Transcript 心力衰竭
心力衰竭 Heart Failure 浙江大学医学院附属第一医院 陶谦民 定义 • 心力衰竭是心脏各种疾病发展到中、末 期导致心脏功能障碍，出现心功能不全 （cardiac insufficiency）的一组临床综合 征，多指临床出现心肌收缩力下降使心 排血量不能满足机体代谢的需求，器官、 组织血液灌注不足，同时出现肺循环和/ 或体循环淤血的表现。 病因 • 心肌本身病变——原发性心肌损害 1.缺血性心肌损害：冠心病心肌缺血（长 期）和/或心肌梗死 2.心肌炎和心肌病，以病毒性心肌炎和原 发性扩张性心肌病最为常见 3.心肌代谢障碍性疾病：如糖尿病性心肌 病、心肌淀粉样变性等 病因 • 心脏负荷过重，心肌本身功能无异常，但因长 期的高强负荷致心脏功能受损 1.压力负荷（后负荷）过重，如高血压、主动脉 瓣狭窄、肺动脉高压、肺动脉瓣狭窄等 2.容量负荷（前负荷）过重，因大量的血液回流 长期造成心脏功能损害，可见于：⑴心脏瓣膜 关闭不全，如主动脉瓣关闭不全、二尖瓣关闭 不全等；⑵先天性心脏病如间隔缺损、动脉导 管未闭、动静脉瘘等；⑶慢性重度贫血、甲状 腺功能亢进等伴有全身血容量增多或循环血量 增多等 • 心脏扩张受到限制，如大量心包积液或心包缩 窄 诱因 • 有基础心脏病的患者，其心力衰竭的症状通常由一些 增加心脏负荷的因素所诱发，这些常见的诱发心力衰 竭的因素有： 1.感染，以呼吸道感染最为常见，感染性心内膜炎和风 湿活动也是诱发心力衰竭常见而隐匿的原因 2.心律失常，心房颤动是器质性心脏病常见的心律失常， 也是诱发心力衰竭最重要的因素 3.血容量增，如摄入钠盐过多，静脉输入液体过多、过 快等 4.过度体力活动，劳累或情绪激动，如妊娠后期及分娩 过程，情绪波动如暴怒等 5.治疗不当，所谓医源性因素，如不恰当停用洋地黄类 药物或降压药物，某些心脏功能抑制性药物 6.原有心脏疾病加重或并发加重心脏负担的疾病，如冠 心病发生心肌梗死，风湿性心瓣膜病出现风湿活动， 合并甲状腺功能亢进或贫血等 类型 • 左心衰、右心衰和全心衰 左心衰以肺循 环淤血为特征，临床主要表现为呼吸困 难；右心衰主要见于肺源性心脏病和某 些先天性心脏病，以体循环淤血为特征， 临床出现浮肿、腹水和肝肿大等；全心 衰则综合左右心衰的临床表现 • 急性和慢性心衰 • 收缩性和舒张性心衰 Heart Failure (HF) Definition A complex clinical syndrome in which the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return. HF Incidence and Prevalence • Prevalence – Worldwide, 22 million1 – United States, 5 million2 • Incidence – Worldwide, 2 million new cases annually1 – United States, 500,000 new cases annually2 • HF afflicts 10 out of every 1,000 over age 65 in the U.S.2 1 World Health Statistics, World Health Organization, 1995. 2 American Heart Association, 2002 Heart and Stroke Statistical Update. Prevalence of HF by Age and Gender United States: 1988-94 10 8 Percent of Population Males Females 6 4 2 0 20-24 25-34 35-44 45-54 55-64 65-74 Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association 75+ New York Heart Association Functional Classification Class I: No symptoms with ordinary activity Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest HF Classification: Evolution and Disease Progression • Four Stages of HF (ACC/AHA Guidelines): Stage A: Patient at high risk for developing HF with no structural disorder of the heart Stage B: Patient with structural disorder without symptoms of HF Stage C: Patient with past or current symptoms of HF associated with underlying structural heart disease Stage D: Patient with end-stage disease who requires specialized treatment strategies Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 Severity of Heart Failure Modes of Death NYHA II NYHA III CHF CHF 12% Other 26% 59% Sudden Death 24% 64% Other 15% n = 103 Sudden Death n = 103 NYHA IV CHF Other 33% 56% 11% Sudden Death n = 27 MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07. Etiology of Heart Failure What causes heart failure? • The loss of a critical quantity of functioning myocardial cells after injury to the heart due to: – – – – – – – Ischemic Heart Disease Hypertension Idiopathic Cardiomyopathy Infections (e.g., viral myocarditis, Chagas’ disease) Toxins (e.g., alcohol or cytotoxic drugs) Valvular Disease Prolonged Arrhythmias The Donkey Analogy Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living… Left Ventricular Dysfunction • Systolic: Impaired contractility/ejection – Approximately two-thirds of heart failure patients have systolic dysfunction1 • Diastolic: Impaired filling/relaxation 30% (EF > 40 %) (EF < 40%) 70% Diastolic Dysfunction Systolic Dysfunction 1 Lilly, L. Pathophysiology of Heart Disease. Second Edition p 200 Cardiac Output • Cardiac output is the amount of blood that the ventricle ejects per minute Cardiac Output = HR x SV Determinants of Ventricular Function Contractility Afterload Preload Stroke Volume • Synergistic LV Contraction • Wall Integrity • Valvular Competence Heart Rate Cardiac Output Left Ventricular Dysfunction Volume Overload Pressure Overload Loss of Myocardium Impaired Contractility LV Dysfunction EF < 40% End Systolic Volume Cardiac Output Hypoperfusion End Diastolic Volume Pulmonary Congestion Hemodynamic Basis for Heart Failure Symptoms Hemodynamic Basis for Heart Failure Symptoms LVEDP Left Atrial Pressure Pulmonary Capillary Pressure Pulmonary Congestion Left Ventricular Dysfunction Systolic and Diastolic • Symptoms • Physical Signs – Dyspnea on Exertion – Basilar Rales – Paroxysmal Nocturnal Dyspnea – Pulmonary Edema – Tachycardia – S3 Gallop – Cough – Pleural Effusion – Hemoptysis – Cheyne-Stokes Respiration Right Ventricular Failure Systolic and Diastolic • Symptoms • Physical Signs – Abdominal Pain – Peripheral Edema – Anorexia – Jugular Venous Distention – Nausea – Abdominal-Jugular Reflux – Bloating – Hepatomegaly – Swelling Consequences of Decreased Mean Arterial Pressure Mean Arterial Pressure (BP) = Cardiac Output x Total Peripheral Resistance Compensatory Mechanisms • Frank-Starling Mechanism • Neurohormonal Activation • Ventricular Remodeling Compensatory Mechanisms Frank-Starling Mechanism a. At rest, no HF b. HF due to LV systolic dysfunction c. Advanced HF Compensatory Mechanisms Neurohormonal Activation Many different hormone systems are involved in maintaining normal cardiovascular homeostasis, including: • Sympathetic nervous system (SNS) • Renin-angiotensin-aldosterone system (RAAS) • Vasopressin (a.k.a. antidiuretic hormone, ADH) Compensatory Mechanisms: Sympathetic Nervous System Decreased MAP Sympathetic Nervous System Contractility Tachycardia Vasoconstriction MAP = (SV x HR) x TPR Sympathetic Activation in Heart Failure CNS sympathetic outflow Cardiac sympathetic activity 1receptors 2receptors Sympathetic activity to kidneys + peripheral vasculature 1receptors Myocardial toxicity Increased arrhythmias 1- Activation of RAS Vasoconstriction Sodium retention Disease progression Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52. 1- Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS) Angiotensinogen Renin Angiotensin I Angiotensin Converting Enzyme Angiotensin II AT I receptor Vasoconstriction Oxidative Stress Cell Growth Vascular remodeling LV remodeling Proteinuria Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS) Renin-Angiotensin-Aldosterone ( renal perfusion) Salt-water retention Thirst Sympathetic augmentation Vasoconstriction MAP = (SV x HR) x TPR Compensatory Mechanisms: Neurohormonal Activation – Vasopressin Decreased systemic blood pressure Central baroreceptors - Increased systemic blood pressure Vasoconstriction Stimulation of hypothalamus, which produces vasopressin for release by pituitary gland Release of vasopressin by pituitary gland Compensatory Neurohormonal Stimulation: Summary Decreased Cardiac Output Sympathetic nervous system Contractility Heart rate Renin-angiotensin system Vasoconstriction Anteriolar + + Stroke volume Circulating volume Venous Maintain blood pressure Cardiac output Antidiuretic hormone (vasopressin) Venous return to heart ( preload) - Peripheral edema and pulmonary congestion Compensatory Mechanisms Ventricular Remodeling Alterations in the heart’s size, shape, structure, and function brought about by the chronic hemodynamic stresses experienced by the failing heart. Curry CW, et al. Mechanical dyssynchrony in dilated cardiomyopathy with intraventricular conduction delay as depicted by 3D tagged magnetic resonance imaging. Circulation 2000 Jan 4;101(1):E2. Other Neurohormones • Natriuretic Peptides: Three known types – Atrial Natriuretic Peptide (ANP) • Predominantly found in the atria • Diuretic and vasodilatory properties – Brain Natriuretic Peptide (hBNP) • Predominantly found in the cardiac ventricles • Diuretic and vasodilatory properties – C-type Natriuretic Peptide (CNP) • Predominantly found in the central nervous system • Limited natriuretic and vasodilatory properties Pharmacological Actions of hBNP Hemodynamic (balanced vasodilation) R I SS D S M S K G R L G H G F R C R C S S K V L G K P M V S Q G S • veins • arteries • coronary arteries Neurohormonal aldosterone norepinephrine Renal diuresis & natriuresis Abraham WT and Schrier RW, 1994 Endothelium-Derived Vasoactive Substances Produced by a thin lining of cells within the arteries and veins called the endothelium Endothelium-derived relaxing factors (EDRF) – Vasodilators: • Nitric Oxide (NO) • Bradykinin • Prostacyclin Endothelium-derived constricting factors (EDCF) – Vasoconstrictors: • Endothelin I Mediators of Heart Failure Cytokines • Small protein molecules produced by a variety of tissues and cells • Negative inotropes • Elevated levels associated with worse clinical outcomes • Examples: – Tumor necrosis factor (TNF)-alpha – Interleukin 1-alpha – Interleukin-2 – Interleukin-6 – Interferon-alpha Vicious Cycle of Heart Failure LV Dysfunction Increased cardiac workload (increased preload and afterload) Increased cardiac output (via increased contractility and heart rate) Increased blood pressure (via vasoconstriction and increased blood volume) Decreased cardiac output and Decreased blood pressure Frank-Starling Mechanism Remodeling Neurohormonal activation Neurohormonal Responses to Impaired Cardiac Performance Initially Adaptive, Deleterious if Sustained Response Short-Term Effects Long-Term Effects Salt and Water Retention Augments Preload Pulmonary Congestion, Anasarca Vasoconstriction Maintains BP for perfusion of vital organs Exacerbates pump dysfunction (excessive afterload), increases cardiac energy expenditure Sympathetic Stimulation Increases HR and ejection Increases energy expenditure Jaski, B, MD: Basics of Heart Failure: A Problem Solving Approach Assessing Heart Failure Assessing Heart Failure • Patient History • Physical Examination • Laboratory and Diagnostic Tests Diagnostic Evaluation of New Onset Heart Failure • Determine the type of cardiac dysfunction (systolic vs. diastolic) • Determine Etiology • Define prognosis • Guide therapy Diagnostic Evaluation of New Onset Heart Failure Initial Work-up: • ECG • Chest x-ray • Blood work • Echocardiography Diagnostic Evaluation of New Onset Heart Failure LV RV Septum LV cavity LV Wall M-Mode Echo LA RA 2D Echo Current Treatment of Heart Failure The Vicious Cycle of Heart Failure Management Chronic HF Diurese & Home Hospitalization IV Lasix or Admit Emergency Room SOB Weight MD’s Office PO Lasix General Measures Medical Considerations: Lifestyle Modifications: • Treat HTN, hyperlipidemia, diabetes, arrhythmias • Weight reduction • Coronary revascularization • Discontinue smoking • Anticoagulation • Avoid alcohol and other cardiotoxic substances • Immunization • Exercise • Close outpatient monitoring • Sodium restriction • Daily weights Pharmacologic Management Digoxin • Enhances inotropy of cardiac muscle • Reduces activation of SNS and RAAS • Controlled trials have shown long-term digoxin therapy: – Reduces symptoms – Increases exercise tolerance – Improves hemodynamics – Decreases risk of HF progression – Reduces hospitalization rates for decompensated HF – Does not improve survival Digitalis Compounds Like the carrot placed in front of the donkey 应用洋地黄的注意事项 • 不用于无症状患者（房颤除外） • 不主张早期应用，应与ACEI、利尿剂合用 • 避免采用较大剂量给药，一般耐受良好 • 应根据年龄、肾功能、合并用药调整剂量 • 注意观察心率变化，尤其与阻滞剂合用时 • 定期复查电解质 Pharmacologic Management Diuretics • Used to relieve fluid retention • Improve exercise tolerance • Facilitate the use of other drugs indicated for heart failure • Patients can be taught to adjust their diuretic dose based on changes in body weight • Electrolyte depletion a frequent complication • Should never be used alone to treat heart failure • Higher doses of diuretics are associated with increased mortality Pharmacologic Management ACE Inhibitors • Blocks the conversion of angiotensin I to angiotensin II; prevents functional deterioration • Recommended for all heart failure patients • Relieves symptoms and improves exercise tolerance • Reduces risk of death and decreases disease progression • Benefits may not be apparent for 1-2 months after initiation Diuretics, ACE Inhibitors Reduce the number of sacks on the wagon ESC心力衰竭诊断和治疗指南-2005 血管紧张素转化酶抑制剂（ACEI） • 用于所有LVEF降低（<40-45%）的患者， 以改善存活、症状、减少住院次数（1A） • 对没有液体潴留的患者，可以作为起始用 药，对液体潴留患者，ACEI应与利尿剂合 用（1A） • 采用ACEI有效剂量治疗（1A），不能根据 症状改善与否确定用药剂量 Pharmacologic Management Beta-Blockers • Cardioprotective effects due to blockade of excessive SNS stimulation • In the short-term, beta blocker decreases myocardial contractility; increase in EF after 1-3 months of use • Long-term, placebo-controlled trials have shown symptomatic improvement in patients treated with certain beta-blockers1 • When combined with conventional HF therapy, beta-blockers reduce the combined risk of morbidity and mortality, or disease progression1 1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 p. 20. ß-Blockers Limit the donkey’s speed, thus saving energy ESC心力衰竭诊断和治疗指南 β受体阻滞剂 • 推荐在标准治疗的基础上，用于所有稳定的、轻 中重度（NYHA II-IV） 、缺血性或非缺血性心 力衰竭患者，除非有禁忌症（1A） • 推荐比索洛尔、卡维地洛、美托洛尔琥珀酸盐和 奈比洛尔 (nebivolol) 用于心力衰竭治疗 (1A） ESC心力衰竭诊断和治疗指南 β受体阻滞剂用于抗心律失常治疗 • β受体阻滞剂减少心力衰竭的猝死（1A） • 在持续或非持续性室性快速心律失常的治 疗中，β受体阻滞剂可以单用，或与胺碘酮 或非药物治疗联合使用（IIa, C） 阻滞剂治疗心衰注意事项 • 心功能相对稳定，无其它禁忌症 • 无明显液体潴留的证据 • 利尿剂 ±地高辛，不必要在ACEI调整完毕后使用 • 极低剂量开始，每2～4周剂量倍增，调整合并用药。 阻滞剂的耐受性为80～90% • 病情稳定的心功能IV级患者，在有经验的专科医生指 导下用药 • 以靶剂量或最大耐受量长期维持 Pharmacologic Management Aldosterone Antagonists • Generally well-tolerated • Shown to reduce heart failure-related morbidity and mortality • Generally reserved for patients with NYHA Class III-IV HF • Side effects include hyperkalemia and gynecomastia. Potassium and creatinine levels should be closely monitored Pharmacologic Management Angiotensin Receptor Blockers (ARBs) • Block AT1 receptors, which bind circulating angiotensin II • Examples: valsartan, candesartan, losartan • Should not be considered equivalent or superior to ACE inhibitors • In clinical practice, ARBs should be used to treat patients who are ACE intolerant due to intractable cough or who develop angioedema Angiotensin II Receptors AT1 receptor AT2 receptor • Vasoconstriction • Vasodilation • Growth Promotion • Growth inhibition • Anti-apoptotic • Pro-apoptotic • Pro-fibrotic • ? Fibrosis • Pro-thrombotic • ? Thrombosis • Pro-oxidant • ? redox ESC心力衰竭诊断和治疗指南 血管紧张素II受体拮抗剂（ARB） • 在不能耐受ACEI的有症状患者，ARB可作 为ACEI的替代药物以改善患病率和病死率 （1B） • 在仍有症状的患者，ARB可以与ACEI合用 Assessment and Treatment of the Heart Failure Patient Treatment Approach for the Patient with Heart Failure Stage A Stage B Stage C Stage D At high risk, no structural disease Structural heart disease, asymptomatic Structural heart disease with prior/current symptoms of HF Refractory HF requiring specialized interventions Therapy Therapy Therapy Therapy • Treat Hypertension • All measures under stage A • All measures under stage A • All measures under stages A,B, and C • ACE inhibitors in appropriate patients Drugs: • Mechanical assist devices • Treat lipid disorders • Encourage regular exercise • Discourage alcohol intake • ACE inhibition • Beta-blockers in appropriate patients • Diuretics • ACE inhibitors • Beta-blockers • Digitalis • Dietary salt restriction • Heart transplantation • Continuous (not intermittent) IV inotropic infusions for palliation • Hospice care Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 Cardiac Resynchronization Therapy Increase the donkey’s (heart) efficiency Cardiac Resynchronization Therapy Patient Indications CRT device: – Moderate to severe HF (NYHA Class III/IV) patients – Symptomatic despite optimal, medical therapy – QRS 130 msec – LVEF 35% CRT plus ICD: – Same as above with ICD indication Cardiac Resynchronization Therapy Follow-up Care • Standard medical management of HF by primary physician as defined by practice guidelines • Device follow-up may be performed by physician specializing in implantable devices Cardiac Resynchronization Therapy: Creating Realistic Patient Expectations • Approximately two-third of patients should experience improvement (responders vs. non-responders)1 – Some patients may not experience immediate improvement Note: CRT is adjunctive and is not intended to replace medical therapy. Patients will continue to be followed by HF Specialist and Physician managing implantable devices. 1 Abraham, WT, et. Al. Cardiac Resynchronization in Chronic Heart Failure. N Engl J Med 2002;346:1845-53 Cardiac Resynchronization Therapy: Creating Realistic Patient Expectations • Have patients set their own goals of what they would like to do following CRT: – Grocery shopping – Decreasing Lasix dose – Walking to the mailbox without stopping – Lying flat to sleep • Encourage them to be part of the group that responds to their therapy First Medical Follow-up Visit 7-10 Days Post-implant* • Follow daily weights closely • Check wound site • Physical Exam – Assess volume status • Patients typically over-diurese following CRT • Ascertain quality of life – Subtle improvements? • Check electrolytes including BUN/Cr • Give patients encouragement! * This is not a complete list for many practitioners and is presented here only as a guideline. Summary • Heart failure is a chronic, progressive disease that is generally not curable, but treatable • Most recent guidelines promote lifestyle modifications and medical management with ACE inhibitors, beta blockers, digoxin, and diuretics • It is estimated 15% of all heart failure patients may be candidates for cardiac resynchronization therapy (see later section for details) • Close follow-up of the heart failure patient is essential, with necessary adjustments in medical management