Heart Failure

A pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements off the metabolising tissues. Heart failure describes the clinical syndrome that develops when the heart cannot maintain an adequate cardiac output, or can do so only at the expense of an elevated filling pressure. In mild to moderate forms of heart failure, cardiac output is adequate at rest and only becomes inadequate when the metabolic demand increases during exercise or some other form of stress. Heart failure may be diagnosed whenever a patient with significant heart disease develops the signs or symptoms of: o a low cardiac output, o pulmonary congestion or o systemic venous congestion.

Key variables determining cardiac output are grouped as follows: o Preload events (filling pressure of the ventricles) o Contractility events (events inside the monocyte particularly associated with [Ca2+] and [H+]) o Afterload events o Heart regulation The first 3 determine the stroke volume of each ventricle (Starlings law) and the heart rate is primarily regulated by the baroreceptor reflex which keeps atrial pressure quite constant. Clinical presentation often involves a rather vague collection of symptoms: Breathlessness Muscle weakness/Tiredness Ankle swelling/ peripheral oedemas Exercise intolerance

Cardiac arrhythmias Pulmonary congestion and breathlessness will not necessarily occur unless the underlying defect is fairly substantial or long-lasting. Ankle swelling is specifically a characteristic of right heart failure. The onset of pulmonary and peripheral oedema is due to high atrial pressures compounded by salt and water retention caused by impaired renal perfusion and secondary hyperaldosteronism.

Pathophysiology In patients without valvular disease, the primary abnormality is impairment of ventricular function leading to a fall in cardiac output. This activates counter-regulatory neurohumoral mechanisms that in normal physiological circumstances would support cardiac function, but in the setting of impaired ventricular function can lead to a deleterious increase in both afterload and preload. A vicious circle may be established because any additional fall in cardiac output will cause further neurohumoral activation and increasing peripheral vascular resistance. Stimulation of the renin-angiotensin-aldosterone system leads to vasoconstriction, salt and water retention, and sympathetic nervous system activation. This is mediated by angiotensin II, a potent constrictor of arterioles in both the kidney and the systemic circulation. Activation of the sympathetic nervous system may initially maintain cardiac output through an increase in myocardial contractility, heart rate and peripheral vasoconstriction. However, prolonged sympathetic stimulation leads to cardiac myocyte apoptosis, hypertrophy and focal myocardial necrosis. Salt and water retention is promoted by the release of aldosterone, endothelin-1 (a potent vasoconstrictor peptide with marked effects on the renal vasculature) and, in severe heart failure, antidiuretic hormone (ADH). Natriuretic peptides are released from the atria in response to atrial stretch, and act as physiological antagonists to the fluid-conserving effect of aldosterone. After MI, cardiac contractility is impaired and neurohumoral activation causes hypertrophy of non-infarcted segments, with thinning, dilatation

and expansion of the infarcted segment. This leads to further deterioration in ventricular function and worsening heart failure.
Starling's Law. Normal (A), mild (B), moderate (C) and severe (D) heart failure. Ventricular performance is related to the degree of myocardial stretching. An increase in preload (end-diastolic volume, enddiastolic pressure, filling pressure or atrial pressure) will therefore enhance function; however, overstretching causes marked deterioration. In heart failure the curve moves to the right and becomes flatter. An increase in myocardial contractility or a reduction in afterload will shift the curve upwards and to the left (green arrow).

Epidemiology and prognosis In UK, heart failure is responsible for about 5% of hospital admissions Heart failure is frequently due to CAD, tends to affect elderly people and often leads to prolonged disability. The prevalence of heart failure rises from 1% in those aged 50-59 years to over 10% in those aged 80-89 years. In the UK, most patients admitted to hospital with heart failure are > 70 years old and remain hospitalised for a week or more. Although the outlook depends to some extent on the underlying cause of the problem, heart failure carries a very poor prognosis; approximately 50% of patients with severe heart failure due to left ventricular dysfunction will die within 2 years. Many patients die suddenly from malignant ventricular arrhythmias or MI. Types of Heart Failure When cardiac function is impaired or the work load increases, several physiologic mechanisms maintain arterial pressure and perfusion of vital organs. These adaptive mechanisms may be adequate to maintain normal cardiac output in the face of heart disease, but their capacity to do so may ultimately be overwhelmed. The most important of these are the following:

o The Frank-Starling mechanism, in which increased filling volumes dilate the heart and thereby increase functional cross-bridge formation within the sarcomeres, enhancing contractility. o Myocardial adaptations, including hypertrophy with or without cardiac chamber dilation. The collective molecular, cellular, and structural changes that occur as a response to injury or changes in loading conditions are called ventricular remodeling. Often adaptive, especially in early stages, these changes can culminate in impaired cardiac function. In many pathologic states, heart failure is preceded by cardiac hypertrophy, the compensatory response of the myocardium to increased mechanical work. o Activation of neurohumoral systems, especially i. release of noradrenaline by adrenergic cardiac nerves of the autonomic NS (which increases heart rate and augments myocardial contractility and vascular resistance); ii. activation of the renin-angiotensin-aldosterone system; and iii. release of atrial natriuretic peptide Impaired systolic function is the commonest cause of heart failure. However, 30-40% of all patient diastolic dysfunction is a major contributor and sometimes the primary cause of congestive cardiac failure. Primary left heart failure is more common than primary right heart failure.

Left, right and biventricular heart failure: Left-sided heart failure: o Left sided failure is the commonest cause of right heart failure, as any increase in pressure in the pulmonary circulation incidental to left-sided failure inevitably burdens the right side of the heart o There is a reduction in the left ventricular output and an increase in the left atrial or pulmonary venous pressure. o An acute increase in left atrial pressure (blood enters atria at slower rate due to high pressure) causes pulmonary congestion or pulmonary oedema o A more gradual increase in left atrial pressure, as occurs with mitral stenosis, leads to reflex pulmonary vasoconstriction, which protects the patient from pulmonary oedema at the cost of increasing pulmonary hypertension o Left-sided heart failure can be divided on clinical grounds into systolic and diastolic failure. Right-sided heart failure: o There is a reduction in right ventricular output for any given right atrial pressure. o Causes of isolated right heart failure include chronic lung disease (cor pulmonale), multiple pulmonary emboli and pulmonary valvular stenosis. o The clinical features of isolated right-sided heart failure are those related to systemic (and portal) venous congestion, and include hepatosplenomegaly, peripheral edema, pleural effusions, and ascites.

o Organs that are prominently affected in right-sided heart failure include the kidney and the brain. o Congestion of the kidneys is more marked with right-sided than leftsided heart failure, leading to greater fluid retention and peripheral edema, and more pronounced azotemia. o Venous congestion and hypoxia of the central nervous system can produce deficits of mental function that are essentially identical to those described in left-sided heart failure. Biventricular heart failure o In many cases of chronic cardiac decompensation, the patient presents in biventricular CHF with symptoms that encompass the clinical syndromes of both right-sided and left-sided heart failure. o Failure of the left and right heart may develop because the disease process (e.g. dilated cardiomyopathy or IHD) affects both ventricles or because disease of the left heart leads to chronic elevation of the left atrial pressure, pulmonary hypertension and right heart failure.

Different forms of cardiac failure: Mixed systolic//diastolic Mainly systolic dysfunction: dysfunction: o Ischaemic heart disease o Hypertension o Dilated myocardiopathy o Aortic vavle stenosis o Decreased myocyte o Cardiac hypertrophy contractility Mainly diastolic dysfunction o Impaired relaxation due to fibrosis o Mitral or tricuspid valve stenosis o Constrictive pericarditis

Diastolic and systolic dysfunction Heart failure may develop as a result of impaired myocardial contraction (systolic dysfunction) but can also be due to poor ventricular filling and high filling pressures caused by abnormal ventricular relaxation (diastolic dysfunction). The latter is caused by a stiff non-compliant ventricle and is commonly found in patients with left ventricular hypertrophy. Systolic and diastolic dysfunction often coexist, particularly in patients with CAD. High-output failure

Conditions such as large arteriovenous shunt, beri-beri, severe anaemia or thyrotoxicosis can occasionally cause heart failure due to an excessively high cardiac output. Acute and chronic heart failure Heart failure may develop suddenly (eg. MI), or gradually (eg. progressive valvular heart disease). When there is gradual impairment of cardiac function, a variety of compensatory changes may take place. The term 'compensated heart failure' is sometimes used to describe those with impaired cardiac function in whom adaptive changes have prevented the development of overt heart failure. A minor event (e.g. intercurrent infection or development of atrial fibrillation) may precipitate overt or acute heart failure. Acute left heart failure occurs either de novo or as an acute decompensated episode on a background of chronic heart failure, so-called acute-on-chronic heart failure. Investigations Serum urea and electrolytes, haemoglobin, thyroid function, ECG and chest X-ray may help to establish the nature and severity of the underlying heart disease and detect any complications. Brain natriuretic peptide (BNP) is elevated in heart failure and is a marker of risk; it is useful in the investigation of patients with breathlessness or peripheral oedema. Echocardiography is very useful and is used to: determine the aetiology detect hitherto unsuspected valvular heart disease (eg. occult mitral stenosis) and other conditions identify patients who will benefit from long-term therapy with drugs, such as ACE inhibitors Chest X-ray: A rise in pulmonary venous pressure from left-sided heart failure first shows on the chest X-ray as an abnormal distension of the upper lobe pulmonary veins. The vascularity of the lung fields becomes more prominent, and the right and left pulmonary arteries dilate. Subsequently, interstitial oedema causes thickened interlobular septa and dilated lymphatics. These are evident as horizontal lines in the costophrenic angles (septal or 'Kerley B' lines). More advanced changes due to alveolar oedema cause a hazy opacification spreading from the hilar regions, and pleural effusions. Complications In advanced heart failure, the following may occur: Renal failure is caused by poor renal perfusion due to a low cardiac output and may be exacerbated by diuretic therapy, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. Hypokalaemia may be the result of treatment with potassium-losing diuretics or hyperaldosteronism caused by activation of the reninangiotensin system and impaired aldosterone metabolism due to hepatic congestion. Most of the body's potassium is intracellular and there may be

substantial depletion of potassium stores, even when the plasma potassium concentration is in the normal range. Hyperkalaemia may be due to the effects of drug treatment, particularly the combination of ACE inhibitors and spironolactone (which both promote potassium retention), and renal dysfunction. Hyponatraemia is a feature of severe heart failure and is a poor prognostic sign. It may be caused by diuretic therapy, inappropriate water retention due to high ADH secretion, or failure of the cell membrane ion pump. Impaired liver function is caused by hepatic venous congestion and poor arterial perfusion, which frequently cause mild jaundice and abnormal liver function tests; reduced synthesis of clotting factors can make anticoagulant control difficult. Thromboembolism. Deep vein thrombosis and pulmonary embolism may occur due to the effects of a low cardiac output and enforced immobility, whereas systemic emboli may be related to arrhythmias, atrial flutter or fibrillation, or intracardiac thrombus complicating conditions such as mitral stenosis, MI or left ventricular aneurysm. Atrial and ventricular arrhythmias are very common and may be related to electrolyte changes (e.g. hypokalaemia, hypomagnesaemia), the underlying structural heart disease, and the pro-arrhythmic effects of increased circulating catecholamines or drugs. Sudden death occurs in up to 50% of patients with heart failure and is often due to a ventricular arrhythmia. Frequent ventricular ectopic beats and runs of non-sustained ventricular tachycardia are common findings in patients with heart failure and are associated with an adverse prognosis.