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Heart failure: a medical hydra
THE
LANCET
Heart failure: a medical hydra The Hydra was a malign, mythical, many-headed beast that plagued ancient Argos. Despite his strength and skill, the hero Hercules succeeded only in making matters worse, because each time he severed one head two more grew in its place. Only with the aid of his charioteer Iolaus, who cauterised the stumps as the heads were severed to prevent regrowth, did Hercules finally manage to slay the monster, burying the last and immortal head under a rock. The Hydra and heart failure have much in common, even their names. Both Hydra and an old-fashioned name for heart failure, hydrops, perhaps reflect the malign aspects of a surfeit of water. However, reality is unlikely to reach the satisfactory conclusion of the Preventive therapies myth. There is no obvious therapy with which to Aim prevent the proliferation of Prevention of heart failure heart failure. Primary As the term hydrops Secondary suggests, the earliest concepts of the pathophysiology of heart failure Prevention in heart failure centred around salt and Tertiary water retention. However, haemodynamic concepts, including vasodilator therapy, were well established by the beginning of this century. The recognition that the haemodynamic derangements we measure do not alone explain many of the features of heart failure has led to the search for other pathophysiological processes, including neuroendocrine, cytokine, and immune activation, ventricular remodelling, and programmed cell death. More recently, the importance of clinical events that may govern the progression of heart failure, such as myocardial ischaemia and infarction or atrial fibrillation, has been rediscovered. Clearly, Hydra-Hydrops reigns victorious, with each pathophysiological hypothesis multiplied as it is dissected. The prevalence of heart failure, or at least the rate of morbidity and mortality, appears to be increasing in younger as well as older age-groups. This increase may reflect the effects of improved secondary prevention. For example, improved management after myocardial infarction is likely to increase the prevalence of heart failure because treatment has its greatest impact on survival among patients at risk of developing heart failure. A new concept may be prevention in rather than prevention of heart failure (panel) with inhibitors of angiotensin-converting enzyme (ACE) and B-blockers. B-blockers may worsen symptoms in the short term, while reducing the lon~-term risk of deterioration. 1 These sfi
drugs therefore appear ideally suited for prevention in heart failure. This tertiary role, of course, complements that of [3-blockers for primary and secondary prevention. Preventive measures may allow individual patients to enjoy a longer life with fewer symptoms, and may delay the development of heart failure, but they are unlikely to change the lifetime risl~ and may, paradoxically, increase the prevalence of heart failure precisely because they are effective in reducing mortality. Another victory for Hydra-Hydrops? Treatment for heart failure may be directed at relieving symptoms or at improving prognosis; retarding the progressive decline in cardiac function is likely to influence both favourably in the long term. Accordingly, the dominant aim of current Target/agent research in heart failure is to alter the progression of heart Hypertension failure rather than to improve Hyperlipidaemia symptoms. This approach is ACE inhibitors appropriate for patients who 13-blockers (probable) are only mildly symptomatic but may be of little help 13-blockers for those with severe heart ACE inhibitors failure. Early treatment may retard the progression of heart failure and delay the onset of severe symptoms, but is unlikely to arrest the process altogether. Eventually, the number of patients developing severe heart failure will be as great or even greater than before. Moreover, severe heart failure is not necessarily preceded by a long period of milder cardiac dysfunction. Up to 50% of heart failure occurs as a direct consequence of a first myocardial infarction, and heart failure may be severe from the outset in many cases. 2 Severe heart failure still carries a 1-year mortality of 50% or more. Current treatments are obviously inadequate to contain or manage the problem. There is little evidence, so far, that interventions such as dietary salt restriction or exercise rehabilitation affect outcome in heart failure. Despite clinical trials with a great variety of agents, for most patients with leftventricular systolic dysfunction, only diuretics, ACE inhibitors, and [3-blockers (preferably in combination) are of unequivocal benefit. The treatment of heart failure due to left-ventricular diastolic dysfunction, which may constitute up to 50% of patients, remains virtually unexplored. Proven treatments for heart failure are in short supply. Allograft heart transplantation has long been considered the most effective treatment for patients with advanced heart failure, but there are problems with this gold standard. Supply of donor organs is limited and Heart failure - Vol 352 • 1998
THE LANCET
declining. A 25-year-old who receives a heart transplant has a less than 50% chance of being alive on his 35th birthday. Moreover, disquiet has been caused by the relatively low mortality of patients who have survived on the transplant list for 6 months but not undergone transplantation3 This finding suggests that improved selection for transplant listing may be required. However, a valid, altemative approach is not to undertake transplantation for prognostic reasons at all but to select on the basis of a failure of medical treatment to control symptoms adequately. Many alternative strategies for the management of advanced heart failure are being researched. The first cardiac porcine xenotransplants will probably occur within the next 5 years, but it will be some years before the feasibility of this approach is clear. More than 2000 patients have already received totally implantable leftventricular assist systems, usually as a temporary measure while awaiting heart transplantation but sometimes as a bridge to recovery of the native heart. 4 Many patients have been maintained, out of hospital, for some years by these devices ~vhile awaiting heart transplantation, and some have even been able to return to work. Smaller less expensive devices could make this approach part of the routine definitive management of many patients with advanced heart failure. Another novel approach is left-ventricular or multisite pacing, a treatment that may be especially effective among the 20-30% of patients who have heart failure and bundle-branch block or an intraventricular conduction defect. 5 Some experimental surgical approaches, such as cardiomyoplasty, have been all but abandoned except by a few centres and have been replaced by newer concepts such as surgical left-ventricular reduction. 6 The diversity of strategies indicates that no single technique has proven entirely satisfactory at present. Studies of implantable defibrillators also show how the natural history of heart failure can thwart even highly effective therapy. Reduction of the risk of sudden death may not reduce the risk of death due to pump failure and
Heart failure • Vo1352 • 1998
vice versa. Any therapeutic strategy that deals with only one mode of death may have little impact on prognosis. The success of [3-blockers and ACE inhibitors reflects their ability to reduce the risk of both sudden and progressive heart failure deaths. We should not lose sight of the fact that delaying the onset of heart failure and its progression is of major importance to individual patients. However, it is obvious to any clinical researcher in heart failure that the best we can hope to do, in population terms, for the foreseeable future is to slow the increase in prevalence of and morbidity associated with heart failure. Heart failure is an increasingly expensive disorder to manage owing, partly, to frequent and long hospital stays. Health providers will be forced to invest in more hospital beds or in more effective ways of managing heart failure. The alternative, involuntary euthanasia, either by neglect or deliberate withholding of inexpensive and cost-effective treatment, is unacceptable.
John G F Cleland Department of Cardiology, Castle Hill Hospital, University of Hull, Hull HU16 5JQ, UK 1
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4
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6
Cleland JGF, Bristow M, E r d m a n n E, Remme W~, Swedberg K, Waggstein F. Beta-blocking agents in heart failure: should they be used and how? EurHeartJ 1996; 17: 1629-39. Kober L, Torp Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N EnglJ Med 1995; 333: 1670-76. Stevenson LW, Hamilton MA, Tillisch IH, et al. Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. J A m Coll Cardio11991; 18: 919-25. Oz M C , Argenziano M, Cantanese KA, et al. Bridge experience with long-term implantable left ventricular assist devices: are they an alternative to transplantation? Circulation 1997; 9 5 : 1 8 4 4 52. Daubert JP, Ritter P, Le Breton H , et al. Permanent left ventricular pacing with transvenous leads inserted into the coronary veins. PACE 1998; 21 (suppl): 239~t5. Angelini G D , Pryn S, Mehta D, et al. Left-ventricular-volume reduction for end-stage heart-failure. Lancet 1997; 350: 489.
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LANCET
Heart failure: a medical hydra The Hydra was a malign, mythical, many-headed beast that plagued ancient Argos. Despite his strength and skill, the hero Hercules succeeded only in making matters worse, because each time he severed one head two more grew in its place. Only with the aid of his charioteer Iolaus, who cauterised the stumps as the heads were severed to prevent regrowth, did Hercules finally manage to slay the monster, burying the last and immortal head under a rock. The Hydra and heart failure have much in common, even their names. Both Hydra and an old-fashioned name for heart failure, hydrops, perhaps reflect the malign aspects of a surfeit of water. However, reality is unlikely to reach the satisfactory conclusion of the Preventive therapies myth. There is no obvious therapy with which to Aim prevent the proliferation of Prevention of heart failure heart failure. Primary As the term hydrops Secondary suggests, the earliest concepts of the pathophysiology of heart failure Prevention in heart failure centred around salt and Tertiary water retention. However, haemodynamic concepts, including vasodilator therapy, were well established by the beginning of this century. The recognition that the haemodynamic derangements we measure do not alone explain many of the features of heart failure has led to the search for other pathophysiological processes, including neuroendocrine, cytokine, and immune activation, ventricular remodelling, and programmed cell death. More recently, the importance of clinical events that may govern the progression of heart failure, such as myocardial ischaemia and infarction or atrial fibrillation, has been rediscovered. Clearly, Hydra-Hydrops reigns victorious, with each pathophysiological hypothesis multiplied as it is dissected. The prevalence of heart failure, or at least the rate of morbidity and mortality, appears to be increasing in younger as well as older age-groups. This increase may reflect the effects of improved secondary prevention. For example, improved management after myocardial infarction is likely to increase the prevalence of heart failure because treatment has its greatest impact on survival among patients at risk of developing heart failure. A new concept may be prevention in rather than prevention of heart failure (panel) with inhibitors of angiotensin-converting enzyme (ACE) and B-blockers. B-blockers may worsen symptoms in the short term, while reducing the lon~-term risk of deterioration. 1 These sfi
drugs therefore appear ideally suited for prevention in heart failure. This tertiary role, of course, complements that of [3-blockers for primary and secondary prevention. Preventive measures may allow individual patients to enjoy a longer life with fewer symptoms, and may delay the development of heart failure, but they are unlikely to change the lifetime risl~ and may, paradoxically, increase the prevalence of heart failure precisely because they are effective in reducing mortality. Another victory for Hydra-Hydrops? Treatment for heart failure may be directed at relieving symptoms or at improving prognosis; retarding the progressive decline in cardiac function is likely to influence both favourably in the long term. Accordingly, the dominant aim of current Target/agent research in heart failure is to alter the progression of heart Hypertension failure rather than to improve Hyperlipidaemia symptoms. This approach is ACE inhibitors appropriate for patients who 13-blockers (probable) are only mildly symptomatic but may be of little help 13-blockers for those with severe heart ACE inhibitors failure. Early treatment may retard the progression of heart failure and delay the onset of severe symptoms, but is unlikely to arrest the process altogether. Eventually, the number of patients developing severe heart failure will be as great or even greater than before. Moreover, severe heart failure is not necessarily preceded by a long period of milder cardiac dysfunction. Up to 50% of heart failure occurs as a direct consequence of a first myocardial infarction, and heart failure may be severe from the outset in many cases. 2 Severe heart failure still carries a 1-year mortality of 50% or more. Current treatments are obviously inadequate to contain or manage the problem. There is little evidence, so far, that interventions such as dietary salt restriction or exercise rehabilitation affect outcome in heart failure. Despite clinical trials with a great variety of agents, for most patients with leftventricular systolic dysfunction, only diuretics, ACE inhibitors, and [3-blockers (preferably in combination) are of unequivocal benefit. The treatment of heart failure due to left-ventricular diastolic dysfunction, which may constitute up to 50% of patients, remains virtually unexplored. Proven treatments for heart failure are in short supply. Allograft heart transplantation has long been considered the most effective treatment for patients with advanced heart failure, but there are problems with this gold standard. Supply of donor organs is limited and Heart failure - Vol 352 • 1998
THE LANCET
declining. A 25-year-old who receives a heart transplant has a less than 50% chance of being alive on his 35th birthday. Moreover, disquiet has been caused by the relatively low mortality of patients who have survived on the transplant list for 6 months but not undergone transplantation3 This finding suggests that improved selection for transplant listing may be required. However, a valid, altemative approach is not to undertake transplantation for prognostic reasons at all but to select on the basis of a failure of medical treatment to control symptoms adequately. Many alternative strategies for the management of advanced heart failure are being researched. The first cardiac porcine xenotransplants will probably occur within the next 5 years, but it will be some years before the feasibility of this approach is clear. More than 2000 patients have already received totally implantable leftventricular assist systems, usually as a temporary measure while awaiting heart transplantation but sometimes as a bridge to recovery of the native heart. 4 Many patients have been maintained, out of hospital, for some years by these devices ~vhile awaiting heart transplantation, and some have even been able to return to work. Smaller less expensive devices could make this approach part of the routine definitive management of many patients with advanced heart failure. Another novel approach is left-ventricular or multisite pacing, a treatment that may be especially effective among the 20-30% of patients who have heart failure and bundle-branch block or an intraventricular conduction defect. 5 Some experimental surgical approaches, such as cardiomyoplasty, have been all but abandoned except by a few centres and have been replaced by newer concepts such as surgical left-ventricular reduction. 6 The diversity of strategies indicates that no single technique has proven entirely satisfactory at present. Studies of implantable defibrillators also show how the natural history of heart failure can thwart even highly effective therapy. Reduction of the risk of sudden death may not reduce the risk of death due to pump failure and
Heart failure • Vo1352 • 1998
vice versa. Any therapeutic strategy that deals with only one mode of death may have little impact on prognosis. The success of [3-blockers and ACE inhibitors reflects their ability to reduce the risk of both sudden and progressive heart failure deaths. We should not lose sight of the fact that delaying the onset of heart failure and its progression is of major importance to individual patients. However, it is obvious to any clinical researcher in heart failure that the best we can hope to do, in population terms, for the foreseeable future is to slow the increase in prevalence of and morbidity associated with heart failure. Heart failure is an increasingly expensive disorder to manage owing, partly, to frequent and long hospital stays. Health providers will be forced to invest in more hospital beds or in more effective ways of managing heart failure. The alternative, involuntary euthanasia, either by neglect or deliberate withholding of inexpensive and cost-effective treatment, is unacceptable.
John G F Cleland Department of Cardiology, Castle Hill Hospital, University of Hull, Hull HU16 5JQ, UK 1
2
3
4
5
6
Cleland JGF, Bristow M, E r d m a n n E, Remme W~, Swedberg K, Waggstein F. Beta-blocking agents in heart failure: should they be used and how? EurHeartJ 1996; 17: 1629-39. Kober L, Torp Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N EnglJ Med 1995; 333: 1670-76. Stevenson LW, Hamilton MA, Tillisch IH, et al. Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. J A m Coll Cardio11991; 18: 919-25. Oz M C , Argenziano M, Cantanese KA, et al. Bridge experience with long-term implantable left ventricular assist devices: are they an alternative to transplantation? Circulation 1997; 9 5 : 1 8 4 4 52. Daubert JP, Ritter P, Le Breton H , et al. Permanent left ventricular pacing with transvenous leads inserted into the coronary veins. PACE 1998; 21 (suppl): 239~t5. Angelini G D , Pryn S, Mehta D, et al. Left-ventricular-volume reduction for end-stage heart-failure. Lancet 1997; 350: 489.
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