Medical Care: Medical therapy of heart failure focuses on 3 main goals: (1) preload reduction, (2) reduction of systemic vascular resistance (afterload reduction), and (3) inhibition of both the RAAS systems and vasoconstrictor neurohumoral factors produced by the sympathetic nervous system in patients with heart failure. The first 2 goals provide symptomatic relief. While reducing symptoms, inhibition of the RAAS and neurohumoral factors also results in significant reductions in morbidity and mortality rates.
Preload reduction results in decreased pulmonary capillary hydrostatic pressure and reduction of fluid transudation into the pulmonary interstitium and alveoli. Afterload reduction results in increased cardiac output and improved renal perfusion, which allows for diuresis in the patient with fluid overload. Inhibition of the RAAS and sympathetic nervous system results in favored vasodilation and reduction of neurohumoral vasoconstrictors, thereby increasing cardiac output and reducing blood volume and myocardial oxygen demand.
Patients with severe LV dysfunction or acute valvular disorders may present with hypotension. These patients may not tolerate medications to reduce their preload and afterload and may require inotropic support to maintain adequate blood pressure.
Patients who remain hypoxic despite supplemental oxygen or who demonstrate severe respiratory distress require mechanical ventilation, in addition to maximal medical therapy.
" Preload reduction
o Nitroglycerin
" Nitroglycerine (NTG) is the most effective, predictable, and rapid-acting medication available for preload reduction.
" Multiple studies comparing NTG to furosemide or morphine sulfate have demonstrated greater efficacy and safety and a faster onset of action for NTG.
" Use of sublingual NTG is associated with preload reduction within 5 minutes and some afterload reduction.
" Topical NTG may be as effective as sublingual NTG in most patients with heart failure, but it should be avoided in patients with severe LV failure because of poor skin perfusion (manifesting as skin pallor or mottling) and resultant poor absorption.
" Intravenous NTG at higher dosages provides rapid and titratable preload and afterload reduction and has been demonstrated to be an excellent single-agent therapy for patients with severe decompensated CHF.
o Loop diuretics
" Loop diuretics are the cornerstone of heart failure treatment and have been considered as such for many decades. Furosemide is most commonly used. Bumetanide has a higher bioavailability and may be more effective in patients with severe CHF.
" Loop diuretics are presumed to decrease preload through 2 mechanisms: diuresis and direct pulmonary artery vasodilation and venodilation.
" In most patients, diuresis does not occur for at least 20-90 minutes; thus, the effect is delayed.
" In some patients with heart failure, particularly those with diastolic heart failure who are minimally fluid overloaded, continued diuretic use after resolution of acute symptoms may be associated with adverse outcomes, including electrolyte derangements and hypotension.
" Use of medications that decrease preload (eg, NTG) and afterload (eg, ACE inhibitors), either concomitantly or before the administration of loop diuretics, can prevent potential adverse hemodynamic changes.
o Potassium-sparing diuretics
" Numerous studies have shown spironolactone to be as beneficial in the management of CHF as loop diuretics.
" Some of the beneficial effects of spironolactone may be due to its neurohormonal actions.
o Morphine sulfate
" Morphine sulfate use in acute CHF for preload reduction has been commonplace for many years.
" Use should be weighed against potential adverse effects (eg, nausea/vomiting, local or systemic allergic reactions, respiratory depression) that may outweigh any potential benefit, especially given the availability of much more effective medications for preload reduction (eg, NTG).
" Any beneficial hemodynamic effect probably is due to anxiolysis, with a resulting decrease in catecholamine production and systemic vascular resistance.
" Vasodilators (combined afterload and preload reducers)
o ACE inhibitors
" Although initial studies focused on the efficacy of ACE inhibitors in the treatment of chronic CHF, recent studies have demonstrated excellent results for treatment of acute decompensated CHF.
" Studies demonstrate that the use of ACE inhibitors in acute heart failure is associated with reduced admission rates to ICUs and decreased endotracheal intubation rates.
" Hemodynamic effects of ACE inhibitors include reduced afterload, improved stroke volume and cardiac output, and reduced preload.
" ACE inhibitors must be initiated with extreme care in individuals presenting with borderline hemodynamic parameters.
" When administered by intravenous (enalapril 1.25 mg) or sublingual routes, hemodynamic and subjective improvements are noted within 10 minutes; improvements occur more slowly with the oral route.
" ACE inhibitors prolong survival in heart failure. Furthermore, compared to the combination of hydralazine and long-acting nitrates, ACE inhibitors showed a trend to a greater prolongation of survival, had improved hemodynamics, and were better tolerated.
o Ang II receptor inhibitors
" Ang receptor inhibitors, such as losartan and candesartan, are highly recommended alternatives to ACE inhibitors in patients who cannot tolerate ACE inhibitors because of adverse effects, most notably, coughing.
" Furthermore, these agents have gained wider use based on their low adverse effect profile and early study findings, which indicated that combined ACE inhibition and Ang II receptor inhibition is beneficial.
o Hydralazine
" Hydralazine was the first oral balanced (afterload and preload reduction) vasodilator and was popular before the availability of ACE inhibitors. It is a direct vasodilator, unlike ACE inhibitors or Ang receptor inhibitors, which are vasodilators through inhibition of the RAAS system.
" When combined with long-acting nitrates, hydralazine was shown, in the Veterans Administration Heart Failure Trial (VHEFT) studies, to prolong survival in patients with CHF.
" Hydralazine has one main advantage over ACE inhibitors in that it is safe in pregnancy. It also is not known to worsen renal function in patients with heart failure who have reduced renal function and is not associated with the risk of hyperkalemia. Additionally, hydralazine use is recommended in patients who cannot tolerate ACE inhibitors.
" Hydralazine, as a single agent, has less reduction in myocardial oxygen demand than ACE inhibitors because of a slight increase in heart rate that usually results from its use.
o Nitroprusside
" Nitroprusside results in simultaneous preload and afterload reduction through direct smooth muscle relaxation, although it has a greater effect on afterload.
" Afterload reduction is associated with increased cardiac output.
" Potency and rapidity of onset and offset of effect make this an ideal medication for patients who are critically ill.
" It may induce precipitous falls in blood pressure; intraarterial blood pressure monitoring often is recommended.
" Use nitroprusside cautiously in the setting of acute myocardial infarction because of its potential to induce hypotension.
" If nitroprusside is used, convert patients to oral or alternative intravenous vasodilator therapy as soon as possible because prolonged use is associated with thiocyanate toxicity.
" Use in pregnancy is associated with fetal thiocyanate toxicity.
" Inotropic support
o Digoxin (cardiac glycoside)
" Digoxin has been a cornerstone for the treatment of heart failure for decades and is the only oral inotropic support agent currently used in clinical practice.
" Digoxin acts by inhibiting the Na+/K+-ATPase transport pump and inhibits sodium and potassium transport across cell membranes. This increases the velocity and shortening of cardiac muscle, resulting in a shift upward and to the left of the ventricular function (Frank-Starling) curve relating stroke volume to filling volume or pressure. This occurs in healthy as well as failing myocardium and in atrial as well as ventricular muscle. The positive inotropic effect is due to an increase in the availability of cytosolic calcium during systole, thus increasing the velocity and extent of myocardial sarcomere shortening.
" No evidence indicates that digoxin affects peripheral vascular resistance or systemic blood pressure.
" All evidence suggests that digoxin provides, even in the short term, a moderate and metabolically efficient positive inotropic effect, an important consideration in ischemic cardiomyopathies.
" Although the incidence and severity of digitalis intoxication is decreasing, vigilance for this important complication of therapy is essential. Drugs that interact with digoxin are numerous and include amiodarone, propafenone, quinidine, verapamil, nifedipine, diltiazem, levothyroxine, cyclosporine, flecainide, disopyramide, omeprazole, tetracycline, and erythromycin. These agents affect clearance or absorption of digoxin, thus necessitating dose alteration of digoxin in patients taking these medications. Furthermore, patients with renal insufficiency may need to have their digoxin dose adjusted downward to avoid digitalis intoxication.
" Numerous studies confirm that digoxin does not prolong survival in patients with systolic heart failure, but it is associated with reduced hospital admissions, improved functional class, reduced symptoms of heart failure, and improved quality of life.
" Digoxin is also an effective agent against atrial tachyarrhythmias at rest in patients with LV dysfunction, but it has limited efficacy in controlling the ventricular rate of atrial arrhythmias during exertion.
o Dobutamine (sympathomimetic agent)
" Dobutamine mainly serves as a beta1-receptor agonist, although it has some beta2-receptor and minimal alpha-receptor activity.
" Intravenous dobutamine induces significant positive inotropic effects with mild chronotropic effects. It also induces mild peripheral vasodilation (decrease in afterload).
" The combination effect of increased inotropy with decreased afterload results in a significant increase in cardiac output.
" Combination use with intravenous NTG may be ideal for patients with myocardial infarction and decompensated heart failure and mild hypotension in order to provide simultaneous preload reduction with increased cardiac output. In the setting of acute myocardial infarction, dobutamine use could increase infarct size because of the increase in myocardial oxygen consumption that may ensue.
" In general, avoid dobutamine in patients with moderate or severe hypotension (eg, systolic blood pressure <80 mm Hg) because of the peripheral vasodilation.
o Dopamine (sympathomimetic agent)
" Vascular and myocardial receptor effects are dose dependent.
" Low dosages (0.5-3 mcg/kg/min) cause stimulation of dopaminergic receptors within the renal and splanchnic vascular beds, causing vasodilation and increased diuresis.
" Moderate dosages (3-10 mcg/kg/min) cause stimulation of beta-receptors in the myocardium, resulting in increased cardiac contractility and heart rate.
" High dosages (10-20 mcg/kg/min) cause stimulation of alpha-receptors, resulting in peripheral vasoconstriction (increased afterload), increased blood pressure, and no further improvement in cardiac output.
" As with other inotropic agents, moderate and high dosages are arrhythmogenic and also result in increased myocardial oxygen demand (potential for myocardial ischemia); therefore, use dopamine only in patients with heart failure who cannot tolerate the use of dobutamine because of severe hypotension (eg, systolic blood pressure <60-80 mm Hg).
o NE (sympathomimetic agent)
" NE primarily stimulates alpha-receptors, resulting in significant increases in afterload (and potential myocardial ischemia) and reduced cardiac output.
" Use of NE is generally reserved for patients with profound hypotension (eg, systolic blood pressure <60 mm Hg). Once blood pressure is restored, add other medications to maintain cardiac output.
o Phosphodiesterase inhibitors (milrinone, amrinone)
" Phosphodiesterase inhibitors (PDIs) increase intracellular cAMP, which results in a positive inotropic effect on the myocardium and peripheral vasodilation (decreased afterload) and a reduction in pulmonary vascular resistance (decreased preload).
" PDIs, unlike catecholamine inotropes, are not dependent on adrenoreceptor activity; therefore, patients are less likely to develop tolerance to these medications. Tolerance to catecholamine inotropes can develop rapidly through down-regulation of the adrenoreceptors.
" PDIs are less likely than catecholamine inotropes to cause adverse effects that are typically associated with adrenoreceptor activity (eg, increased myocardial oxygen demand, myocardial ischemia).
" Several studies directly comparing the use of PDIs (milrinone, amrinone) to dobutamine in patients with heart failure have demonstrated that milrinone produced equal or greater improvements in stroke volume, cardiac output, PCWPs (preload), and systemic vascular resistance (afterload). They are also associated with less tachycardia and myocardial oxygen consumption. However, PDIs have been associated with a significantly greater incidence of adverse events (eg, tachyarrhythmias) than has dobutamine.
" At present, oral PDIs have no role. Their use was associated with a 53% increase in mortality rates in patients with NYHA Class IV heart failure in the Prospective Randomized Milrinone Survival Evaluation (PROMISE) trial, prompting an early termination of that study.
" Unfavorable results were also evident in a smaller trial that compared oral milrinone to digoxin or placebo. Furthermore, sustained hemodynamic improvement with oral milrinone was lacking, and the incidence of adverse events, particularly cardiac arrhythmias, was greater.
" Beta-adrenergic blocking agents (metoprolol, carvedilol)
o A large and increasing body of evidence indicates that these agents improve symptoms, exercise tolerance, cardiac hemodynamics, and LV ejection fraction and that they decrease mortality rates in patients with heart failure, particularly those with both ischemic and idiopathic cardiomyopathy.
o A growing body of evidence suggests that long-term beta-adrenergic antagonist administration improves cardiac function, reduces myocardial ischemia, improves ventricular-arterial coupling, and decreases myocardial oxygen consumption. These agents may also reduce the incidence of sudden death due to primary ventricular arrhythmias in patients with heart failure, although this latter benefit has yet to be definitively proven.
o Detectable improvements in ventricular function are usually not apparent for a minimum of 1-3 months, and longer-term structural changes, such as a decline in ventricular volume or mass, may take 12-18 months.
o Beta-adrenergic antagonists with vasodilator activity, such as carvedilol and labetalol, have the added benefit of further afterload reduction because of arterial vasodilation from alpha1-receptor blockade.
" Treatment of heart failure with predominant diastolic dysfunction: The therapeutic approach to diastolic dysfunction has 2 major components. The first involves attempts to reverse the abnormal cardiac diastolic properties. The second is directed toward reducing LV filling pressure and thereby venous congestion.
o Treatment of diastolic dysfunction
" Pericardiectomy for constrictive pericarditis
" Relief of ventricular systolic overload
" ACE inhibitors and Ang receptor inhibitors slow, arrest, or even reverse myocardial fibrosis in the presence of systolic overload, thus improving diastolic dysfunction.
" Anti-ischemic agents, such as beta-adrenergic blocking agents, calcium channel blocking agents, and nitroglycerin, are effective in immediately improving diastolic dysfunction in patients with coronary artery disease by eliminating or reducing myocardial ischemia, thus improving ventricular relaxation. Thrombolysis, mechanical revascularization (percutaneous transluminal coronary angioplasty [PTCA]), and coronary artery bypass graft surgery (CABGS), in combination with anti-ischemic agents or alone, all improve diastolic function in patients with acute and chronic myocardial ischemia by improving ventricular relaxation.
" Calcium channel antagonists, especially verapamil, accelerate ventricular relaxation, particularly in patients with hypertensive heart disease and hypertrophic cardiomyopathy, and are useful in the treatment of diastolic dysfunction.
" Regression of ventricular hypertrophy
" Aggressive control of hypertension with beta-adrenergic blocking agents, calcium channel blocking agents, diuretics, ACE inhibitors, Ang receptor inhibitors, and central-acting antihypertensive agents (eg, methyldopa) reduces ventricular hypertrophy, thereby improving diastolic function.
" Aortic valve replacement for aortic stenosis also reduces ventricular hypertrophy and improves diastolic function.
" Relief of valvular, supravalvular, and subvalvular obstruction to ventricular outflow by operation or balloon valvuloplasty improves diastolic function by relieving ventricular pressure overload, thus regressing ventricular hypertrophy.
o Reduction of ventricular filling pressure and secondary venous congestion: These approaches are usually highly effective in patients presenting with a CHF exacerbation primarily caused by a diastolic dysfunction. Indeed, a hallmark of diastolic dysfunction is the rapid improvement in response to the therapies described below.
" Restriction of dietary sodium
" Administration of diuretics and venodilators
" Administration of NTG or long-acting nitrates
" Maintenance of normal heart rate and rhythm: Digoxin has no established place in the management of patients with predominant diastolic dysfunction and well-preserved ventricular ejection fraction, and it could potentially have an adverse effect in this group of patients.
" Newer therapies for heart failure
o Nesiritide, a recombinant BNP, is from an exciting new class of peptides that has several unique properties.
" Nesiritide is a balanced vasodilator, slightly more venous than arterial, rapidly improves symptoms of congestion, does not increase heart rate, decreases myocardial oxygen demand, and is not proarrhythmic.
" Nesiritide decreases aldosterone and ET-1 release through neurohumoral suppression, does not exhibit tachyphylaxis, and induces a mild diuresis and natriuresis. It significantly reduces ventricular filling pressures to a greater extent than standard care with ACE inhibitors and diuretics, even more than the combination of ACE inhibitors, diuretics, and nitroglycerin.
" Nesiritide should be avoided in patients with systolic blood pressure of less than 80-85 mm Hg. The primary adverse event (occurring in 4% of the patients in the Veterans Administration Medical Center [VAMC] study on nesiritide) was hypotension.
" Nesiritide has no drug interactions with any of the other treatments used in CHF, thus making it useful as an effective adjunct in patients with severe, acute decompensated CHF without cardiogenic shock.
" Study results indicate that treatment with nesiritide could lead to a reduced length of stay in the critical care unit, decreased recurrence of decompensation, and less likelihood of rehospitalization.
o Eplerenone, a selective aldosterone-blocking agent, has been shown to reduce rates of all-cause mortality, cardiovascular mortality, and sudden cardiac death in patients with myocardial infarction and left ventricular systolic dysfunction who are in CHF and already being treated with a beta-blocker and an ACE inhibitor or Ang II blocker. Close monitoring of potassium levels and appropriate dosage adjustments or use of diuretics are necessary because a small percentage of patients taking eplerenone develop hyperkalemia.
Surgical Care: Kantrowitz initially described intraaortic balloon pumping (IABP) in 1953, but the procedure was first used clinically in 1969 in a patient with cardiogenic shock. Since the 1980s, IABP has been increasingly used in various clinical situations as a lifesaving intervention to obtain hemodynamic stabilization prior to definite therapy.
" Procedure
o The intraaortic balloon pump is inserted percutaneously via the femoral artery using a modified Seldinger technique. The distal end of the pump is placed just distal to the aortic knob and the origin of left subclavian artery.
o Fluoroscopy may be used for correct positioning of the balloon, and a subsequent chest radiograph should be obtained to document satisfactory balloon placement.
" Proper timing of IABP for optimal hemodynamic support
o Proper timing of counterpulsation is necessary for maximum hemodynamic support. The timings of balloon inflation and deflation are best evaluated and adjusted at a pump frequency of 1:2.
o Inflation of the balloon should occur in early diastole, just after aortic valve closure, and should correspond to the dicrotic notch of the aortic pressure waveform. Balloon deflation should occur in early systole, just before the aortic valve opens.
o Proper inflation leads to an assisted peak diastolic pressure higher than the unassisted peak systolic arterial pressure. Proper deflation results in assisted aortic end-diastolic pressure approximately 10 mm Hg lower than the unassisted end-diastolic pressure.
o Diastolic augmentation enhances perfusion of the coronary circulation and carotid arteries. The reduction in end-diastolic pressure decreases aortic impedance (afterload) and augments systole.
o IABP reduces aortic impedance and systolic pressure, leading to a 15-25% reduction in LV wall stress. This level of afterload reduction improves LV volume, LV emptying, and myocardial oxygen consumption.
o Diastolic aortic pressure augmentation enhances myocardial perfusion and coronary blood flow. The effects on coronary blood flow may be variable but generally range from a boost of 10-20% in ischemic territories.
o IABP can decrease LV filling pressures by 20-25% and can improve cardiac output by 20% in patients with cardiogenic shock; therefore, IABP reduces myocardial oxygen demand significantly, although the beneficial effect of increased oxygen supply to the myocardium may also occur in some clinical situations.
" Indications for IABP
o IABP is very effective in providing temporary support to patients in cardiogenic shock while definite therapies such as angioplasty or cardiac bypass surgery are undertaken. At most institutions, IABP is generally considered to be a bridge to a definite revascularization procedure or to implementation of an LV assist device.
o IABP is effective in stabilizing patients with unstable angina refractory to medical therapy prior to a definitive revascularization procedure.
o IABP may be a lifesaving intervention in patients with acute mitral regurgitation secondary to papillary muscle ischemia, infarction, and other causes such as infectious endocarditis or myxomatous degeneration. IABP reduces afterload (thereby reducing the severity of mitral regurgitation), enhances forward cardiac output, reduces left atrial pressure, and improves pulmonary edema.
o IAPB is used to stabilize patients, which allows time to plan the definitive surgical procedure in patients who are hemodynamically unstable.
o IABP could also provide hemodynamic support in the perioperative and postoperative period.
" Contraindications and complications
o The absolute contraindications for IABP counterpulsation are aortic dissection, severe aortic regurgitation, presence of a large arteriovenous shunt, and severe coagulopathy.
o The relative contraindications are severe peripheral vascular disease, recent thrombolytic therapy, and bleeding diathesis.
o IABP can cause several complications that should be monitored while the patient is maintained on IABP support. Generally, a mild reduction in platelet counts occurs; however, these usually do not fall below 100,000/ L
o Complications may occur during cannulation of the femoral artery and include perforation, laceration, or dissection of the artery (1-6%). Thrombosis of the iliofemoral artery and distal emboli may also occur (1-7%), and limb ischemia has been reported in up to 40% of patients. The limb ischemia is reversible upon removing the intraaortic balloon pump unless thrombosis has developed, which requires embolectomy to save the limb.
o The other complications are localized bleeding (3-5%), infection (2-4%), thrombocytopenia (<1%), and intestinal ischemia (<1%).
" Ventricular assist device: This is generally considered a short-term therapy (eg, acute myocarditis) or bridge to transplant, though a recent study suggested improved survival when used long term.
" Biventricular pacing (cardiac resynchronization): A new therapy, biventricular pacing may improve left ventricular pumping efficacy in patients with relatively severe cardiomyopathy and wide QRS complex.
" Cardiac transplantation
Diet: Patients admitted with heart failure or pulmonary edema should maintain a low-salt diet in order to minimize fluid overload. Monitor fluid balance closely.
Activity:
" Patients with decompensated heart failure should be placed on complete bed rest until their decompensation is resolved. This is necessary to maximally reduce myocardial oxygen demand and to avoid exacerbation of the abnormal hemodynamics and symptoms of heart failure.
" Once the patient with heart failure has been stabilized, activity should be gradually and progressively increased. Emphasize the importance of cardiac rehabilitation to all patients with heart failure who require improved cardiac fitness. Encourage patients to exercise daily for at least 20-30 minutes in a low-intensity, endurance-enhancing activity such as walking, biking, or swimming. Regular exercise improves the quality of life for these patients and improves efficiency of oxygen utilization at the tissue level, thus reducing the workload of the heart in the role of oxygen delivery to end organs and muscles.
DRUG TREATMENT :
1. HUMAN B-TYPE NATRIURETIC PEPTIDES - DILATES VEINS & ARTRIES. USED IN TREATMENT OF ACUTE SEVERE CHF
- NESIRITIDE
2. DIURETICS :
- FRUSEMIDE
- BUMETANIDE
- TORSEMIDE
- SPIRONOLACTONE
3. ACE INHIBITORS :
- ENALAPRIL
- CAPTOPRIL
- QUINAPRIL
- LISINOPRL
- RAMIPRIL
- FOSINOPRIL
4. ANGIOTENSIN RECEPTOR BLOCKERS :
- LOSARTAN
5. VASODILATORS :
- NITROGLYCERIN
- ISOSORBIDE DINITRATE
- ISOSORBIDE MONONITRATE
- HYDRALAZINE
- NITROPRUSIDE
6. INOTROPIC AGENTS :
- DIGOXIN
- DOBUTAMINE
- DOPAMINE
- NOREPINEPHRINE
7. PHOSPHODIESTERASE ENZYME INHIBITORS : DIFFERENT FROM BOTH DIGITALIS GLYCOSIDES & CATECHOLAMINES. THESE ARE BALANCED VASODILATORS, HAVING EQUAL REDUCTION IN BOTH AFTER LOAD
- MILRINONE
- AMRINONE
8. BETA BLOCKERS :
- CARVEDILOL
- METOPROLOL