A Guide to the Etiology, Pathophysiology, Diagnosis, and Treatment of Heart Failure Dr Badri Paudel GMC Part I: Etiology and Pathophysiology of Heart Failure 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 million 1 United States, 5 million 2 Incidence Worldwide, 2 million new cases annually 1 United States, 500,000 new cases annually 2 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 Coronary artery disease is the leading cause of heart failure in the UK United States: 1988-94 Percent of Population 10 8 6 4 Males Females Idiopathic (no CAD) 17 (13%) Other 7 (5%) Undetermined (no angiographic data) 13 (10%) Results based on full investigation (including coronary angiography) in new patients aged <75 years identified in a UK population-based study 2 AF alone 4 (3%) Coronary artery disease 71 (52%) 0 20-24 25-34 35-44 45-54 55-64 65-74 75+ Alcohol 5 (4%) Valve disease 13 (10%) Source: NHANES III (1988-94), CDC/NCHS and the American Heart Association Hypertension alone 6 (4%) Fox et al, Eur. Heart J., 2001
The poor prognosis of heart failure Survival 1.00 0.75 0.50 0.25 0.00 London Heart Failure Study Kaplan-Meier survival estimates with 95% pointwise confidence bands Median survival: 3 years from diagnosis 0 2 4 6 8 Analysis time (years) 552 incident cases followed up to March 2002; 338 deaths! EPIDEMIOLOGY AND HEALTH SERVICE IMPACT Cowie et al, Heart, 2000 EPIDEMIOLOGY AND HEALTH SERVICE IMPACT Size of the problem Summary Common Affects 1-2% of the population Annual incidence is 0.5-1% Serious Mortality is 40% by 12 months after new diagnosis, and 10% per year thereafter Increasing Due to ageing population and?more effective treatment of acute myocardial infarction Disabling Symptoms have enormous impact on quality of life worse than many other chronic conditions Expensive Accounts for 1-2% of NHS budget, 5% of acute admissions, and 10% of bed occupancy BMJ, 2002; Eur J Heart Failure, 1999; NICE, 2003; BHF, 2002; DOH 2003 New York Heart Association Functional Classification Severity of Heart Failure Modes of Death NYHA II 64% 12% 24% CHF Other Sudden Death n = 103 NYHA III 26% 59% 15% CHF Other Sudden Death NYHA IV CHF n = 103 33% 11% 56% Other 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) Toxins (e.g., alcohol or cytotoxic drugs) Valvular Disease Prolonged Arrhythmias Heart Failure Can be due to: dysfunction of the left ventricle dysfunction of the right ventricle or due to inadequate perfusion despite normal or elevated cardiac output
Classification of Heart Failure Acute develops quickly Chronic conditions gradually increase demands on the heart; when the heart and circulatory system can no longer adapt the result is heart failure Can lead to acute failure with excessive cardiac demand Types of Heart Failure High output vs. Low output High output Anemia Septicemia Hyperthroidism (thyrotoxicosis) Beriberi Low output Decreased pumping ability and cardiac output Right-sided vs. Left sided Heart Failure Right-sided HF Most common cause is left heart failure Can occur independently in primary lung disease conditions COPD, ARDS, cystic fibrosis Cor pulmonale Left-sided HF Decreased output to body Blood backs up Systolic vs. Diastolic HF Systolic decreased contraction leads to decreased output and poor perfusion of tissues Diastolic --Decreased compliance of left ventricle and abnormal diastolic relaxation- results in increased pressure in ventricle at the end of diastole 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 dysfunction 1 Diastolic: Impaired filling/relaxation (EF < 40%) (EF > 40 %) 30% 70% Diastolic Dysfunction Systolic Dysfunction
Determinants of Ventricular Function Left Ventricular Dysfunction Contractility Volume Overload Pressure Overload Loss of Myocardium Impaired Contractility Preload Synergistic LV Contraction Wall Integrity Valvular Competence Stroke Volume Cardiac Output Afterload Heart Rate Cardiac Output Hypoperfusion LV Dysfunction EF < 40% End Systolic Volume 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 Right Ventricular Failure Systolic and Diastolic Symptoms Physical Signs Symptoms Physical Signs Dyspnea on Exertion Basilar Rales Abdominal Pain Peripheral Edema Paroxysmal Nocturnal Dyspnea Tachycardia Cough Hemoptysis Pulmonary Edema S3 Gallop Pleural Effusion Cheyne-Stokes Respiration Anorexia Nausea Bloating Swelling Jugular Venous Distention Abdominal-Jugular Reflux Hepatomegaly
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 ( antidiuretic hormone, ADH) Compensatory Mechanisms: Sympathetic Nervous System Decreased MAP Sympathetic Activation in Heart Failure CNS sympathetic outflow Sympathetic Nervous System Cardiac sympathetic activity Sympathetic activity to kidneys + peripheral vasculature Contractility Tachycardia Vasoconstriction β 1 - receptors β 2 - receptors α 1 - receptors α 1 - β 1 - Activation of RAS MAP = ( SV x HR) x TPR Myocardial toxicity Increased arrhythmias Packer. Progr Cardiovasc Dis. 1998;39(suppl I):39-52. Disease progression Vasoconstriction Sodium retention
Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS) Compensatory Mechanisms: Renin-Angiotensin-Aldosterone (RAAS) Renin Angiotensin Converting Enzyme Angiotensinogen Angiotensin I Angiotensin II Renin-Angiotensin-Aldosterone ( renal perfusion) AT I receptor Salt-water retention Thirst Sympathetic augmentation Vasoconstriction Vasoconstriction Vascular remodeling Oxidative Stress LV remodeling MAP = ( SV x HR) x TPR Cell Growth Proteinuria Renin Angiotensin Activation Compensatory Mechanisms: Neurohormonal Activation Vasopressin Results in Vasoconstriction and increased cardiac work Salt and water retention Toxic effects on heart Blocking system results in Improved prognosis Improved symptoms - Increased systemic blood pressure Decreased systemic blood pressure Central baroreceptors Stimulation of hypothalamus, which produces vasopressin for release by pituitary gland Vasoconstriction Release of vasopressin by pituitary gland Compensatory Neurohormonal Stimulation: Summary Sympathetic nervous system Decreased Cardiac Output Renin-angiotensin system Antidiuretic hormone (vasopressin) Contractility Heart Vasoconstriction Circulating volume rate + Anteriolar Maintain blood pressure Cardiac output + Stroke volume Venous - Venous return to heart ( preload) Peripheral edema and pulmonary congestion 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
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 Neurohormonal Responses to Impaired Cardiac Performance LV Dysfunction Initially Adaptive, Deleterious if Sustained Short-Term Effects Long-Term Effects Response 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 Salt and Water Retention Augments Preload Pulmonary Congestion, Anasarca Vasoconstriction Sympathetic Stimulation Maintains BP for perfusion of vital organs Exacerbates pump dysfunction (excessive afterload), increases cardiac energy expenditure Increases HR and ejection Increases energy expenditure Jaski, B, MD: Basics of Heart Failure: A Problem Solving Approach Assessing Heart Failure Patient History Physical Examination Part II: Assessing Heart Failure 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 Septum LV cavity RV LV Part III: Current Treatment of Heart Failure LV Wall RA LA M-Mode Echo 2D Echo
General Measures Lifestyle Modifications: Weight reduction Discontinue smoking Avoid alcohol and other cardiotoxic substances Exercise Medical Considerations: Treat HTN, hyperlipidemia, diabetes, arrhythmias Coronary revascularization Anticoagulation Immunization Sodium restriction Daily weights Close outpatient monitoring 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 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 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 Angiotensin Receptor Blockers (ARBs) Block AT 1 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
Diuretics, ACE Inhibitors Reduce the number of sacks on the wagon 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-blockers 1 When combined with conventional HF therapy, betablockers reduce the combined risk of morbidity and mortality, or disease progression 1 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 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 Treatment Approach for the Patient with Heart Failure Stage A Stage B Stage C Stage D Part IV: Assessment and Treatment of the Heart Failure Patient At high risk, no structural disease Therapy Treat Hypertension Treat lipid disorders Encourage regular exercise Discourage alcohol intake ACE inhibition Structural heart disease, asymptomatic Therapy All measures under stage A ACE inhibitors in appropriate patients Beta-blockers in appropriate patients Structural heart disease with prior/ current symptoms of HF Therapy All measures under stage A Drugs: Diuretics ACE inhibitors Beta-blockers Digitalis Dietary salt restriction Refractory HF requiring specialized interventions Therapy All measures under stages A,B, and C Mechanical assist devices 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 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