浙江大学医学院附属第一医院心内科 胡晓晟 陶谦民 CRT-D？ CRT-P？ 浙江大学医学院附属第一医院心内科 胡晓晟 陶谦民

病例一：病 史 患者女性，62岁。 反复乏力、气急四年于09.6.18入院。 于08.4.24 2 2 2

辅助检查 胸片：心胸比0.69 EKG:左束支传导阻滞 QRS时限 0.15s 3

超声检查 4

诊断 扩张型心肌病 (EF 18%) 左束支传导阻滞 （QRS时限 0.15s） 二尖瓣关闭不全（中度） 心功能III级 5

你的处理？ 遇到类似的病例你会如何选择？ CRT-P CRT-D

CRT－D植入 09年6月22日植入CRT－D 成功植入电极于冠状静脉的左侧外静脉、右心室、右心房。 ICD：一级预防。术中未诱颤。 心动过速200次/分以上，进入室颤处理程序，20J×1、30J×5. 7

出院带药 术后第4天出院 地高辛 速尿 1# qd 安体舒通 1# qd 倍他乐克 6.25mg Bid 可达龙 0.2 Bid 8

再入院 术后第11天(7月3日) 晚 7：00左右，突发晕厥，两眼上翻，四肢抽搐，持续1分钟左右。 急送我院，查EKG:频发室早。 9

程控记录7:03pm提示：VF发作 30J 10

20J 30J 11

30J 30J 30J 12

器械功能：正常 VF为正确诊断，除颤阈值增高，余无殊 CRT-D 程控： 起搏、感知、阻抗均正常

本例特点分析 14

动态心电图变化 CRT植入前6.19：室早 21次/24h 偶发多源室性早搏，偶呈短阵室速（1阵） CRT植入后6.25：（术后第2天） 频发多源室性早搏，部分成对（10对），偶呈短阵室速（1阵） 再入院出院时7.7：（术后第15天） 未见室早/24h 15

电解质变化 CRT植入前 4.29 mmol/dl CRT植入后 4.07 mmol/dl 7.3再入院时 4.11 mmol/dl 16

出院带药: 无变化 地高辛 速尿 1# qd 安体舒通 1# qd 倍他乐克 6.25mg Bid 可达龙 0.2 Bid 17

再出院后随访：1年 植入前 2009.6.18 植入1年后 2010.7.6 心功能 III-IV I-II 胸片 心胸比 0.69 0.56 超声 EF 18% LV 7.2cm 二尖瓣中度反流 EF 38% LV 6.1cm 二尖瓣轻度反流 18

19

心胸比：0.69 20

心胸比：0.56 21

2011.2.20 22

再出院后随访：1年 此后未发生晕厥、电击等类似事件。 目前用药： 停地高辛 速尿 安体舒通 间断服用 倍他乐克 25mg bid 可达龙 0.1 qd 间断服用 23

病例二：病 史 患者女性，52岁。 活动后气急半年于10.12.19入院。 于08.4.24 24 24 24

辅助检查 胸片：心胸比0.69 EKG:左束支传导阻滞 QRS时限 0.14s 25

诊断 扩张型心肌病 (EF 28%) 左束支传导阻滞 （QRS时限 0.14s） 二尖瓣关闭不全（中-重度） 心功能III级 26

你的处理？ CRT-P？ CRT-D？

CRT－D植入 10年12月25日植入CRT－D ICD：一级预防。术中未诱颤。 28

出院带药 术后第 天出院 地高辛 速尿 安体舒通 倍他乐克 可达龙 29

再入院 术后1个月(2011年1月22日) 电风暴 30

电风暴：2011-1-23共发作55次VF

2011-1-22心动过速发作2次

2011-1-23心动过速发作（54）

2011-1-23心动过速发作（56）

2011-1-23心动过速发作（57）

器械功能：正常 57次全部为正确诊断，第一次电击治疗就能成功转复。 CRT-D 程控： 起搏、感知、阻抗均正常

本例特点分析 37

动态心电图变化 CRT植入前12.17：室早 7290次/24h 频发多源室性早搏，部分成对（221对），短阵室速（4阵） 频发多源室性早搏，部分成对（61对） 38

电解质变化 CRT植入前 4.15 mmol/dl CRT植入后 3.9 mmol/dl 电风暴时（外院） 2.9mmol/dl 39

出院带药:无变化 地高辛 速尿 安体舒通 倍他乐克 可达龙 0.2 Bid 40

心功能等指标变化 植入前 2010.12.25 再入院时 2011.1.23 心功能 III 超声 EF 28% 左室7.0cm 二尖瓣中重度反流 EF 30% 左室7.2cm 二尖瓣轻中度反流 41

再出院后随访：9个月 植入前 2010.12.25 九个月后 2011.8.16 心功能 III I-II 超声 EF 28% LVDd 7.0cm EF41% LVDd 6.3cm 42

再出院后随访：1年 此后未发生晕厥、电击等类似事件。 目前用药： 停地高辛 速尿 安体舒通 间断服用 倍他乐克 可达龙 0.1 qd 43

遇到类似的病例你会如何选择？ CRT-P？ CRT-D？

充血性心力衰竭与猝死 有症状的心力衰竭患者在确诊后2.5年内，有20%-25%患者发生意外死亡 其主要原因为VT/VF引起的猝死

尽管给予理想的药物治疗， 心衰患者的猝死率仍非常高 1 MERIT-HF Study Group.Effect of metroprolol CR/XL in chronic heart failure.Lancet.1999;353:2001-2007. 2 CIBIS Investigations and Committees.The cardiac insufficiency bisprolol study II (CIBIS-II).Lancet.1999;353:9-13. 3 Packer M,Bristow MR,Cohn JN,et al.The effect of carvedilol on morbitity and nortality in patients with chronic heart failure.U.S.Carvedilol Heart Failure Study Group.N Engl J Med.1996;334:1349-1355. 4 The RALE Investigators.Effectiveness of spironolactone added to an aniotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure(the Randomized Aldactone Evaluation Study[RALES].Am J Cardiol.1997;78:902.

心衰的死亡模式 NYHA II NYHA III CHF CHF 12% 其他 26% 其他 24% 猝死 59% 64% 猝死 15% NYHA IV MERIT-HF研究死亡模式分析发现,NYHA II/III的患者猝死比例高于心衰恶化 CHF 33% 其他 56% 猝死 11% (N = 27) 1 MERIT-HF Study Group. LANCET. 1999;353:2001-2007.

LVEF与SCA的相关性 SCA危险性增加了6+ 倍 % SCA Victims LVEF 7.5% 5.1% 2.8% 1.4% 1 Gorgels, PMA Out-of-hospital cardiac arrest-the relevance of heart failure.The Maastricht Circulatory Arrest Registry.European Heart Journal.2003;24:1204-1209.

CRT治疗改善生活质量和NYHA 分级 平均生活质量评分变化 (MLWHF) NYHA: 改善至少1级 * P < 0.05 Main purpose: Show concordance of proof from randomized controlled trials that CRT improves quality of life and functional status. Key messages: Results from blinded studies that randomized 1,000 NYHA Class III/IV heart failure patients with a wide QRS show that CRT dramatically improves patients’ perceived quality of life and the clinicians’ assessment of functional status. The so-called placebo effect was expected. These studies were designed to assess whether there was a treatment effect, and all consistently demonstrated a positive effect. Additional information: Slide 13 shows there is a placebo effect with drugs as well. MIRACLE ICD reprint: UC200400265 EN * P < 0.05 1. NEJM 2002;346:1845-53 2. NEJM 2001;344:873-80 3. Eur Heart J 2002;23:1780-1787 4. http://www.fda.gov/cdrh/pdf/P010012b.pdf. Accessed August 2, 2002 5. JAMA 2003; 289:2685-94

Cardiac Resynchronization-Heart Failure (CARE-HF) 研究结果证实了CRT对中－重度心衰患者的价值，全文发表在2005新英格兰医学杂志 CRT治疗不仅能够改善症状及心功能，同时能够降低左室功能不全及室性心律紊乱患者的死亡率和再住院率，无论在缺血还是非缺血患者中都有效。 研究证明了CRT可以改善全因死亡率（在没有CRT-D的支持下）

CARE-HF ：NYHA III/IV, LVEF<35%, QRS>=120ms 1.00 CRT : 159 pts (39%) 3 48 118 232 292 404 Medical Therapy 7 68 166 273 323 409 CRT Number at risk 500 1000 1500 0.00 0.25 0.50 0.75 HR 0.63 (95% CI 0.51 to 0.77) Event-free Survival Days P < .0001 Medical : 224 pts Therapy (55 %) Key Messages: The primary composite end-point (death or an unplanned hospitalization for a major cardiovascular event) was reduced substantially by CRT. There was no early hazard from device implantation. The curves began to separate within the first 90 days and remained separated during the follow up period. The absolute difference between the CRT and Medical Therapy arms in the percentage of patients reaching the primary endpoint during 29.5 months was 16%. 心脏再同步治疗与对照组相比使所有原因死亡率或心血管病因住院联合终点下降37% The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Eng J Med 2005; 352: 1539 - 49

CARE-HF Extension Study Time to Sudden Death 1.00 两年的随访中两条 曲线趋势一致 CRT 0.75 Medical Therapy Hazard Ratio 0.54 (95% CI 0.35 to 0.84; P=0.006) Survival 0.50 Main Study： CRT = 29 sudden deaths （7.1%） Medical Therapy = 38 sudden deaths (9.4%） CARE-HF also demonstrated, for the first time, that CRT also strikingly reduces the risk of sudden death. Indeed, sudden death dominated the clinical picture in the extension phase. This provides powerful evidence that CRT-induced improvements in cardiac function and efficiency also reduce the risk of sudden death. Potentially, many of the patients who died suddenly despite CRT might have survived had they received a CRT device with a defibrillator function (CRT-D). Further research is required to determine how best to select patients for CRT or CRT-D. 0.25 CRT = 32 sudden deaths (7.8%) Medical Therapy = 54 sudden deaths (13.4%) 0.00 400 800 1200 1600 Time (days) Longer-term effects of cardiac resynchronization therapy on mortality in heart failure [the Cardiac Resynchronziation-Heart Failure (CARE-HF) trial extension phase]. Eur Heart J 2006; 16: 1928 – 32

Cardiac Resynchronization-Heart Failure (CARE-HF) many of the patients who died suddenly despite CRT might have survived had they received a CRT device with a defibrillator function (CRT-D).

Pay attention to SCD 应重视CRT植入后心衰患者的 猝死

CRT植入后心衰患者 猝死机制 心功能 EF 电解质紊乱 药物副作用 左室电极致心律失常作用

选择 CRT-D 的理由 带有ICD功能的CRT，在改善心功能的同时提供有效的安全保障，是心衰患者生命的“安全带” 植入在前：心功能III 发生VF时：心功能III 目前：心功能I-II 心衰患者在病程中随时可发生猝死 即使对CRT反应良好的病例， 心功能改善初期也容易发生猝死 带有ICD功能的CRT，在改善心功能的同时提供有效的安全保障，是心衰患者生命的“安全带”

选择 CRT-D 的理由 带有ICD功能的CRT， 在发生恶性心律失常时提供有效的安全保障 心功能不全，胃肠道淤血等 药物副作用 电解质紊乱 心衰患者在病程中容易发生恶性心律失常 带有ICD功能的CRT， 在发生恶性心律失常时提供有效的安全保障

选择 CRT-D 的理由 CRT的致心律失常作用？

CRT and ventricular arrhythmia 使QT间期延长、跨室壁复极离散度增加, 可导致室性早搏、单形性或多形性室性心动过速的发生.

Does CRT have proarrhythmic potential ? Case : a patient in whom transvenous left ventricular pacing lead placement at the time of a biventricular upgrade led to an exacerbation of clinical monomorphic ventricular tachycardia (MVT). Slow left ventricular pacing repeatedly induced sustained MVT. However, testing of the biventricular pacing showed no MVT inducibility. (JCE 2003)

Dose CRT have proarrhythmic potential ? Case : a patient, whitout a previous history of arrhythmic episodes, in which the onset of several episodes of VT presented immediatly after CRT and did not occur after BivP discontinuation. J Interv Card Electrophysiol. 2005

CRT and ventricular arrhythmia Mayo Clinic followed-up 52 patients with heart failure II-III upgraded from an ICD to a CRT -D. CRT not decrease the frequency of ventricular arrhythmia or appropriate device therapy. Heart 2008; 94:186-190

CRT and ventricular arrhythmia a neutral effect of CRT on ventricular arrhythmias is consistent with the findings of the CONTAK-CD and Multisite InSync Randomized Clinical Evaluation-ICD (MIRACLE-ICD) trials, which also found no effect of CRT on ventricular arrhythmias

选择 CRT-D 的理由 大型临床研究

COMPANION：研究设计 患者按1:2:2比例随机分入以下3组 OPT 患者 入选 基础水平 测试 随机 分组 OPT+ CRT －优化的药物治疗 （OPT) 患者 入选 基础水平 测试 随机 分组 OPT+ CRT －OPT+CRT OPT+ CRT-D －OPT+CRT+ICD 从随机分组到植入的目标时间≤2天

COMPANION： 所有原因死亡的次级终点

MILOS 研究：CRT-P vs CRT-D 疗效研究 N=1298, Age: 64+/-9 ICM: 43% EF: 24+/-7 CRTD: 56% AF: 19% 有ICD作为后备的CRT治疗猝死率下降20%

Madit, Companion, SCD-HeFT 减少CRT治疗的HF患者死亡率的策略 在选择的HF患者中希望 通过CRT/ICD进一步减少 HF Mortality CRT Sudden Cardiac Death ICD Main purpose: Set up discussion for next slide. Key messages: Despite the significant contributions of ACE inhibitors and beta blockers to help heart failure patients live longer, the annual mortality of heart failure patients remains high. As previously shown, moderate to severe heart failure patients with a wide QRS are at higher risk. Cardiac resynchronization and ICD therapies can help this higher risk group live longer Additional information: SOLVD-T was a landmark trial reported in 1991 that showed ACE inhibitors reduced mortality in symptomatic heart failure patients. The MERIT-HF (metroprolol study in Europe and North America) and the CIBIS II (bucindilol in Europe) studies reported in 1999, demonstrated that the addition of beta blockade to conventional treatment, including ACE-inhibitors, further improved survival. The results from these trials are consistent with those reported from the US cardvedilol trial. As reported in the same review paper, if one extracts NYHA III/IV patients from the combined CIBIS II, MERIT-HF and US carvedilol trials, 1- year mortality in the control and treatment groups are 15.15 and 9.5% respectively. Care-HF Madit, Companion, SCD-HeFT With respect to clinical contraindication to ICD Adapted from McMurray JJV; Heart 1999

在CRT治疗中SCD预防是极为重要的， 时间越长，CRT患者从CRT-D中的获益也越多

how best to select patients for CRT or CRT-D.

真实世界：你会如何选择？ CRT-P？ CRT-D？

谢谢