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ABSTRACT: Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF.
One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P=0.003) and TF (P=0.013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (> or =median) TF (P=0.011), and IL-6 (P=0.023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P=0.007). A strong correlation was present between TF and IL-6 levels (r=0.59; P<0.0001) and with VEGF levels (r=0.43; P<0.0001).
IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression.
European Journal of Clinical Investigation 11/2003; 33(11):941-8. · 3.02 Impact Factor
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ABSTRACT: Heart failure predisposes to stroke and thromboembolism, which in turn contribute to the high mortality and morbidity in heart failure.
To determine the effect of antiplatelet agents, compared to placebo or anticoagulant therapy, on death and/or major thromboembolic events in adults with heart failure who are in sinus rhythm.
Systematic review of randomized parallel group placebo or controlled trials comparing oral antiplatelet therapy with control or anticoagulation therapy in adults with chronic heart failure in sinus rhythm.
Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data.
These included duration of treatment of at least 1 month, and adults with heart failure due to any underlying cause. To assess any adverse effects, cohort study and non-randomized controlled studies were assessed. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. No meta-analyses were performed, as no data were available from randomized comparisons.
One randomized controlled trial of warfarin vs. aspirin vs. no antithrombotic therapy was found, but no definitive data have yet been published. Three retrospective, non-randomized cohort studies from large trials examining the role of ACE inhibitors have examined the role of aspirin therapy with and without anticoagulant therapy in patients with heart failure and/or left ventricular systolic dysfunction were identified, but the results from these trials were conflicting. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is from retrospective analyses of trial cohorts.
At present there is no evidence from long term RCTs to recommend use of aspirin to prevent thromboembolism in patients with heart failure in sinus rhythm. There is also no evidence to indicate superior effects from oral anticoagulation, when compared to aspirin, in patients with heart failure in sinus rhythm.
QJM: monthly journal of the Association of Physicians 08/2002; 95(7):461-8. · 2.33 Impact Factor
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ABSTRACT: Chronic heart failure (CHF) is associated with an increased risk of thrombosis and thromboembolic events, including stroke and venous thromboembolism. which may be related to a prothrombotic or hypercoagulable state. Acute vigorous exercise has been associated with activation of hemostasis, and this risk may well be particularly increased in patients with CHF.
The study was undertaken to determine whether acute exercise would adversely affect abnormalities of hemorheological (fibrinogen, plasma viscosity, hematocrit), endothelial (von Willebrand factor), and platelet markers (soluble P selectin) in patients with CHF.
We studied 22 ambulant outpatients (17 men; mean age 65+/-9 years) with stable CHF (New York Heart Association class II-III and a left ventricular ejection fraction of < or =40%) who were exercised to exhaustion on a treadmill. Results were compared with 20 hospital controls (patients with vascular disease, but free of CHF) and 20 healthy controls.
Baseline von Willebrand factor (p = 0.01) and soluble P-selectin (p = 0.006) levels were significantly elevated in patients with CHF when compared with controls. In the patients with CHF who were exercised, plasma viscosity, fibrinogen, and hematocrit levels increased significantly, both immediately post exercise and at 20 min into the recovery period (repeated measures analysis of variance, all p<0.05). There was a positive correlation between exercise workload and the maximal changes in plasma viscosity in the patients with CHF (Spearman r = 0.5, p = 0.02). Plasma viscosity levels increased with exercise in the hospital control group, although no other exercise-induced changes were noted in this group.
The present study indicates that the hemorheological indices. fibrinogen, and hematocrit specifically increase during acute exercise in patients with CHF. Although moderate exercise should be encouraged in patients with CHF, vigorous exercise should probably be avoided in view of its potential prothrombotic effects in this high-risk group of patients.
Clinical Cardiology 11/2001; 24(11):724-9. · 2.15 Impact Factor
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ABSTRACT: There is increasing evidence that chronic atrial fibrillation (AF) is associated with a prothrombotic or hypercoagulable state.
This study was undertaken to determine whether short-term exercise in patients with chronic AF would shift the overall hemostatic balance toward a more prothrombotic state with a reduction in fibrinolytic potential.
We recruited 20 patients (13 men; mean age 65 years +/- 11 standard deviation [SD]) with chronic AF who were not treated with antithrombotic therapy and exercised them to exhaustion using a multistage treadmill exercise (standard Bruce) protocol. Blood samples were taken pre exercise, immediately after cessation of exercise, and at 20 min post exercise. The prothrombotic state was quantified by fibrinogen (an index of hemorheology and a coagulation factor), soluble P-selectin (sP-sel, marking platelet activation), von Willebrand factor (vWF, an index of endothelial dysfunction), and plasminogen activator inhibitor-1 (PAI-1, a regulator of fibrinolytic activity) levels. There were two groups of age- and gender-matched controls in sinus rhythm: (1) healthy controls, and (2) "hospital controls" who were patients with vascular disease.
Baseline levels of vWf (p = 0.034) and fibrinogen (p < 0.0001), but not sP-sel (p = 0.075) were significantly elevated in patients with AF compared with both control groups in sinus rhythm. The PAI-1 levels were highest in the hospital control patients, but not in chronic AF (p = 0.041). Following treadmill exercise, achieving a mean metabolic equivalent of 4.9 METS (+/- 1.75 SD) and total exercise duration of 4.9 min (+/- 2 SD), there was a significant rise in plasma fibrinogen (repeated measures analysis of variance [ANOVA] p = 0.047) and a reduction in PAI-1 levels (p = 0.025) in patients with AF. There were no significant changes seen in vWf (p = 0.308) or sP-sel (p = 0.071) levels. No significant changes in these indices were seen in hospital controls (all p = not significant), despite a much longer duration of exercise with greater workload.
Patients with chronic AF have increased vWf and fibrinogen levels compared with sinus rhythm. Exercise to exhaustion influences the hypercoagulable state in chronic AF, with a rise in plasma fibrinogen and possible increase in fibrinolytic activity. Nevertheless, acute exercise does not appear to have a significant influence on endothelial dysfunction or platelet activation in patients with AF.
Clinical Cardiology 05/2001; 24(5):409-14. · 2.15 Impact Factor
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ABSTRACT: To investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and beta-blockers would beneficially affect the measured indices.
In the cross-sectional analysis, plasma viscosity (P=0.001), fibrinogen (P=0.02), vWF (P<0.0001), and soluble P-selectin (P<0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P<0.05). Plasma viscosity (P=0.009) and fibrinogen (P=0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III-IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P=0.016) and vWF (P=0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of beta-blocker therapy, apart from a rise in mean platelet count (P<0.001).
Abnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of beta-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.
Circulation 04/2001; 103(13):1746-51. · 14.74 Impact Factor
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ABSTRACT: Patients with chronic heart failure (heart failure) are at risk of thromboembolic events, including stroke, pulmonary embolism and peripheral arterial embolism, whilst coronary ischaemic events also contribute to the progression of heart failure. Long-term oral anticoagulation is established in certain groups, including patients with heart failure and atrial fibrillation but there is wide variation in the indications and use of oral anticoagulation in the broader heart failure population.
To determine whether long-term oral anticoagulation reduces total deaths and/or major thromboembolic events in patients with heart failure, when compared to placebo.
Reference lists of papers resulting from this search, electronic database searching (MEDLINE, EMBASE, DARE), and abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. Relevant authors of these studies were contacted to obtain further data.
Randomised controlled trials (RCTs) comparing oral anticoagulants with control or placebo. Non-randomised studies were included as they may help in assessing side-effects. Duration of treatment at least 1 month, adults with heart failure due to any underlying cause. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party.
Data were collected by two reviewers independently and where appropriate data from RCTs were meta-analysed.
One recent pilot RCT compared warfarin, aspirin and no antithrombotic therapy, but no definitive data have yet been published. Three small prospective studies of warfarin in heart failure were also identified, but were over 50 years old with methods not considered reliable by modern standards. Anticoagulation was more efficacious than control for the reduction of all cause death (odds ratio 0.64 95% CI 0.45,0.90) and the reduction of cardiovascular events (0.26 95% CI 0.16, 0.43). Four retrospective non-randomised cohort analyses and three small observational studies of oral anticoagulation in heart failure included differing populations of heart failure patients and reported contradictory results.
Evidence from the RCTs and observational studies found a reduction in mortality and cardiovascular events with anticoagulants compared to control. This evidence needs to be interpreted with caution. Although oral anticoagulation is indicated in certain groups of patients with heart failure (eg atrial fibrillation), the data available does not support its routine use in heart failure patients who remain in sinus rhythm. A large randomised trial of warfarin in heart failure patients in sinus rhythm is currently in progress data from which will be useful addition to this story.
Cochrane database of systematic reviews (Online) 02/2001; · 5.72 Impact Factor
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ABSTRACT: The aim of the study was to determine the aetiology of large and symptomatic pericardial effusions and to review the management and subsequent outcome. A survey was done on a consecutive cases of patients who had undergone percutaneous pericardiocentesis over a 10 year period in a city centre general hospital serving a multiethnic catchment population. In all, 46 patients (24 male, 22 female; age range 16 to 90 years, mean 54 years) underwent a total of 51 pericardial drainage procedures (or attempted pericardiocentesis) between 1989 and 1998. Malignancy (44%), tuberculosis (26%), idiopathic (11%), and post-cardiac surgery (9%) were the most common causes of pericardial effusion. The most common presenting symptoms were breathlessness (90%), chest pain (74%), cough (70%), abdominal pain (61%) (presumed to be related to hepatic congestion), and unexplained fever (28%). In the 12 cases of tuberculous pericarditis, nine occurred in patients of Indo-Asian origin, and three in patients of Afro-Caribbean origin. Fever, night sweats, and weight loss were common among these patients, occurring in over 80% of cases of tuberculous pericarditis. Pulsus paradoxus was the most specific sign (100%) for the presence of echocardiographic features of tamponade, with strongest positive predictive value (100%). Although malignancy remains the most common cause in developed countries, tuberculous disease should be considered in patients from areas where tuberculosis is endemic. Percutaneous pericardiocentesis remains an effective measure for the immediate relief of symptoms in patients with cardiac tamponade, although its diagnostic yield in tuberculous pericarditis is relatively low.
Postgraduate Medical Journal 01/2001; 76(902):809-13. · 1.94 Impact Factor
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ABSTRACT: Morbidity and mortality in patients with symptomatic chronic heart failure is high, it predisposes to stroke and thromboembolism which in turn contribute to high mortality in heart failure.
To determine effect of antiplatelet agents when compared to placebo or anticoagulant therapy on death and/or major thromboembolic events in adults with heart failure who are in sinus rhythm.
Systematic search of electronic databases (MEDLINE, EMBASE, DARE). Abstracts from cardiology meetings and reference lists of relevant papers were searched. Authors of studies were contacted for further information.
Randomised parallel group placebo or controlled trials comparing antiplatelet therapy with control or anticoagulation in adults with chronic heart failure in sinus rhythm. Treatment for at least 1 month. To assess any adverse effects cohort study & non-randomised controlled studies were assessed. Orally administered antiplatelet agents e.g. non-steroidal anti-inflammatory agents, TICLOPIDINE, CLOPIDOGREL, DIPYRIDAMOLE, ASPIRIN compared with anticoagulant agents e.g. COUMARINS, WARFARIN or placebo.
Data were extracted by two reviewers independently. No meta-analyses were performed as no data were available from randomised comparisons. The data extracted included data relating to the complexities of the topic area, such as patient characteristics and concomitant treatments, as well as data relating to study eligibility, quality, and outcomes. Non-randomised studies were used to identify side-effects caused by anticoagulants.
One RCT of warfarin, aspirin versus no antithrombotic therapy was found but no definitive data have yet been published. Three retrospective, non-randomised cohort studies from the V-HeFT, SOLVD and SAVE trials examining the role of ACE inhibitors have examined the role of aspirin therapy +/- anticoagulant therapy in patients with heart failure and/or left ventricular systolic dysfunction. The results from these trials were conflicting.
At present there is no evidence from long term RCTs to recommend use of aspirin to prevent thromboembolism in patients with heart failure in sinus rhythm. A possible interaction with ACE inhibitors may reduce the efficacy of aspirin, although this evidence is from retrospective analyses of trial cohorts. There is also no evidence to indicate superior effects from oral anticoagulation, when compared to aspirin, in patients with heart failure in sinus rhythm.
Cochrane database of systematic reviews (Online) 01/2001; · 5.72 Impact Factor
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Clinical Cardiology 05/2000; 23(4):293-4. · 2.15 Impact Factor
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BMJ 03/2000; 320(7234):559-62. · 14.09 Impact Factor
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BMJ 03/2000; 320(7233):495-8. · 14.09 Impact Factor
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BMJ 03/2000; 320(7231):366-9. · 14.09 Impact Factor
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Journal of Cardiovascular Risk 03/2000; 7(1):9-13.
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BMJ 03/2000; 320(7232):428-31. · 14.09 Impact Factor
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ABSTRACT: Acute and chronic management strategies in heart failure are aimed at improving both symptoms and prognosis, although management in individual patients will depend on the underlying aetiology and the severity of the condition. It is imperative that the diagnosis of heart failure is accompanied by an urgent attempt to establish its cause, as timely intervention may greatly improve the prognosis in selected cases—for example, in patients with severe aortic stenosis.View this table:View PopupView InlineSurvival rates (%) compared with chronic heart failure
Management of acute heart failure
Assessment
Common presenting features include anxiety, tachycardia, and dyspnoea. Pallor and hypotension are present in more severe cases: the triad of hypotension (systolic blood pressure <90 mm Hg), oliguria, and low cardiac output constitutes a diagnosis of cardiogenic shock. Severe acute heart failure and cardiogenic shock may be related to an extensive myocardial infarction, sustained cardiac arrhythmias (for example, atrial fibrillation or ventricular tachycardia), or mechanical problems (for example, acute papillary muscle rupture or postinfarction ventricular septal defect).
View this table:View PopupView InlineKillip classification
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Chest × ray film in patient with acute pulmonary oedema
Severe acute heart failure is a medical emergency, and effective management requires an assessment of the underlying cause, improvement of the haemodynamic status, relief of pulmonary congestion, and improved tissue oxygenation. Clinical and radiographic assessment of these patients provides a guide to severity and prognosis: the Killip classification has been developed to grade the severity of acute and chronic heart failure.
Treatment
Basic measures should include sitting the patient in an upright position with high concentration oxygen delivered via a face mask. Close observation and frequent reassessment are required in the early hours of treatment, and patients with acute severe heart failure, or refractory symptoms, should be monitored in a high dependency unit. Urinary catheterisation facilitates accurate assessment of fluid balance, while arterial blood gases provide valuable information about oxygenation and acid-base balance. The “base excess” is a guide to actual tissue perfusion in patients with acute heart failure: a worsening (more negative) base excess generally indicates lactic acidosis, which is related to anaerobic metabolism, and is a poor prognostic feature. Correction of hypoperfusion will correct the metabolic acidosis; bicarbonate infusions should be reserved for only the most refractory cases.
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Acute heart failure: basic measures and initial drug treatment
Intravenous loop diuretics, such as frusemide (furosemide), induce transient venodilatation, when administered to patients with pulmonary oedema, and this may lead to symptomatic improvement even before the onset of diuresis. Loop diuretics also increase the renal production of vasodilator prostaglandins. This additional benefit is antagonised by the administration of prostaglandin inhibitors, such as non-steroidal anti-inflammatory drugs, and these agents should be avoided where possible. Parenteral opiates or opioids (morphine or diamorphine) are an important adjunct in the management of severe acute heart failure, by relieving anxiety, pain, and distress and reducing myocardial oxygen demand. Intravenous opiates and opioids also produce transient venodilatation, thus reducing preload, cardiac filling pressures, and pulmonary congestion.
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Acute heart failure: second line drug treatment and advanced management
Nitrates (sublingual, buccal, and intravenous) may also reduce preload and cardiac filling pressures and are particularly valuable in patients with both angina and heart failure. Sodium nitroprusside is a potent, directly acting vasodilator, which is normally reserved for refractory cases of acute heart failure.
Short term inotropic support
In cases of severe refractory heart failure in which the cardiac output remains critically low, the circulation can be supported for a critical period of time with inotropic agents. For example, dobutamine and dopamine have positive inotropic actions, acting on the β1 receptors in cardiac muscle. Phosphodiesterase inhibitors (for example, enoximone) are less commonly used, and long term use of these agents is associated with increased mortality. Intravenous aminophylline is now rarely used for treating acute heart failure. Inotropic agents in general increase the potential for cardiac arrhythmias.
Intravenous inotropes and circulatory assist devices
Short term support with intravenous inotropes or circulatory assist devices, or with both, may temporarily improve haemodynamic status and peripheral perfusionSuch support can act as a bridge to corrective valve surgery or cardiac transplantation in acute and chronic heart failure
Chronic heart failure
Chronic heart failure can be “compensated” or “decompensated.” In compensated heart failure, symptoms are stable, and many overt features of fluid retention and pulmonary oedema are absent. Decompensated heart failure refers to a deterioration, which may present either as an acute episode of pulmonary oedema or as lethargy and malaise, a reduction in exercise tolerance, and increasing breathlessness on exertion. The cause or causes of decompensation should be considered and identified; they may include recurrent ischaemia, arrhythmias, infections, and electrolyte disturbance. Atrial fibrillation is common, and poor control of ventricular rate during exercise despite adequate control at rest should be addressed.
Management of chronic heart failure
General advice
Counselling—about symptoms and complianceSocial activity and employmentVaccination (influenza, pneumococcal)Contraception
General measures
Diet (for example, reduce salt and fluid intake)Stop smokingReduce alcohol intakeTake exercise
Treatment options—pharmacological
Diuretics (loop and thiazide)Angiotensin converting enzyme inhibitorsβBlockersDigoxinSpironolactoneVasodilators (hydralazine/nitrates)AnticoagulationAntiarrhythmic agentsPositive inotropic agents
Treatment options—devices and surgery
Revascularisation (percutaneous transluminal coronary angioplasty and coronary artery bypass graft)Valve replacement (or repair)Pacemaker or implantable cardiodefibrillatorVentricular assist devicesHeart transplantation
Common features of chronic heart failure include breathlessness and reduced exercise tolerance, and management is directed at relieving these symptoms and improving quality of life. Secondary but important objectives are to improve prognosis and reduce hospital admissions.
Initial management
Non-pharmacological and lifestyle measures should be addressed. Loop diuretics are valuable if there is evidence of fluid overload, although these may be reduced once salt and water retention has been treated. Angiotensin converting enzyme inhibitors should be introduced at an early stage, in the absence of clear contraindications. Angiotensin II receptor antagonists are an appropriate alternative in patients who are intolerant to angiotensin converting enzyme inhibitors. βBlockers (carvedilol, bisoprolol, metoprolol) are increasingly used in stable patients, although these agents require low dose initiation and cautious titration under specialist supervision. Oral digoxin has a role in patients with left ventricular systolic impairment, in sinus rhythm, who remain symptomatic despite optimal doses of diuretics and angiotensin converting enzyme inhibitors. Warfarin should be considered in patients with atrial fibrillation.
Supervised exercise programmes are of proved benefit, and regular exercise should be encouraged in patients with chronic stable heart failure
Severe congestive heart failure
Despite conventional treatment with diuretics and angiotensin converting enzyme inhibitors, hospital admission may be necessary in severe congestive heart failure. Fluid restriction is important—fluid intake should be reduced to 1-1.5 litres/24 h, and dietary salt restriction may be helpful.
Weighing the patient daily is valuable in monitoring the response to treatment
Education, counselling, and support
A role is emerging for heart failure liaison nurses in educating and supporting patients and their families, promoting long term compliance, and supervising treatment changes in the communityDepression is common, underdiagnosed, and often undertreated; counselling is therefore important for patients and families, and the newer antidepressants (particularly the selective serotonin reuptake inhibitors) seem to be well tolerated and are useful in selected patients
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.
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Example of management algorithm for left ventricular dysfunction
Special procedures
Intra-aortic balloon pumping and mechanical devices
Intra-aortic balloon counterpulsation and left ventricular assist devices are used as bridges to corrective valve surgery, cardiac transplantation, or coronary artery bypass surgery in the presence of poor cardiac function. Mechanical devices are indicated if (a) there is a possibility of spontaneous recovery (for example, peripartum cardiomyopathy, myocarditis) or (b) as a bridge to cardiac surgery (for example, ruptured mitral papillary muscle, postinfarction ventricular septal defect) or transplantation. Intra-aortic balloon counterpulsation is the most commonly used form of mechanical support.
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Left ventricular assist device
Revascularisation and other operative strategies
Impaired ventricular function in itself is not an absolute contraindication to cardiac surgery, although the operative risks are increased. Ischaemic heart disease is the most common precursor of chronic heart failure in Britain: coronary ischaemia should be identified and revascularisation considered with coronary artery bypass surgery or occasionally percutaneous coronary angioplasty. The concept of “hibernating” myocardium is increasingly recognised, although the most optimal and practical methods of identifying hibernation remain open to debate. Revascularisation of hibernating myocardium may lead to an improvement in the overall left ventricular function.
Indications and contraindications to cardiac transplantation in adults
Indications
End stage heart failure—for example, ischaemic heart disease and dilated cardiomyopathyRarely, restrictive cardiomyopathy and peripartum cardiomyopathyCongenital heart disease (often combined heart-lung transplantation required)
Absolute contraindications
Recent malignancy (other than basal cell and squamous cell carcinoma of the skin)Active infection (including HIV, Hepatitis B, Hepatitis C with liver disease)Systemic disease which is likely to affect life expectancySignificant pulmonary vascular resistance
Relative contraindications
Recent pulmonary embolismSymptomatic peripheral vascular diseaseObesitySevere renal impairmentPsychosocial problems—for example, lack of social support, poor compliance, psychiatric illnessAge (over 60–65 years)
Correction of valve disease, most commonly in severe aortic stenosis or mitral incompetence (not secondary to left ventricular dilatation), relieves a mechanical cause of heart failure; closure of an acute ventricular septal defect or mitral valve surgery for acute mitral regurgitation, complicating a myocardial infarction, may be lifesaving. Surgical excision of a left ventricular aneurysm (aneurysectomy) is appropriate in selected cases. Novel surgical procedures such as extensive ventricular reduction (Batista operation) and cardiomyoplasty have been associated with successful outcome in a small number of patients, although the high mortality, and the limited evidence of substantial benefit, has restricted the widespread use of these procedures.
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Number of heart transplantations worldwide and mean age of donors
Cardiac transplantation
The outcome in cardiac transplantation is now good, with long term improvements in survival and quality of life in patients with severe heart failure. However, although the demand for cardiac transplantation has increased over recent years, the number of transplant operations has remained stable, owing primarily to limited availability of donor organs.
Key referencesDargie HJ, McMurray JJ.Diagnosis and management of heart failure. BMJ 1994;308: 321–8.ACC/AHA Task Force Report.Guidelines for the evaluation and management of heart failure. J Am Coll Cardiol 1995;26: 1376–98.Hunt SA.Current status of cardiac transplantation. JAMA 1998;280: 1692–8.Remme WJ.The treatment of heart failure. The Task Force of the Working Group on Heart Failure of the European Society of Cardiology. Eur Heart J 1997;18: 736–53.
The procedure now carries a perioperative mortality of less than 10%, with approximate one, five, and 10 year survival rates of 92%, 75%, and 60% respectively (much better outcomes than with optimal drug treatment, which is associated with a one year mortality of 30-50% in advanced heart failure). Cardiac transplantation should be considered in patients with an estimated one year survival of <50%. Well selected patients over 55–60 years have a survival rate comparable to those of younger patients. Patients need strong social and psychological support; transplant liaison nurses are valuable in this role.
The long term survival of the transplanted human heart is compromised by accelerated graft atherosclerosis which results in small vessel coronary artery disease and an associated deterioration in left ventricular performance. This can occur as early as three months and is the major cause of graft loss after the first year. The anti-rejection regimens currently used may result in an acceleration of pre-existing atherosclerotic vascular disease—hence the exclusion of patients who already have significant peripheral vascular disease. Rejection is now a less serious problem, with the use of cyclosporin and other immunosuppressant agents.
Nevertheless, the supply of donors limits the procedure. The Eurotransplant database (1990–5) indicates that 25% of patients listed for transplantation die on the waiting list, with 60% receiving transplants at two years (most within 12 months). Although ventricular assist devices may be valuable during the wait for transplantation, the routine use of xenotransplants is unlikely in the short or medium term.
Acknowledgments
The graph showing cardiac transplantations worldwide is adapted with permission from Hosenpud et al (J Heart Lung Transplant 1998;17:656-8). The table showing survival rates is adapted from Hobbs (Heart 1999;82(suppl IV):IV8-10).
Footnotes
T Millane is consultant cardiologist in the department of cardiology, City Hospital, Birmingham; G Jackson is consultant cardiologist in the department of cardiology at Guy's and St Thomas's Hospital, London.
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.
BMJ. 02/2000; 320(7234):559 - 562.
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ABSTRACT: Digoxin
Use of digoxin for heart failure varies between countries across Europe, with high rates in Germany and low rates in the United Kingdom. It is potentially invaluable in patients with atrial fibrillation and coexistent heart failure, improving control of the ventricular rate and allowing more effective filling of the ventricle. Digoxin is also used in patients with chronic heart failure secondary to left ventricular systolic impairment, in sinus rhythm, who remain symptomatic despite optimal doses of diuretics and angiotensin converting enzyme inhibitors, where it acts as an inotrope.
Digoxin should be considered in patients with sinus rhythm plus (a) continued symptoms of heart failure despite optimal doses of diuretics and angiotensin converting enzyme inhibitors; (b) severe left ventricular systolic dysfunction with cardiac dilatation; or (c) recurrent hospital admissions for heart failure
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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)
Study of effect of digoxin on mortality and morbidity in patients with heart failure*
Number of participants: 6800
Design: prospective, randomised, double blind, placebo controlled
Participants: left ventricular ejection fraction <45%
Intervention: randomised to digoxin (0.125-0.500 mg) or placebo; follow up at 37 months
Results:
Reduced admissions to hospital owing to heart failure (greater absolute and relative benefits in the patients with resistant symptoms and more severe impairment of left ventricular systolic function)No effect on overall survival
Evidence of symptomatic benefit from digoxin in patients with chronic heart failure in sinus rhythm has been reported in several randomised placebo controlled trials and several smaller trials. The RADIANCE and PROVED trials, for example, reported that the withdrawal of digoxin from patients with congestive heart failure who had already been treated with the drug was associated with worsening heart failure and increased hospital readmission rates. The Digitalis Investigation Group's large study found that digoxin was associated with a symptomatic improvement in patients with congestive heart failure, when added to treatment with diuretics and angiotensin converting enzyme inhibitors. Importantly, there were greater absolute and relative benefits in the patients who had resistant symptoms and more severe impairment of left ventricular systolic function. However, although there was a reduction in the combined end points of admission and mortality resulting from heart failure, there was no significant improvement in overall survival.β Blockers were used rarely in the Digitalis Investigation Group's study, and as a result it is not clear whether digoxin is additive to both the β blockers and angiotensin converting enzyme inhibitors in congestive heart failure.
Digoxin: practical aspects
Ensure a maintenance dose of 125-375 μg (0.125-0.375 mg) dailyGive a reduced maintenance dose in elderly people, when renal impairment is present, and when used with drugs that increase digoxin concentrations (amiodarone, verapamil)Concentrations should be monitored especially in cases of uncertainty about whether therapeutic levels have been achieved (range 6 hours after dose: 1.2-1.9 ng/ml)Monitor potassium concentrations (avoid hypokalaemia) and renal functionDigoxin toxicity may be associated with: (a) adverse symptoms (for example, nausea, vomiting, headache, confusion, visual symptoms); and (b) arrhythmias (for example, atrioventricular junctional rhythms, atrial tachycardia, atrioventricular block, ventricular tachycardia)Serious toxicity should be treated by correcting potassium concentrations and with drugs such as β blockers and glycoside binding agents (cholestyramine), and in severe cases specific digoxin antibodies (Digibind)
Source of information: Uretsky et al (J Am Coll Cardiol 1993;22:955) and Packer et al (N Engl J Med 1993;329:1)
Other inotropes
The potential role of inotropic agents other than digoxin in chronic heart failure has been addressed in several studies. Although these drugs seem to improve symptoms in some patients, most have been associated with an increase in mortality.
View this table:View PopupView InlineInotropic drugs associated with increased mortality in chronic heart failure
For example, the PRIME II trial (a prospective randomised study) examined ibopamine, a weak inotrope, in patients with chronic heart failure who were already receiving standard treatment. An excess mortality was shown, however, particularly in those with severe symptoms; this was possibly related to an excess of arrhythmias. In addition, a previous trial evaluating intermittent dobutamine infusions in patients with chronic heart failure was stopped prematurely because of excess mortality in the group taking dobutamine. Xamoterol, a β receptor antagonist with mild agonist inotropic effects, also failed to show any positive benefits in patients with heart failure
Potential mechanisms and benefits of β blockers: improved left ventricular function; reduced sympathetic tone; improved autonomic nervous system balance; up regulation of β adrenergic receptors; reduction in arrhythmias, ischaemia, further infarction, myocardial fibrosis, and apoptosis
In overall terms, no evidence exists at present to support the use of oral catecholamine receptor (or postreceptor pathway) stimulants in the treatment of chronic heart failure. Digoxin remains the only (albeit weak) positive inotrope that is valuable in the management of chronic heart failure.
βBlockers
βAdrenoceptor blockers have traditionally been avoided in patients with heart failure due to their negative inotropic effects. However, there is now considerable clinical evidence to support the use of βblockers in patients with chronic stable heart failure resulting from left ventricular systolic dysfunction. Recent randomised controlled trials in patients with chronic heart failure have reported that combining βblockers with conventional treatment with diuretics and angiotensin converting enzyme inhibitors results in improvements in left ventricular function, symptoms, and survival, as well as a reduction in admissions to hospital.
View this table:View PopupView InlineRandomised, placebo controlled β;blocker trials in congestive heart failure
Recently, two randomised controlled trials have studied the effects of carvedilol, a βblocker with alpha blocking and vasodilator properties, in patients with symptomatic heart failure. The US multicentre carvedilol study programme was stopped early because of a highly significant (65%) mortality benefit in patients receiving carvedilol, when compared to placebo, and the Australia/New Zealand heart failure study reported a 41% reduction in the combined primary end point of all cause hospital admission and mortality. Bisoprolol has also been studied, and, although the first cardiac insufficiency bisoprolol study (CIBIS I) reported a trend towards a reduction in mortality and need for cardiac transplantation, there was no conclusive survival benefit. The recent CIBIS II study, however, was stopped prematurely because of the beneficial effects of active treatment on both morbidity and mortality. Metoprolol has also shown similar prognostic advantages in the metoprolol randomised intervention trial in heart failure (MERIT-HF), which was also stopped early. In summary, evidence is now available to support the use of βblockers in chronic heart failure, as the benefits supplement those already obtained from angiotensin converting enzyme inhibitors.
View this table:View PopupView InlineMeta-analysis of effects of βblockers on mortality and admissions to hospital in chronic heart failure
Summary of the cardiac insufficiency bisoprolol study II (CIBIS II)*
Randomised, double blind, parallel group study2647 participants (class III-IV (moderate to severe) according to classification of the New York Heart Association)Bisoprolol, increased in dose to a maximum of 10 mg a dayTrial stopped because of significant mortality benefit in patients treated with bisoprolol:(a)32% reduction in all cause mortality(b)32% reduction in admissions to hospital for worsening heart failure(c)42% reduction in sudden death
Carvedilol is now licensed in the United Kingdom for use in mild to moderate chronic stable heart failure, although at present its use is still not recommended in patients with severe symptoms (New York Heart Association class IV). This latter group has been underrepresented in the trials to date.
In general, β blockers should be started at very low doses, with the dose being slowly increased, under expert supervision, to the target dose if tolerated. In the short term there may be a deterioration in symptoms, which may improve with alterations in other treatment, particularly diuretics.
View this table:View PopupView InlineDose and titration of βblockers in large, placebo controlled heart failure trials
Antithrombotic treatment
In patients with chronic heart failure the incidence of stroke and thromboembolism is significantly higher in the presence of atrial and left ventricular dilatation, particularly in severe left ventricular dysfunction. Nevertheless, there is conflicting evidence of benefit from routine treatment of patients with heart failure who are in sinus rhythm with antithrombotic treatment, although anticoagulation should be considered in the presence of mobile ventricular thrombus, atrial fibrillation, and severe cardiac impairment. Large scale, prospective randomised controlled trials of antithrombotic treatment in heart failure are in progress, such as the WATCH study (a trial of warfarin and antiplatelet therapy); the full results are awaited with interest.
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Echocardiogram showing thrombus at left ventricular apex in patient with dilated cardiomyopathy (A=thrombus, B=left ventricle, C=left atrium)
The combination of atrial fibrillation and heart failure (or evidence of left ventricular systolic dysfunction on echocardiography) is associated with a particularly high risk of thromboembolism, which is reduced by long term treatment with warfarin. Aspirin seems to have little effect on the risk of thromboembolism and overall mortality in such patients.
Antiarrhythmic treatment
Chronic heart failure and atrial fibrillation
Restoration and long term maintenance of sinus rhythm is less successful in the presence of severe structural heart disease, particularly when the atrial fibrillation is longstanding. In patients with a deterioration in symptoms that is associated with recent onset atrial fibrillation, treatment with amiodarone increases the long term success rate of cardioversion. Digoxin is otherwise appropriate for controlling ventricular rate in most patients with heart failure and chronic atrial fibrillation, with the addition of amiodarone in resistant cases.
The use of class I antiarrhythmic agents in patients with atrial fibrillation and chronic heart failure substantially increases the risk of mortality
Chronic heart failure and ventricular arrhythmias
Ventricular arrhythmias are a common cause of death in severe heart failure. Precipitating or aggravating factors should thus be addressed, including electrolyte disturbance (for example, hypokalaemia, hypomagnesaemia), digoxin toxicity, drugs causing electrical instability (for example, antiarrhythmic drugs, antidepressants), and continued or recurrent myocardial ischaemia.
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Survival curves from GESICA trial (see key references box), showing difference between patients taking amiodarone and controls
Amiodarone is effective for the symptomatic control of ventricular arrhythmias in chronic heart failure, although most studies have reported that long term antiarrhythmic treatment with amiodarone has a neutral effect on survival. An Argentinian trial (the GESICA study)of empirical amiodarone in patients with chronic heart failure reported, however, that active treatment was associated with a 28% reduction in total mortality, although this trial included a high incidence of patients with non-ischaemic heart failure. In contrast, in the survival trial of antiarrhythmic therapy in congestive heart failure (CHF-STAT), amiodarone did not improve overall survival, although there was a significant (46%) reduction in cardiac death and admission to hospital in the patients with non-ischaemic chronic heart failure.
View this table:View PopupView InlineSummary of drug management in chronic heart failure
In general, amiodarone should probably be reserved for patients with chronic heart failure who also have symptomatic ventricular arrhythmias. Interest has also developed in implantable cardioverter defibrillators, which reduce the risk of sudden death in high risk patients with ventricular arrhythmias (MADIT and AVID studies), although the role of these devices in patients with chronic heart failure still remains to be established.
Key referencesAustralia/New Zealand Heart Failure Research Collaborative Group. Randomized, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease. Lancet 1997; 349: 375–80.Lip GYH. Intracardiac thrombus formation in cardiac impairment: investigation and the role of anticoagulant therapy. Postgrad Med J 1996; 72: 731–8.Massie BM, Fisher SG, Radford M, Deedwania PC, Singh BN, Fletcher RD, et al., for the CHF-STAT Investigators. Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure. Circulation 1996; 93: 2128–34.MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet 1999; 353: 2001–7.Doval HC, Nul DR, Grancelli HO, Perrone SV, Bortman GR, Curiel R, et al. Randomised trial of low-dose amiodarone in severe congestive heart failure [GESICA trial]. Lancet 1994; 344: 493–8.Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. Effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 334: 1349–55.Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med 1997; 336: 525–33.
Acknowledgments
The survival graph is adapted with permission from Doval et al (Lancet 1994;344:493-8). The table of inotropic drugs is adapted with permission from Niebauer et al (Lancet 1997;349:966). The table of results of a meta-analysis of effects of βblockers is adapted with permission from Lechat P et al (Circulation 1998;98:1184-91). The table on doses and titration of βblockers is adapted with permission from Remme WJ (Eur Heart J 1997;18:736-53).
Footnotes
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.
BMJ. 02/2000; 320(7233):495 - 498.
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ABSTRACT: In the past 15 years several large scale, randomised controlled trials have revolutionised the management of patients with chronic heart failure. Although it is clear that some drugs improve symptoms, others offer both symptomatic and prognostic benefits, and the management of heart failure should be aimed at improving both quality of life and survival.
Aims of heart failure management
To achieve improvement in symptoms
Diuretics
Digoxin
ACE inhibitors
To achieve improvement in survival
ACE inhibitors
βblockers (for example, carvedilol and bisoprolol)
Oral nitrates plus hydralazine
Spironolactone
Diuretics and angiotensin converting enzyme (ACE) inhibitors, when combined with non-pharmacological measures, remain the basis of treatment in patients with congestive heart failure. Digoxin has a possible role in some of these patients, however, and the potential benefits of β blockers and spironolactone (an aldosterone antagonist) in chronic heart failure are now increasingly recognised.
Diuretics
Diuretics are effective in providing symptomatic relief and remain the first line treatment, particularly in the presence of oedema. Nevertheless, there is no direct evidence that loop and thiazide diuretics confer prognostic benefit in patients with congestive heart failure.
In general, diuretics should be introduced at a low dose and the dose increased according to the clinical response. There are dangers, however, in either undertreating or overtreating patients with diuretics, and regular review is necessary
Loop diuretics
Loop diuretics—frusemide (furosemide) and bumetanide—have a powerful diuretic action, increasing the excretion of sodium and water via their action on the ascending limb of the loop of Henle. They have a rapid onset of action (intravenously 5 minutes, orally 1–2 hours; duration of action 4–6 hours). Oral absorption of frusemide may be reduced in congestive heart failure, although the pharmacokinetics of bumetanide may allow improved bioavailability.
How to use diuretics in advanced heart failure
Optimise diuretic doseConsider combination diuretic treatment with a loop and thiazide (or thiazide-like) diureticConsider combining a low dose of spironolactone with an ACE inhibitor, provided that there is no evidence of hyperkalaemia …
BMJ. 02/2000; 320(7232):428 - 431.
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ABSTRACT: Approaches to the management of heart failure can be both non-pharmacological and pharmacological; each approach complements the other. This article will discuss non-pharmacological management.
Non-pharmacological measures for the management of heart failure
Compliance—give careful advice about disease, treatment, and self help strategiesDiet—ensure adequate general nutrition and, in obese patients, weight reductionSalt—advise patients to avoid high salt content foods and not to add salt (particularly in severe cases of congestive heart failure)Fluid—urge overloaded patients and those with severe congestive heart failure to restrict their fluid intakeAlcohol—advise moderate alcohol consumption (abstinence in alcohol related cardiomyopathy)Smoking—avoid smoking (adverse effects on coronary disease, adverse haemodynamic effects)Exercise—regular exercise should be encouragedVaccination—patients should consider influenza and pneumococcal vaccinations
Counselling and education of patients
Effective counselling and education of patients, and of the relatives or carers, is important and may enhance long term adherence to management strategies. Simple explanations about the symptoms and signs of heart failure, including details on drug and other treatment strategies, are valuable. Emphasis should be placed on self help strategies for each patient; these should include information on the need to adhere to drug treatment. Some patients can be instructed how to monitor their weight at home on a daily basis and how to adjust the dose of diuretics as advised; sudden weight increases (>2 kg in 1-3 days), for example, should alert a patient to alter his or her treatment or seek advice.
Lifestyle measures
Urging patients to alter their lifestyle is important in the management of chronic heart failure. Social activities should be encouraged, however, and care should be taken to ensure that patients avoid social isolation. If possible, patients should continue their regular work, with adaptations to accommodate a reduced physical capacity where appropriate.
Self help strategies for patients with heart failure
Contraceptive advice
Advice on contraception should be offered to women of childbearing potential, particularly those patients with …
BMJ. 02/2000; 320(7231):366 - 369.
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BMJ 02/2000; 320(7230):297-300. · 14.09 Impact Factor
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BMJ 02/2000; 320(7229):236-9. · 14.09 Impact Factor
