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

Causes of systolic dysfunction (decreased contractility) are:  reduction in muscle mass (e.g., myocardial infarction [MI]).  dilated cardiomyopathies, and ventricular hypertrophy. Ventricular hypertrophy can be caused by:  pressure overload (e.g., systemic or pulmonary hypertension.  aortic or pulmonic valve stenosis) or volume overload (e.g., valvular regurgitation, shunts, high-output states).

Causes of diastolic dysfunction (restriction in ventricular filling) are.  increased ventricular stiffness.  ventricular hypertrophy.  infiltrative myocardial diseases.  myocardial ischemia and infarction.  mitral or tricuspid valve stenosis, and pericardial disease (e.g., pericarditis, pericardial tamponade).

 The most common underlying etiologies are ischemic heart disease, hypertension, or both.  As cardiac function decreases, the heart relies on the following compensatory mechanisms:  (1) tachycardia and increased contractility through sympathetic nervous system activation;  (2) the Frank-Starling mechanism, whereby increased preload increases stroke volume;  (3) vasoconstriction; and  (4) ventricular hypertrophy and remodeling. Although these compensatory mechanisms initially maintain cardiac function, they are responsible for the symptoms of heart failure and contribute to disease progression.

 Common precipitating factors that may cause a previously compensated patient to decompensate include noncompliance with diet or drug therapy, coronary ischemia, inappropriate medication use, cardiac events (e.g., MI, atrial fibrillation), and pulmonary infections.  Drugs may precipitate or exacerbate HF because of their negative inotropic, cardiotoxic, or sodium- retaining properties.

 The patient presentation may range from asymptomatic to cardiogenic shock.  The 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 results in pulmonary congestion and peripheral edema.  Nonspecific symptoms may include nocturia, hemoptysis, abdominal pain, anorexia, nausea, bloating, ascites, and mental status changes.  Physical examination findings may include pulmonary crackles, an S 3 gallop, pleural effusions, Cheyne-Stokes respiration, tachycardia, cardiomegaly, peripheral edema, jugular venous distention, hepatojugular reflux, and hepatomegaly.

 A diagnosis of HF should be considered in patients exhibiting characteristic signs and symptoms.  A complete history and physical examination with appropriate laboratory testing are essential in the initial evaluation of patients suspected of having HF.  Ventricular hypertrophy can be demonstrated on chest x- ray or electrocardiogram (ECG).  Echocardiography is essential to estimate LV Ejection fraction for systolic function.

 The therapeutic goals for chronic HF are to improve symptoms and quality of life, reduce symptoms, reduce hospitalizations, slow disease progression, and prolong survival.

 GENERAL PRINCIPLES  The first step in managing chronic HF is to determine the etiology or precipitating factors. Treatment of underlying disorders (e.g., anemia, hyperthyroidism) may obviate the need for treatment of HF.  Nonpharmacologic interventions include cardiac rehabilitation and restriction of fluid intake (maximum 2 L/day from all sources) and dietary sodium (approximately 1.5 to 2 g of sodium per day).

 Standard First-Line Therapies Angiotensin-Converting Enzyme Inhibitors (ACEI) β Blockers Diuretics Digoxin  Second line Therapies Aldosterone Antagonists Angiotensin II Receptor Blockers (ARBs) Nitrates and Hydralazine

 ACE inhibitors decrease angiotensin II and aldosterone, attenuating many of their deleterious effects, including reducing ventricular remodeling, myocardial fibrosis, myocyte apoptosis, cardiac hypertrophy, norepinephrine release, vasoconstriction, and sodium and water retention.  Hemodynamic effects observed with long-term therapy include significant increases in cardiac index, stroke work index, and stroke volume index, as well as significant reductions in left ventricular filling pressure, systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate.  Significant improvements in clinical status, functional class, exercise tolerance, left ventricular size, and mortality are also well documented.

 Beneficial effects β blockers may result from slowing or reversing the detrimental ventricular remodeling caused by sympathetic simulation, decreased myocyte death from catecholamine-induced necrosis or apoptosis, antiarrhythmic effects, and prevention of other effects of sympathetic nervous system activation.  These drugs consistently increase left ventricular ejection fraction, decrease ventricular mass, and reduce systolic and diastolic volumes.  There is overwhelming evidence that stable patients initiated on low doses of a β blocker with slow upward dose titration over several weeks derive significant benefits, including slowed disease progression and reduced hospitalizations and mortality.

 Compensatory mechanisms in HF stimulate excessive sodium and water retention, often leading to systemic and pulmonary congestion.  Consequently, diuretic therapy is indicated for all patients with evidence of fluid retention. However, because they do not alter disease progression or prolong survival, they are not considered mandatory therapy for patients without fluid retention.

 In patients with HF and supraventricular tachyarrhythmias such as atrial fibrillation, digoxin should be considered early in therapy to help control ventricular response rate.  For patients in normal sinus rhythm, digoxin does not improve survival, but its positive inotropic effects, symptom reduction, and its effect on symptom reduction and quality-of-life improvement are evident in patients with mild to severe HF. Therefore, it should be used together with other standard HF therapies (ACE inhibitors, β blockers, and diuretics) in patients with symptomatic HF.  Consideration should be given to adding it after instituting β- blocker therapy so that digoxin-associated bradycardia does not preclude β-blocker use.

 Spironolactone is an inhibitor of aldosterone that produces a weak potassium-sparing diuretic effect.  It has been studied in HF because aldosterone is a neurohormone that plays an important role in ventricular remodeling particularly by causing increased collagen deposition and cardiac fibrosis.  The most common adverse effect was gynecomastia, which occurred in 10% of men. There was a statistically significant (but probably clinically unimportant) mean increase in serum potassium concentration (0.3 mEq/L).

 The angiotensin II receptor blockers (e.g., losartan, candesartan, valsartan) block the angiotensin II receptor subtype AT 1, preventing the deleterious effects of angiotensin II, regardless of its origin.  They do not appear to affect bradykinin and are not associated with the side effect of cough that sometimes results from ACE inhibitor-induced accumulation of bradykinin. Also, direct blockade of AT 1 receptors allows unopposed stimulation of AT 2 receptors, causing vasodilation and inhibition of ventricular remodeling.

 Nitrates (e.g., isosorbide dinitrate [ISDN]) and hydralazine were combined originally in the treatment of HF because of their complementary hemodynamic actions. Nitrates are primarily venodilators, producing reductions in preload.  Hydralazine is a direct vasodilator that acts predominantly on arterial smooth muscle to reduce SVR and increase stroke volume and cardiac output. Furthermore, nitrates may inhibit the ventricular remodeling process, and hydralazine prevents nitrate tolerance and may interfere with HF progression.

 Diuretics  Positive Inotropic Agents  Vasodilators

 IV loop diuretics, including furosemide, bumetanide, and torsemide, are used for advanced HF, with furosemide being the most widely studied 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.

 Dobutamine is a β 1 and β 2 receptor agonist with some α 1 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 or higher on the basis of clinical and hemodynamic responses.

Amrinone and milrinone are bipyridine derivatives that inhibit phosphodiesterase III and produce positive inotropic and vasodilating effects; hence, these drugs are referred to as inodilators. During IV administration, amrinone or milrinone increases stroke volume (and cardiac output) with little change in heart rate. Amrinone and milrinone should be used cautiously as single agents in severely hypotensive HF patients because these drugs will not increase, and may even decrease, arterial blood pressure.

 Dopamine should generally be avoided in advanced HF, but its pharmacologic actions may be preferable to dobutamine or milrinone in two circumstances: (1) 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; and (2) to directly attempt to improve renal function in patients with inadequate urine output despite volume overload and high ventricular filling pressures.

 Sodium nitroprusside is a mixed arterial-venous vasodilator that acts directly on vascular smooth muscle to increase cardiac index and decrease venous pressure.  Hypotension is an important dose-limiting adverse effect of nitroprusside and other vasodilators. Therefore, nitroprusside is primarily used in patients who have a significantly elevated SVR.

 The major hemodynamic effects of IV nitroglycerin are decreased preload and pulmonry artery occlusion pressure PAOP because of functional venodilation and mild arterial vasodilation. It is used primarily as a preload reducer for patients with pulmonary congestion and low-normal cardiac output or in combination with inotropic agents for patients with severely depressed systolic function and pulmonary edema.  Hypotension and an excessive decrease in PAOP are important dose-limiting side effects. Some tolerance develops in most patients over 12 to 72 hours of continuous administration.

 Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide (BNP) secreted by the ventricular myocardium in response to volume overload.  Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation, increased natriuresis and diuresis, and decreased cardiac filling pressures, blood pressure, and sympathetic nervous system and renin- angiotensin-aldosterone system activity.

 Intra-aortic Balloon Pump  The intra-aortic balloon pump (IABP), typically, is employed in patients with advanced HF who do not respond adequately to drug therapy, those with intractable myocardial ischemia, or patients in cardiogenic shock.  Ventricular Assist Devices  Ventricular assist devices (VADs) are surgically implanted and assist, or in some cases replace, the pumping functions of the right and/or left ventricles.