心肌肥厚鉴别诊疗惠汝太

1、心肌肥厚鉴别诊疗惠汝太 没有利益冲突2/513/5195% HCM-心肌排列紊乱正常心肌HCM4/5195% HCM-心肌排列紊乱伴间质纤维化广泛的纤维化：红箭头5/51HCM病理表现-与临床表型有关1, 心脏肥厚，2，心肌排列紊乱，3，纤维化，4，小血管病变6/517/518/51 核磁对肥厚型心肌病的诊断价值突出1，能评价心脏功能，大小，最大壁厚度，肥厚的分布，全 心重量指数（overall mass index）.2，评价左室流出道梗阻3，核磁可以检查HCM患者是否存在心肌纤维化； 方法：钆-DTPA 反转恢复心肌延迟增强技术9/51IVSLVFree wall.RV 室间隔肥厚，左室游

2、离壁正常 Reproduced with permission of AHA; from Maron MS et al. (28).10/51Reproduced with permission of American Heart Association; from Maron MS et al. (28).仅仅局限于室间隔前基地部的肥厚 (arrows)11/51 左室心尖部肥厚 (asterisk); *LVReproduced with permission of American Heart Association; from Maron MS et al. (28).12/51CMR

3、 可以发现2D发现不了的肥厚型心肌病. 有家族 HCM史的患者2D超声正常. B. 同一个患者, 核磁发现左室前侧壁节段性肥厚 (asterick) Reproduced with permission of American Heart Association; from Maron MS et al. (28).13/51心尖部心肌肥厚：2D易漏诊 超声不能确诊HCM,B. 同一个患者，CMR可以清楚证明心尖部肥厚，可确诊为心尖部 HCM. Reproduced with permission of American Heart Association; from Maron MS et

4、al. (28).14/51心超与核磁的比较：A. 2D超声：舒张末期4腔心-心尖无室壁瘤征象。B. 同一患者， CMR 发现心尖部有一个小的室壁瘤（薄边，(arrowheads), 延迟钆增强显像：透壁疤痕. Reproduced with permission of American Heart Association; from Maron MS et al. (28). LVLAVS15/51HCM患者：肥厚区域与非肥厚区域相间排列RVLV16/51HCM患者，左室重量正常，仅表现为乳头肌增大数目增多。乳头肌LVIVSRV乳头肌数目增多：4个 (arrows)1/5117/51Shar

5、lene M. Day18/51Sharlene M. DaySharlene M. Day19/5120/51HCM 存在：小动脉周围轻度增厚与纤维化 ，导致心肌内小动脉壁/腔比率增加，心内膜下缺血，冠脉血流储备障碍。造成死亡的原因之一。21/51 1，最常见的心脏肥厚原因：HCM，高血压, 淀粉样变，主 动脉狭窄，运动员心脏. 2，心肌细胞排列紊乱：不是HCM 特征性的表现， 可见于: 主动脉狭窄， 先天性心脏病 高血压性心脏病 肥厚型心肌病 Noonan综合征， 克山病，交感刺激，Myocyte disarray develops in papillary muscles release

6、d from normal tension after mitral valve replacement（Circulation. 1982 Oct;66(4):841-6.）。22/5123/5124/5125/5126/5127/51Clinical DataMYH7(n=52)MYBPC3(n=18)BasicLast F-upBasicLast F-upSex, male，n (%)27(51.9)13(72.2)SD FH, n(%)27(51.9)*1(5.6)Onset age (yrs)34.614.0*39.913.750.015.054.713.6NYHA, n (%)NY

7、HA I IINYHA III IV38(73.1)14(26.9)31(59.6)21(40.4)15(83.3)3(16.7)12(66.7)6(33.3)Af, n (%)12(23.1)16(30.8)1(5.6)4(22.2)New Af4/403/17EchoLVEDD (mm)44.25.945.66.746.63.646.94.3MLVWT (mm)20.55.719.25.319.96.519.46.8PWT (mm)10.32.19.81.710.62.610.22.4LAD (mm)41.76.742.66.944.66.844.87.1LVOG30mmHg，n(%)21

8、(40.4%)18(34.6)2(11.1%)2(11.1%)28/51随访6年*The major intervention included surgical septal myectomy, Alcohol septal ablation and DDD pacemaker CharacteristicsDuration of follow-up (yrs)HCM-causing geneP value(MYH7 vs MYBPC3)nsMYH7(n=52)5.91.8MYBPC3(n=18)5.71.7Major intervention *, n800.001Death relate

9、d to HCM, n, (%/1000 person-year, 95% CI)10(32.1, 12.5-51.5)4(35.2, 13.9-68.9) nsSudden death7030mmHg, n (%)16(39)14(34.1)5（45）4(36.4)31/51MYH7头、杆部突变 及 MYBPC3 突变患者的Kaplane-Meier 生存曲线 32/5133/5134/5135/51挑战左室肥厚是HCM的特征性表现，但是，携带基因突变的患者，在出生时很少有左室肥厚，HCM患者的心肌肥厚通常从青春期后慢慢发展起来的， 也有60-70岁才开始出现； 左心室肥厚的分布：多是局部性

10、、不对称性， 即使同一家族，变异特别大；左室重量不一定超过正常（21%的HCM患者心脏重量正常）； 为何室间隔肥厚、心尖部肥厚较多见，为何出现上述多样性？-modifier？36/51HCM主要遗传突变基因是编码肌小节蛋白的基因，仅在心肌细胞表达；但是，HCM 临床表型不仅如此: 心肌排列紊乱, 间质纤维化, 二尖瓣异常，微血管重塑；提示其他细胞系同样参与。肌小节基因突变与HCM广泛的表型之间的联系仍然不清楚。37/51HCM各种表现可能与共同始祖细胞-心外膜源多能干细胞（pluripotent epicardium-derived cells ，EPDCs)有关。在心脏 发育时期, EPDC

11、s 分化成为间质成纤维细胞, 冠脉平滑肌细胞, 房室心内膜垫，如间充质干细胞. We propose that the cross-talk between healthy EPDCs and abnormally contracting cardiomyocytes might account for the diverse manifestations of HCM, by a putative mechanism of mechanotransduction leading to abnormal gene expression and differentiation.38/5139/5

12、1Modifier Gene for HCM, not for hypertension hypertrophy40/51Subjects with high Blood pressure 2004,11-2005,8， 7 communities，60 villages, 15835 Han nationality， Final: 13444（Male 5270，Female 8174） Hypertension prevalence 40.3%， 5421with Hypertension enrolled, Echocardiography was performed in 4869（8

13、9.8%）;41/51 CharacteristicCharacteristicWhole group(n= 4270)Men(n=1416)Women(n=2854)age（y）58.68.059.88.2*58.07.9SBP（mmHg）165.422.7163.622.3166.322.8 *DBP（mmHg）97.911.899.111.7*97.411.7BMI,kg/m226.243.6925.73.426.53.8 *glucose5.61.75.61.65.61.8triglyceride1.71.31.61.41.71.2*cholesterol5.61.15.41.15.6

14、1.1 *HDL1.60.31.50.31.60.3 *LDL3.20.93.10.83.20.9 *p0.0542/51Prevalence of Left Ventricular HypertrophyAge group (y)Whole group Men WomenNumber(n) LVH (%) Number(n) LVH (%) Number(n) LVH (%) Total427042.8141637.4285445.440156236.743533.311273855166246.852540.6111049.965104645.442937.561750.943/51Mod

15、ifiers for Left Ventricular HypertrophyVariablesBefore Adjust OR(95% CI)After Adjust OR(95% CI)Age (Each 10 years increase)1.2(1.2-1.3) *1.2(1.1-1.3)*Sex (F/M)1.4(1.2-1.6) *1.3(1.2-1.5) *SBP(Each 10 mmHg increase)1.2(1.1-1.2) *1.2(1.1-1.3) *BMI (Each 2 kg/m2)1.3(1.2-1.4) *1.4(1.3-1.5) *TG (Each mmol

16、/L)1.1(1.0-1.1) *1.1(1.0-1.2) *HDL-C (Each mmol/L)0.7(0.6-0.8) *0.9(0.7-1.1)44/51Additive Effects of hypertrophic Risk FactorsNumber of Risk Factors*Odds ratio(95% CI)0 (n=327)-1 (n=1,286)1.4 (1.1-1.8)2 (n=1,580)2.1(1.6-2.6)3 (n=780)2.5 (1.9-3.3)4 (n=297)3.7 (2.4-5.5)45/51We tested whether PGC-1alpha is a modifier for cardi