Clinical case studies in heart failure management

Therapeutic aspects of heart failure management

The outlook for patients with cardiac failure has improved substantially in the last 15 years. This is largely due to the application of the results of multicentre clinical trials of new and older drugs and a better understanding of outcomes for individual patients. Interest has focused on systolic dysfunction in both symptomatic and asymptomatic patients. Less is known about the definition and management of diastolic dysfunction.

The following case studies have been chosen to illustrate the basis for therapeutic management of systolic heart failure and outline the remaining gaps in knowledge, of which there are several. The issues apply across the spectrum of patients seen in clinical practice.

Acute stabilization and chronic management of systolic failure

Case history

A 74-year-old female patient was admitted from home with progressive increase in breathlessness, orthopnoea and ankle oedema over the previous 3 weeks. Her general practitioner had prescribed oral coamoxiclav and coamilofruse (substituting the latter for bendrofluazide). She had suffered from dyspepsia, increasing over recent weeks, and the general practitioner had noted a new murmur.

She was apyrexial yet tachypnoeic (25 beats min⁻¹); with a low volume pulse. Sitting blood pressure was 110/70 mm Hg. The apex beat was in the anterior axillary line and a parasternal lift was prominent. A pansystolic murmur was audible and late inspiratory crackles were heard throughout both lung fields. There was sacral oedema.

The ECG confirmed sinus tachycardia (110 beats min⁻¹) with antero-lateral Q waves of previous infarction and the chest X-ray confirmed cardiomegaly and interstitial oedema. Routine chemistry showed Na⁺ 128 mmol l⁻¹; K⁺ 5.8 mmol l⁻¹; urea 9 mmol l⁻¹; creatinine 155 mmol l⁻¹. A creatine kinase series was unremarkable. Echocardiography showed a dilated heart (left ventricular end diastolic distension (LVEDD) 650 mm) with anterior and septal hypokinesis and apical dilatation compatible with previous anterior infarction. The posterior wall was contracting vigorously. A high velocity jet (4.7 m s⁻¹) of mitral regurgitation was noted but the left atrial size was normal.

Comments

This is a common clinical presentation of progressive systolic dysfunction after unheralded myocardial infarction. A number of therapeutic and general management steps should be considered for all such patients. Whereas in stable patients clinical identification or grading of the severity of heart failure is unreliable [1], recent studies suggest that in acute heart failure clinical diagnosis is much more secure [2]. Any abnormality of the ECG in a breathless patient is supportive evidence for a cardiac cause of dyspnoea. A normal ECG usually suggests another diagnosis [3]. Radiological cardiomegaly is also supportive of a diagnosis of heart failure [4]. This is not the case for more subtle radiological signs, even in the hands of experienced radiological staff [5] where the clinical context can significantly affect the interpretation. Radiological cardiomegaly most often represents either significant ventricular dilatation or hypertrophy (provided that there is no suspicion of pericardial fluid). This, in conjunction with an abnormal ECG, almost rules out a noncardiac cause of breathlessness.

Echocardiography provides definitive diagnosis. Although a lack of quantitative images is a frequent practical problem, this may not be of importance to clinical management [6].

Immediate therapeutic strategies

While there is a lack of controlled clinical trial evidence to support the use of diuretics as initial therapy, effective diuresis and consequent adjustment of the loading conditions of the failing heart is generally regarded as essential [7]. Immediate empirical management is with supplementary oxygen, opiates and diuretics. Vasodilatation appears to be an important effect of intravenous diuretics although clear evidence for this is scant. However, relief of symptoms appears to precede diuresis and natriuresis.

Intravenous nitrate infusion provides balanced arterio-venous dilatation and is widely employed, supported by beneficial central haemodynamic changes in small studies [8], although little is known about its effects on either morbidity or mortality [9]. Intravenous ACE inhibitors also produce beneficial haemodynamic effects [10]. These drugs are not used routinely intravenously due to difficulties with appropriate dosage regimens, unpredictable and protracted hypotensive effects and concerns over an adverse effect on survival in haemodynamically unstable patients in the early stages after myocardial infarction [11]. More recent data suggest that there may yet be a role for intravenous administration of ACE inhibitors in unstable patients [12].

Long-term therapeutic issues

ACE inhibitors It is now clear that patients with either symptomatic or asymptomatic left ventricular dysfunction benefit from ACE inhibitor drugs. Morbidity is reduced with symptomatic improvement, improved exercise duration and improved quality of life indices. Mortality is reduced at all stages of the illness with greater absolute benefit the greater the degree of left ventricular impairment. Treatment is effective regardless of age, gender or aetiology of cardiac impairment. Further coronary events are also reduced in patients with ischaemic cardiomyopathy [13] although the reasons for this are obscure.

Research now focuses on the reasons why ACE inhibitors remain under used in the management of heart failure [14]. They are cost-effective in comparison with other cardiovascular treatments [15] (e.g. lipid lowering in patients with ischaemic heart disease; control of mild hypertension) even when used for treatment of mild (NYHA Grade I/II) heart failure. The reasons why individual patients do not receive an ACE inhibitor need to be clearly defined but may relate to unfounded concerns about side effects. The implications for such patients are a significantly worse prognosis for symptom control, repeated hospitalization and survival.

The degree of neurohormonal suppression by the ACE inhibitor is linked to survival in individual patients [16]. Some patients taking long-term ACE inhibitor therapy still have normal or elevated levels of the key mediator hormones aldosterone and angiotensin II. The reasons for this are unclear. It may be due to the secondary rise in active renin in response to treatment, failure of compliance, the use of short-acting agents (although these are undoubtedly better than placebo) or to alternative control pathways for generating angiotensin II (the tissue chymase system) and aldosterone (K⁺ or ACTH).

Despite 20 years of study the minimum effective dose of an ACE inhibitor to treat heart failure remains unknown [17]. It is possible that the symptomatic and mortality benefits occur at different doses and are achieved through a combination of haemodynamic, hormonal or structural effects on the heart and/or the kidneys. One large but short-duration study of enalapril (NETWORK) [18] has suggested that high dosages may be unnecessary to reduce mortality. The results of a larger study with lisinopril (ATLAS) [19] suggest high doses may provide additional benefits.

The need for long-term loop diuretic treatment in stable patients taking an ACE inhibitor is unclear and has received little attention. Few studies address the effects of ACE inhibition alone compared with those of an ACE inhibitor plus diuretic, either in the short or long-term. Patients treated with and without a loop diuretic after myocardial infarction in the SAVE study appeared to benefit from captopril [20]. Those requiring a loop diuretic might have more significant impairment of left ventricular systolic function but this is by no means always the case. Although the left ventricular ejection fraction is an accurate predictor of mortality, it is poorly correlated with exercise capacity. Discontinuation of frusemide in patients with stable heart failure appears to be feasible in a minority of patients, usually those with lesser degrees of impairment of left ventricular function [21]. In practice this is rarely attempted and chronic diuretic therapy is usual for patients who have had one episode of overt heart failure requiring hospital admission.

Newer agents to suppress the renin angiotensin aldosterone system

Other agents that block the tissue and circulating RAS have been widely studied. Inhibitors of renin have been available for many years but there are few published data from controlled trials [22]. Low oral bioavailability has seriously compromised the value of this drug class although they are undoubtedly active biochemically and haemodynamically after intravenous administration [23].

More promising are the selective orally active nonpeptide antagonists of the angiotensin II AT₁ receptor (ARAs) of which there are now several [24]. Haemodynamic activity is predictable and all produce prolonged hormone suppression. These drugs have a significant advantage for some patients, since they do not produce the dry cough which results from potentiation of kinins during treatment with an ACE inhibitor [25].

A recent trial has shown a useful improvement in short-term survival with the AT₁ ARA losartan compared with thrice daily captopril in elderly patients with grade II/III heart failure [26]. This study was designed to examine the safety of losartan with respect to renal function. The reasons for reduced mortality in the group receiving losartan are unclear. The large body of experimental work suggesting that potentiation of the effects of kinins by ACE inhibitors has an important adjuvant role in the therapeutic effects of ACE inhibitors in heart failure [27] now appears to be in doubt. Before the use of ARAs can be recommended in preference to ACE inhibitors for the management of heart failure, this result must be confirmed in outcome trials. At present, ARAs are a useful alternative for patients intolerant of ACE inhibitors.

Other therapeutic options in systolic heart failure

Combination high dose oral nitrate and hydralazine therapy was shown in the mid 1980s to be effective in relieving symptoms of heart failure [28] although the impact on survival was less than that achieved by an ACE inhibitor [29]. The efficacy of nitrates or hydralazine alone has not been tested. The combination should be considered when an ACE inhibitor is contraindicated, e.g. in bilateral reno-vascular stenosis. The main limitation to this therapy is intolerable vasodilator side-effects in a substantial proportion of patients. Nitrate tolerance must be avoided by ensuring an 8 h wash-out phase overnight.

Management and course of the illustrative case

The patient was symptomatically improved by initial intravenous diuretics and supplemental oxygen correction of the fluid imbalance (1.5 l fluid restriction; oral coamilofruse twice daily) resulted in a weight loss of 4.5 kg over 5 days. Although supine blood pressure remained low (≈100 mmHg), an ACE inhibitor (perindopril 2 mg daily) was introduced without difficulty and she experienced no postural symptoms. Renal function improved in response to the changes in therapy. No other therapy was required long-term and diuretic dose was subsequently reduced to coamilofruse one daily). While remaining functionally limited at discharge, she was able to live independently. Having remained well during out-patient review and with no further cardiac admissions, she died suddenly at home some 18 months after presentation.

Optimization of therapy in established cardiac failure

Case history

A 53-year-old man who had sustained previous inferior and anterior myocardial infarctions presented with gradually increasing fatigue and oedema despite increasing diuretic therapy. He was being treated with frusemide 80 mg three times daily, captopril 50 mg three times daily, aspirin 150 mg once daily, isosorbide mononitrate SR 60 mg once daily and amlodipine 10 mg once daily.

On examination he had dependent oedema to the mid thigh and basal fine crepitations. He had a resting tachycardia of 105 beats min⁻¹ in sinus rhythm. Mitral and tricuspid regurgitation were evident and the supine blood pressure was low at 95/48 mmHg. Laboratory investigation revealed a reduced serum sodium (125 mmol l⁻¹) with impaired renal function (urea 12.8 mmol l⁻¹; creatinine 189 μmol l⁻¹). The chest radiograph showed minimal interstitial oedema, a right sided pleural effusion and marked cardiomegaly. A 24-h ECG shows repetitive but nonsustained ventricular tachycardia (4 episodes of 10–20 beats with rate >150 beats min⁻¹) and multifocal ventricular ectopy (>15 000 aberrant beats/24 h). Repeat echocardiography revealed poor left ventricular contractility with global impairment, marked dilatation (LVEDD 750 mm) and functional mitral regurgitation. Radionuclide scintigraphy indicated a left ventricular ejection fraction of 11%.

Comments

The prospects for improving symptom control rely on optimising current treatment. Multiple drug therapy involves the risk of patient confusion over the medicines and a failure of compliance. This is a neglected area in the care of patients with heart failure [30] yet well known to be associated with poor clinical outcome in cardiac patients [31]. Most decompensated patients require hospital admission for assessment and observation although community based care is increasingly being studied to reduce costs (see below).

Isolated dependent oedema may be drug-related. Although amlodipine does not appear to cause deterioration in heart failure [32] unlike some calcium antagonists [33], marked oedema can occur in some patients. Unless active myocardial ischaemia is present and there are no other management options, withdrawal should be considered.

Diuretic resistance and optimising diuretic therapy

Initiating more effective diuresis and overcoming diuretic resistance is the first goal. Increasing the dosage or frequency of dosing with an oral loop diuretic has limited value for diuretic resistance. Improved efficacy can be achieved by a variety of means [34]. Oral combination diuretic therapy with the addition of a thiazide drug such as bendrofluazide is one option. Although metolazone is often used, it offers no greater benefit and may cause a greater incidence of adverse effects [35]. The combination of a loop diuretic with a potassium sparing diuretic is another possibility. If the patient is taking an ACE inhibitor, such an approach is not generally advised but can be used with success given careful control (see below). Combination diuretic treatment requires close monitoring. Once a diuresis is established, it may be possible to stop the additional drug. Long-term combination therapy has not been shown to be beneficial and the risks of electrolyte depletion and induction of dysrhythmia (although this remains controversial) raises concerns. If a combination of diuretics is continued, regular biochemical monitoring is desirable.

Another method to overcome resistance to loop diuretic therapy is intravenous administration either by bolus dosing or by continuous infusion [36]. The latter is particularly effective as it delivers a constant efficient concentration of frusemide at the tubular lumen. Careful monitoring of renal function and the extent of the diuresis are desirable.

Diuresis can also be enhanced by the addition of low-dose dopamine infusion to facilitate renal vasodilatation [37]. This may be used in combination with intravenous or oral loop diuretic. Oral dopamine agonist drugs have not been demonstrated to be useful [38].

Improving neurohormonal blockade of aldosterone and angiotensin II

Failure to suppress plasma angiotensin II and/or aldosterone concentrations may be associated with an adverse outcome in heart failure [39]. Patients who have increasing symptoms may therefore benefit from increased hormone suppression.

The short-acting agent captopril provides incomplete hormone suppression over 24 h unless used in multiple daily doses. Nevertheless, it is widely used in heart failure. The case for using a longer-acting ACE inhibitor in preference is poorly documented. Comparative studies of long and short-acting ACE inhibitors are few and do not address improvement in symptoms or mortality. Short-acting drugs are sometimes used on the pretext of a lower risk of producing significant biochemical renal dysfunction [40]. However, adverse renal effects induced by the combination of loop diuretic and ACE inhibitor are generally predictable, minor and are probably unrelated to the duration of action of the ACE inhibitor selected [41]. Increased dosage or increased dose frequency of the ACE inhibitor might be useful for some patients, although the optimal dose of ACE inhibitor remains uncertain.

Due to the strength of the evidence suggesting that neurohormonal activation in heart failure is integral both to the progression of symptoms and pathology [42] the combination of ACE inhibitor and ARA is being examined as an option. By blocking the negative feedback loop promoting renin release following treatment with an ACE inhibitor and in addition by providing receptor blockade, levels of bioactive angiotensin II are markedly reduced [43]. This strategy is currently under investigation using enalapril and valsartan in a multicentre outcome study (ValHeFT).

As aldosterone has control systems independent of the renin-angiotensin axis and since it may be independently detrimental in heart failure, the use of additional aldosterone blockade may have a role. Spironolactone has a variety of beneficial effects on surrogate markers of prognosis in heart failure [44]. Whether this can be translated to an improved outcome will be demonstrated by the multicentre RALES study [45]. Preliminary reports of this study suggest that mortality is significantly reduced by this combination. The combination of loop diuretic, ACE inhibitor and spironolactone increases the risk of renal dysfunction and significant electrolyte imbalance, particularly potassium retention. In small trials it is not possible to assess the frequency of such potential adverse events in routine clinical practice, since treatment and biochemical changes are closely monitored.

Additional therapies

Digoxin The role of digoxin in patients with heart failure already treated with an ACE inhibitor and diuretics and who are in sinus rhythm has been a matter of controversy for many years. However, digoxin withdrawal was demonstrated to be detrimental in the PROVED trial [46]. Recent studies have confirmed that there is no adverse effect on mortality in heart failure [47] when digoxin is added to patients on diuretics and ACE inhibitors. However, there were useful reductions in recurrent hospitalization after the addition of digoxin. Digoxin should be considered in patients with persistent symptoms despite optimal dosage of a diuretic and an ACE inhibitor. Care should be exercised when there is impairment of renal function and/or suspicion of impaired AV conduction or sinus node disease, in view of the effects of digoxin on cardiac conduction.

β-adrenoceptor blockade

More recently considerable interest has arisen in the use of β-adrenoceptor blockade in heart failure. Importantly these studies have been conducted in patients who were already receiving an ACE inhibitor and diuretic. The combination of data from several studies using carvedilol, a non selective β-adrenoceptor antagonist with additional α₁-adrenoceptor blocking effects, show its efficacy in unselected patients with heart failure. Carvedilol improves survival in patients already receiving an ACE inhibitor and diuretic [48]. Worsening heart failure was not more frequent in the β-adrenoceptor blocker treated patients and benefits only emerge over weeks, with a vaguely defined period of increased symptoms during the early phase of treatment. Cardioselective (β₁)-adrenoceptor blockade has been studied for some years in the management of idiopathic dilated cardiomyopathy. Recently preliminary data from a multicentre trial of bisoprolol in unselected heart failure have shown unequivocal evidence of further reductions in mortality. Although the overall mortality reductions appear small, significant reductions in symptomatic decompensation were evident [49]. A retrospective (though nonrandomised) analysis of the SAVE study database [50] suggested that in patients with asymptomatic left ventricular dysfunction after myocardial infarction there is a 30% reduction in cardiovascular death and a 21% reduction in the development of heart failure with the addition of anyβ-adrenoceptor blocker to captopril.

Small scale studies suggest greater improvements in central haemodynamics and a more significant impact on cardiac adrenergic tone with carvedilol in comparison with metoprolol [51]. Overall the impact of β-adrenoceptor blockade on exercise capacity is variable, positive in some studies but negative or insubstantial in others dependent on the method of testing [52].

If β-adrenoceptor blockade is to be widely accepted as a treatment for heart failure, significant practical issues remain to be addressed. There is no clear definition of those patients who stand to benefit most. The treatment appears to be well tolerated in small studies (7–8% intolerance for cardioselective and/or vasodilating β-adrenoceptor blockers; [53]) but many patients in routine clinical practice will have occult peripheral vascular disease or airways obstruction related to smoking which may complicate the use of these drugs.

The best methods for initiation of treatment is uncertain. Large doses of a β-adrenoceptor bocker can induce hypotension, bradycardia and shock due to the withdrawal of myocardial adrenergic support. As the benefits of β-adrenoceptor blockade appear to emerge gradually during chronic therapy [54] slow dosage titration is desirable. In most instances weekly medical reviews including daily weight records and regular blood pressure and renal function assessment are recommended for safe treatment [53]. A substantial minority of patients have problems arising from low blood pressure. As with the ACE inhibitors the optimal dose of β-adrenoceptor blockers is unknown and titration to the ‘maximum tolerated’ dose is currently recommended.

The mechanism of action of β-adrenoceptor blockers in heart failure is unclear. As many patients have overt or covert coronary disease they may simply reduce the impact of ischaemia in otherwise stable cardiac failure. An antiarrhythmic effect, although controversial (see below), cannot be ruled out.

Balanced vasodilator therapy

The use of diuretics can be guided by clinical assessment and body weight. For other treatments, the use of invasive pressure measurements can be valuable. Optimal use of vasodilator/vasoconstrictor agents and inotropic drugs in conjunction with diuretics can sometimes be guided by readings from a central haemodynamic monitoring catheter. This is particularly helpful for patients who have uncontrolled breathlessness and oedema or as a prelude to cardiac transplantation [55]. This approach can be effective in restoring a compensated state to an otherwise decompensated and deteriorating patient. Most patients who develop major haemodynamic and symptomatic decline despite an ACE inhibitor and effective diuresis are in an almost intractable position. Intensive intravenous therapy, more commonly employed in North America and in younger patients, is not widely used in Europe. Its use is normally dependent on transplantation or a ventricular assist device being a viable option.

Anti-arrhythmic therapy

Control of dysrhythmia in heart failure remains a major concern. Many patients die suddenly, usually attributed to some form of dysrhythmia (both tachydysrhythmias and bradydysrhythmias are common). The numbers who die in this way may be increasing with the increasing use of therapies that reduce uncontrolled pump failure as the mode of death.

The use of antiarrhythmic therapy in left ventricular dysfunction is restricted following the results from the CAST studies which demonstrated increased mortality with some treatments in patients with coexistent left ventricular (LV) dysfunction [56]. A particular concern reflects the use of potent drugs with the potential for pro-arrhythmic effects in patients who had minimal levels of electrical instability. Amiodarone appears to be an exception. Although results from four major trials have not shown consistent improvement in survival in established LV dysfunction [57, 58], amiodarone is the best available drug for overt dysrhythmia in the face of impaired LV function. In general it can be used without preliminary electrophysiological testing [59].

Nonsustained ventricular tachycardia (VT) is common in symptomatic heart failure and is an independent marker of increased risk of sudden death in severe heart failure [60]. Whether amiodarone should be prescribed in all patients with heart failure who have non sustained and asymptomatic VT is not yet clear.

The role of drug therapy in comparison with electrical devices allowing sophisticated pacing detection and including the implantable cardioverter/defibrillator remains an important area for study [61]. At present these devices are generally restricted to patients with documented syncopal dysrhythmia or resuscitated arrest. Patients who survive arrhythmogenic cardiac arrest generally have significant pre-existent heart failure and structurally abnormal hearts. In Europe the application of such technology remains relatively limited and adequate trials comparing this therapy with drug treatments, although underway, are not yet available for guidance. These devices may play a significant role in heart failure in the management of selected patients.

Pulsed inotropic therapy and inotropic-vasodilator drugs

The use of inotropic agents in heart failure has encountered many problems. In the 1980s and early 1990s many agents were developed with effects on the heart and vascular tree combining a central inotropic stimulus with peripheral arterial vasodilatation. These have been uniformly unsuccessful during chronic dosing and often result in increased mortality [62–64] (e.g. flosequinan; ibopamine) As a result, the development of new drugs in this class has been all but halted. The major problems have been selection of appropriate patients and the narrow therapeutic index for such treatments. However, these drugs may have a role in the short term to relieve symptoms without the increase in mortality that occurs during protracted use [65].

In a different approach to inotropic therapy, Adamopoulos and colleagues employed intermittent dobutamine infusion in 20 patients with severe heart failure in an attempt to up-regulate myocardial β₁-adrenoceptors [66]. In the short term, there were no clinical complications of treatment, but also no increase in diuresis. Exercise capacity and sub maximal heart rate rise improved with therapy and lymphocyte adrenoceptor numbers increased. This result is in contrast to the adverse effects of chronic inotropic therapy [64]. A fine balance may have be struck to improve adrenoreceptor responsiveness but to avoid excessive stimulation or adrenoceptor down-regulation.

Multidisciplinary care and hospitalization

Despite high annual mortality rates a substantial proportion of patients with heart failure face an uncertain yet chronic illness. Many patients are elderly and need repeated hospital admission. These admissions are both psychologically and financially taxing. In common with many chronic diseases, management of these patients can be improved by contact with many varied health professionals concerned not only with cardiac care but social circumstances; promotion of drug compliance and psychological support [67, 68]. Non-pharmacological approaches such as increased exercise and training within limits has important and demonstrable physical [69] as well as psychological effects [70]. There are few instances where a supervised increase in physical exercise is not of benefit to the patient with heart failure.

Surgical management

Surgical treatment need not be considered as a final line of therapy. Increasingly important is the application of surgical revascularization for occult or overt ischaemia in patients with heart failure. This is often the best way to improve contractility although the operative management may be complicated and associated with increased perioperative mortality. Less well demonstrated are the benefits of scar reduction; cardiomyoplasty or the most recent and most dramatic innovation of ventricular reduction/ventriculotomy. As yet these procedures are limited in their application to a few selected patients and with generally no agreed role.

Cardiac transplantation is a proven therapy but restricted by organ availability and delay prior to intervention. Assessment is usually based on the severity of cardiac impairment on objective testing during treatment with maximal therapies. It is increasingly recognized that many patients with very poor left ventricular function can survive for many years without transplant. Functional exercise capacity is seen as the main delineator of those patients who should be entered onto an urgent transplantation waiting list or those who can safely remain on drug therapy [71, 72]. The long-term problems of rejection and accelerated atherosclerosis and their effects on survival after transplantation will not be considered here. The outlook for the transplanted patient is dramatically better than those who await transplantation.

Management and course of the illustrative case

Following emergency admission, initiation of diuresis required bolus doses of intravenous frusemide combined with continuous intravenous infusion of dopamine and fluid and sodium restriction. Although he was considered a good candidate for invasive pulmonary pressure monitoring, this proved unnecessary. Following temporary withdrawal of captopril during stabilisation of renal function and diuresis, an ACE inhibitor was subsequently reintroduced without difficulty (lisinopril 10 mg daily). Renal function improved and blood pressure stabilised. Following discharge he remained symptomatic. Oral digoxin was introduced with only modest benefit. Repeat outpatient ambulatory ECG recording confirmed persistent episodes of non-sustained ventricular tachycardia. He was treated with prophylactic oral amiodarone despite his lack of symptoms. Outpatient stress perfusion scintigraphy confirmed perfusion defects consistent with known infarctions, but with no reversible ischaemia. Maximal cardiopulmonary exercise testing confirmed severe functional incapacity and very poor maximal oxygen consumption at peak exertion (13 ml kg⁻¹ min⁻¹). He was therefore referred for consideration of orthotopic cardiac transplantation.

Key therapeutic points

Case 1 Acute stabilization and chronic management of systolic failure

• Establishing aetiology must be part of diagnosis but does not importantly affect therapeutic strategies

• Diuretic therapy is a key element although formally untested in symptomatic patients. Diuretics were given to nearly all the patients in trials assessing the efficacy of ACE inhibitors.

• ACE inhibition must be considered in all patients and failure to provide this treatment requires clear justification. Morbidity and mortality benefits are unequivocal and generally greater the more significant the impairment of LV function. Minor or relative contraindications to use (e.g. asymptomatic hypotension; minor pretreatment renal impairment) should be weighed against the significant consequences of failure to treat.

• Angiotensin receptor antagonists may be an effective substitute for patients unable to tolerate an ACE inhibitor.

Case 2 Optimization of therapy in established heart failure

• In-hospital stabilization is usually necessary if the patient is already taking diuretics and an ACE inhibitor.

• Optimising diuretic therapy may involve:

• high doses

• intravenous treatment

• combination therapy

• and/or haemodynamic (Swan Ganz catheter) monitoring

• Consider adjuvant digoxin for symptom control even in sinus rhythm

• Consider adjuvant β-adrenoceptor blockade

• dose titration may be protracted and complex

• the effects of selection bias (patient tolerance to treatment) on clinical trial results is unclear and may be important when considering treatment in routine practice

• Pulsed inotropic therapy or balanced vasodilator/inotropic therapy may be useful in selected patients

• Surgical revascularization or myocardial reconstruction may be feasible and useful options but are unproven in formal clinical trials

• Transplantation is effective when available but ‘survivors’ live to receive transplants