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ABC of heart failure: Aetiology ABC of heart failure Aetiology G Y H Lip, C R Gibbs, D G Beevers
The relative importance of aetiological factors in heart failure is dependent on the nature of the population being studied, as coronary artery disease and hypertension are common causes of heart failure in Western countries, whereas valvar heart disease and nutritional cardiac disease are more common in the developing world. Epidemiological studies are also dependent on the clinical criteria and relevant investigations used for diagnosis, as it remains difficult, for example, to distinguish whether hypertension is the primary cause of heart failure or whether there is also underlying coronary artery disease. Coronary artery disease and its risk factors Coronary heart disease is the commonest cause of heart failure in Western countries. In the studies of left ventricular dysfunction (SOLVD) coronary artery disease accounted for almost 75% of the cases of chronic heart failure in male white patients, although in the Framingham heart study, coronary heart disease accounted for only 46% of cases of heart failure in men and 27% of chronic heart failure cases in women. Coronary artery disease and hypertension (either alone or in combination) were implicated as the cause in over 90% of cases of heart failure in the Framingham study. Recent studies that have allocated aetiology on the basis of non.invasive investigations-such as the Hillingdon heart failure study-have identified coronary artery disease as the primary etiology in 36% of cases of heart failure. In the Hillingdon study, however, researchers were not able to identify the primary aetiology in 34% of cases; this methodological failing has been addressed in the current Bromley heart failure study, which uses coronary angiography as well as historical and non.invasive findings. Coronary risk factors, such as smoking and diabetes mellitus, are
also risk markers of the development of heart failure. Smoking is
an independent and strong risk factor for the development of heart
failure in men, although the findings in women are less consistent.
In the prevention arm of SOLVD diabetes was an independent risk factor (about twofold) for mortality, the development of heart failure, and admission to hospital for heart failure, whereas in the Framingham study diabetes and left ventricular hypertrophy were the most significant risk markers of the development of heart failure. Body weight and a high ratio of total cholesterol concentration to high density lipoprotein cholesterol concentration are also independent risk factors for heart failure. Clearly, these risk factors may increase the risks of heart failure through their effects on coronary artery disease, although diabetes alone may induce important structural and functional changes in the myocardium, which further increase the risk of heart failure. Hypertension Hypertension has been associated with an increased risk of heart failure in several epidemiological studies. In the Framingham heart study, hypertension was reported as the cause of heart failure-either alone or in association with other factors-in over 70% of cases, on the basis of non.invasive assessment. Other community and hospital based studies, however, have reported hypertension to be a less common cause of heart failure, and, indeed, the importance of hypertension as a cause of heart failure has been declining in the Framingham cohort since the 1950s. Recent community based studies that have assessed aetiology using clinical criteria and relevant non.invasive investigations have reported hypertension to be the cause of heart failure in 10.20%. However, hypertension is probably a more common cause of heart failure in selected patient groups, including females and black populations (up to a third of cases).
Hypertension predisposes to the development of heart failure via
a number of pathological mechanisms, including left ventricular
hypertrophy. Left ventricular hypertrophy is associated with left
ventricular systolic and diastolic dysfunction and an increased
risk of myocardial infarction, and it predisposes to both atrial
and ventricular arrhythmias. Electrocardiographic left ventricular
hypertrophy is strongly correlated with the development of heart
failure, as it is associated with a 14.fold increase in the risk
of heart failure in those aged 65 years or under.
Dilated cardiomyopathy Dilated cardiomyopathy describes heart muscle disease in which the predominant abnormality is dilatation of the left ventricle, with or without right ventricular dilatation. Myocardial cells are also hypertrophied, with increased variation in size and increased extracellular fibrosis. Family studies have reported that up to a quarter of cases of dilated cardiomyopathy have a familial basis. Viral myocarditis is a recognised cause; connective tissue diseases such as systemic lupus erythematosus, the Churg.Strauss syndrome, and polyarteritis nodosa are rarer causes. Idiopathic dilated cardiomyopathy is a diagnosis of exclusion. Coronary angiography will exclude coronary disease, and an endomyocardial biopsy is required to exclude underlying myocarditis or an infiltrative disease. Dilatation can be associated with the development of atrial and ventricular arrhythmias, and dilatation of the ventricles leads to "functional" mitral and tricuspid valve regurgitation. Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy has a familial inheritance (autosomal dominant), although sporadic cases may occur. It is characterised by abnormalities of the myocardial fibres, and in its classic form involves asymmetrical septal hypertrophy, which may be associated with aortic outflow obstruction (hypertrophic obstructive cardiomyopathy). Nevertheless, other forms of hypertrophic cardiomyopathy exist-apical hypertrophy (especially in Japan) and symmetrical left ventricular hypertrophy (where the echocardiographic distinction between this and hypertensive heart disease may be unclear). These abnormalities lead to poor left ventricular compliance, with high end diastolic pressures, and there is a common association with atrial and ventricular arrhythmias, the latter leading to sudden cardiac death. Mitral regurgitation may contribute to the heart failure in these patients. Restrictive and obliterative cardiomyopathies
Restrictive cardiomyopathy is characterised by a stiff and poorly compliant ventricle, which is not substantially enlarged, and this is associated with abnormalities of diastolic function (relaxation) that limit ventricular filling. Amyloidosis and other infiltrative diseases, including sarcoidosis and haemochromatosis, can cause a restrictive syndrome. Endomyocardial fibrosis is also a cause of restrictive cardiomyopathy, although it is a rare cause of heart failure in Western countries. Endocardial fibrosis of the inflow tract of one or both ventricles, including the subvalvar regions, results in restriction of diastolic filling and cavity obliteration.
Valvar disease Rheumatic heart disease may have declined in certain parts of the world, but it still represents an important cause of heart failure in India and other developing nations. In the Framingham study rheumatic heart disease accounted for heart failure in 2% of men and 3% of women, although the overall incidence of valvar disease has been steadily decreasing in the Framingham cohort over the past 30 years. Mitral regurgitation and aortic stenosis are the most common causes of heart failure, secondary to valvar disease. Mitral regurgitation (and aortic regurgitation) leads to volume overload (increased preload), in contrast with aortic stenosis, which leads to pressure overload (increased afterload). The progression of heart failure in patients with valvar disease is dependent on the nature and extent of the valvar disease. In aortic stenosis heart failure develops at a relatively late stage and, without valve replacement, it is associated with a poor prognosis. In contrast, patients with chronic mitral (or aortic) regurgitation generally decline in a slower and more progressive manner.
Arrhythmias Cardiac arrhythmias are more common in patients with heart failure and associated structural heart disease, including hypertensive patients with left ventricular hypertrophy. Atrial fibrillation and heart failure often coexist, and this has been confirmed in large scale trials and smaller hospital based studies. In the Hillingdon heart failure study 30% of patients presenting for the first time with heart failure had atrial fibrillation, and over 60% of patients admitted urgently with atrial fibrillation to a Glasgow hospital had echocardiographic evidence of impaired left ventricular function. Atrial fibrillation in patients with heart failure has been associated with increased mortality in some studies, although the vasodilator heart failure trial (V.HeFT) failed to show an increase in major morbidity or mortality for patients with atrial fibrillation. In the stroke prevention in atrial fibrillation (SPAF) study, the presence of concomitant heart failure or left ventricular dysfunction increased the risk of stroke and thromboembolism in patients with atrial fibrillation. Ventricular arrhythmias are also more common in heart failure, leading to a sudden deterioration in some patients; such arrhythmias are a major cause of sudden death in patients with heart failure. Alcohol and drugs Alcohol has a direct toxic effect on the heart, which may lead to acute heart failure or heart failure as a result of arrhythmias, commonly atrial fibrillation. Excessive chronic alcohol consumption also leads to dilated cardiomyopathy (alcoholic heart muscle disease). Alcohol is the identifiable cause of chronic heart failure in 2.3% of cases. Rarely, alcohol misuse may be associated with general nutritional deficiency and thiamine deficiency (beriberi). Chemotherapeutic agents (for example, doxorubicin) and antiviral drugs (for example, zidovudine) have been implicated in heart failure, through direct toxic effects on the myocardium. Other causes Infections may precipitate heart failure as a result of the toxic metabolic effects (relative hypoxia, acid base disturbance) in combination with peripheral vasodilation and tachycardia, leading to increased myocardial oxygen demand. Patients with chronic heart failure, like patients with most chronic illnesses, are particularly susceptible to viral and bacterial respiratory infections. "High output" heart failure is most often seen in patients with severe anaemia, although thyrotoxicosis may also be a precipitating cause in these patients. Myxoedema may present with heart failure as a result of myocardial involvement or secondary to a pericardial effusion. The table of epidemiological studies of the aetiology of heart failure is adapted and reproduced with permission from Cowie MR et al (Eur Heart J 1997;18:208.25). The table showing relative risks for development of heart failure (36 year follow up) is adapted and reproduced with permission from Kannel WB et al (Br Heart J 1994;72:S3.9). D G Beevers is professor of medicine in the university department of medicine and the department of cardiology, City Hospital, Birmingham. The ABC of heart failure is edited by C R Gibbs, M K Davies, and
G Y H Lip. CRG is research fellow and GYHL is consultant cardiologist
and reader in medicine in the university department of medicine
and the department of cardiology, City Hospital, Birmingham; MKD
is consultant cardiologist in the department of cardiology, Selly
Oak Hospital, Birmingham. The series will be published as a book
in the spring
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