Management of Chronic Heart Failure

Etiology and Pathogenesis

Coronary artery disease (CAD) is the single most common cause of HF, accounting for 50% of cases. Patients with a previous myocardial infarction (MI) can develop both systolic dysfunction and diastolic impairment due to interstitial fibrosis and scar formation. Hibernating myocardium due to severe CAD can also cause HFrEF, which is potentially reversible with revascularization. Idiopathic cardiomyopathy, hypertension, and valvular heart disease are common causes. Familial cardiomyopathies may account for up to one-third of cardiomyopathies believed to be idiopathic. Other etiologies of dilated cardiomyopathy include thyroid disease, chemotherapy, myocarditis, HIV infection, diabetes, alcohol, cocaine, connective tissue disease, systemic lupus erythematosus, peripartum cardiomyopathy, and arrhythmias. Hypertrophic and restrictive cardiomyopathies are less common. It is crucial to identify the cause of HF because the degree of reversibility, and hence, the progression and management of HF depend on the etiology. Treatment of uncontrolled hypertension, thyroid disease, tachycardia, and active ischemia may result in significant improvement in LV function.

Heart Failure With Reduced Ejection Fraction

HFrEF, also called systolic heart failure, has been variously defined as an EF of <40% to 50%. Most clinical trials include patients with an EF ≤40%; therefore, specific pharmacological therapy is recommended in these patients. The initial insult, most often due to ischemia or increased pressure or volume load, results in a reduction in cardiac output that triggers activation of the renin-angiotensin-aldosterone system (RAAS), which results in salt and water retention. Declining blood pressure activates the sympathetic nervous system and increases endogenous hormones that result in systemic vasoconstriction. The short-term benefit of vasoconstriction—increased perfusion of critical organs—is followed by worsening HF due to chronically increased LV afterload. There is a compensatory increase in the A-type natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which bind to NP receptors and generate diuresis, natriuresis, and myocardial relaxation and antiremodeling. ANP and BNP also inhibit renin and aldosterone secretion. Unfortunately, many of these beneficial peptides and bradykinin are degraded by neprilysin to inactive metabolites. The newest drug approved for treatment of HFrEF, Entresto (sacubitril/valsartan), is a combination of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor.

LV remodeling, a maladaptive response, results in myocyte lengthening with a subsequent increase in chamber volume. Myocyte hypertrophy occurs, along with myocyte loss due to apoptosis or necrosis, and fibroblast proliferation and fibrosis ( Fig. 29.1 ). The heart remodels eccentrically, becoming less elliptical, and more spherical and dilated. The mitral valve annulus often becomes dilated, which results in mitral regurgitation and further increased wall stress resulting in worsening HF.

Heart Failure With Preserved Ejection Fraction

HFpEF, previously referred to as diastolic heart failure, accounts for ≥50% of HF cases, is challenging to diagnose, and is often a diagnosis of exclusion. Several criteria have been proposed, including symptoms and/or signs of HFpEF (EF ≥50%), objective evidence of other underlying cardiac structural and/or functional abnormalities, and elevated BNP/proBNP levels. Patients with an intermediate EF (41%−49%) are often grouped with HFpEF. Ischemic heart disease and hypertension are the most common causes of isolated HFpEF. Compared with HFrEF patients, hospitalizations and deaths in patients with HFpEF are more likely to be noncardiovascular.

Typically, the ventricular size is normal in HFpEF. However, ventricular dilation can occur due to mitral or aortic valve regurgitation, or a high-output state (anemia or thiamine deficiency). Hypertrophic and restrictive cardiomyopathies, and constrictive pericarditis can result in a clinical presentation consistent with HFpEF. HFpEF is generally characterized by a normal end-diastolic volume, myocyte hypertrophy, and increased wall thickness that results in concentric remodeling compared with the increased end-diastolic volume and eccentric remodeling seen in HFrEF ( Fig. 29.2 ). There is an increased extracellular matrix, abnormal calcium handling, and neurohormonal activation. These pathophysiological changes result in impaired ventricular relaxation, high LV diastolic pressure, high left atrial filling pressures, and resulting HF symptoms and signs.

Clinical Presentation

Signs of HF include pulmonary congestion, edema, or inadequate organ perfusion. Symptoms include dyspnea on exertion, exercise intolerance, orthopnea, paroxysmal nocturnal dyspnea, cough, chest pain that may or may not represent angina, weakness, fatigue, edema, nocturia, insomnia, depression, and weight gain. Patients with end-stage disease may also complain of nausea, abdominal pain, oliguria, confusion, and weight loss. Physical examination should include assessment of jugular venous pressure, rales, wheezing, pleural effusion, displaced point of maximal intensity, right ventricular heave, increased intensity of P ₂ , S ₃ , and S ₄ , murmurs, hepatomegaly, hepatojugular reflux, low-volume pulses, and peripheral edema. Patients with end-stage disease may also exhibit pulsus alternans, tachycardia, ascites, cool, pale extremities, and cachexia.

The clinical presentation of HFrEF and HFpEF may be indistinguishable ( Fig. 29.3 ). The cardiac silhouette may be enlarged in both, with cardiomegaly due to ventricular dilation in HFrEF and from hypertrophy in HFpEF. An assessment of LV function is essential for determining the optimal approach to treatment.

Diagnostic Approach

The diagnosis is made by taking a careful history, performing a directed examination, assessing cardiac structure and function, and laboratory evaluation. Transthoracic echocardiography (TTE) is the method of choice for cardiac examination. Information on chamber volumes, systolic and diastolic function, wall thickness, valve function, and pulmonary hypertension is readily determined. Measurement of natriuretic peptides, which correlate with elevated filling pressures, is a useful initial diagnostic test. Although an elevated BNP and/or proBNP level does not rule out pulmonary causes of dyspnea, normal levels argue against HF as the predominant cause. Although levels are generally higher in HFrEF, these tests cannot distinguish between HFrEF and HFpEF. Other conditions can cause elevated levels, including pulmonary hypertension, cor pulmonale, pulmonary embolism, critical illness, and renal dysfunction; obese patients may have normal levels. Initial laboratory evaluation should also include electrolytes, estimated glomerular filtration rate, hemoglobin, white blood cell count, glucose, glycosylated hemoglobin, lipids, albumin, liver function tests, urinalysis, thyroid-stimulating hormone, ferritin, and serum transferrin. Additional diagnostic tests should be considered when there is a clinical suspicion of a particular pathology, including genetic testing. Laboratory results, together with ECG, cardiac x-ray, and pulmonary function testing, will eliminate most noncardiac diagnoses.

Cardiac MRI is the best alternative cardiac imaging modality for patients with a nondiagnostic TTE and is the method of choice in patients with complex congenital heart disease. MRI provides an accurate assessment of size, mass, and function of both ventricles. It can be useful in clarifying myocardial viability and identifying infiltrative disease. Its usefulness is enhanced by gadolinium contrast, but this should not be used in patients with moderate to severe kidney disease. The presence of pacemakers and defibrillators is typically a contraindication for MRI, although new devices and protocols are in development.

Ischemic heart disease should be evaluated in every patient, because revascularization of a hibernating myocardium can result in significant improvement in systolic function. Focal wall motion abnormalities most commonly indicate CAD, but not always. Global LV dysfunction does not rule out an ischemic etiology. Testing options include cardiac catheterization and exercise or pharmacological echocardiographic or nuclear stress testing, CT angiography, MRI, and PET. Patients with left bundle branch block should not be evaluated with stress echocardiography because the conduction delay can result in a false-positive result.

Determining New York Heart Association (NYHA) classification is important for prognosis, as an indication for medical therapies and device placement, and as an evaluation of response to treatment.

Management and Therapy

It is critical to identify the cause and type of HF to determine the specific treatment and specific pharmacological therapy that will result in the best outcome. Next, it is important to correct precipitating factors, including ischemia, dietary nonadherence, uncontrolled hypertension, atrial fibrillation (AF), hypoxemia, thyroid disease, anemia, and medication nonadherence. An algorithm for management of symptomatic HFrEF is presented ( Fig. 29.4 ).

Revascularization should be considered in ischemic patients, even with marked systolic dysfunction. The National Institutes of Health–sponsored STICH (Surgical Treatment for Ischemic Heart Failure) trial randomized patients with significant CAD (left anterior descending or multivessel disease) disease and EF ≤35% to coronary artery bypass grafting plus optimal medical therapy (OMT) versus OMT alone. Revascularization + OMT resulted in a significant decrease in death or cardiovascular hospitalization. Although there was no total mortality benefit at 5 years, the extension STICHES study found that coronary artery bypass grafting plus OMT significantly reduced mortality at 10 years. All patients with CAD should be treated with aspirin unless there is a contraindication. Patients who have had percutaneous intervention should also receive a P2Y12 inhibitor. We recommend a statin in ischemic patients. One of two trials reported a reduction in hospitalization in ischemic patients. The effect of withdrawal of a statin is unknown. There are no data to support statin therapy in nonischemic patients.