老年心力衰竭的特点及治疗策略 西安交通大学医学院第一附属医院心内科 白 玲

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1 老年心力衰竭的特点及治疗策略 西安交通大学医学院第一附属医院心内科 白 玲
老年心力衰竭的特点及治疗策略 西安交通大学医学院第一附属医院心内科 白 玲 老年患者占心衰总数的75%。心衰又是造成老年人死亡的常见原因，其猝死发生率5倍于普通人群。老年心力衰竭患者特殊的病理生理机制导致老年心力衰竭的症状和治疗具有特殊性。如何正确识别和处理老年人心衰，降低其发病率和病死率，是一个重大的医学问题。 1

2 目 录 老年心力衰竭的流行病学特点 老年心力衰竭的的病理生理特点 老年心力衰竭的临床特点 老年心力衰竭的治疗特点

3 我国心力衰竭流行病调查结果同样发现，心衰患者中≥60岁的患者占50%以上
【心力衰竭主要发生在中老年】 患病率: 岁1﹪，≥80岁10﹪，50岁以后,每增加10岁,其患病率升高1倍。老年人心衰占心衰总数的75﹪ 在住院的心衰患者中80%年龄＞65岁 死亡率: 心衰是造成老年人死亡的最常见原因,猝死发生率是正常人的5倍 我国心力衰竭流行病调查结果同样发现，心衰患者中≥60岁的患者占50%以上

4 心力衰竭主要发生在中老年 美国心血管健康研究（CHS） 心衰患病率% 70岁 85岁 年龄 女 20 男 15 10 5 18.4%
14.3% 15 10 7.8% 5 4.1% 70岁 85岁 年龄 美国心血管健康研究（CHS）

5 目录 老年心力衰竭的流行病学特点 老年心力衰竭的的病理生理特点 老年心力衰竭的临床特点 老年心力衰竭的治疗特点

6 【老年心衰的病理生理特点】 1、心排出量较成年患者减少更为明显 2、较易发生低氧血症 3、心率反应性减低，心衰时心率可不增快
正常老年人最大心排出量（17~20 L/min）比成年人 (25~30L/min)明显减少 2、较易发生低氧血症   老年患者呼吸功能减退、低心排出量、肺淤血、肺通气/血流比例失调等原因，容易出现低氧血症 3、心率反应性减低，心衰时心率可不增快 （1）心排出量明显降低：由于心脏增龄性变化，老年人最大心排出量（17-20L/min）比非老年人（25-30 L/min）明显减少，老年人心衰时心排出量比非老年患者减少更明显。（2）较易发生低氧血症：老年人心衰时，由于增龄性呼吸功能减退，低心排出量，肺瘀血、肺通气/血流比例失调等原因，容易出现低氧血症，即使轻度心衰也有明显的低氧血症。（3）心率对负荷的反应低下：老年人因窦房结等传导组织的退行性变，患有心衰时心率可以不增快，即使在运动和发热等负荷情况下，心率增快也不明显，这与非老年人心衰不同。更容易发生DHF：老年人由于心肌增大及其间质纤维化、导致心室顺应性降低、心室充盈障碍，比非老年人更易发生DHF，占老年人心衰的40%。70岁以上老年人心衰患者中DHF占50%以上。 4、更容易发生DHF

7 目录 老年心力衰竭的流行病学特点 老年心力衰竭的的病理生理特点 老年心力衰竭的临床特点 老年心力衰竭的治疗特点

8 【老年心衰多病因共存】 冠心病 高血压病 肺心病 退行性瓣膜病
【老年心衰多病因共存】 冠心病 高血压病 肺心病 退行性瓣膜病 两种或两种以上心脏病并存的检出率高达65%，一种为主要原因，另一种促进发生发展 95%的患者合并至少 1 种非心脏性疾病，且55%有 4 种甚至更多非心脏性合并症，最常见为高血压、糖尿病和慢阻肺 这些因素的整合对心脏的影响更大，使心衰发展更迅速，症状不明显，病程更短、更复杂 老年人心衰的病因以冠心病、高血压病、肺心病居多，高血压病、冠心病为最常见原因。 目前高血压已能有效控制，冠心病越来越成为老年人心衰的最主要原因。 随着寿命延长，退行性瓣膜病和心肌淀粉样变发病率也越来越多。

9 【诱因更重要】 主要诱因有： ①感染：尤其是呼吸道感染，患肺炎的老年人9%死于心衰
②心肌缺血：老年人因冠状动脉储备功能下降，由心肌缺血诱发心衰者（10.3%）明显高于成年人（2.8%） ③心律失常：老年人心律失常诱发心衰占6.7%-8.8%，尤其是快速心律失常 ④输液 由于老年人心脏储备功能差和心脏病相对较重，诱因在老年人心衰中所起的作用比非老年人更重要。

10 【老年人心衰症状不典型】 无症状：可无典型表现，甚至已处于中度心衰可完全无症状，一旦存在某种诱因，则可发生重度心衰，危及生命。
常有的非特异性症状： 疲乏无力 大汗淋漓 慢性咳嗽（干咳） 胃肠道症状明显 精神神经症状突出 症状常不典型：由于老年人反应差，部分轻、中度心力衰竭患者可完全无症状；或主要表现为心力衰竭诱因所引起的临床症状，如表现为肺部感染而漏诊心力衰竭；或由于老年人有多种疾病并存，症状交叉、重叠、相互影响，而掩盖了心力衰竭的症状与体征，造成诊断困难。

11 【并发症多】 心律失常：以窦性心动过缓和心房纤颤最多见，诱发或加重心衰
肾功能不全：尿少和肾前性氮肥质血症，其检出率高达65%，增加了治疗的难度和病死率，肾衰是影响心衰患者生存率最重要的因素。 水电解质及酸碱平衡失调：限钠，食欲减退，继发性酮固酮增加及利尿剂等因素，易发生电解质紊乱；还可发生代谢性碱中毒和酸中毒，使病情恶化，加速死亡 认知功能障碍：比无心衰者高1.96倍，主要与心排出量减少所致的脑缺血、脑白质损害及药物的影响有关。 心律失常：以窦性心动过缓和心房纤颤最多见，室性心律失常，房室传导阻滞亦为常见，这些心律失常可诱发或加重心衰 肾功能不全：因肾灌注不足可引起尿少和肾前性氮肥质血症，其检出率高达65%，心衰伴肾衰不仅增加了治疗的难度，而且增加了病死率，肾衰是影响心衰患者生存率最重要的因素。 水电解质及酸碱平衡失调：老年人心衰时因限钠，食欲减退，继发性酮固酮增加及利尿剂等因素，易发生低钾、低镁、低钠、低氯等电解质紊乱；还可发生代谢性碱中毒和酸中毒，使病情恶化，加速死亡 认知功能障碍：老年人心衰时很容易发生认知障碍，其发生率比无心衰者高1.96倍，主要与心排出量减少所致的脑缺血、脑白质损害及药物的影响有关。 再入院者多：与非老年患者比较，老年心衰患者入院次数更多，住院时间更多，心衰是导致老年人反复住院最常见的原因，其主要原因是患者对饮食和药物治疗的依从性差。

12 European Heart Journal (2009) 30, 478–486

13 目录 老年心力衰竭的流行病学特点 老年心力衰竭的的病理生理特点 老年心力衰竭的临床特点 老年心力衰竭的治疗特点 包含有老年人群的临床试验
老年人心衰治疗的循证医学证据大规模临床实验中的亚组分析 包含有老年人群的临床试验 专为老年人群设计的临床试验 老年心力衰竭的治疗特点

14 【处理老年心衰时我们应该考虑】 老年心力衰竭患者的治疗目标是什么? 延缓死亡 减少住院事件 改善症状和运动耐量 提高生活质量
节省心力衰竭治疗的医疗费用 风险获益比 临床试验的结果能否直接应用于临床？

15 Euro Heart Failure Survey Ⅱ
European Heart Journal (2009) 30, 478–486

16 【基础治疗】 1. 重视病因和诱因治疗 2. 限钠不必太严 3. 预防致残 4. 吗啡减半
4. 吗啡减半 老年人心衰常常是多种病因所致，治疗应全面考虑，作相应治疗。 肾脏保钠能力随增龄而降低，心衰时进食少和利尿剂的应用，老年人过度限钠可导致或加重低钠血症。 限钠只对重度SHF (LVEF<20%)和肾功能不全的老年人有益，对轻、中度SHF(LVEF≥35%)可能没有必要，尤其是伴低钠血症者。 心衰是导致老年人残疾的常见原因之一。 老年心衰患者过度休息可引起血栓形成、关节挛缩及卧床不起等一系列的残疾问题，一旦发生，怡疗十分困难，应重在预防。 运动增加衰竭心脏的负荷而导致病情恶化的观点已被废除，运动潜在的益处逐渐受到人们的重视。老年心衰患者进行适当的运动，不仅增加肌力和平衡能力，防止跌倒和损伤，而且能降低心源性死亡率和心衰再住院率。 对老年患者经抢救病情缓解后，应在康复医师指导下进行合适的运动，以防止致残 老年心衰的限钠没有成年人严格，主要限于重度SHF。 老年人急性心肌梗死可以心衰为主要表现其治疗应以病因治疗(抗心肌缺血)为主，辅以抗心衰治疗。 感染、心肌缺血、缺氧等诱因在老年人心衰发生中起重要作用，应尽快纠正。 对急性肺水肿患者，常用吗啡来减少躁动达到镇静的目的。 老年人由于白蛋白降低和分布容积缩小，吗啡的用量应比成年人少一半。通常将l0mg吗啡溶于l0ml生理盐水中。先静脉推注2-3mg，必要时20分钟后重复一次。 对伴慢性阻塞性肺病的老年人使用吗啡应十分镇重，若有呼吸抑制的迹象，应禁止使用。

17 【老年人心衰的治疗】 药物治疗 非药物治疗 ACEI 运动训练 ARB CRT Β受体阻断剂 ICD 醛固酮受体拮抗剂 …… 非保钾类利尿剂
地高辛 非药物治疗 运动训练 CRT ICD ……  90年代～ 修复衰竭心肌的生物学性质 阻断神经内分泌、细胞因子系统的激活和 心肌重塑之间的恶性循环——治疗的关键 心衰治疗概念的根本性转变： 从短期的、血液动力学/ 药理学措施转变为 长期的、修复性策略、目的是有利地 改变衰竭心脏的生物学性质

18 【 ACEI和ARB 】 ACEI是最早证实可以改善慢性心力衰竭患者预后的药物。

19 Total Mortality Or Hospitalization For CHF
JAMA. 1995；273：

20 Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) -Overall programme Background:Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity. Methods:In parallel, randomised, double-blind, controlled,clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensinconverting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF.Analysis was by intention to treat. Findings:Median follow-up was 37·7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0·91 [95% CI 0·83–1·00],p=0·055; covariate adjusted 0·90 [0·82–0·99], p=0·032),with fewer cardiovascular deaths (691 [18%] vs 769 [20%],unadjusted 0·88 [0·79–0·97], p=0·012; covariate adjusted 0·87 [0·78–0·96], p=0·006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p<0·0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concernsabout renal function, hypotension, and hyperkalaemia. Interpretation:Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects. Lancet : 759–66. 20

21 CHARM Low-Left Ventricular Ejection Fraction Trials
Background—Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and even an aldosterone antagonist. To determine whether the angiotensinreceptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized,double-blind, placebo-controlled, multicenter, international trial program. Methods and Results—New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of ≤40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P＜0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P＜0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, β-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P＜0.001). Conclusion—Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF≤40% when added to standard therapies including ACE inhibitors, -blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted. Circulation 2004;110; 21

22 老年心衰患者可以应用ACEI或ARB，可以降低死亡率，特别是因心衰的再住院率。

23 【β-受体阻滞剂】 大量的随机研究包括80岁患者的研究均显示β受体阻滞剂能够改善老年患者临床症状，左室功能 ，心室重塑
在标准治疗的基础上提高生存率，降低死亡率，而且是有效降低猝死率的药物

24 比索洛尔：CIBISⅠ和CIBIS II研究荟萃分析
Β受体阻断剂各亚组分析 比索洛尔：CIBISⅠ和CIBIS II研究荟萃分析 Am Heart J 2002;143:301-7.

25 卡维地洛对严重心功能不全生存率的影响 tCombined Risk of Death or Hospitalization
for Any Reason in Subgroups Death from Any Cause in Subgroups N Engl J Med 2001;344:1651-8

26 老年人应用β-受体阻滞剂需注意： 老年人肾上腺素能受体功能相应降低,β-受体敏感性也降低，β-受体阻滞剂代谢—清除能力减弱，常同时合并存在其它疾病，因此更应严密观察，从小剂量开始，逐渐调整剂量，用药更应个体化

27 【利尿剂】 老年心衰病人几乎都有不同程度的水钠潴留，因此，应用利尿剂是处理老年心衰的重要一环；利尿剂副作用较多，老年人各种生理代偿功能低下，尤易发生，故应严格掌握适应证

28 RALES Randomized Aldactone Evaluation Study （1999)
氨体舒通 重度心衰 N Engl J Med. 1999:341:709-17

29 EPHESUS Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study ，2003
依普利酮，心梗后心衰 N Engl J Med 2003;348:

30 EMPHASIS-HF Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure （2011）
（依普利酮，轻中度心衰） N Engl J Med 2011;364:11-21.

31 Br J Clin Pharmacol.58(5): 554–557
警惕高钾血症和肾功能不全加重 Br J Clin Pharmacol.58(5): 554–557

32 老年患者应用利尿剂的基本原则 剂量适当: 小量开始，缓慢利尿 保钾排钾利尿药联合应用（醛固酮受体拮抗剂地位肯定） 监测血生化指标
联合用药（可与ACEI、β- 受体阻滞剂、地高辛合用）

33 Cardiac Resynchronization in Heart Failure Study(CARE-HF）
【CRT和ICD】 Cardiac Resynchronization in Heart Failure Study(CARE-HF） background Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. We evaluated its effects on morbidity and mortality. methods Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving standard pharmacologic therapy were randomly assigned to receive medical therapy alone or with cardiac resynchronization. The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event. The principal secondary end point was death from any cause. results A total of 813 patients were enrolled and followed for a mean of 29.4 months. The primary end point was reached by 159 patients in the cardiac-resynchronization group, as compared with 224 patients in the medical-therapy group (39 percent vs. 55 percent; hazard ratio, 0.63; 95 percent confidence interval, 0.51 to 0.77; P<0.001). There were 82 deaths in the cardiac-resynchronization group, as compared with 120 in the medical- therapy group (20 percent vs. 30 percent; hazard ratio 0.64; 95 percent confidence interval, 0.48 to 0.85; P<0.002). As compared with medical therapy, cardiac resynchronization reduced the interventricular mechanical delay, the end-systolic volume index, and the area of the mitral regurgitant jet; increased the left ventricular ejection fraction; and improved symptoms and the quality of life (P<0.01 for all comparisons). conclusions In patients with heart failure and cardiac dyssynchrony, cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients. 心因死亡和再住院 全因的死亡 N Engl J Med 2005;352: 33

34 REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction)
262 recipients of CRT pacemakers with QRS 120 ms and LV ejection fraction 40% to active (CRT ON; n 180) versus control (CRT OFF; n 82) treatment, for 24 months Objectives The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Background Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. Methods We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS 120 ms and LV ejection fraction 40% to active (CRT ON; n 180) versus control (CRT OFF; n 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). Results In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p 0.01). The LVESVi decreased by a mean of ml/m2 in the CRT ON, versus ml/m2 in the CRT OFF group (p 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p ) was significantly delayed by CRT. Conclusions After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT ) J Am Coll Cardiol 2009 34

35 the risk of death or heart-failure events
MADIT-CRT Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy the risk of death or heart-failure events EF≤ 30% and QRS ≥ 130msec and NYHA I or II . Patients were randomly assigned in a 3:2 ratio to receive CRT＋ICD (1089 patients) or an ICD alone (731 patients). Background This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. Methods During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter– defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heartfailure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. Results During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. Conclusions CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT ) N Engl J Med 2009;361: 35

36 【小 结】 老年心力衰竭患者女性、舒张性心功能不全比例更高，合并疾病更多 指南推荐的治疗方案对老年心力衰竭患者同样适用
【小 结】 老年心力衰竭患者女性、舒张性心功能不全比例更高，合并疾病更多 指南推荐的治疗方案对老年心力衰竭患者同样适用 但应注意增龄因素对药物的影响,肾功能不全是影响药物治疗效果的重要因素 CRT或CRT-D对老年慢性心力衰竭患者疗效确切

37 谢谢