Figure 11 Renin-angiotensin-aldosterone axis in heart failure
Related Figures (61)
Southey’s tubes were at one time used for removing fluid from oedematous peripheries in patients with heart failure The foxglove was used as a medicine in heart disease as long ago as Roman times Contemporary studies of the epidemiology of heart failure in United Kingdom In 1785 William Withering of Birmingham published an account of medicinal use of digitalis It was not until the 20th century that diuretics were developed. The early, mercurial agents, however, were associated with substantial toxicity, unlike the thiazide diuretics, which were introduced in the 1950s. Vasodilators were not widely used until the development of angiotensin converting enzyme inhibitors in the 1970s. The landmark CONSENSUS-I study (first cooperative north Scandinavian enalapril survival study), published in 1987, showed the unequivocal survival benefits of enalapril in patients with severe heart failure. Mortality curves from the CONSENSUS-I study Prevalence of heart failure (per 1000 population), Framingham heart study Because of rounding, totals may not equal 100%. *Total exceeds 100% as coronary artery disease and hypertension were not considered as mutually exclusive causes. Epidemiological studies of aetiology of heart failure. Values are percentages Relative risks for development of heart failure: 36 year follow up in Framingham heart study Two dimensional echocardiogram (top) and M mode echocardiogram (bottom) showing left ventricular hypertrophy. A=interventricular septum; B=posterior left ventricular wall Two dimensional, apical, four chamber echocardiogram showing dilated cardiomyopathy. A=left ventricle; B=left atrium; C=right atrium; D=right ventricle Two dimensional (long axis parasternal view) echocardiogram (top) and M mode echocardiogram (bottom) showing severely impaired left ventricular function in dilated cardiomyopathy Colour Doppler echocardiograms showing mitral regurgitation (left) and aortic regurgitation (right) Electrocardiogram showing atrial fibrillation with a rapid ventricular response CONSENSUS = cooperative north Scandinavian enalapril survival study. *Classification of the New York Heart Association. Neurohormonal mechanisms and compensatory mechanisms in heart failure Sympathetic activation in chronic heart failure Norepinephrine concentrations and prognosis in chronic heart failure Effect of angiotensin converting enzyme inhibitors in heart failure Contrast left ventriculogram in patient with poor systolic function (diastolic (left) and systolic (right) views) Two dimensional echocardiogram in patient with hypertrophic cardiomyopathy showing asymmetrical septal hypertrophy Process of ventricular remodelling Risk of heart failure and relation with age and history of myocardial infarction Contrast left ventriculogram in patient with hypertrophic cardiomyopathy (diastolic (left) and systolic (right) views) Sensitivity, specificity, and predictive value of symptoms, signs, and chest x ray findings for presence of heart failure (ejection fraction <40%) in 1306 patients with coronary artery disease undergoing cardiac catheterisation 24 Hour Holter tracing showing frequent ventricular extrasystoles EF ejection fraction. SOLVD-P, SOLVD-T = studies of left ventricular dysfunction prevention arm (P) and treatment arm (T). H-ISDN = hydralazine and isosorbide dinitrate. *Treatment with H-ISDN. Cardiac mortality in placebo controlled heart failure trials Chest radiographs showing gross cardiomegaly in patient with dilated cardiomyopathy (top); cardiomegaly and pulmonary congestion with fluid in horizontal fissure (bottom) Electrocardiograms showing previous anterior myocardial infarction with Q waves in anteroseptal leads (top) and left bundle branch block (bottom) Transthoracic echocardiograms: two dimensional apical view (top) and Doppler studies (bottom) showing severe calcific stenosis, with an estimated aortic gradient of over 70 mm Hg (A=left ventricle, B=aortic valve, and C=left atrium) Multigated ventriculography scan in patient with history of extensive myocardial infarction and coronary bypass grafting (left ventricular ejection fraction of 30%) + + =Great importance; + =some importance. Assessments for the investigation and diagnosis of heart failure Self help strategies for patients with heart failure Heart failure cooperation card: patients and doctors are able to monitor changes in clinical signs (including weight), drug treatment, and baseline investigations. Patients should be encouraged to monitor their weight between clinic visits Exercise class for group of patients with heart failure (published with permission of participants) M mode echocardiogram showing left ventricular hypertrophy in hypertensive patient (A=interventricular septum; B=posterior wall of left ventricle) Electrocardiogram showing left ventricular hypertrophy on voltage criteria, with associated T wave and ST changes in the lateral leads (“strain pattern”) Diagram of nephron showing sites of action of different diuretic classes: 1=loop (eg frusemide); 2=thiazide (eg bendrofluazide); and 3=potassium sparing (eg amiloride) Front view and side view of woman with angio-oedema related to treatment with ACE inhibitors (published with permission of patient) If patient is “high risk” consider hospital admission to start treatment Survival curve for randomised aldactone evaluation study (RALES) showing 30% reduction in all cause mortality when spironolactone (up to 25 mg) wa: added to conventional treatment in patients with severe (New York Heart Association class IV) chronic heart failure The two main potassium sparing diuretics, amiloride and spironolactone, have a weak diuretic action when used alone; amiloride is most commonly used in fixed dose combinations with a loop diuretic—for example, co-amilofruse ACE inhibitors in left ventricular dysfunction: best benefit for ACE inhibitors in higher risk group Cumulative mortality in V-HeFT II trial: enalapril v hydralazine plus isosorbide dinitrate in patients with congestive heart failure (mild to moderate) Incidence of death or admission to hospital due to worsening heart failure in two groups of patients: those receiving digoxin and those receiving placebo (Digitalis Investigation Group’s study—see key references box at end of article) Meta-analysis of effects of B blockers on mortality and admissions to hospital in chronic heart failure Inotropic drugs associated with increased mortality in chronic heart failure Randomised, placebo controlled B blocker trials in congestive heart failure .eferences: Waagstein F et al (Lancet 1993;342:1442-6), Packer M et al (N Engl J Med 1996;334:1349-55), and CIBIS II Investigators and Committee (Lance 999;353:9-13). 1I=no increase in dose. Dose and titration of f blockers in large, placebo controlled heart failure trials Echocardiogram showing thrombus at left ventricular apex in patient with dilated cardiomyopathy (A=thrombus, B=left ventricle, C=left atrium) Survival curves from GESICA trial (see key references box), showing difference between patients taking amiodarone and controls Summary of drug management in chronic heart failure Survival rates (%) compared with chronic heart failure Acute heart failure: basic measures and initial drug treatment Chest x ray film in patient with acute pulmonary oedema Acute heart failure: second line drug treatment and advanced management Example of management algorithm for left ventricular dysfunction Short term bed rest is valuable until signs and symptoms improve: rest reduces the metabolic demand and increases renal perfusion, thus improving diuresis. Although bed rest potentiates the action of diuretics, it increases the risk of venous thromboembolism, and prophylactic subcutaneous heparin should be considered in immobile inpatients. Full anticoagulation is not advocated routinely unless concurrent atrial fibrillation is present, although it may be considered in patients with very severe impairment of left ventricular systolic function, associated with significant ventricular dilatation. Intravenous loop diuretics may be administered to overcome the short term problem of gut oedema and reduced absorption of tablets, and these may be used in conjunction with an oral thiazide or thiazide-like diuretic (metolazone). Low dose spironolactone (25 mg) improves morbidity and mortality in severe (New York Heart Association class IV) heart failure, when combined with conventional treatment (loop diuretics and angiotensin converting enzyme inhibitors). Potassium concentrations should be closely monitored after the addition of spironolactone. Number of heart transplantations worldwide and mean age of donors Diagnostic algorithm for suspected heart failure in primary care. Based on guidance from the north of England evidence based guideline development project (see key references box) Strategies for preventing progression to symptomatic heart failure in high risk asymptomatic patients Role of specialist nurse in management of patients with heart failure Cumulative survival curves from the Adelaide nurse intervention study: 18 month follow up (see Stewart et al, key references box at end of article)
