Heart Failure

Introduction

Heart failure (HF) is a progressive clinical syndrome caused by inability of the heart to pump sufficient blood to meet the body’s metabolic needs. HF can result from any disorder that reduces ventricular filling (diastolic dysfunction) and/or myocardial contractility (systolic dysfunction).

CLINICAL PRESENTATION

• Patient presentation may range from asymptomatic to cardiogenic shock.
• Primary symptoms are dyspnea (particularly on exertion) and fatigue, which lead to exercise intolerance. Other pulmonary symptoms include orthopnea, paroxysmal nocturnal dyspnea, tachypnea, and cough.
• Fluid overload can result in pulmonary congestion and peripheral edema.
• Nonspecific symptoms may include fatigue, nocturia, hemoptysis, abdominal pain, anorexia, nausea, bloating, ascites, poor appetite, mental status changes, and weight gain.
• Physical examination findings may include pulmonary crackles, S3 gallop, cool extremities, Cheyne–Stokes respiration, tachycardia, narrow pulse pressure, cardiomegaly, symptoms of pulmonary edema (extreme breathlessness and anxiety, sometimes with coughing and pink, frothy sputum), peripheral edema, jugular venous distention, hepatojugular reflux, and hepatomegaly.

DIAGNOSIS

• Consider diagnosis of HF in patients with characteristic signs and symptoms. A complete history and physical examination with appropriate laboratory testing are essential in evaluating patients with suspected HF.
• Laboratory tests for identifying disorders that may cause or worsen HF include complete blood cell count; serum electrolytes (including calcium and magnesium); renal, hepatic, and thyroid function tests; urinalysis; lipid profile; and A1C. B-type natriuretic peptide (BNP) will generally be greater than 100 pg/mL.
• Ventricular hypertrophy can be demonstrated on chest radiograph or electrocardiogram (ECG). Chest radiograph may also show pleural effusions or pulmonary edema.
• Echocardiogram can identify abnormalities of the pericardium, myocardium, or heart valves and quantify left ventricular ejection fraction (LVEF) to determine if systolic or diastolic dysfunction is present.
• The New York Heart Association Functional Classification System is intended primarily to classify symptomatic HF patients according to the physician’s subjective evaluation. Functional class (FC)-I patients have no limitation of physical activity, FC-II patients have slight limitation, FC-III patients have marked limitation, and FC-IV patients are unable to carry on physical activity without discomfort.
• The American College of Cardiology/American Heart Association (ACC/AHA) staging system provides a more comprehensive framework for evaluating, preventing, and treating HF.

TREATMENT OF CHRONIC HEART FAILURE

Goals of Treatment: Improve quality of life, relieve or reduce symptoms, prevent or minimize hospitalizations, slow disease progression, and prolong survival.

PHARMACOLOGIC THERAPY

Diuretics:

Furosemide: Usual daily dose (oral) 20–160 mg/day

Bumetanide: 0.5–4 mg/day

Torsemide: 10–80 mg/day

ACEIs

Captopril (Capoten) 6.25 mg three times daily, Target dose 50 mg three times daily OR

Lisinopril (Zestril) initial dose 2.5–5 mg daily, target dose 20–40 mg daily

Ramipril (Altace) Initial dose1.25–2.5 mg twice daily, target dose 5 mg twice daily

β-Blockers

✓ Carvedilol, 3.125 mg twice daily initially; target dose 25 mg twice daily (the target dose for patients weighing >85 kg [187 lb] is 50 mg twice daily).

✓ Carvedilol CR (Carveda), 10 mg once daily initially; target dose 80 mg once daily. This product should be considered in patients with difficulty maintaining adherence to the immediate-release carvedilol formulation.

✓Metoprolol succinate CR/XL (Merol), 12.5 to 25 mg once daily initially; target dose 200 mg once daily.

✓ Bisoprolol, (Concor)1.25 mg once daily initially; target dose 10 mg once daily

TREATMENT OF ACUTE DECOMPENSATED HEART FAILURE

• Goals of Treatment: Relieve congestive symptoms, optimize volume status, treat symptoms of low cardiac output, and minimize risks of drug therapy so the patient can be discharged in a compensated state on oral drug therapy.

Diuretics

• IV loop diuretics, including furosemide, bumetanide, and torsemide, are used for ADHF, with furosemide being the most widely studied and used agent.
• Bolus diuretic administration decreases preload by functional venodilation within 5 to 15 minutes and later (>20 min) via sodium and water excretion, thereby improving pulmonary congestion. However, acute reductions in venous return may severely compromise effective preload in patients with significant diastolic dysfunction or intravascular depletion
• Because diuretics can cause excessive preload reduction, they must be used judiciously to obtain the desired improvement in congestive symptoms while avoiding a reduction in cardiac output, symptomatic hypotension, or worsening renal function.
• Diuretic resistance may be overcome by administering larger IV bolus doses or continuous IV infusions of loop diuretics. Diuresis may also be improved by adding a second diuretic with a different mechanism of action (e.g., combining a loop diuretic with a distal tubule blocker such as metolazone or hydrochlorothiazide). The loop diuretic–thiazide combination should generally be reserved for inpatients who can be monitored closely for the development of severe sodium, potassium, and volume depletion. Very low doses of the thiazide-type diuretic should be used in the outpatient setting to avoid serious adverse events.

Positive Inotropic Agents

Dobutamine

• Dobutamine is a β1 - and β2 -receptor agonist with some α1 -agonist effects. The net vascular effect is usually vasodilation. It has a potent inotropic effect without producing a significant change in heart rate. Initial doses of 2.5 to 5 mcg/kg/min can be increased progressively to 20 mcg/kg/min on the basis of clinical and hemodynamic responses.
• Dobutamine increases cardiac index because of inotropic stimulation, arterial vasodilation, and a variable increase in heart rate. It causes relatively little change in mean arterial pressure compared with the more consistent increases observed with dopamine.
• Although concern over attenuation of dobutamine’s hemodynamic effects with prolonged administration has been raised, some effect is likely retained. Consequently, the dobutamine dose should be tapered rather than abruptly discontinued.

Milrinone

• Milrinone inhibits phosphodiesterase III and produces positive inotropic and arterial and venous vasodilating effects (an inodilator). It has supplanted use of amrinone, which has a higher rate of thrombocytopenia.
• The usual loading dose of milrinone is 50 mcg/kg over 10 minutes. If rapid hemodynamic changes are unnecessary, eliminate the loading dose because of the risk of hypotension. Most patients are simply started on the maintenance continuous infusion of 0.1 to 0.3 mcg/kg/min (up to 0.75 mcg/kg/min).

Dopamine

• Dopamine should generally be avoided in ADHF, but its pharmacologic actions may be preferable to dobutamine or milrinone in patients with marked systemic hypotension or cardiogenic shock in the face of elevated ventricular filling pressures, where dopamine in doses greater than 5 mcg/kg/min may be necessary to raise central aortic pressure.
• Dopamine produces dose-dependent hemodynamic effects because of its relative affinity for α1 -, β1 -, β2 -, and D1 - (vascular dopaminergic) receptors. Positive inotropic effects mediated primarily by β1 -receptors become more prominent with doses of 2 to 5 mcg/kg/min. At doses between 5 and 10 mcg/kg/min, chronotropic and α1 -mediated vasoconstricting effects become more prominent.

Vasodilators

• Arterial vasodilators reduce afterload and cause a reflex increase in cardiac output. Venodilators reduce preload by increasing venous capacitance, improving symptoms of pulmonary congestion in patients with high cardiac filling pressures. Mixed vasodilators act on both arterial resistance and venous capacitance vessels, reducing congestive symptoms while increasing cardiac output.

Nitroprusside

Nitroprusside has a rapid onset and a duration of action less than 10 minutes, which necessitates use of continuous IV infusions. Initiated therapy with a low dose (0.1–0.2 mcg/kg/min) to avoid excessive hypotension, and increase by small increments (0.1–0.2 mcg/kg/min) every 5 to 10 minutes as needed and tolerated. Usual effective doses range from 0.5 to 3 mcg/kg/min. Taper nitroprusside slowly when stopping therapy because of possible rebound after abrupt withdrawal. Nitroprusside induced cyanide and thiocyanate toxicity are unlikely when doses less than 3 mcg/kg/ min are administered for less than 3 days, except in patients with serum creatinine levels greater than 3 mg/dL (>265 μmol/L).

Nitroglycerin

• Initiate nitroglycerin at 5 to 10 mcg/min (0.1 mcg/kg/min) and increase every 5 to 10 minutes as necessary and tolerated. Maintenance doses usually range from 35 to 200 mcg/min (0.5–3 mcg/kg/min). Hypotension and an excessive decrease in PCWP are important dose-limiting side effects. Some tolerance may develop over 12 to 72 hours of continuous administration.

Nesiritide

• Nesiritide is a recombinant product that is identical to endogenous BNP secreted by the ventricular myocardium in response to volume overload. Nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation; increased cardiac output; natriuresis and diuresis; and decreased cardiac filling pressures, sympathetic nervous system activity, and renin– angiotensin–aldosterone system activity.
• The role of nesiritide in pharmacotherapy of ADHF remains controversial. Compared with nitroglycerin or nitroprusside, it produces marginal improvement in clinical outcomes and is substantially more expensive. Concerns about potential negative effects on renal function and increased morality are also unsettled.

Vasopressin Receptor Antagonists

• The vasopressin receptor antagonists currently available affect one or two arginine vasopressin (AVP; antidiuretic hormone) receptors, V1A or V2. Stimulation of V1A receptors (located in vascular smooth muscle cells and myocardium) results in vasoconstriction, myocyte hypertrophy, coronary vasoconstriction, and positive inotropic effects. V2 receptors are located in renal tubules, where they regulate water reabsorption.

✓ Tolvaptan selectively binds to and inhibits the V2 receptor. It is an oral agent indicated for hypervolemic and euvolemic hyponatremia in patients with syndrome of inappropriate antidiuretic hormone (SIADH), cirrhosis, and HF. Tolvaptan is typically initiated at 15 mg orally daily and then titrated to 30 or 60 mg daily as needed to resolve hyponatremia. It is a substrate of cytochrome P450-3A4 and is contraindicated with potent inhibitors of this enzyme. The most common side effects are dry mouth, thirst, urinary frequency, constipation, and hyperglycemia.

✓ Conivaptan nonselectively inhibits both the V1A and V2 receptors. It is an IV agent indicated for hypervolemic and euvolemic hyponatremia due to a variety of causes; however, it is not indicated for hyponatremia associated with HF.

SURGICAL THERAPY

Orthotopic cardiac transplantation is the best therapeutic option for patients with chronic irreversible New York Heart Association class IV HF, with a 10-year survival of ~50% in well-selected patients.