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(jìn)展 HCM的DDD治療進(jìn)展,肥厚性心肌?。℉CM）是一種復(fù)雜的、相對(duì)常見的遺傳性心臟疾病。 經(jīng)過40年的嚴(yán)密調(diào)查和注冊(cè)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(duì)于心血管專家來說，HCM的治療依然存在許多爭(zhēng)議。,基本特征（1）,HCM年死亡率約為1.4%，其中猝死0.7%，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(huì)持續(xù)在所有年齡組中發(fā)生,基本特

2、征（2）,猝死的主要危險(xiǎn)因素: 持續(xù)室速 家族性猝死史 惡性突變類型（如：-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(jìn)展 HCM的DDD治療進(jìn)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(rèn)為有心臟性猝死的危險(xiǎn)性。 肥厚性心肌病猝死高?；颊撸? 1)猝死幸存者；(2)自發(fā)持續(xù)性心動(dòng)過速；( 3)猝死家族史；( 4)不明原因暈厥史；(5)運(yùn)動(dòng)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。

3、50以上的肥厚性心肌病高?；颊?0年內(nèi)將發(fā)生心臟性猝死。 肥厚性心肌病是35歲以下運(yùn)動(dòng)員心臟性猝死的最主要原因。,心臟性猝死的一級(jí)和二級(jí)預(yù)防的多個(gè)前瞻性多中心隨機(jī)臨床試驗(yàn)的結(jié)果（AVID、CASH、MADIT、MADIT-、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(jí)和二級(jí)預(yù)防的建議合并，對(duì)SCD的一級(jí)預(yù)防提到更加顯著位置，HCM患者出現(xiàn)以下情況為植入ICD類適應(yīng)癥：1）自發(fā)持續(xù)性VT、無論血液動(dòng)力學(xué)

4、是否穩(wěn)定。2）有暈厥史、電生理檢查明確誘發(fā)有血液動(dòng)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(xiàng)以上主要SCD危險(xiǎn)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(yùn)動(dòng)時(shí)血壓反應(yīng)異常，建議植入ICD。-,心臟性猝死（SCD）的發(fā)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 sten

5、osis; CAD, coronary artery disease; CHD, *Regarded as possible (but not definitive) evidence for hypertrophic cardiomyopathy at autopsy with mildly increased LV wall thickness (1519 mm) and heart weight (44776 g). Includes most commonly, Kawasaki disease, sickle cell trait and sarcoid.,Maron BJ,Circ

6、ulation 2009; 119: 1085 1092,HCM心律失常的發(fā)生具有不可預(yù)測(cè)性 Time interval between implantation of implantable cardioverter-defibrillator (ICD) and first appropriate intervention. Variable time delay after implantation is evident, with some device discharges occurring relatively early and others 510 years later (

7、blue bars). Hourly distribution of appropriate ICD interventions over the 24-h day for 126 ventricular tachycardia/ ventricular fibrillation events in 63 patients with HCM.,心臟猝死的危險(xiǎn)分層 Pyramid profile currently used to identify patients at highest risk for SCD who are potential candidates for an impla

8、ntable cardioverter-defibrillator (ICD). BP, blood pressure; LV, left ventricular; LVH, left ventricular hypertrophy;NSVT, nonsustained ventriculartachycardia; VT, ventricular tachycardia. *Following alcohol septal ablation, sustained VT has been reported in a significant minority of patients (10%)

9、over the short term. Direct relation between magnitude of LV hypertrophy (maximummax wall thickness by echocardiography)and SCD risk. Mild hypertrophygenerally conveys lower riskand extreme hypertrophy (wall thickness30 mm) is associated with thehighest risk.,HCM合并持續(xù)性室性心動(dòng)過速的影像和病理特征 (A)Massive hypert

10、rophy with ventricular septal (VS) thickness of 55 mm. (B) Akinetic thin-walled 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 an

11、eurysm 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 with permission). (D) “End-stage” heart showing extensive and transmural septal sca

12、rring, 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, including nonsustained VT (NSVT), are significantly more frequent in the presence of DE. PVC, premature ventricular contraction; SVT, supraventricular tachycardia. A

13、 21-year-old man with hypertrophic cardiomyopathy (HCM) and septal scarring who survived an episode of ventricular fibrillation (VF) because of ICD intervention (A). Contrast-enhanced CMR image showing transmural DE with high signal intensity occupying substantial proportion of septum (arrows). (B)

14、Without contrast, showing moderate asymmetric hypertrophy of the ventricular septum (VS; 21 mm). (C) Intracardiac electrogram showing VF interrupted by defibrillation shock (arrow).,Maron BJ, Am J Cardiol 2008;,肌節(jié)組成及突變示意圖 Schematic representation of the components of a half sarcomere. Components in

15、which cardiomyopathy-associated mutations are found are underlined.,MHC突變Arg403-Gln猝死患者的心肌細(xì)胞形態(tài)特征 A, Gross heart specimen 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 rig

16、ht ventricular wall); B, marked disarray 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 HCM; C, LV myocardium showing several abnormal

17、intramural coronary arteries with markedly thickened walls and narrowed lumen, dispersed within replacement fibrosis,Maron, B. J. JAMA 2002;287:1308-1320,Copyright restrictions may apply.,糖原儲(chǔ)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

18、mm (heart weight 1,425 g). (B) Clusters of myocytes with vacuolated sarcoplasm (stained red) 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 car

19、dioverter-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 implantable cardioverter-defibrillator (ICD). From a 35-year-old man wit

20、h hypertrophic cardiomyopathy who received prophylactic ICD because of family history of SCD and marked ventricular septal thickness (31 mm). (A) Ventricular tachycardia (VT) begins abruptly, at 200 beats/min. (B) Defibrillator senses VT and charges. (C) VT deteriorates into ventricular fibrillation

21、 (VF) (D) defibrillator issues 20-J shock (arrow), restoring sinus rhythm immediately. Virtually identical sequence occurred 9 years later during sleep; patient is now 52 years old and asymptomatic. (Reproduced with permission.) (Bottom) Flow-chart of ICD-related outcome in 506 highrisk HCM patients

22、 from an international, multicenter ICD registry,HCM主要危險(xiǎn)因素與預(yù)后 (Top) Appropriate implantable cardioverter-defibrillator (ICD) intervention rates (per 100 person-years) are not significantly different with respect to 1, 2 or 3 risk factors. (Bottom) Cumulative rates for first appropriate device interv

23、ention in patients with 1, 2 or 3 risk factors.,Maron BJ,Circulation 2009; 119: 1085 1092,HCM的基本特征 HCM的ICD 治療進(jìn)展 HCM的DDD治療進(jìn)展,內(nèi)容提要,肥厚型心肌病伴竇房結(jié)功能異?；蚍渴覀鲗?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(shí)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(jí)別A級(jí)）推薦。（強(qiáng)調(diào)個(gè)體化治療） 有SCD風(fēng)險(xiǎn)（主要SCD風(fēng)險(xiǎn)：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(yùn)動(dòng)

24、時(shí)血壓反應(yīng)異常；可能的SCD風(fēng)險(xiǎn)：房顫、心肌缺血、左室流出道梗阻、突變高危、強(qiáng)競(jìng)技性體力活動(dòng)時(shí)）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(dòng)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6.36.2年。結(jié)論：休息下LVOT壓差30mmHg是HOCM死亡、心衰的獨(dú)立危險(xiǎn)因素。,Martin S N Engl 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(cè)流出道壓差

25、,起搏前,起搏治療后,LV 收縮壓,動(dòng)脈壓,DDD起搏器植入后,多中心,隨機(jī),雙盲,3個(gè)月交叉試驗(yàn) 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(dòng)起搏（DDD，最適AV間期）對(duì)非主動(dòng)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,LVOT壓差50mmHg 隨機(jī)雙盲3個(gè)月交叉試驗(yàn) 在雙盲試驗(yàn)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(gè)月非盲試驗(yàn)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

26、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)性房顫,DDD起搏治療梗阻性HCM的技術(shù)參數(shù),心室起搏位點(diǎn)：起搏電極必須置于真正的右室尖 AV間期（25msec125msec)：必須短于竇性心律的PR間期 AV間期程控期間監(jiān)測(cè)左室和主動(dòng)脈壓力，必要時(shí)行激發(fā)試驗(yàn) 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(fù)荷 Jeanrenaud觀察13例不同AVD的血流動(dòng)力學(xué)變化,Lancet,1992,339:1318-1323,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(dòng)提前不適當(dāng)（AV延遲值過長(zhǎng)） 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