Chronic heart failure is a complex and progressive disorder that occurs when the heart is incapable of generating sufficient cardiac output (CO) to meet the demands of the body. Initially, compensatory mechanisms may allow adequate CO to be maintained at rest but not during exercise (exercise intolerance). Eventually CO cannot be maintained at rest (decompensation); this can be precipitated by acute illness (e.g. influenza), stress or drugs (e.g. NSAIDs). Chronic heart failure is predominantly a disease of old age. It occurs in ∼2% of patients under 50 years, but >10% over 65; 5-year survival is <50%. Acute heart failure describes a sudden loss of cardiac function, for example acute coronary syndrome (see Chapter 44). It may cause pulmonary congestion and oedema (see below) and cardiogenic shock (see Chapter 31).
The most common cause (∼70% cases) is impaired ventricular contraction with an ejection fraction <45% (systolic failure; Figure 46a), generally a consequence of ischaemic heart disease (IHD). Diastolic failure is due to impaired filling, caused by reduced ventricular compliance (flexibility; e.g. fibrosis, hypertrophy), restriction (e.g. pericarditis) or impaired relaxation (see below). Ejection fraction may be normal or increased. Systolic failure is generally accompanied by diastolic failure, while the latter can occur alone. Both involve increased filling pressures, so have similar clinical manifestations.
As IHD generally affects the left ventricle, left heart failure is most common, and is associated with dyspnoea (breathlessness), an enlarged heart and fatigue (see below). Right heart failure may result from chronic lung disease (cor pulmonale), pulmonary hypertension or embolism, and valve disease, but usually it is secondary to left heart failure (congestive or biventricular heart failure) (Figure 46b). Central venous pressure (CVP) is greatly increased, with consequent jugular venous distension, swelling of the liver (hepatomegaly), peripheral oedema and peritoneal fluid accumulation (ascites). High output failure occurs when a healthy heart is unable to meet grossly elevated demands for output due to anaemia or a drastically reduced peripheral resistance (e.g. septic shock).
The pathophysiology of chronic heart failure is largely a consequence of mechanisms that compensate for reduced cardiac function. Impaired cardiac function causes accumulation of venous blood and thus raised filling pressures, so CO increases as a consequence of Starling’s law (Figure 46a,b; see Chapter 17). Neurohumoral mechanisms are activated by the baroreceptor reflex (Figure 46c; see Chapter 28), and the autonomic nervous system and circulating catecholamines stimulate increases in heart rate and contractility, arterial vasoconstriction (raises TPR) and venoconstriction (raises CVP) (see Chapters 12 and 17). Sympathetic stimulation of renal granular cells and reduced renal perfusion cause release of renin, and consequently angiotensin II and aldosterone; vasopressin (antidiuretic hormone, ADH) also increases. These cause renal sodium and water retention and so elevate blood volume and CVP (and thus CO through Starling’s law) (see Chapter 29). Angiotensin II and vasopressin also increase TPR. In mild disease these mechanisms can maintain CO and blood pressure without overt symptoms. However, end-diastolic pressure (EDP) and volume (EDV) are always elevated (Figure 46a, A) so ejection fraction is reduced, an early sign of heart failure.
As cardiac function declines, CO can only be maintained by an ever-increasing CVP and heart rate (Figure 46a, B), fostering further myocardial damage (see below). This vicious circle drives a relentless decay towards decompensation and death. Although adequate CO may be maintained at rest even in quite severe failure, this is at the expense of greatly increased venous pressures as the function curve flattens and Starling’s law becomes less effective (Figure 46a, A,B; see Chapter 17). High venous pressures underlie most signs and symptoms of heart failure.
Consequences of compensation (Figure 46b)
Initially, symptoms only appear during exertion, which exacerbates the rise in venous pressures (Figure 46a, C); this limits the ability to exercise (exercise intolerance). Any increase in contractility and heart rate during exercise is small because they are already strongly stimulated at rest, and in late disease β-adrenoceptor density and sensitivity are reduced. Dyspnoea on exertion is often the first symptom of left heart failure. It is caused by pulmonary congestion due to the raised pulmonary venous pressure, making the lungs stiffer and so promoting the sensation of breathlessness. Redistribution of blood to the lungs on lying down or during sleep can instigate dyspnoea (orthopnoea; paroxysmal nocturnal dyspnoea), and in severe failure and decompensation pulmonary oedema, when fluid enters the alveoli. This is a life-threatening condition causing extreme dyspnoea and hypoxaemia.
A high CVP similarly causes peripheral oedema (see Chapter 21), hepatomegaly and ascites, common features of right and congestive heart failure. High EDP eventually lead to cardiac dilation and a greatly enlarged heart (see below), and is associated with an S3/S4 gallop rhythm (see Chapter 16). In more severe disease diversion of blood flow from skeletal muscle and non-essential tissues leads to weakness and fatigue, and contributes to exercise intolerance.
Myocardial dysfunction and remodelling
Chronic heart failure is characterized by progressive cardiac dysfunction, accompanied by myocardial remodelling.
Compensation forces an already compromised heart to work harder. This leads to energy deficit, dysfunction of ATP-dependent transporters (e.g. Ca2+-ATPases and Na+ pump) (see Chapters 10 and 12), and consequent Ca2+ overload (Figure 46c). This impairs relaxation and fosters lengthening of the action potential (e.g. acquired long QT syndrome; see Chapter 54) and generation of arrhythmias, a major cause of sudden death. Mitochondrial dysfunction worsens the energy deficit. Oxidative stress, and cytokines promote further damage, structural alterations and apoptosis (programmed cell death). Myocardial remodelling is potentiated by direct action of noradrenaline, angiotensin II and aldosterone (Figure 46c).
Dilatation reduces cardiac efficiency, as pressure in a sphere is proportional to wall tension (i.e. myocardial force) divided by radius (Law of Laplace). Large dilated hearts therefore have to contract harder in order to develop the same pressure as smaller hearts.
Cardiac dilatation must not be confused with hypertrophy, where cardiac myocytes grow larger and ventricular wall thickness increases in response to a sustained increase in afterload (e.g. hypertension, aortic stenosis). Hypertrophy is not usually associated with IHD. Although force is increased, the thicker ventricle is less compliant, which impedes filling and contributes to diastolic failure. Capillary density is reduced, lowering coronary reserve (difference between maximum and resting coronary flow), so myocardial perfusion may be limited. Changes in contractile protein isoforms (myosin, tropomyosin) decrease contraction velocity and contractility. Gross hypertrophy may physically impair valve operation.