated micro RNAs,is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2014,63(9):920-927.DOI:10.1016/j.jacc.2013.09.041.
[11]D'Amato R,Tomberli B,Castelli G,et al.Prognostic value of N-terminal pro-brain natriuretic peptide in outpatients with hypertrophic cardiomyopathy[J].Am J Cardiol,2013,112(8):1190-1196.DOI:10.1016/j.amjcard.2013.06.018.
[12]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines[J].Circulation,2011,124(24):e783-e831.DOI:10.1161/CIR.0b013e318223e230.
[13]Wang S,Cui H,Yu Q,et al.Excision of anomalous muscle bundles as an important addition to extended septal myectomy for treatment of left ventricular outflow tract obstruction[J].J Thorac Cardiovasc Surg,2016,152(2):461-468.DOI:10.1016/j.jtcvs.2016.01.051.
[14]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.急性心力衰竭诊断和治疗指南[J].中华心血管病学杂志,2010,38(3):195-208.DOI:10.3760/cma.j.issn.0253-3758.2010.03.002.
[15]Lang RM,Bierig M,Devereux RB,et al.Recommendations for chamber quantification:a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group,developed in conjunction with the European Association of Echocardiography,a branch of the European Society of Cardiology[J].J Am Soc Echocardiogr,2005,18(12):1440-1463.DOI:10.1016/j.echo.2005.10.005.
[16]Robbins RC,Stinson EB.Long-term results of left ventricular myotomy and myectomy for obstructive hypertrophic cardiomyopathy[J].J Thorac Cardiovasc Surg,1996,111(3):586-594.
[17]O'Hanlon R,Grasso A,Roughton M,et al.Prognostic significance of myocardial fibrosis in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2010,56(11):867-874.DOI:10.1016/j.jacc.2010.05.010.
[18]Gaggin HK,Szymonifka J,Bhardwaj A,et al.Head-to-head comparison of serial soluble ST2,growth differentiation factor-15,and highly-sensitive troponin T measurements in patients with chronic heart failure[J].JACC:Heart Failure,2014,2(1):65-72.DOI:10.1016/j.jchf.2013.10.005.
[19]Meijers WC,Januzzi JL,Defilippi C,et al.Elevated plasma galectin-3is associated with near-term rehospitalization in heart failure:a pooled analysis of 3 clinical trials[J].Am Heart J,2014,167(6):853-860.DOI:10.1016/j.ahj.2014.02.011.
[20]Srivatsan V,George M,Shanmugam E.Utility of galectin-3 as a prognostic biomarker in heart failure:where do we stand?[J].Eur J Prev Cardiol,2015,22(9):1096-1110.DOI:10.1177/2047487314552797.
[21]van der Velde AR,Gullestad L,Ueland T,et al.Prognostic value of changes in galectin-3 levels over time in patients with heart failure:data from CORONA and COACH[J].Circ Heart Fail,2013,6(2):219-226.DOI:10.1161/CIRCHEARTFAILURE.112.000129.
[22]Nishimura RA,Seggewiss H,Schaff HV.Hypertrophic obstructive cardiomyopathy:surgical myectomy and septal ablation[J].Circ Res,2017,121(7):771-783.DOI:10.1161/CIRCRESAHA.116.309348.
[23]Frioes F,Lourenco P,Laszczynska O,et al.Prognostic value of s ST2added to BNP in acute heart failure with preserved or reduced ejection fraction[J].Clin Res Cardiol,2015,104(6):491-499.DOI:10.1007/s00392-015-0811-x.
[24]López B,González A,Ravassa S,et al.Circulating biomarkers of myocardial fibrosis:the need for a reappraisal[J].J Am Coll Cardiol,2015,65(22):2449-2456.DOI:10.1016/j.jacc.2015.04.026.