肥厚性心肌病器械治療阜外心血管病醫(yī)院滕思勇

1、肥厚性心肌病的器械治療,阜外心血管病醫(yī)院 滕思勇,內(nèi)容提要,HCM的基本特征HCM的ICD 治療進展HCM的DDD治療進展,肥厚性心肌病（HCM）是一種復(fù)雜的、相對常見的遺傳性心臟疾病。經(jīng)過40年的嚴密調(diào)查和注冊研究，發(fā)現(xiàn) HCM是所有年齡段的患者致殘和死亡的重要原因。由于臨床表現(xiàn)、自然史和預(yù)后的顯著差異，對于心血管專家來說，HCM的治療依然存在許多爭議。,基本特征（1）,HCM年死亡率約為1.4%，其中猝死0.

2、7%，心衰0.5%，中風(fēng)0.2%。猝死可為HCM的首發(fā)表現(xiàn)。猝死也可發(fā)生在疾病平穩(wěn)期雖然大部分猝死發(fā)生于青少年，但猝死并不局限于青少年，猝死會持續(xù)在所有年齡組中發(fā)生,基本特征（2）,猝死的主要危險因素: 持續(xù)室速家族性猝死史惡性突變類型（如：β-MHC基因Arg403-Gln的家系）暈厥史反復(fù)發(fā)作的非持續(xù)性室速左室肥厚（室壁≥30mm）,基本特征（3）,HCM的基本特征HCM的ICD 治療進展HCM的DDD治

3、療進展,內(nèi)容提要,心臟性猝死是肥厚性心肌病患者死亡的常見原因。大約有10％的肥厚性心肌病患者被認為有心臟性猝死的危險性。肥厚性心肌病猝死高危患者：( 1)猝死幸存者；(2)自發(fā)持續(xù)性心動過速；( 3)猝死家族史；( 4)不明原因暈厥史；(5)運動后血壓反應(yīng)異常，收縮壓不升高反而降低者；(6)左室壁或室間隔厚度≥30mm；流出道壓力階差>50mmHg。50％以上的肥厚性心肌病高危患者10年內(nèi)將發(fā)生心臟性猝死。肥厚性心肌病是35

4、歲以下運動員心臟性猝死的最主要原因。,心臟性猝死的一級和二級預(yù)防的多個前瞻性多中心隨機臨床試驗的結(jié)果（AVID、CASH、MADIT、MADIT-Ⅱ、MUSTT、SCD-HeFT、COMPANION）已經(jīng)充分證明ICD是肯定的效果最佳和唯一可靠的預(yù)防心臟性猝死的選擇，能夠有效降低心臟性猝死高?；颊叩牟∷缆?。,2008年ACC /AHA /ESC室性心律失常治療和心臟性猝死預(yù)防指南把SCD一級和二級預(yù)防的建議合并，對S

5、CD的一級預(yù)防提到更加顯著位置，HCM患者出現(xiàn)以下情況為植入ICDⅠ類適應(yīng)癥：1）自發(fā)持續(xù)性VT、無論血液動力學(xué)是否穩(wěn)定。2）有暈厥史、電生理檢查明確誘發(fā)有血液動力學(xué)不穩(wěn)定的持續(xù)性VT或VF。肥厚型心肌病患者有一項以上主要SCD危險因素，包括心臟驟停史、自發(fā)持續(xù)性VT、自發(fā)非持續(xù)性VT、SCD家族史、不明原因暈厥史、左室厚度≥30mm、運動時血壓反應(yīng)異常，建議植入ICD。------------------,心臟性猝死（SCD）的發(fā)

6、病年齡 Single most frequent cause of SCD in youn competitive athletes in the U.S.. ARVC, arrhythmogenic right ventricular cardiomyopathy; AS, aortic valve stenosis; CAD, coronary artery disease; CHD, *Regarded as possib

7、le (but not definitive) evidence for hypertrophic cardiomyopathy at autopsy with mildly increased LV wall thickness (15–19 mm) and heart weight (447±76 g). ?Includes most commonly, Kawasaki disease, sickle cell trai

8、t and sarcoid.,Maron BJ,Circulation 2009; 119: 1085 – 1092,HCM心律失常的發(fā)生具有不可預(yù)測性Time interval between implantation of implantable cardioverter-defibrillator(ICD) and first appropriate intervention. Variable time delay aft

9、er implantationis evident, with some devicedischarges occurring relatively early and others 5–10 years later (blue bars). Hourly distribution of appropriate ICD interventions over the 24-h day for 126 ventricular tach

10、ycardia/ventricular fibrillation events in63 patients with HCM.,心臟猝死的危險分層 Pyramid profile currently used to identify patients at highest risk for SCDwho are potential candidates for animplantable cardioverter-defib

11、rillator(ICD). BP, blood pressure; LV, leftventricular; LVH, left ventricular hypertrophy;NSVT, nonsustained ventriculartachycardia; VT, ventriculartachycardia. *Following alcohol septalablation, sustained VT has bee

12、nreported in a significant minority ofpatients (≈10%) over the short term.Direct relation between magnitude of LV hypertrophy (maximum[max] wall thickness by echocardiography)and SCD risk. Mild hypertrophygenerally c

13、onveys lower riskand extreme hypertrophy (wall thickness≥30 mm) is associated with thehighest risk.,HCM合并持續(xù)性室性心動過速的影像和病理特征 (A)Massive hypertrophy with ventricular septal (VS) thickness of 55 mm. (B) Akinetic thin-walled

14、 LV apical aneurysm with midcavity muscular apposition. D, distal (cavity); LA, left atrium; P, proximal (cavity); (B1) Contrast-cardiovascular magnetic resonance shows delayed enhancement (ie, scar) involving the thin a

15、neurysm rim (arrowheads) and contiguous myocardium (large arrow); small apical thrombus is evident (small arrow). (C) Large transmural ventricular septal scar (arrow) resulting from alcohol ablation(arrow) (reproduced wi

16、th permission). (D) “End-stage” heart showing extensive and transmural septal scarring,extending into the anterior wall (arrowheads).,HCM心臟核磁顯像延遲提示致心律失?；|(zhì)的存在Ventricular tachyarrhythmias on ambulatory (Holter) ECG, inc

17、luding nonsustained VT (NSVT), are significantly more frequent in the presence of DE. PVC, premature ventricular contraction; SVT, supraventricular tachycardia.A 21-year-old man with hypertrophic cardiomyopathy (HCM) an

18、d septal scarring who survived anepisode of ventricular fibrillation (VF)because of ICD intervention (A). Contrast-enhanced CMR image showing transmural DE with high signal intensity occupying substantial proportion of

19、 septum (arrows). (B) Without contrast,showing moderate asymmetrichypertrophy of the ventricular septum (VS; 21 mm). (C) Intracardiac electrogramshowing VF interrupted bydefibrillation shock (arrow).,Maron BJ, Am J

20、Cardiol 2008;,肌節(jié)組成及突變示意圖 Schematic representation of the components of a half sarcomere. Components in which cardiomyopathy-associated mutations are found are underlined.,MHC突變Arg403-Gln猝死患者的心肌細胞形態(tài)特征A, Gross heart spe

21、cimen from a 13-year-old male competitive athlete showing isproportionate thickening of the ventricular septum (VS) with respect to the left ventricular (LV) free wall (RV indicates right ventricular wall); B, marked d

22、isarray of cardiac muscle cells in the isproportionately thickened VS with adjacent hypertrophied cells arranged in a chaotic pattern at oblique and perpendicular angles, forming the typical disorganized architecture of

23、 HCM; C, LV myocardium showing several abnormal intramural coronary arteries with markedly thickened walls and narrowed lumen, dispersed within replacement fibrosis,Maron, B. J. JAMA 2002;287:1308-1320,Copyright restric

24、tions may apply.,糖原儲積性疾病表現(xiàn)為HCM和WPW,LAMP2型心肌病特征 (A) From a 14-year-old boy with sudden cardiac death and a septal thickness of 65 mm(heart weight 1,425 g). (B) Clusters of myocytes with vacuolated sarcoplasm (stained re

25、d) embedded in an area of scar(stained blue; Masson trichrome). (C) Disorganized arrangement of myocytes most typical of sarcomeric hypertrophic cardiomyopathy.(D) Intracardiac electrogram. The implantable cardioverter-

26、defibrillator elicited 5 defibrillation shocks that failed to interrupt ventricular fibrillation (280 beats/min).,心臟性猝死的家族史 (Top) Intracardiac electrogram obtained at 1:20 am while asleep 5 years after placement of an

27、implantable cardioverter-defibrillator (ICD). From a 35-year-old man with hypertrophic cardiomyopathy who received prophylactic ICD because of family history of SCD and markedventricular septal thickness (31 mm).(A) Ve

28、ntricular tachycardia (VT) beginsabruptly, at 200 beats/min. (B)Defibrillator senses VT and charges.(C) VT deteriorates into ventricularfibrillation (VF) (D) defibrillator issues20-J shock (arrow), restoring sinusr

29、hythm immediately. Virtually identicalsequence occurred 9 years laterduring sleep; patient is now 52 yearsold and asymptomatic. (Reproducedwith permission.) (Bottom) Flow-chartof ICD-related outcome in 506 highrisk

30、HCM patients from an international,multicenter ICD registry,HCM主要危險因素與預(yù)后 (Top) Appropriate implantablecardioverter-defibrillator (ICD) intervention rates(per 100 person-years) are not significantly different with res

31、pectto 1, 2 or ≥3 risk factors. (Bottom) Cumulative ratesfor first appropriate device intervention in patients with 1, 2or ≥3 risk factors.,Maron BJ,Circulation 2009; 119: 1085 – 1092,HCM的基本特征HCM的ICD 治療進展HCM的DDD治療

32、進展,內(nèi)容提要,肥厚型心肌病伴竇房結(jié)功能異常或房室傳導(dǎo)阻滯需植入永久性起搏器者。（伴或不伴左室流出道梗阻）藥物治療無效、靜息或應(yīng)激時流出道梗阻的肥厚型心肌病患者，不推薦植入永久性起搏器，為IIb類（證據(jù)級別A級）推薦。（強調(diào)個體化治療）有SCD風(fēng)險（主要SCD風(fēng)險：心臟驟停史，自發(fā)持續(xù)性VT，自發(fā)非持續(xù)性VT，SCD家族史，暈厥，左室厚度≥30mm，運動時血壓反應(yīng)異常；可能的SCD風(fēng)險：房顫、心肌缺血、左室流出道梗阻、突變高危、

33、強競技性體力活動時）應(yīng)植入DDD-ICD。無癥狀或有癥狀但藥物可控制、沒有左室流出道梗阻證據(jù)的肥厚型心肌病患者禁止植入永久性起搏器。,HCM起搏器治療指南（2008年AHA/HRS),HCM梗阻型的血流動力學(xué)異常,,,LV流出道,,二尖瓣前葉,增厚的間隔,舒張期,收縮期,,1101例HCM隨訪6.3±6.2年。結(jié)論：休息下LVOT壓差>30mmHg是HOCM死亡、心衰的獨立危險因素。,Martin S N Engl

34、 J Med 2003; 348:295-303,DDD起搏器植入后,舒張期,收縮期,,起搏導(dǎo)線,,,,經(jīng)導(dǎo)管測流出道壓差,起搏前,起搏治療后,LV收縮壓,動脈壓,DDD起搏器植入后,,多中心,隨機,雙盲,3個月交叉試驗藥物治療無效的83例患者，平均年齡53歲,隨訪1年。比較主動起搏（DDD，最適AV間期）對非主動起搏（AAI起搏，30次/分）的療效。84%患者生活質(zhì)量和癥狀改善.,PIC 研究,,藥物治療無效的48例患者,L

35、VOT壓差?50mmHg隨機雙盲3個月交叉試驗在雙盲試驗階段，患者生活質(zhì)量和癥狀改善,DDD起搏和AAI起搏組無差別。6個月非盲試驗階段患者生活質(zhì)量和癥狀在DDD組明顯改善。 安慰劑效應(yīng)？,,M-PATHY 研究,DDD起搏治療梗阻型HCM的適應(yīng)癥,LVOT壓差靜息>30mmHg 激發(fā)后>50mmHg室間隔基部而非心尖部、心室中部的心肌肥厚無慢性或頻繁發(fā)作的陣發(fā)性

36、房顫,DDD起搏治療梗阻性HCM的技術(shù)參數(shù),心室起搏位點：起搏電極必須置于真正的右室尖AV間期（25msec~125msec)：必須短于竇性心律的PR間期AV間期程控期間監(jiān)測左室和主動脈壓力，必要時行激發(fā)試驗盡量保證竇性心律,最佳AV間期的程控,最佳AVD調(diào)整原則：有效的AVD短于自身PR間期保持適當(dāng)房室同步，維持左室的前負荷Jeanrenaud觀察13例不同AVD的血流動力學(xué)變化,Lancet,1992,339:1318-

37、1323,DDD起搏治療不能改善LVOT梗阻的原因,起搏器參數(shù)程控不當(dāng) 心室激動提前不適當(dāng)（AV延遲值過長） 干擾左房排空（ AV延遲值過短）其他相關(guān)的異常 心室電極位于室間隔的近端或高位 異位乳頭肌阻塞LOVT 原發(fā)的二尖瓣反流 左室腔中部梗阻 心房或/和心室的快速心律失常 左室舒張功能障礙 藥物治療不當(dāng),DDD起搏對HOCM的遠期療效仍爭論，沒

38、有證據(jù)表明DDD起搏可改善HOCM患者的預(yù)后。嚴格選擇病例-HOCM伴竇性心動過緩/不能耐受BB者程控最佳的AVD藥物控制房顫,爭論還將繼續(xù)？,Simultaneous measurement of aortic and left ventricular pressures.,Haruki S et al. Eur J Heart Fail 2010;12:94-97,Published on behalf of the Euro

39、pean Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.,Simultaneous measurement of aortic and left ventricular pressures. (A) The b

40、aseline pressure gradient was 127 mmHg. (B) DDD pacing at a rate of 80/min and an atrioventricular interval of 150 ms reduced the gradient to 27 mmHg. (C) After 5 min of disopyramide infusion (1.0 mg/kg) without DDD paci