This is a middle-aged man with diabetes and an ischemic cardiomyopathy who presents with New York Heart Association (NYHA) functional class III heart failure. There is clinical and laboratory evidence of left ventricular systolic dysfunction, and “bedside” hemodynamic assessment reveals volume overload without evidence of decreased systemic perfusion. In addition, his echocardiogram shows findings consistent with left ventricular remodeling without intracavitary thrombus formation. He has been compliant with his medications and fluid and salt restriction, and does not drink alcohol. His blood sugars have been well controlled, and he has had no recent infection. A complete blood count and thyroid function tests should be checked to rule out anemia and hyperthyroidism, respectively. One possible precipitating factor in this case is his use of a thiazolidinedione for glucose control, a class of medications that has been shown to worsen heart failure symptoms and may increase the risk of cardiovascular events.^1,2 The patient should be switched to an alternative antidiabetic medication, such as a sulfonylurea or insulin. Metformin is relatively contraindicated in patients with heart failure and renal dysfunction due to a small risk of lactic acidosis.

After identifying and addressing a precipitating factor, it is reasonable to consider treatment of the underlying cause of heart failure.³ The patient is a diabetic status post myocardial infarction several years ago and may have developed recurrent ischemia, either silent or with dyspnea as an anginal equivalent. An exercise study with imaging should be performed to rule out reversible ischemia. If this is negative, an assessment of myocardial viability with low-dose dobutamine stress echocardiography, resting thallium scintigraphy or positron emission tomography should be considered.⁴ Several studies have shown that patients with ischemic cardiomyopathy and viable myocardium have significant improvement in left ventricular function following surgical revascularization. However, in the absence of angina or inducible ischemia, the superiority of surgery over medical therapy in prolonging survival in patients with ischemic cardiomyopathy remains unproven.

Sleep-disordered breathing is a common co-morbidity in heart failure. As many as 30–30% of heart failure patients may have obstructive or central sleep apnea, or both.⁵ Frequent apneic episodes lead to sympathetic activation, hypertension and diastolic dysfunction, which may worsen heart failure symptoms. The most extreme form of central sleep apnea, Cheyne-Stokes periodic breathing, is present in more severe forms of heart failure. Routine screening for sleep apnea should be performed in all heart failure patients by asking the patient and spouse about snoring, nocturnal apneic episodes, and daytime somnolence.⁶ The cornerstone of sleep apnea therapy is positive airway pressure, often with supplemental oxygen. Positive pressure therapy has been shown to improve ejection fraction and six-minute walk distance, but not survival.⁷ Prospective studies are needed to evaluate the impact of sleep apnea on heart failure outcomes, including sudden death.

The overall goals in the management of heart failure are to eliminate symptoms, improve quality of life, and prolong survival. Non-pharmacologic management of heart failure should be reviewed with the patient and family. The importance of salt and fluid restriction and daily weight monitoring should be reinforced, and alcohol moderation or cessation should be advised. Once euvolemia has been achieved, a submaximal aerobic exercise program (e.g. walking, stationary bicycle) should be encouraged. Exercise training may result in improvement in symptoms and functional capacity, enhanced blood flow and skeletal muscle metabolism, and reduced heart failure hospitaliza-tions.^8,9 In a National Institutes of Healtlvsponsored trial (HF4ACTION), exercise training had no significant effect on survival in heart failure.¹⁰

Pharmacologic therapy should be optimized according to consensus guidelines.^11–11 The patient is currently taking captopril, an angiotensin-converting enzyme (ACE) inhibitor, at a relatively low dose. Several large prospective randomized controlled trials have demonstrated the beneficial effects of ACE inhibitors on exercise tolerance, salt and water balance, symptoms, neurohormonal activation, quality of life and survival in patients with chronic heart failure.¹⁴ As demonstrated in SAVE, captopril reduces the risk of recurrent myocardial infarction and stroke in patients with post-MI left ventricular dysfunction.¹⁵ In this patient with mild diabetic nephropathy, ACE inhibitor or angiotensin-II receptor blocker (ARB) therapy may also slow the progression of renal dysfunction. The optimal dosing of ACE inhibitors remains controversial. One prospective study (ATLAS) demonstrated the modest superiority of high-dose versus low-dose ACE inhibitor therapy in patients with chronic heart failure without increased toxicity.¹⁶ Current guidelines recommend increasing the dose of captopril to 50mg tid as blood pressure and renal function tolerate. For improved medication compliance, a change to once-daily ACE inhibitor dosing may also be considered since these drugs exhibit a class effect. Despite previous concerns that aspirin use may attenuate ACE inhibition, recent studies indicated no adverse effects of combining aspirin and ACE inhibitors.^17,18 Therefore it is reasonable to continue low-dose aspirin for secondary prevention of coronary artery disease.

Treatment of systemic and pulmonary venous congestion warrants more aggressive diuresis. The daily dose of furosemide or other loop diuretic should be increased until the required response is achieved (e.g. absence of jugular venous distension, hepatomegaly and edema). This “dry weight” should be recorded and used as a euvolemic baseline to guide future diuretic therapy, although further weight loss in advanced heart failure may be due to cardiac cachexia.¹⁹ If this strategy is not effective, combination therapy with a thiazide diuretic should be tried. Adequate diuresis will generally result in improved symptoms and may slow the progression of chamber dilation by reducing ventricular filling pressures. However, diuretic therapy may also cause renal dysfunction, electrolyte depletion and neurohormonal activation. It should be emphasized that there have been no randomized controlled trials demonstrating the long-term efficacy and safety of diuretic therapy in patients with heart failure. Furthermore, studies are needed to address the safety and efficacy of diuretic withdrawal in stable heart failure patients.

The patient remains moderately symptomatic despite treatment with an ACE inhibitor and diuretic. What is the next step?

The next step is to initiate beta-adrenergic antagonist therapy. Multiple randomized controlled trials have demonstrated that beta-blockers improve symptoms and cardiac function, and reduce morbidity and mortality in patients with chronic heart failure due to left ventricular systolic dysfunction.^20–20 Consensus guidelines recommend using beta-blockers, in addition to ACE inhibitors and diuretics, in the management of patients with left ventricular systolic dysfunction.¹¹ Once euvolemia has been achieved, beta-blocker therapy with carvedilol, bisoprolol or sustained-release metoprolol can be initiated safely at a low dose and titrated gradually at regular intervals (e.g. every 1–1 weeks). Despite concerns that beta-blockers may increase insulin resistance, reduce insulin secretion or mask hypoglycemia, they have been shown to be safe and effective in treating symptomatic systolic dysfunction in diabetic patients.²⁴ In heart failure patients, carvedilol, a non-selective beta-blocker with alpha₁-blocking properties, has a lower rate of new-onset diabetes and diabetic events when compared to metoprolol.²⁵

Given this patient’s multiple exacerbations of chronic heart failure, complicated by diabetes and renal insufficiency, it would be appropriate to refer him to a comprehensive disease management program in heart failure. Either clinic or home-based disease management programs significantly reduce readmission rates and costs, while improving functional status and quality of life for heart failure patients.^26,27 Such programs promote self-care, emphasize behavioral strategies to increase adherence, increase access to providers, and give early attention to signs and symptoms of fluid overload.²⁸