Heart Failure - Pharmacotherapeutics Textbook

Front 1

Two causes of HF

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HF can result from any disorder that reduces ventricular filling (diastolic dysfunction) and/or myocardial contractility (systolic dysfunction).

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Causes of systolic dysfunction (decreased contractility)

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are reduction in muscle mass (e.g., myocardial infarction [MI]), dilated cardiomyopathies - The deterioration of the myocardium ,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.

Front 3

Causes of diastolic dysfunction

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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.

Front 4

The leading causes of HF

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• The leading causes of HF are coronary artery disease and hypertension.

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compensatory mechanisms:

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• As cardiac function decreases after myocardial injury, 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 HF and contribute to disease progression.

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chest x-ray or ECG use

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Ventricular hypertrophy can be demonstrated on chest x-ray or ECG. Chest x-ray may also show pleural effusions or pulmonary edema.

Front 7

The New York Heart Association Functional Classification System

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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.

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The therapeutic goals for chronic HF

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

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Progression of heart failure

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1) Stage A Patients at high risk for developing HF. E. G Hypertension, coronary artery or other atherosclerotic vascular disease,diabetes, obesity, metabolic syndrome

2) Development of structural heart disease

3) Stage B Patients with structural heart disease but no HF signs or symptoms e.g- Previous MI, left ventricular hypertrophy, left ventricular systolic dysfunction

4) HF symptoms develop

5) Stage C Patients with structural heart disease and current or previous symptoms e.g Left ventricular systolic dysfunction and symptoms such as dyspnea, fatigue, and reduced exercise tolerance

6) Treatment-resistant symptoms

7) Stage D Refractory HF requiring specialized interventions e.g. Patients with treatment refractory symptoms at rest despite maximal medical therapy (e.g., patients requiring recurrent hospitalization or who cannot be discharged without mechanical assist devices or inotropic therapy)

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The first step in managing chronic HF

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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 treating HF.

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Nonpharmacologic interventions

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Nonpharmacologic interventions include cardiac rehabilitation--(Cardiac rehab is a medically supervised program designed to improve your cardiovascular health if you have experienced heart attack, heart failure, angioplasty or heart surgery. Cardiac rehab has three equally important parts: Exercise counseling and training, Education for heart-healthy living, Counseling to reduce stress) and restriction of fluid intake (maximum 2 L/day from all sources) and dietary sodium (approximately 2 to 3 g of sodium per day).

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Stage A: intervention

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Stage A: The emphasis is on identifying and modifying risk factors to prevent development of structural heart disease and subsequent HF.Strategies include smoking cessation and control of hypertension, diabetes mellitus, and dyslipidemia according to current treatment guidelines.Angiotensin-converting enzyme (ACE) inhibitors (or angiotensin tor blockers [ARBs]) should be strongly considered for antihypertensive therapy in patients with multiple vascular risk factors..

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Stage B:intervention

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Stage B: In these patients with structural heart disease but no symptoms,treatment is targeted at minimizing additional injury and preventing or slowing the remodeling process. In addition to treatment measures outlined for stage A, patients with a previous MI should receive both ACE inhibitors (or ARBs in patients intolerant of ACE inhibitors) and βblockers regardless of the ejection fraction. Patients with reduced ejection fractions (less than 40%) should also receive both agents, regardless of whether they have had an MI.

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Stage C- intervention

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Stage C: Most patients with structural heart disease and previous or current HF symptoms should receive the treatments for Stages A and B as well as initiation and titration of a diuretic (if clinical evidence of fluid retention), ACE inhibitor, and β-blocker (if not already receiving a βblocker for previous MI, left ventricular [LV] dysfunction, or other indication). If diuresis is initiated and symptoms improve once the patient is euvolemic, long-term monitoring can begin. If symptoms do not improve, an aldosterone receptor antagonist, ARB (in ACE inhibitorintolerant patients), digoxin, and/or hydralazine/isosorbide dinitrate (ISDN) may be useful in carefully selected patients. Other general measures include moderate sodium restriction, daily weight measurement,immunization against influenza and pneumococcus, modest physical activity, and avoidance of medications that can exacerbate HF.

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Stage D: intervention

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Stage D: Patients with symptoms at rest despite maximal medical therapy should be considered for specialized therapies, including mechanical circulatory support, continuous intravenous positive inotropic therapy,cardiac transplantation, or hospice care.

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What to do in patients with fluid retention.

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Compensatory mechanisms in HF stimulate excessive sodium and water retention, often leading to systemic and pulmonary congestion. Consequently, diuretic therapy (in addition to sodium restriction) is recommended in all patients with clinical evidence of fluid retention.

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Limitations of Thiazide diuretics

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Thiazide diuretics (e.g., hydrochlorothiazide) are relatively weak diuretics and are used alone infrequently in HF. However, thiazides or the thiazidelike diuretic metolazone can be used in combination with a loop diuretic to promote effective diuresis. Thiazides may be preferred over loop diuretics in patients with only mild fluid retention and elevated blood pressure because of their more persistent antihypertensive effects.

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Loop diuretics advantage

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Loop diuretics (furosemide, bumetanide, torsemide) are usually necessary to restore and maintain euvolemia in HF. In addition to acting in the thick ascending limb of the loop of Henle, they induce a prostaglandin-mediated increase in renal blood flow that contributes to their natriuretic effect. Unlike thiazides, loop diuretics maintain their effectiveness in the presence of impaired renal function, although higher doses may be necessary.

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ACEIs

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Angiotensin-Converting Enzyme Inhibitors • 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.

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Beneficial effects of β-blockers

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Beneficial effects of β-blockers may result from antiarrhythmic effects,slowing or reversing ventricular remodeling, decreasing myocyte death from catecholamine-induced necrosis or apoptosis, preventing fetal gene expression, improving LV systolic function, decreasing heart rate and ventricular wall stress and thereby reducing myocardial oxygen demand,and inhibiting plasma renin release.

Patients should receive a βblocker even if symptoms are mild or well controlled with ACE inhibitor and diuretic therapy. It is not essential that ACE inhibitor doses be optimized before a β-blocker is started because the addition of a β-blocker is likely to be of greater benefit than an increase in ACE inhibitor dose.

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Why are beta blockers titrated slowly?

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Because of their negative inotropic effects, β-blockers should be started in very low doses with slow upward dose titration to avoid symptomatic worsening or acute decompensation. Patients should be titrated to target doses when possible to provide maximal survival benefits. However, even lower doses have benefits over placebo, so any dose is likely to provide some benefit.

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Examples of beta blockers and doses

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Metoprolol CR/XL, carvedilol, and bisoprolol are the only β-blockers shown to reduce mortality in large HF trials. ✓ Carvedilol, 3.125 mg twice daily initially; target dose, 25 mg twice daily✓ Metoprolol succinate CR/XL, 12.5 to 25 mg once daily initially; target dose, 200 mg once daily.✓ Bisoprolol, 1.25 mg once daily initially; target dose, 10 mg once daily.