UNIT 2 HEART FAILURE

Structure
2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Objectives Introduction Causes of Heart Failure Adaptive Mechanisms Types of Heart Failure Clinical Presentation Investigations Pulmonary Edema Treatment of Heart Failure
2.8.1 2.8.2 2.8.3 General Principles in Treatment of Heart Failure Non-pharmacological Measures Pharmacological Treatment

2.9 2.10 2.11 2.12 2.13

Diastolic Heart Failure Staging of Heart Failure Let Us Sum Up Answers to Check Your Progress Further Readings

2.0

OBJECTIVES

After reading this unit, you should be able to:

enlist the causes of heart failure; describe the short-term and long-term adaptive mechanism of heart failure; describe various types of heart failure; and manage a case of heart failure.

2.1

INTRODUCTION

It is a clinical syndrome wherein heart fails to pump blood at a rate required by the tissues of the body or it can do so only with an elevated filling pressure. This may be due to insufficient cardiac filling or impaired contractility and emptying. Various compensatory mechanisms set in to increase blood volume, heart rate and cardiac muscle mass. Despite these compensatory mechanisms, the ability of the heart to contract and relax may decline leading to worsening heart failure. 1

An alternative definition stresses on the clinical consequences of heart failure. Heart failure has been defined as a complex clinical syndrome i.e. characterized by abnormal left ventricular function and neurohormonal regulation, leading to effort intolerance, fluid retention and reduced longevity. Other terms like myocardial failure and circulatory failure should be differentiated from the term heart failure. Myocardial failure denotes abnormal systolic and diastolic function of the heart, which may be symptomatic or asymptomatic. Circulatory failure can be due to noncardiac conditions like haemorrhagic shock, while cardiac function is preserved.

2.2

CAUSES OF HEART FAILURE

It is important to recognise underlying causes and precipitating factors of heart failure for its appropriate management. That would also help in prevention and treatment of heart failure. The causes could be broadly classified as those due to myocardial damage or volume overload or pressure overload or arrhythmias. Myocardial Damage Coronary artery disease (myocardial ischemia or infarction), myocarditis, cardiomyopathies could lead to myocardial dysfunction. Volume Overload Conditions Valvular diseases (e.g. aortic regurgitation, mitral regurgitation) and congenital heart diseases (e.g. ventricular septal defect, patent ductus arteriosus) Pressure Overload Conditions Hypertension, aortic stenosis, coarctation of aorta impose pressure overload on the heart. Precipitating Causes of Heart Failure In majority of the cases one is often able to identify a precipitating cause of heart failure. Arrhythmias Cardiac arrhythmias are common in patients with various types of heart diseases and may precipitate or worsen heart failure through several mechanisms: a) Tachyarrhythmias reduce ventricular filling, increase myocardial oxygen demand and in patients with coronary artery disease aggravate myocardial ischemia. This results in both systolic and diastolic dysfunction. If persistent it may cause a reversible cardiomyopathy (tachyarrhythmias induced cardiomyopathy). Marked bradycardia in patients with underlying heart disease depresses cardiac output. Atrioventricular dissociation results in loss of atrial boost leading to impaired ventricular filling, lower cardiac output and raised atrial pressure. Abnormal intraventricular conduction impairs myocardial performance due to asynchronous ventricular contraction.

b) c) d)

Myocardial Ischemia

In patients with coronary artery disease an acute coronary syndrome event can precipitate heart failure. Mitral regurgitation occurring as a result of papillary muscle ischemia contributes to heart failure and may even produce acute pulmonary edema. Systemic Infection Serious infections increase total body metabolism and thus impose hemodynamic burden on the heart. Increased heart rate associated with infections is an additional burden. Circulating inflammatory cytokines are known to impair myocardial function and thus precipitate heart failure. The infectious process may also have an element of myocarditis. Pulmonary Embolism Patients with heart failure are at a higher risk of developing deep vein thrombosis and pulmonary embolism. Pulmonary thrombo-embolism exerts hemodynamic stress on the right side of the heart. Other Factors Stress in any form be it physical, emotional or environmental, development of unrelated illness, exposure to cardiac depressants drugs (cancer chemotherapy, negative inotropic drugs), cardiac toxins (alcohol, cocaine), pregnancy, anemia, thyroid disorders are some of the common conditions that may precipitate heart failure. Non-compliance Inappropriate reduction of therapy or noncompliance of therapy is an important cause to be kept in mind when encountered with worsening heart failure. One should make a diligent and systematic search for these precipitating factors and they should be treated adequately and appropriate steps should be taken to avoid recurrences. Identifying precipitating factors generally denotes better prognosis for the patients.

2.3

ADAPTIVE MECHANISMS

The adaptive mechanisms may be short term ones which come into play within minutes or hours of the onset of myocardial dysfunction. These are: Frank-Starling Mechanism In the Frank-Starling mechanism increased preload helps in sustaining cardiac performance. Starlings law essentially means that stroke volume is related to the end-diastolic volume. Frank proposed that the greater initial left ventricular volume leads to more rapid rate of rise of pressure, greater peak pressure and faster rate of relaxation. So the Frank-Starling law accounts for increased inotropic state and increased diastolic filling. Neuro Hormones Activation of neurohumoral systems resulting in release of noradrenaline leading to augmentation of myocardial contractility. Renin-Angiotensin-Aldosterone System Activation of renin-angiotensin-aldosterone system which helps in maintaining arterial pressure and perfusion of vital organs. Myocardial Hypertrophy and Remodeling

The long term adaptive mechanisms involve myocardial hypertrophy and remodeling which occurs slowly over weeks to months. The capacity of these adaptive mechanisms meant to sustain cardiac performance is not infinite and over a period of time maladaption sets in. Short term effects are mainly adaptive and occur in acute heart failure whereas long term effects are mainly deleterious and occur in chronic heart failure. For example, salt and water retention augments preload as short-term effect but causes pulmonary congestion and edema in the long term. Vasoconstriction helps to maintain blood pressure and perfusion of vital organs but it aggravates pump dysfunction by increasing afterload. Sympathetic stimulation increases heart rate and stroke volume but also increases energy expenditure. Hypertrophy helps to unload individual muscle fibers but leads to death of cardiac cells and cardiomyopathy of overload. Sympathetic Activity In heart failure there is adrenergic activation and parasympathetic withdrawal. This results in increase in myocardial contractility, tachycardia, sodium retention, renin release and generalized vasoconstriction. Renin-Angiotensin System (RAS) As heart failure sets in, there is activation of RAS (Fig 2.1). Adrenergic stimulation of beta-1 receptors in juxtaglomerular apparatus of the kidneys results in release of renin. Another mechanism i.e. responsible for renin release is baroreceptor stimulation in renal vascular bed by reduction of renal blood flow. Angiotensin II that is released is a powerful vasoconstrictor and stimulates the release of aldosterone. It also causes remodeling of cardiac myocytes. Aldosterone retains sodium and has direct effects on myocardium. The result is increased systemic vascular resistance and development of edema. Hence the interruption of this renin-angiotensin-aldosterone axis by angiotensin-converting enzyme inhibitors (ACE-Inhibitors) or angiotensin receptor blockers (ARBs) has salutary effects as there is reduction in systemic vascular resistance, afterload reduction, mild diuresis and improvement in the cardiac output. Angiotensin II also has direct role in modifying the structure and function of myocardium (Fig. 2.1).

Fig. 2.1: Renin-angiotensin system

Natriuretic Peptides

There are three natriuretic peptidesatrial (ANP) stored mainly in the atrium, brain (BNP) stored mainly in the ventricular myocardium and C-natriuretic peptide (CNP) located primarily in the vasculature. Circulating levels ANP and BNP are elevated in heart failure. They are vasodilatory and natriuretic.

2.4

TYPES OF HEART FAILURE

The various types and their description of Heart failure are as follows: Left Sided Versus Right Sided Heart Failure Predominantly left sided failure is seen in left ventricular infarction, hypertension, aortic and mitral valve diseases. The symptoms are due to pulmonary congestion (backward failure) and manifest as various degrees of dyspnoea to acute pulmonary edema. Fatigue, muscle weakness and mental confusion may also be seen as a result of forward failure.

The commonest cause of right-sided failure is left-sided failure, but is also seen in pulmonary hypertension due to other causes. Raised jugular venous pressure, hepatic congestion and edema are classical features of right-sided failure. Acute Versus Chronic Heart Failure When the syndrome sets in at a rapid rate before the compensatory mechanisms become operative, acute heart failure develops. The examples are acute heart failure due to acute myocardial infarction, tachyarrhythmias, acute mitral regurgitation and rupture of sinus of Valsalva aneurysm. If the anatomical abnormalities progress gradually and there is sufficient time for the adaptive mechanisms to develop, chronic heart failure sets in. Low Output Versus High Output Heart Failure Most forms of cardiac diseases, like hypertension, valvular diseases and coronary artery diseases manifest as low output heart failure. Systemic vasoconstriction with cold extremities is a feature. High cardiac output failure is seen in thyrotoxicosis, beriberi, arterio-venous fistula and anemia. Warm extremities and wide pulse pressure are the features. Systolic Versus Diastolic Failure Systolic heart failure is a classic heart failure where the inotropic (contractile) state is impaired and the expulsion of blood is not adequate. So the main manifestations of systolic failure are due to inadequate cardiac output and fluid retention. Diastolic failure has been a less familiar entity so far and is due to a defect in ventricular filling. The ability of ventricles to accept blood is impaired. In this, there is incomplete ventricular relaxation, transiently as in myocardial ischemia, or in a sustained form as in restrictive cardiomyopathy. The major manifestations are due to elevated ventricular filling pressures, leading to pulmonary or systemic venous congestion in the presence of preserved left ventricular systolic function (i.e. normal left ventricular ejection fraction and end-diastolic volume).

2.5

CLINICAL PRESENTATION
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There is a wide spectrum of potential clinical presentations with heart failure. Most patients have signs and symptoms of pulmonary congestion including dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Symptoms Dyspnoea Breathlessness or dyspnoea is a cardinal symptom of left ventricular failure and the patient may present with exertional dyspnoea or orthopnoea or paroxysmal nocturnal dyspnoea or acute pulmonary edema. Exertional Dyspnoea Degree of physical activity goes on decreasing as the heart failure progresses. Orthopnoea is dyspnoea that develops in recumbent position and is relieved by sitting up. It develops within few minutes of assuming recumbency and occurs when the patient is awake. Decreased pooling of fluid in the lower limbs and shift of fluid to the intrathoracic compartment resulting in increased preload causes orthopnoea. Paroxysmal Nocturnal Dyspnoea Here the patient, after going to sleep for sometime, suddenly gets up with dyspnoea and suffocation and sits upright gasping for breath. Bronchospasm may be present and hence is often referred to as cardiac asthma. With patient asleep at night, the increased resorption of fluid into the vascular space, increased intrathoracic volume, elevation of diaphragms due to recumbency, reduced sympathetic support during night and nocturnal depression of respiratory center during night are the factors operative producing paroxysmal nocturnal dyspnoea. New York Heart Association (NYHA) Classification It is a useful classification in follow up of patients in heart failure. Class I No limitation. Ordinary physical activity does not cause fatigue, dyspnoea or palpitation. Class II Slight limitation of physical activity. Ordinary physical activity results in fatigue, dyspnoea or palpitation. Class III Marked limitation of physical activity. Less than ordinary activity results in symptoms. Class IV Inability to carry out any physical activity without symptoms. Symptoms are present even at rest. Fatigue and Weakness: These symptoms are usually related to poor perfusion of the musculature as a result of low cardiac output. These may also occur due to excessive diuresis due to diuretic therapy or due to beta blocker treatment. Urinary Symptoms: Nocturia and in later stages oliguria may occur. Cerebral Symptoms: These are often seen in older patients who have associated cerebral arteriosclerosis. Confusion, impaired memory, insomnia and disorientation may occur. Cough: Cough is due to pulmonary congestion and is a dyspnoea equivalent or orthopnoea equivalent. It may also be due to use of ACE inhibitors.

Symptoms of Right-sided Failure: The symptoms are due to systemic venous congestion pain in right hypochondrium from enlargement of the liver, anorexia, nausea and edema. Hemoptysis: This can result from backpressure, rupture of pulmonary venules, respiratory infections and pulmonary embolism. Embolism: Embolism can occur to any part of the body like a cerebral embolism. They are most often related to atrial fibrillation or mural thrombi in the ventricle.

Check Your Progress 1 1) Name any six conditions that can precipitate heart failure. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 2) Name two conditions that can impose a pressure overload on the heart. ................................................................................................................................. ................................................................................................................................. 3) What are the adaptive mechanisms to counter myocardial dysfunction? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 4) What is the Frank-Starling mechanism? ................................................................................................................................. ................................................................................................................................. 5) What are the symptoms of left-sided heart failure? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 7

................................................................................................................................. ................................................................................................................................. 6) What additional symptoms are prominent in right-sided heart failure? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 7) What is meant by diastolic and systolic heart failure? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 8) What are the factors responsible for paroxysmal nocturnal dyspnea? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 9) What is Class IV in the New York Heart Association classification of heart failure? ................................................................................................................................. ................................................................................................................................. Signs General Examination The patient will appear anxious and dyspnoeic. Patients in chronic heart failure are usually malnourished and even cachectic. Chronic passive venous congestion may produce exophthalmos. Cyanosis, icterus and edema may be present. Pulse There is usually tachycardia associated with coldness of extremities due to adrenergic activity. Irregularly irregular pulse suggests atrial fibrillation, which could have precipitated heart failure. Jugular Venous Pressure Elevated jugular venous pressure reflects raised right atrial pressure. V-wave and y descent will be prominent if there is severe tricuspid regurgitation. Jugular venous pressure which is normal at rest gets abnormally elevated when right upper abdominal quadrant is compressed (hepatojugular reflux) Liver

The liver is often enlarged and tender. It is pulsatile in the presence of severe tricuspid regurgitation. Edema Peripheral, symmetrical, pitting edema, particularly in the dependent parts, noticeable in the ambulant patients towards evening is a cardinal feature of heart failure. In bed-ridden patients, the edema is seen over the sacral area. Long standing edema leads to skin pigmentation. Pleural Effusion Pleural veins drain into both systemic and pulmonary veins. When both the venous systems are involved, pleural effusion develops. It is usually bilateral, but when confined to one side, it is generally seen on the right side. Ascites Ascites denotes chronic systemic venous hypertension. In tricuspid regurgitation and constrictive pericarditis, ascites may be more prominent than peripheral edema. Cardiac Findings Findings related specifically to the underlying cardiac lesions like valvular lesions, shunts or pericardial disease will be present. There are some general findings: Cardiac Enlargement This is generally seen in chronic systolic heart failure. In acute heart failure and diastolic heart failure, cardiomegaly is not a feature. Heart Sounds Presence of left ventricular third heart sound denotes systolic dysfunction. Fourth heart sound may be present. With tachycardia the extra sounds result in a gallop rhythm either early diastolic or presystolic gallop. With pulmonary hypertension, pulmonary component of the second sound is accentuated. Functional mitral and tricuspid regurgitation murmurs appear with ventricular dilatation. Pulsus Alternans It is seen in systolic heart failure and indicates advanced myocardial disease. It tends to disappear with successful treatment of heart failure. Cheyne Stokes Respiration This is periodic or cyclical breathing, where periods of apnoea alternates with periods of hyperpnoea during sleep. Left ventricular failure leading to sluggish cerebral circulation is the cause.

2.6 INVESTIGATIONS
The initial evaluation of new onset heart failure should include an electrocardiogram, chest radiograph, and B-type natriuretic peptide assay. The cardiac rhythm may be normal sinus, sinus tachycardia, or atrial fibrillation. Left ventricular hypertrophy, left bundle branch block, intraventricular conduction delay, and non-specific ST segment and T wave changes support a diagnosis of heart failure. Q waves in contiguous leads strongly implicate a previous myocardial infarction and coronary atherosclerosis as the etiology. Chest radiographic findings of heart failure include cardiomegaly, pulmonary vascular redistribution, pulmonary venous congestion, Kerley B lines, alveolar edema, and pleural effusions. Chest X-ray

Increase in cardio-thoracic ratio is a relatively specific indicator of left ventricular end-diastolic volume. Left atrial enlargement is seen as double density shadow, lifting up of the left main bronchus and left atrial appendage enlargement. When pulmonary venous pressure rises to 12 to 18 mmHg, pulmonary blood flow is redirected to upper lobes in the erect position. Thus prominent upper lobar veins indicate pulmonary venous hypertension (cephalisation). With pressure above 18 mmHg, interstitial edema develops. Kerley B lines are seen in interstitial pulmonary edema. Kerley B lines are interlobular septal lines and are seen as thin horizontal lines at both lung bases perpendicular to the lateral pleural surface. When the pulmonary venous pressure exceeds 25 mmHg, alveolar edema occurs. Acute pulmonary edema produces butterfly or bat wing pattern in the chest X-ray seen in the inner two thirds of the lung. The outer third of the lung has better ventilation, better pumping action during respiration, better compliance and better lymphatic drainage. Onset of pulmonary arterial hypertension leads to prominent central vessels with peripheral pruning (Centralisation). ECG Sinus tachycardia is common. ECG abnormalities may reflect the underlying coronary artery disease by way of pathological Q-waves, ST-T wave abnormalities. Left ventricular hypertrophy and left atrial enlargement show changes on ECG. Atrial fibrillation with rapid ventricular rate may act as a precipitating factor for the heart failure or it may occur due to the underlying dilated cardiomyopathy. Ventricular ectopics are common in heart failure and may indicate adverse prognosis. Left bundle branch block (LBBB) is usually associated with underlying heart disease. LBBB in coronary artery disease indicates severe disease, poor left ventricular function and decreased survival. Echocardiography Both global and regional systolic function are to be checked. Global measures include ejection fraction, stroke volume, end systolic volume. (For measurement of systolic function using Mmode and 2D echocardiography refer to the section on Echocardiography.) In diastolic dysfunction there is generally presence of left ventricular hypertrophy. The transmitral flow is studied by pulsed Doppler. In normals the early filling velocity (E-wave) is larger than the velocity during atrial contraction (A-wave) and the descent is fast. In diastolic dysfunction there are in general 2 types of patterns. When relaxation is impaired the E-wave becomes smaller and its deceleration time is prolonged and the A-wave becomes taller. With restrictive physiology the E-wave becomes taller and the deceleration time is shorter and the Awave is smaller. There are also abnormalities in the pulmonary venous flow patterns. Laboratory Tests Routine blood tests like haemoglobin, creatinine, electrolytes are useful to plan treatment. More recently the blood natriuretic peptide levels have been used to assess heart failure. BNP (brain natriuretic peptide) may be increased early in left ventricular dysfunction. It is synthesized mainly by the ventricles and released early in heart failure. The Framingham study group has come out with criteria for diagnosis of heart failure incorporating symptoms, signs, investigations and response to treatment. It is a useful criteria for the clinicians. (Table 2.1).

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Table 2.1: Framingham Criteria for Diagnosis of Heart Failure

Major Criteria Paroxysmal nocturnal dyspnoea Neck vein distention Rales Radiographic cardiomegaly Acute pulmonary edema S3 gallop Central venous pressure >16 cm H2O Circulation time >25 sec Hepatojugular reflux Pulmonary adema, visceral congestion, or cardiomegaly at autopsy Weight loss >4.5 kg in 5 days in response to treatment of congestive heart failure. Minor Major Bilateral ankle edema Nocturnal cough Dyspnoea on ordinary exertion Hepatomegaly Pleural effusion Decrease in vital capacity by one third from maximal value recorded Tachycardia (rate >120 beats/min) Note: The diagnosis of congestive heart failure in this study required that two majoror one major and two minor criteria be present concurrently. Minor criteria were acceptable only if they could not be attributed to another medical condition. Source: Ho, K.L., Pinsky, J.L., Kannel, W.B., Levy, D. The Epidemiology of Heart Failure: The Framingham Study, J Am Coll Cardiol 22, (Suppl A): 6A, 1993.

2.7

PULMONARY EDEMA

Pulmonary edema occurs when movement of liquid from the blood to the interstitial space and/or into the alveoli exceeds the return of liquid to the blood and its drainage through the lymphatics. Causes of Pulmonary Edema Imbalance of Starling Forces

Increased pulmonary capillary pressure Hypoalbuminemia increased Negative interstitial pressure

The two most common forms of pulmonary edema are that initiated by an imbalance of Starling forces and that initiated by disruption of one or more components of the alveolar-capillary membrane. Altered Alveolar-Capillary Membrane Permeability (ARDS) Primary alveolar-capillary membrane damage (Acute Respiratory Distress Syndrome)

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Lymphatic Insufficiency

Post lung transplant Lymphangitis carcinomatosis Fibrosing lymphangitis

Unknown or Incompletely Understood High-altitude pulmonary edema Neurogenic pulmonary edema Narcotic overdose pulmonary edema Pulmonary embolism Eclampsia Post cardioversion Post anesthesia Post cardiopulmonary bypass

Cardiogenic Pulmonary Edema Acute cardiogenic pulmonary edema is the symptom of left-sided heart failure. Causes

Impaired left ventricular systolic and/or diastolic function Mitral stenosis Any condition that elevates left atrial and pulmonary capillary pressures significantly.

Effects of Cardiogenic Pulmonary Edema Interference with oxygen transfer in the lungs Depression arterial oxygen tension Sense of suffocation and oppression in the chest Elevates heart rate and blood pressure further restricting ventricular filling.

The increased work of breathing place an additional load on the heart, and cardiac function becomes depressed further by the hypoxia leading to a vicious. Development of acute pulmonary edema is a terrifying experience with extreme breathlessness developing suddenly, and the patient becomes extremely anxious, coughs, and expectorates pink, frothy liquid, with a feeling of drowning. The patient sits upright, or may stand, exhibits air hunger, respiratory rate is elevated, the alae nasi are dilated, and there is inspiratory retraction of the intercostal spaces and supraclavicular fossae that reflects the large negative intrapleural pressures required for inspiration. The patient often grasps the sides of the bed to allow use of the accessory muscles of respiration. Respiration is noisy, with loud inspiratory and expiratory gurgling sounds that are 12

often easily audible across the room. Sweating is profuse, and the skin is usually cold, ashen, and cyanotic, reflecting low cardiac output and increased sympathetic drive. Auscultation reveals crepitations and occasionally rhonchi, which appear initially over the lung bases but then extend upward with worsening of the condition. An S3 gallop and loud pulmonic component of the second heart sound are frequently present. Arterial pressure is usually elevated as a result of excitement and discomfort, which cause adrenergically mediated vasoconstriction. And this usually does not represent chronic systemic hypertension. Optic fundus examination may be useful in differentiating the two conditions. Sometimes it may be difficult to differentiate between acute pulmonary edema and acute exacerbation of bronchial asthma. Some of the points that may be of clinical use in such a situation are given in the table below.
Table 2.2: Differentiation between Pulmonary Edema and Bronchial Asthma Clinical features Previous similar episodes and awareness of disgnosis Profuse sweating Cyanosis Chest expansion and resonance Adventitious sounds rhonchi Cardiogenic pulmonary edema May/may not be present Usually present Frequently cyanotic Dull to percussion, no hyper expansion Mainly crepitations and occasionally less prominent Bronchial asthma Usually present Usually not present Unusual Hyper expansion and hyper resonance Rhonchi present and crepitations

Management of Pulmonary Edema Pulmonary edema is life-threatening condition and therefore, treated as a medical emergency. As is the case with chronic stable heart failure, identification and correction of any precipitating causes should be attempted. However, because of the acute nature of the problem, the initial management includes a number of additional non-specific measures: 1) 2) The patient should be in propped up position (provided the blood pressure is adequate) with the legs dangling along the side of the bed, if possible, which tends to reduce venous return. 100 per cent O2 should be administered to improve oxygenation. If patient is not maintaining oxygen saturation with nasal oxygen intubation and mechanical ventilation should be considered. This increases intra-alveolar pressure, reduces transudation of fluid from the alveolar capillaries, and impedes venous return to the thorax, reducing pulmonary capillary pressure. Morphine is the drug of choice. It is administered intravenously, in doses from 2 to 5 mg intravenously. It reduces anxiety, reduces adrenergic vasoconstrictor stimuli to the arteriolar and venous beds, and thereby helps to break a vicious cycle. An antiemetic is usually given along with morphine to reduce chance of vomiting. Intravenous loop diuretics produce rapid diuresis, reduce circulating blood volume and hasten the relief from pulmonary edema. Furosemide when administered exerts a venodilator

3)

4)

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action, reducing venous return. This helps in improving pulmonary edema even before the diuresis is initiated. 5) 6) 7) 8) Afterload reducing agents e.g. IV sodium nitroprusside at 20 to 30 g/min in patients with systolic BP above 100 mmHg. Inotropic support should be provided by dopamine or dobutamine where necessary. Patients with systolic heart failure who are not receiving digitalis may receive 0.75 to 1.0 mg digoxin intravenously over 15 min. Sometimes, aminophylline (theophylline ethylenediamine), 240 to 480 mg intravenously, is effective in diminishing bronchoconstriction, increasing renal blood flow and sodium excretion, and augmenting myocardial contractility. Rotating tourniquets may be applied in an effort to reduce venous return.

9)

Once the patient has been stabilized and underlying cause determined, treatment directed at correcting/improving the cause.

2.8

TREATMENT OF HEART FAILURE

Over the past decade, the conceptual understanding of heart failure has changed significantly. Several large clinical trials have demonstrated that non-pharmacological and pharmacological interventions can dramatically reduce the morbidity and mortality associated with heart failure. Many clinical trials have extended the therapeutic paradigm for treating heart failure beyond the goal of limiting congestive symptoms of volume overload.

2.8.1 General Principles in Treatmemt of Heart Failure

The goals of treating heart failure are relief of symptoms, improvement in exercise tolerance, and reduction in the number of hospitalizations, decreasing morbidity and mortality by various non-pharmacological and pharmacological measures. The treatment of heart failure requires close attention to both the primary aetiology and the stage of the disease. It also varies depending on whether one is treating acute heart failure or chronic stable heart failure, systolic versus diastolic heart failure. Management of acute heart failure is a medical emergency that includes bed rest, oxygen administration, morphine, intravenous diuretics, ACE inhibitors, digoxin, IABP, ventricular assist devices or even emergency surgery depending on the clinical scenario.

Initial Approach This includes control of factors that may cause or precipitate heart failure and/or augment its manifestations. Treatment is individualized depending on the severity, acuity, aetiology and precipitating factors.

2.8.2 Non-pharmacological Measures

Restriction of physical activities to reduce myocardial work and oxygen consumption. However, care should be taken to prevent deep vein thrombosis. 14

Oxygen administration in dyspnoeic, hypoxic patient. Once patient is stabilized, cardiac rehabilitation and appropriate aerobic exercise may improve functional capacity. Weight loss in obese patients. This will reduce systemic vascular resistance and myocardial oxygen demand. Dietary salt restriction (2-2.5 g sodium or 5-6 g salt per day) should be advised. Fluid and water restriction to 1 to 1.5 L/24 h in patients with advanced heart failure is important in the presence of hyponatremia and volume overload. Very severe fluid restriction may lead to pre-renal azotemia. Discontinuation of negative inotropic agents, if any (beta blockers, diltiazem, verapamil, disopyramide, flecainide) and agents that cause fluid retention (NSAID). Dialysis or ultra-filtration in patients with severe heart failure and renal dysfunction.

Correction of Reversible Causes In the long term reversible causes of heart failure like valvular lesions, myocardial ischemia, uncontrolled hypertension, arrhythmias, alcohol, negative inotropic agents, intracardiac shunts, and high-output states should be identified and corrected. Some metabolic and infiltrative cardiomyopathies may be partially reversible, or their progression may be slowed; these include hemochromatosis, sarcoidosis, and amyloidosis. Reversible causes of diastolic dysfunction include pericardial disease and left ventricular hypertrophy due to hypertension.

2.8.3 Pharmacological Treatment

Diuretic Therapy One of the aims of treatment of congestive heart failure is directed toward controlling salt and water retention (central or peripheral edema). Diuretics provide effective relief of symptoms in patients with moderate to severe congestive heart failure. Though excessive diuresis can lead to electrolyte imbalance and neuro-humoral activation, most of the symptomatic patients require some diuretics for symptom relief. Daily weight measurement is an important guide to the adequacy of this therapy. Thiazide Diuretics and Similar Agents When fluid retention is mild, a thiazide diuretics or a similar type of agent may be sufficient (hydrochlorothiazide, 25-100 mg; metolazone, 2.5-5 mg; chlorthalidone, 25-50 mg; etc). Thiazide agents are generally ineffective when the glomerular filtration rate falls below 30-40 mL/min. Metolazone maintains its efficacy down to a glomerular filtration rate of approximately 20-30 mL/min. Adverse reactions: Hypokalemia, prerenal azotemia, skin rashes, neutropenia and thrombocytopenia, hyperglycemia, hyperuricemia, and hepatic dysfunction. Loop Diuretics Patients with more severe heart failure should be treated with one of the loop diuretics. These agents are active even in severe renal insufficiency. E.g. Furosemide (20-320 mg daily),

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Bumetanide (1-8 mg daily), and Torsemide (20-200 mg daily). They have a rapid onset and a relatively short duration of action. In patients with preserved renal function, two or more doses are preferable to a single larger dose. In acute situations or when gastrointestinal absorption is in doubt, they should be given intravenously. Continuous intravenous rather than intermittent administration of loop diuretics is an effective method of overcoming diuretic resistance in heart failure. Furosemide loading dose 30 to 40 mg followed by infusion at a rate of 2.5 to 3.3 mg/h for 48 h. Adverse reactions: Intravascular volume depletion, prerenal azotemia, and hypotension, hypokalemia, skin rashes, gastrointestinal distress, and ototoxicity. Potassium Sparing Diuretics The potassium-sparing agents spironolactone, triamterene, and amiloride are often useful in combination with the loop diuretics and thiazides. Triamterene and amiloride act on the distal tubule to reduce potassium secretion. Their diuretic potency is only mild and not adequate for most patients with heart failure, but they may minimize the hypokalemia induced by more potent agents. Side effects: Hyperkalemia, gastrointestinal symptoms, renal dysfunction and gynecomastia. Combined Use of Diuretics Combination of diuretics may be indicated in patients previously resistant to furosemide alone. Profound diuresis and clinical improvement may occur after the addition of metolazone to furosemide in patients with CHF. Metolazone is particularly useful because of its prolonged duration of action, lipophilicity, and effectiveness in renal failure. Extreme caution should be exercised with this approach as massive diuresis and electrolyte disturbances may ensue. Inhibitors of the Renin-angiotensin-aldosterone System Angiotensin-converting Enzyme Inhibitors Angiotensin Converting Enzyme Inhibitors (ACEI) has shown to reduce mortality in heart failure to the tune of 16-30 per cent in various large trials. The renin-angiotensin-aldosterone system (RAAS) is activated early in the course of heart failure and plays an important role in the progression of heart failure. Hence, modulation of this system with Angiotensin Converting Enzyme (ACE) inhibitors should be the initial mode of therapy. ACE inhibitors modify neurohormonal activation in heart failure by inhibiting conversion of angiotensin I to angiotensin II (AII) through ACE. This results in the favourable hemodynamic effects of peripheral vasodilatation, reduced afterload, and decreased blood pressure. The reduction in AII, a potent myogenic agent, also may attenuate abnormal left ventricular remodeling; the subsequent reduction in aldosterone decreases sodium and fluid retention. ACE inhibitors also cause down-regulation of the sympathetic nervous system and improve baroreceptor function. Angiotensin-converting enzyme is also involved in the degradation of bradykinin. So ACE inhibition result in higher bradykinin levels, which in turn stimulate synthesis of prostaglandins and nitric oxide, which may be beneficial. Adverse Effects

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Hypotension, hyperkalemia, taste disturbance, angiedema, renal insufficiency. In the absence of any symptoms of hypotension, and normal renal function and K + levels, the dosage should be titrated to the dosages proved effective in clinical trials (captopril 50 mg three times daily, enalapril 10 mg twice daily, lisinopril 10 mg daily, or the equivalent) over a period of 1-3 months. Some patients may exhibit rises in serum creatinine or K +, but they do not require discontinuation if the levels stabilize even at values as high as 3 mg/dl and 5.5 meq/l, respectively. Angiotensin II Receptor Blockers (ARB) Angiotensin receptor blockers block the final common pathway and provide a means of complete blockade of the system. One of two subtypes of AII receptors, the AT1 receptor produces vasoconstriction and induces muscle cell proliferation when activated; the AT2 receptor produces antiproliferative effects upon activation. Currently available ARBs selectively block the AT1 receptor, producing vasodilatation and inhibiting muscle cell proliferation. However, these agents do not produce increases in bradykinin, prostaglandins, and nitric oxide in the heart, blood vessels, and other tissues. They should be considered as alternatives to ACE inhibitors in ACE-intolerant patients especially patients with chronic dry irritating cough and angiedema. Another potential use is to counteract ACE escape, the attenuation of the benefits of ACE inhibition that may occur with time. Various agents available are losartan, valsartan, irbesartan, candesartan, telmisartan and eprosartan. Spironolactone Aldosterone mediates myocardial remodeling and fibrosis, as well as sodium retention and potassium loss at the distal tubules. The anti-aldosterone agent, spironolactone has been shown in RALES trial as an important neuro-hormonal antagonist in the treatment of heart failure. In this trial spironolactone 25 mg daily was compared with placebo in patients with advanced heart failure already receiving ACE inhibitors and diuretics and showed a 29 per cent reduction in mortality. Caution: Potassium levels should be monitored. This drug may cause gynaecomastia. A more selective aldosterone inhibitor, eplerenone does not cause gynaecomastia. Beta-Blockers Beta-blockers have traditionally been considered contraindicated in patients with heart failure because they may block the compensatory actions of the sympathetic nervous system with potential to worsening of symptoms. However, chronically failing heart is adrenergically activated and persistent elevations of catecholamines and sympathetic nervous system activity cause progressive myocardial damage, leading to worsening left ventricular function and dilation. Several large clinical trials have demonstrated that beta-blockers decrease mortality in patients who are already receiving standard heart failure therapy (i.e., angiotensin-converting enzyme [ACE] inhibitors and diuretics with or without digoxin). Hence the role of beta blockade in heart failure management. Beneficial effects of beta-blockers in heart failure include improvement in LV ejection fraction over a period of 3-6 months decrease in LV end-systolic and end-diastolic volumes and mass in 4 to 12 months (reversed remodeling).

17

Large randomized trials have shown mortality reduction to the tune of 35 per cent with betablocker therapy. Current guidelines recommend that beta-blockers be used in patients with systolic dysfunction, ejection fraction less than 40 per cent, and mild to moderate heart failure as judged by New York Heart Association (NYHA) (10) class II or III symptoms. Beta-blockers should be started at low doses and gradually increased to the target goals. Effective beta blockade can be reached progressively by increasing doses of beta-blocker agents every 2 to 3 weeks. Agents found useful in heart failure are second generation selective B 1 agents or third generation agents with vasodilatory action. There is evidence for the usefulness of metoprolol, bisoprolol, and cardvedilol in heart failure. Contraindications for Beta-Blockers Reversible airways obstructive disease, advanced heart block, or episodic decompensation. Vasodilators Agents that dilate arteriolar smooth muscle and lower peripheral vascular resistance reduce left ventricular afterload and agents that diminish venous tone and increase venous capacitance reduce the preload of both ventricles as their principal effect. Nitrates Intravenous vasodilators (sodium nitroprusside or nitroglycerin) are used primarily for acute or severely decompensated chronic heart failure, especially when accompanied by hypertension or myocardial ischemia. Starting dosages of both agents are 10-20 g/kg/min with upward titration by increments of 10 g/kg/min as frequently as every 5-10 minutes. Dosages above 200 g/kg/min are usually not required. Isosorbide Dinitrate: 20-80 mg orally three times daily, has proved effective in several small studies. Side effects: headache, tolerance. Hydralazine Hydralazine is a potent arteriolar dilator and markedly increases cardiac output in patients with congestive heart failure. However, as a single agent, it has not been shown to improve symptoms or exercise tolerance during chronic treatment. The combination of hydralazine and isosorbide dinitrate is an alternative therapy when ACE inhibitors are contraindicated or cannot be tolerated. Daily doses of hydralazine up to 300 mg in combination with isosorbide dinitrate 160 mg in the presence of cardiac glycosides and diuretics have some effect in reducing mortality. Side effect: Gastrointestinal distress, headaches, tachycardia, and hypotension. Check Your Progress 2 1) What happens to the jugular venous pressure and liver in congestive heart failure? .................................................................................................................................

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................................................................................................................................. 2) What are the auscultatory changes in the heart sounds in heart failure? ................................................................................................................................. ................................................................................................................................. 3) What functional murmurs can occur in heart failure? ................................................................................................................................. ................................................................................................................................. 4) What are the auscultatory signs over the chest in acute pulmonary edema? ................................................................................................................................. ................................................................................................................................. 5) What are the features of acute pulmonary edema on the chest X-ray? ................................................................................................................................. ................................................................................................................................. 6) What is the best position for the patient in managing acute pulmonary edema? ................................................................................................................................. ................................................................................................................................. 7) Name two drugs commonly used in the management of acute pulmonary edema. ................................................................................................................................. ................................................................................................................................. 8) Why are diuretics used in congestive heart failure? ................................................................................................................................. .................................................................................................................................

9)

Name two loop diuretics. ................................................................................................................................. .................................................................................................................................

10) What are some of the adverse reactions from diuretic usage? ................................................................................................................................. .................................................................................................................................

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11) How do ACE inhibitors help in heart failure? ................................................................................................................................. ................................................................................................................................. 12) What are the differences between ACE inhibitors and Angiotensin Receptor Blockers? ................................................................................................................................. ................................................................................................................................. 13) What is the effect of Hydralazine in heart failure? ................................................................................................................................. ................................................................................................................................. Inotropic Agents All currently available inotropic agents act to increase Ca2+ for activation in both normal and failing myocardium (Hurst). The use of inotropic agents in the treatment of CHF is predicated on the finding that a major contributing factor in reducing ventricular performance results from depression of myocardial contractility and that this can be reversed, or at least improved, by inotropic drugs. Digitalis Glycosides The digitalis glycosides are the only orally active positive inotropic agents currently available. The positive inotropic occurs through inhibition of the enzyme Na+-K+-ATPase leading to an increase in the cytocyclic Ca2+ concentration resulting in a subsequent increase in previously reduced myocyte contraction (Hurst). It reduces heart rate via parasympathomimetic effects that is useful in enhancing ventricular filling and reduces pulmonary congestion. Potential Disadvantages Arrhythmias especially in presence of hypokalemia, lack of mortality benefit. However, their efficacy in reducing the symptoms of heart failure has been established. Digoxin should be used for patients who remain symptomatic when diuretics and ACE inhibitors as well as for heart failure patients who are in atrial fibrillation and require rate control. In most patients with chronic heart failure it is sufficient to begin with the expected maintenance dose (usually 0.125-0.25 mg daily). Most of the positive inotropic effect is apparent with serum digoxin levels between 0.7 and 1.2 ng/ml, and levels above this range may be associated with a higher risk of arrhythmias and lower survival rates, though clinically evident toxicity is rare with levels below 1.8 ng/ml. Drug Interactions Amiodarone, quinidine, propafenone, and verapamil may increase digoxin levels up to 100 per cent. It is prudent to measure a blood level after 7-14 days (and at least 6 hours after the last dose was administered) especially if there is any suspicion of toxicity. Digitalis Toxicity Symptoms of digitalis toxicity include anorexia, nausea, headache, blurring or yellowing of vision, and disorientation. Cardiac toxicity may take the form of atrioventricular conduction or sinus node depression; junctional, atrial, or ventricular premature beats or tachycardias; or ventricular fibrillation. Serum potassium level should be maintained in the high normal range.

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Lidocaine or phenytoin may be useful for ventricular arrhythmias, as is overdrive pacing. But quinidine, amiodarone, and propafenone should be avoided because they will increase digoxin levels. Electrical cardioversion should be avoided if possible, since it may cause intractable ventricular fibrillation or cardiac standstill. Pacing is indicated for complete heart block and symptomatic or severe AV block (heart rate <40/min) if they persist after treatment with atropine. Digoxin immune fab are available for life-threatening toxicity or large overdoses, but it should be remembered that their half-life is shorter than that of digoxin and so repeat administration may be required. Phosphodiesterase Inhibitors and Other Agents Amrinone and Milrinone are prototypes of type III PDE inhibitors. They decrease the breakdown of cyclic AMP in the myocardium and increase cyclic guanidine monophosphate (cyclic GMP) in vascular smooth muscle, resulting in an increase in myocardial contractility as well as arterial and venous vasodilatation. Dosage: Milrinone 25-75 microgram/kg bolus over 10 minutes followed by a continuous infusion of 0.375-0.75 microgram/kg. Amrinone is not used because of its propensity to cause Thrombocytopenia. Side effects: Thrombocytopenia. Catecholamines Catecholamines increase activation of Ca2+ via beta-adrenergic receptors and the adenyl cyclase system. Dopamine has both alpha1 and beta1 and dopaminergic effects. Its beta1 effects in the heart occur largely through the release of endogenous norepinephrine, which may be largely depleted in a failing heart. As such, the benefits of dopamine administration, if any, occur at low doses (e.g., 0.02 mg/kg per minute), where it may induce renal arterial vasodilatation. In general, it is employed in association with more potent inotropic agents (e.g., dobutamine). Dobutamine characterized by an increase in cardiac output and a decrease in ventricular filling pressure with little change in heart rate. There is modest rise in arterial pressure and decrease in peripheral vascular resistance. The positive inotropic activity of dobutamine is mediated by direct stimulation of beta1-adrenergic receptors in the myocardium. Dobutamine infusion generally is begun at 2 g/kg per minute and titrated to optimize cardiac output while reducing LV filling pressure. The major side effects of dobutamine are an excessive increase in heart rate with high doses and ventricular arrhythmias. Calcium Channel Blockers Calcium antagonists are not recommended for the treatment of CHF because of their negative inotropic effects. However, second-generation dihydropyridine-type calcium antagonists such as amlodipine and felodipine may be used for the treatment of concomitant arterial hypertension or angina. Anticoagulation In patients with left ventricular failure and reduced ejection fractions, the risk of LV thrombus formation and systemic arterial embolization appears to be primarily in patients who are in atrial

21

fibrillation or who have large recent (within 3-6 months) myocardial infarctions. These groups and patients with a history of embolism should be anticoagulated. Antiarrhythmic Therapy Patients with heart failure have a high incidence of both symptomatic and asymptomatic arrhythmias. About 10 per cent of patients have syncope or presyncope resulting from ventricular tachycardia. However Holter monitoring reveals that up to 70 per cent of patients have asymptomatic episodes of nonsustained ventricular tachycardia, which indicate a poor prognosis independent of the severity of left ventricular dysfunction. Implantable Cardioverter Defibrillator Patients with aborted sudden death, hemodynamically unstable ventricular arrhythmias, and unexplained cardiogenic syncope are at high risk for fatal ventricular arrhythmias. If these patients have a reasonable life expectancy and stable, non-refractory heart failure, an implantable defibrillator is the approach of choice (in conjunction with beta blockade). The constraining factor is the high cost involved. Coronary Revascularization When underlying coronary artery disease is the cause of heart failure in the coronary revascularization may both improve symptoms and prevent progression. Patients with angina and those with evidence of viable myocardium should undergo revascularization. In general, bypass surgery is preferable to PTCA in the setting of heart failure because it provides more complete revascularization. Cardiac Resynchronization Therapy This innovative, pacemaker-based approach to the treatment of patients with heart failure who have a wide QRS complex (>140 ms) on 12-lead ECG aims at providing electromechanical coordination and improved ventricular synchrony in symptomatic patients who have severe systolic dysfunction and clinically significant intraventricular conduction defects, particularly left bundle-branch block. A percutaneous, three-lead, biventricular pacemaker system is used; one lead is placed in the right atrium, one is placed in the right ventricle, and a third is passed through the right atrium, through the coronary sinus, and into a cardiac vein on the lateral wall of the left ventricle. Beneficial effects include reverse remodeling, resulting in decreased heart size and ventricular volumes, improved ejection fraction, and decreased mitral regurgitation. Clinical improvements in exercise tolerance, quality of life, and the rate of hospitalization have been documented. However resynchronization therapy has not been shown to enhance survival. Cardiac Transplantation For patients with end-stage heart failure, cardiac transplantation has become a promising therapy especially with the advent of immunosuppressive therapy and more careful screening of donor hearts. The survival of patients after cardiac transplantation has increased considerably. Many centers now have 1-year survival rates exceeding 80-90 per cent, and 5-year survival rates above 70 per cent. Infections, hypertension, and renal dysfunction caused by cyclosporine, rapidly progressive coronary atherosclerosis, and immunosuppressant-related cancers have been the major complications. The high cost and limited number of donor organs require careful patient selection early in the course.

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Other Surgical Treatment Options Cardiomyoplasty This is a procedure wherein the latissimus dorsi muscle is wrapped around the heart and stimulated to contract synchronously with it. It has been largely given up. Ventricular Reduction Surgery A large part of the anterolateral wall is resected to make the heart function more efficiently. Both approaches are too risky in end-stage patients and have not been shown to improve prognosis or symptoms in controlled studies, and for these reasons they have largely been dropped. Ventricular Assist Devices Externally powered and implantable ventricular assist devices are used in patients who require ventricular support either to allow the heart to recover or as a bridge to transplantation. However, complications are frequent, including bleeding, thromboembolism, and infection, and the cost is very high. Even though 1-year survival has shown improvement in a recent trial, all the patients died by 26 months. Gene Therapy In experimental studies, gene therapy has been shown to improve failing human myocardial function. The abnormal function of myocytes obtained from patients with dilated cardiomyopathy could be normalized by transfection of the myocytes in vitro with an adenovirus expressing the sarcoplasmic reticulum Ca2+-ATPase, SERCA2a; transfection increased Ca2+ATPase activity 80 per cent. Some clinical studies have demonstrated the benefits of gene therapy and it appears to be a promising therapy. Palliative Care Despite the technologic advances of recent years, many patients with chronic heart failure are elderly and have multiple comorbidities. Many of them will not experience meaningful improvements in survival with aggressive therapy, and the goal of management should be symptomatic improvement and palliation.

2.9

DIASTOLIC HEART FAILURE

Unfortunately, unlike heart failure due to systolic dysfunction, diastolic heart failure has been studied in few clinical trials, so there is little evidence to guide the care of patients with this condition. Physiological principles used in the treatment of such patients include the control of blood pressure, heart rate, myocardial ischemia, and blood volume.

Check Your Progress 3 1) How do Digitalis glycosides act in heart failure? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. 23

2)

Name three drugs that increase digoxin blood levels if used concurrently. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

3)

What is the difference between Dopamine and Dobutamine? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

4)

What are the common arrhythmias in patients with heart failure? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

5)

What is meant by cardiac resynchronization therapy? ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. ................................................................................................................................. .................................................................................................................................

2.10 STAGING OF HEART FAILURE

Staging and recommended therapy according to the staging is a very useful concept both from prevention point of view and treatment, as prescribed by ACC/AHA guidelines (Table 2.3 and Fig. 2.2).
Table 2.3: Stages of Heart Failure Stage A Description Patients at high risk of developing Examples Systemic hypertension; coronary

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HF because of the presence of conditions that are strongly associated with the development of HF. Such patients have no identified structural or functional abnormalities of the pericardium, or cardiac valves and have never shown signs or symptoms of HF. B Patients who have developed structural heart disease i.e. strongly associated with the development of HF but who have never shown signs or symptoms of HF. Patients who have current or prior symptoms of HF associated with underlying structural heart disease. symptoms of HF. Patients with advanced structural heart disease and marked symptoms of HF at rest despite maximal medical therapy and who require specialized interventions. patients at home receiving symptoms relief or being circulatory assist device; patients management of HF.

artery disease; diabetes mellitus; history of cardiotoxic drug therapy or alcohol abuse; personal history of rheumatic fever; family history of cardiomyopathy.

Left ventricular hypertrophy or fibrosis; left venricular dilatation or hypocontractility; asymptomatic valvular heart disease; previous myocardial infarction. Dyspnoea or fatigue due to left ventricular systolic dysfunction; asymptomatic patients who are undergoing treatment for prior Patients who are frequently hospitalized for HF and cannot be safely discharged from the hospital; patients in the hospital awaiting heart transplantation; continuous intravenous support for supported with a mechanical in a hospice setting for the

2.11 LET US SUM UP

In this unit you have learnt that heart failure is one of the most common conditions seen and results in a high mortality. It can result from failure of the heart muscle as with coronary heart disease, hypertension or cardiomyopathy or as the result of mechanical stresses like valvar regurgitation or stenosis. The heart and circulation have many adaptations to cope with heart failure but in the long term these prove inadequate. There are many grades of heart failure and the two main types are systolic and diastolic heart failure. Echocardiography is of immense value in estimating the ejection fraction, chamber volumes and mechanical problems. There are several lines of treatment including the use of diuretics, angiotensin converting enzyme inhibitors and blockers, inotropic agents like digitalis and the cautious use of beta blockers in special situations. Mechanical and electrical devices are also in use. When all else fails one resorts to cardiac transplantation but the number who can have access to such facilities are very few indeed.

2.12 ANSWERS TO CHECK YOUR PROGRESS

Check Your Progress 1 1) In majority of the cases one is often able to identify a precipitating cause of heart failure.

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a)

Arrhythmias particularly tachyarrhythmias like atrial fibrillation

b) Progression of underlying condition e.g. Myocardial Ischemia In patients with coronary artery disease an acute coronary syndrome event can precipitate heart failure. c) Systemic infection Serious infections increase total body metabolism and thus impose hemodynamic burden on the heart. d) Pulmonary Embolism Patients with heart failure are at a higher risk of developing deep vein thrombosis and pulmonary embolism. e) Other factors Stress in any form be it physical, or pregnancy, anemia, thyroid disorders are some of the common conditions that may precipitate heart failure. f) Non compliance Inappropriate reduction of therapy or noncompliance of therapy is an important cause to be kept in mind when encountered with worsening heart failure. 2) a) Hypertension

b) Aortic stenosis 3) The adaptive mechanisms may be short term ones which come into play within minutes or hours of the onset of myocardial dysfunction. These are: a) Frank-Starling mechanism In the Frank-Starling mechanism increased preload helps in sustaining cardiac performance. b) Neuro hormones Activation of neuro humoral systems resulting in release of noradrenaline leading to augmentation of myocardial contractility. c) Renin-Angiotensin-Aldosterone system Activation of renin-angiotensin-aldosterone system which helps in arterial pressure and perfusion of vital organs. d) Myocardial hypertrophy and remodeling The long term adaptive mechanisms involve myocardial hypertrophy and remodeling which occurs slowly over weeks to months. e) Sympathetic Activity In heart failure there is adrenergic activation and parasympathetic withdrawal. This results in increase in myocardial contractility, tachycardia, sodium retention, renin release and generalized vasoconstriction. maintaining

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f)

Natriuretic Peptides There are three natriuretic peptides atrial (ANP) stored mainly in the atrium, brain (BNP) stored mainly in the ventricular myocardium and C-natriuretic peptide (CNP) located primarily in the vasculature. Circulating levels ANP and BNP are elevated in heart failure. They are vasodilatory and natriuretic.

4)

Starlings law essentially means that stroke volume is related to the end-diastolic volume. Frank proposed that the greater initial left ventricular volume leads to more rapid rate of rise of pressure, greater peak pressure and faster rate of relaxation. a) Dyspnoea: Breathlessness or dyspnoea is a cardinal symptom of left ventricular failure and the patient may present with exertional dyspnoea or orthopnoea or paroxysmal nocturnal dyspnoea or acute pulmonary edema. Fatigue and weakness. Urinary symptoms: Nocturia and in later stages oliguria may occur.

5)

b) c)

d) Cerebral symptoms: These are often seen in older patients who have associated cerebral arteriosclerosis. Confusion, impaired memory, insomnia and disorientation may occur. e) 6) 7) a) Cough: Cough is due to pulmonary congestion and is a dyspnoea equivalent or orthopnoea equivalent. It may also be due to use of ACE inhibitors. Pain over the liver area

b) Oedema and at times ascites. Systolic heart failure is a classic heart failure where the inotropic (contractile) state is impaired and the expulsion of blood is not adequate. This is pump failure. The ejection fraction is decreased. Diastolic failure is due to ventricular stiffening that results in defect in ventricular filling. The ejection fraction or pump function remains near normal. The major manifestations are due to elevated ventricular filling pressures, leading to pulmonary or systemic venous congestion. 8) With patient asleep at night, the increased resorption of fluid into the vascular space, increased intrathoracic volume, elevation of diaphragms due to recumbency, reduced sympathetic support during night and nocturnal depression of respiratory center during night are the factors operative producing paroxysmal nocturnal dyspnea. Class IV Inability to carry out any physical activity without symptoms. Symptoms are present even at rest. The right atrial pressure increases and so: a) 2) The jugular venous pressure rises. b) The liver enlarges and becomes tender. Presence of left ventricular third heart sound denotes systolic dysfunction. Fourth heart sound may be present. With tachycardia the extra sounds result in a gallop rhythm either early diastolic or presystolic gallop. With pulmonary hypertension, pulmonary component of the second sound is accentuated. Functional mitral and tricuspid regurgitation murmurs can appear with ventricular dilatation. 27

9)

Check Your Progress 2 1)

3)

4) 5) 6) 7) 8)

Auscultation reveals crepitations and occasionally rhonchi, which appear initially over the lung bases but then extend upward with worsening of the condition. Acute pulmonary edema produces butterfly or bat wing pattern in the chest X-ray seen in the inner two thirds, perihilar area of the lung. Best managed propped up. Morphine and a diuretic like IV Furosemide. Intravenous loop diuretics produce rapid diuresis, reduce circulating blood volume. Furosemide when administered exerts a venodilator action, reducing venous return. This helps in improving pulmonary edema even before the diuresis is initiated. a) Furosemide

9)

b) Bumetanide 10) a) Hypokalemia

b) Hypotension c) Worsening glucose tolerance

11) ACE inhibitors inhibit conversion of angiotensin I to angiotensin II (AII) through ACE. This results in peripheral vasodilatation, reduced afterload, and decreased blood pressure. Reduction in aldosterone decreases sodium and fluid retention. ACE inhibition result in higher bradykinin levels, which in turn stimulate synthesis of prostaglandins and nitric oxide, which may be beneficial. 12) Angiotensin receptor blockers block the final common pathway and provide a means of complete blockade of the system. These agents do not produce increase in bradykinin, prostaglandins, and nitric oxide in the heart, blood vessels, and other tissues. They should be considered as alternatives to ACE inhibitors in ACE-intolerant patients especially patients with chronic dry irritating cough and angiedema. Another potential use is to counteract ACE escape, the attenuation of the benefits of ACE inhibition that may occur with time. 13) Hydralazine is a potent arteriolar dilator and markedly increases cardiac output in patients with congestive heart failure. The combination of hydralazine and isosorbide dinitrate is an alternative therapy when ACE inhibitors are contraindicated or cannot be tolerated.

Check Your Progress 3 1) The positive inotropic action occurs through inhibition of the enzyme Na+-K+-ATPase leading to an increase in the cytocyclic Ca2+ concentration. It reduces heart rate via parasympathomimetic effects that is useful in enhancing ventricular filling and reduces pulmonary congestion. Amiodarone, propafenone, and verapamil.

2)

28

3)

Dopamine has both alpha1 and beta1 and dopaminergic effects. Its beta1 effects in the heart occur largely through the release of endogenous norepinephrine, which may be largely depleted in a failing heart. Dobutamine: The positive inotropic activity of dobutamine is mediated by direct stimulation of beta1-adrenergic receptors in the myocardium.

4)

Patients with heart failure have a high incidence of both symptomatic and asymptomatic arrhythmias. They may have atrial or ventricular arrhythmias. Some may be related to drug use as with digitalis. About 10 per cent of patients have syncope or presyncope resulting from ventricular tachycardia. However Holter monitoring reveals that up to 70 per cent of patients have asymptomatic episodes of nonsustained ventricular tachycardia.

5)

This pacemaker-based approach is used to treat patients with heart failure who have a wide QRS complex (>140 ms) on 12-lead ECG and aims at providing electromechanical coordination and improved ventricular synchrony in symptomatic patients who have severe systolic dysfunction and clinically significant intraventricular conduction defects, particularly left bundle-branch block.

1.13 FURTHER READINGS

ACC/AHA Guidelines for the Management of Chronic Heart Failure in the Adult, Amer Coll Cardiol, 2001, 38. J

Braunwald, E. Heart Disease: A Text Book of Cardiovascular Medicine, . 6th edn. 2001, W B Saunders Company. Hursts The Heart,10th edn., 2001, McGraw Hill Company.

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