肥厚型心肌病合并心房颤动患者室间隔心肌微血管密度对心肌纤维化的影响
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摘要
目的:分析微血管密度对肥厚型心肌病(HCM)合并心房颤动(房颤)患者心肌纤维化的影响。方法:对48例HCM患者(12例合并房颤,36例未合并房颤)室间隔切除病理标本进行免疫组化和Masson染色,分析微血管密度对HCM合并房颤患者心肌纤维化的影响。结果:与HCM未合并房颤患者相比,合并房颤患者室间隔心肌纤维化百分比(10.8%±5.9%vs 19.1%±8.4%,P=0.007)增高,微血管密度减低[(526±213)个/mm~2 vs (352±63)个/mm~2,P=0.008]。纤维化百分比与微血管密度在所有HCM患者中(r=-0.52,P<0.001)、未合并房颤患者(r=-0.46,P=0.005)、合并房颤患者(r=-0.66,P=0.02)中均呈负相关。多重线性回归分析显示,校正了年龄、左心房内径后,微血管密度下降仍然是HCM合并房颤患者纤维化比例升高的独立危险因素(β=-1.03,P=0.01)。结论:与单纯HCM患者相比,HCM合并房颤患者室间隔心肌纤维化比例明显升高,微血管密度下降。微血管密度下降是HCM合并房颤患者纤维化比例升高的独立危险因素。
Objectives: We sought to evaluate the impact of microvascular density(MVD) on the extent of fibrosis inhypertrophic cardiomyopathy(HCM) patients with atrial fibrillation(AF).Methods: Immunohistochemical staining and Masson staining were performed on surgically removed left ventricular(LV)septal wall specimens from 48 HCM patients(HCM with AF, n=12, HCM without AF, n=36) and analyze the impact of MVD on the extent of fibrosis in HCM patients with or without AF.Results: The extent of fibrosis were significantly higher in HCM patients with AF than in HCM patients without AF([19.1± 8.4] % vs [10.8 ± 5.9]%, P=0.007). MVD was lower in HCM patients with AF than those without AF([352 ± 63]/mm~2 vs [526± 213]/mm~2, P=0.008). MVD was negatively correlated with the extent of fibrosis in all HCM patients(r=-0.52, P< 0.001), in HCM patients with AF(r=-0.66, P=0.02) and HCM patients without AF(r=-0.46, P=0.005). Multiple linear regression analysis showed that the reduced MVD remained as a strong independent predictor of the extent of fibrosis in HCM patients with AF(β=-1.03, P=0.01) after adjusting for age and left atrial diameter.Conclusions: Fibrosis is higher and MVD is lower in HCM patients with AF than in HCM patients without AF.Microvascular rarefaction is a strong independent predictor of the increased extent of fibrosis in HCM patients with AF.
Objectives: We sought to evaluate the impact of microvascular density(MVD) on the extent of fibrosis inhypertrophic cardiomyopathy(HCM) patients with atrial fibrillation(AF).Methods: Immunohistochemical staining and Masson staining were performed on surgically removed left ventricular(LV)septal wall specimens from 48 HCM patients(HCM with AF, n=12, HCM without AF, n=36) and analyze the impact of MVD on the extent of fibrosis in HCM patients with or without AF.Results: The extent of fibrosis were significantly higher in HCM patients with AF than in HCM patients without AF([19.1± 8.4] % vs [10.8 ± 5.9]%, P=0.007). MVD was lower in HCM patients with AF than those without AF([352 ± 63]/mm~2 vs [526± 213]/mm~2, P=0.008). MVD was negatively correlated with the extent of fibrosis in all HCM patients(r=-0.52, P< 0.001), in HCM patients with AF(r=-0.66, P=0.02) and HCM patients without AF(r=-0.46, P=0.005). Multiple linear regression analysis showed that the reduced MVD remained as a strong independent predictor of the extent of fibrosis in HCM patients with AF(β=-1.03, P=0.01) after adjusting for age and left atrial diameter.Conclusions: Fibrosis is higher and MVD is lower in HCM patients with AF than in HCM patients without AF.Microvascular rarefaction is a strong independent predictor of the increased extent of fibrosis in HCM patients with AF.
引文
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[19]Wada Y,Aiba T,Matsuyama TA,et al.Clinical and pathological impact of tissue fibrosis on lethal arrhythmic events in hypertrophic cardiomyopathy patients with impaired systolic function[J].Circ J,2015,79(8):1733-1741.DOI:10.1253/circj.CJ-15-0104.
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[22]Tanaka M,Fujiwara H,Onodera T,et al.Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts,hypertensive hearts,and hearts with hypertrophic cardiomyopathy[J].Circulation,1987,75(6):1130-1139.DOI:10.1161/01.CIR.75.6.1130.
[2]Papavassiliu T,Germans T,Flüchter S,et al.CMR findings in patients with hypertrophic cardiomyopathy and atrial fibrillation[J].J Cardiovasc Magn R,2009,11(1):1-9.DOI:10.1186/1532-429X-11-34.
[3]Olivotto I,Cecchi F,Casey SA,et al.Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy[J].Circulation,2001,104(21):2517-2524.DOI:10.1161/hc4601.097997.
[4]Doi Y,Kitaoka H.Hypertrophic cardiomyopathy in the elderly:significance of atrial fibrillation[J].J Cardiol,2001,37(Suppl 1):133-138.
[5]Yamaji K,Fujimoto S,Yutani C,et al.Does the progression of myocardial fibrosis lead to atrial fibrillation in patients with hypertrophic cardiomyopathy?[J].Cardiovasc Pathol,2001,10(6):297.DOI:10.1016/S1054-8807(01)00086-2.
[6]Tsagalou EP,Anastasiou-Nana M,Agapitos E,et al.Depressed coronary flow reserve is associated with decreased myocardial capillary density in patients with heart failure due to idiopathic dilated cardiomyopathy[J].J Am Coll Cardiol,2008,52(17):1391-1398.DOI:10.1016/j.jacc.2008.05.064.
[7]Cameli M,Mondillo S,Righini FM,et al.Left ventricular deformation and myocardial fibrosis in patients with advanced heart failure requiring transplantation[J].J Card Fail,2016,22(11):901-907.DOI:10.1016/j.cardfail.2016.02.012.
[8]田涛,王怡璐,包镜汝,等.心房颤动对肥厚性心肌病预后的影响[J].中国循环杂志,2013,28(z1):109.
[9]Manuguerra R,Callegari S,Corradi D.Inherited structural heart diseases with potential atrial fibrillation occurrence[J].J Cardiovasc Electr,2015,27(2):242-252.DOI:10.1111/jce.12872.
[10]Moon JC,Mckenna WJ,Mccrohon JA,et al.Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance[J].J Am Coll Cardiol,2003,41(9):1561-1567.DOI:10.1016/S0735-1097(03)00189-X.
[11]Sachdev V,Shizukuda Y,Brenneman CL,et al.Left atrial volumetric remodeling is predictive of functional capacity in nonobstructive hypertrophic cardiomyopathy[J].Am Heart J,2005,149(4):730-736.DOI:10.1016/j.ahj.2004.07.017.
[12]Yang H,Woo A,Monakier D,et al.Enlarged left atrial volume in hypertrophic cardiomyopathy:a marker for disease severity[J].J Am Soc Echocardiog,2005,18(10):1074-1082.DOI:10.1016/j.echo.2005.06.011.
[13]Liu T,Li GP.Potential mechanisms between atrial dilatation and atrial fibrillation[J].Am Heart J,2006,151(2):e1-e3.DOI:10.1016/j.ahj.2005.02.026.
[14]易茜,马瑞彦.心房结构重构在心房颤动的发生及维持中的作用[J].中国循环杂志,2015,30(8):813-816.DOI:10.3969/j.issn.1000-3614.2015.08.024.
[15]Mewton N,Liu CY,Croisille P,et al.Assessment of myocardial fibrosis with cardiovascular magnetic resonance[J].J Am Coll Cardiol,2011,57(8):891-903.DOI:10.1016/j.jacc.2010.11.013.
[16]Yilmaz A,Kindermann I,Kindermann M,et al.Comparative evaluation of left and right ventricular endomyocardial biopsy:differences in complication rate and diagnostic performance[J].Circulation,2010,122(9):900-909.DOI:10.1161/CIRCULATIONAHA.109.924167.
[17]Goto D,Kinugawa S,Hamaguchi S,et al.Clinical characteristics and outcomes of dilated phase of hypertrophic cardiomyopathy:report from the registry data in Japan[J].J Cardiol,2013,61(1-2):65-70.DOI:10.1016/j.jjcc.2012.08.010.
[18]Shirani J,Pick R,Roberts WC,et al.Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death[J].J Am Coll Cardiol,2000,35(1):36-44.DOI:10.1016/S0735-1097(99)00492-1.
[19]Wada Y,Aiba T,Matsuyama TA,et al.Clinical and pathological impact of tissue fibrosis on lethal arrhythmic events in hypertrophic cardiomyopathy patients with impaired systolic function[J].Circ J,2015,79(8):1733-1741.DOI:10.1253/circj.CJ-15-0104.
[20]Varnava AM,Elliott PM,Mahon N,et al.Relation between myocyte disarray and outcome in hypertrophic cardiomyopathy[J].Am J Cardiol,2001,88(3):275-279.DOI:10.1016/S0002-9149(01)01640-X.
[21]Camici PG,Olivotto I,Rimoldi OE.The coronary circulation and blood flow in left ventricular hypertrophy[J].J Mol Cell Cardiol,2012,52(4):857-864.DOI:DOI:10.1016/j.yjmcc.2011.08.028.
[22]Tanaka M,Fujiwara H,Onodera T,et al.Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts,hypertensive hearts,and hearts with hypertrophic cardiomyopathy[J].Circulation,1987,75(6):1130-1139.DOI:10.1161/01.CIR.75.6.1130.