Drugs to Treat Heart Failure

ACE-inhibitors

ACE-inhibitors interrupt the renin-angiotensin pathway be preventing conversion of angiotensin I to angiotensin II in the lungs. ACE inhibitors exert some of their beneficial effects by increasing bradykinin levels in the bloodstream. Bradykinin is a vasodilator, and increased levels of this compound decrease cardiac workload. Normally, ACE is responsible for the enzymatic destruction of bradykinin in the blood stream. ACE inhibitors reduce the breakdown of bradykinin, thereby prolonging the vasodilation effects of this substance. ACE inhibitors are considered a mainstay in therapy for heart failure. They were the first agents proven to reduce mortality in CHF. ACE inhibitors decrease cardiac workload. ACE inhibitors used to treat CHF include benazepril, catopril, and lisinopril.

Digoxin: common adverse effects and implication for physical therapy

Adverse effects: bradycardia, anorexia, nausea/vomiting, drowsiness (BAND) Evaluation: assess for digitalis toxicity (can be a poison in large quantities), increased fall risk, assess weight change, assess vitals during exercise Intervention: assess vitals during exercise, increased fall risk Education: lifestyle changes, report prolonged adverse effects to PCP

ARBs: Common adverse effects and implications for physical therapy

Adverse effects: dizziness, hyperkalemia, hypotension (same as ACE inhibitors minus the dry cough) Evaluation: watch for signs of hyperkalemia, increased fall risk, monitor metabolic alkalosis Intervention: use caution during aerobic exercise, avoid interventions that could cause systemic vasodilation, increased fall risk Education: lifestyle changes, report prolonged adverse effects to PCP

ACE inhibitors: common adverse effects and implications for physical therapy

Adverse effects: dry cough, dizziness, hypotension, hyperkalemia Evaluation: watch for signs of hyperkalemia (FAT Men Wear Big Pants), increased risk for falls, monitor for metabolic alkalosis (Cat Did Not Do Very Much Cleaning) Intervention: use caution during aerobic exercise, avoid interventions that could cause systemic vasodilation, increased fall risk Education: lifestyle changes, report prolonged adverse effects to PCP

Beta-1 antagonists (beta blockers): common adverse effects and implications for physical therapy

Adverse effects: fatigue, erectile dysfunction, weakness, joint pain, bronchospasm Evaluation: assess vitals during exercise, assess bronchospasm, assess joint pain Intervention: assess vitals during exercise, USE RPE for assessment of exercise intensity Education: guidance on exercise monitoring, lifestyle changes, report prolonged adverse effects to PCP

Beta-1 agonists: common adverse effects and implications for physical therapy

Adverse effects: high blood pressure, increased heart rate, premature ventricular contractions, shortness of breath (HIPS) Evaluation: assess vitals during exercise Intervention: assess vitals during exercise, use caution during exercise due to chance of arrhythmias Education: lifestyle changes to benefit the heart, report prolonged adverse effects to PCP

Vasodilators (hydralazine): common adverse effects and implications for physical therapy

Adverse effects: reflexive tachycardia (not as much blood returning to the heart - reduced stroke volume, so heart needs to beat faster to maintain cardiac output), headache, dizziness Evaluation: assess vitals during exercise, increased risk for falls Intervention: assess vitals during exercise, increased risk for falls, avoid interventions that will cause peripheral vasodilation (Hubbard tank) Education: lifestyle changes, report prolonged adverse effects to PCP

Phosphodiesterase inhibitors: common adverse effects and implications for physical therapy

Adverse effects: ventricular arrhythmias, hypokalemia, thrombocytopenia (decreased number of platelets) Evaluation: assess hypokalemia, assess vitals during exercise, assess for signs of thrombocytopenia Intervention: assess vitals during exercise, increased risk for falls Education: lifestyle changes, report prolonged adverse effects to PCP

Spironolactone (aldosterone antagonist): common adverse effects and implications for physical therapy

Adverse effects: hyperkalemia (since we are sparing potassium; FAT Men Wear Big Pants), muscle cramps (possible due too much potassium in the ECF), dizziness, arrhythmias Evaluation: look for sings of hyperkalemia, assess vitals during exercise, increased risk for falls Intervention: caution with interventions that will cause sweating, increased risk for falls, assess vitals during exercise Education: lifestyle changes, report prolonged adverse effects to PCP

Diuretics: common adverse effects and implications for physical therapy

Adverse effects: hypokalemia & hyponatremia, dehydration, metabolic alkalosis, orthostatic hypotension, erectile dysfunction Evaluation: increased fall risk, monitor for metabolic alkalosis Intervention: caution with interventions that will cause sweating, increased fall risk Education: nutrition, physical activity, nicotine cessation, report prolonged adverse effects to PCP

Congestive heart failure

Congestive heart failure is a chronic condition in which the heart is unable to pump a sufficient quantity of blood to meet the needs of the peripheral tissues. Essentially, the heart's pumping ability has been compromised bosom form of myocardial disease or dysfunction. The congestive aspect of heart failure arises from the tendency for fluid to accumulate in the lungs and peripheral tissues because the heart is unable to maintain proper circulation.

Digitalis

Digitalis is a mainstay of heart failure therapy. It increases the ability of the heart to pump at rest and during exercise. Digitalis does not reduce mortality, but it does improve quality of life and reduce exacerbations. Digitalis is commonly combined with other agents. Digoxin is the form of digitalis that is used.

Diuretics

Diuretics increase excretion of sodium and water. These agents are useful in CHF primarily because of their ability to reduce congestion in the lungs and peripheral tissues by excreting excess fluid retained in these tissues. Diuretics also decrease the amount of fluid that the heart must pump (cardiac preload), thereby reducing the failing heart's workload. Less fluid in the body also results in reduced TPR, so the heart does not have to pump against high pressures (also reducing after load). Data does not indicate that diuretics reduce mortality in CHF.

Beta-1 agonists

Dopamine and dobutamine are beta-1 agonists that exert a fairly specific positive inotropic effect (inotropic refers to the force of muscular contraction), primarily through their ability to stimulate beta-1 receptors on the myocardium. Other beta-1 agonists such as epinephrine will also increase myocardial contractility, but most of these other beta-1 agonists will also increase heart rate or have other side effects that prevent their use in congestive heart failure. Dopamine and dobutamine have a minor effect on heart rate and peripheral blood vessels.

Digoxin Toxicity

Gastrointestinal: anorexia, nausea/vomiting, abdominal pain CNS effects: fatigue, weakness, headache, neuralgia, dizziness, confusion, delirium/psychosis

Hypokalemia and the ECG

The T-wave flattens out, a U-wave appears

The vicious cycle of heart failure

1. Decreased cardiac performance/precipitating factors: any number of factors that affect cardiac pumping ability may be responsible for initiating a change in myocardial performance. Factors such as ischemic heart disease, myocardial infarction, valve dysfunction, and hypertension may all compromise the heart's pumping ability. Also, cardiomyopathy may result from other diseases and infections. 2. Neurohormonal compensations: the body responds to the decreased cardiac pumping ability in several ways. In the early stages of failure, cardiac output decreases, and the delivery of oxygen and nutrients to tissues/organs is diminished (decrease in Q). To compensate for this initial decrease, several neural and neurochemical changes occur that increase cardiac contractility and help maintain blood pressure. In particular, the SNS and renin-angiotensin system are activated, and the secretion of aldosterone and antidiuretic hormone/vasopressin increases (fluid reabsorption). Although these compensations are initially helpful in maintaining cardiac function, they actually place more stress on the failing heart. This increased stress initiates the cycle because it causes more damage to the myocardium, which further compromises cardiac pumping ability, causing more neurohormonal activation, more stress on the heart, and so on. the kidneys sense the reduced blood pressure based on the volume of blood coming through the arterioles - the kidney secretes renin which converts angiotensinogen to angiotensin I that is converted to angiotensin II in the lungs. Angiotensin II causes vasoconstriction and stimulates secretion of aldosterone from the adrenal gland, which cause sodium/water reabsorption. This increases blood pressure/total peripheral resistance - the heart has to deal with increased preload and increased after load. 3. Increased cardiac workload: the neurohormonal changes previously described contribute to peripheral vasoconstriction as well as general increase in sodium and water retention. These effects place additional strain on the heart by increasing cardiac preload (i.e. the volume of blood returning to the heart) and cardiac after load (i.e. the pressure that the heart must pump against). 4. Changes in myocardial cell function: the increased workload on the heart can lead to, or cause, exaggerated alterations in cell function and further structural damage to the already compromised myocardial cell. Also, studies on the molecular basis of heart failure have suggested that alterations in calcium transport, contractile protein function, energy production and utilization, free-radical production, and beta-receptor density may occur. Continued stress on the heart may exacerbate these changes, leading to more cellular dysfunction and inappropriate adaptive changes in myocardial cell structure and function, which ultimately leads to abnormal changes in size, shape, and function of the heart (cardiac remodeling). The pathological remodeling results in a further decrease in cardiac performance, thus completing the cycle.

Digoxin Mechanism of action

1. Digoxin inhibits the sodium-potassium pump on the myocardial cell membrane. This is an active transporter than normally transports sodium out of the cell and transports potassium into it. Sodium enters the cardiac cell during the depolarization phase of each action potential, so the sodium-potassium pump is responsible for removing the sodium from the cell. Inhibition of the sodium-potassium pump causes sodium to accumulate within the cell. 2. an increase in intracellular sodium concentration leads to an increase in intracellular calcium. During cardiac excitation, calcium ions normally enter the myocardial cell through specific channels during each action potential. An enzyme known as the sodium-calcium exchange protein removes some of the calcium that enters. This enzyme uses the ionic gradient for sodium entry to help remove calcium from the cell, thus exchanging sodium entry for calcium exit from the cell. Because intracellular sodium concentration has increased, there is a smaller electrochemical gradient/driving force for sodium to enter the cell. If less sodium enters the cel, there is a reduction in the ability of the sodium-calcium exchange protein to remove calcium. Hence, intracellular calcium concentration increases. 3. The increased availability of calcium with the cardiac cell enables it to store more calcium in the SR. As in any type of muscle cell, calcium is normally stored within the SR and released during each AP to facilitate actin-myosin interaction and initiate muscle contraction. Because more calcium is stored in the cardiac cell, the SR releases more calcium during each AP, thereby initiating greater actin-myosin interaction and a stronger cardiac contraction.

Hypokalemia

A SIC WALT Alkalosis Shallow respirations Irritability Confusion, drowsiness Weakness, fatigue Arrhythmias (tachycardia, irregular rhythm, and/or bradycardia) Lethargy Thready pulse (scarcely perceptible) Decreased intestinal motility, and nausea/vomiting

Angiotensin Receptor Blockers (ARBs)

Angiotensin receptor blockers block the effect created by angiotensin II on vasculature. Irbesartan is an ARB that is used to treat CHF. Angiotensin receptor blockers are effective as an alternative therapy for patients unable to tolerate ACE inhibitors.

Beta blockers

Historically, beta blockers were considered detrimental in CHF. Beta blockers are actually beneficial in people with HF because they attenuate/weaken the excessive sympathetic activity associate with this disease. Increased sympathetic activity and other neurohormonal changes often contribute to the vicious cycle associated with heart failure, and excessive sympathetic stimulation can accelerate the pathological changes in the failing heart. Beta blockers reduce the harmful effects of excessive sympathetic stimulation, and the use of these drugs has been shown to reduce the morbidity and mortality associated with heart failure. Beta blockers bind to the beta-1 receptors on the myocardium and block the effects of NE and E. These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Metoprolol is a beta blocker used to treat CHF.

Vasodilators (hydralazine)

Hydralazine is a vasodilator that decreases peripheral vascular resistance via vasodilation. It is not an alpha-1 antagonist. By reducing peripheral vascular resistance, these agents decrease the amount of blood returning to the heart (cardiac preload), and reduce the pressure that the heart must pump against (cardiac after load). Helps alleviate some of the stress on the failing heart, thus slowing the disease progression.

Left heart failure

In left heart failure, the left atrium and ventricle are unable to adequately handle blood returning from the lungs. This causes pressure to build up in the pulmonary veins, and fluid accumulates in the lungs. Consequently, left heart failure is associated with pulmonary edema. There are two types of left heart failure: diastolic and systolic. In diastolic heart failure, thick/stiff ventricular walls result in decreased ability to relax fully during diastole. The ejection fraction is near normal. Ejection fraction is normally about 67% - there is always some blood left in the ventricle (but a much smaller volume of blood is left in the ventricle with exercise). In systolic heart failure, there is decreased contractility of the left ventricle and the walls of the heart are thin/distended. The ventricle cannot generate enough force to push enough blood into the circulation. The ejection fraction is not normal - it is less than 40.

Right heart failure

In right heart failure, the right ventricle cannot efficiently pump blood to the lungs because the right atrium and ventricle are unable to handle blood returning from the systemic circulation. This causes fluid to accumulate in the peripheral tissues - ankle edema and organ congestion (liver, spleen) are typical manifestations. Right heart failure is generally caused by left heart failure. The right side of the heart suffers from increased workload due to the left heart failure, which causes the right side to eventually fail. Other causes of right heart failure may include heart valve dysfunction or coronary artery disease (ischemia).

Congestive heart failure symptoms

Peripheral edema, shortness of breath (likely due to pulmonary edema), dizziness, weakness/fatigue, cyanosis Jugular distention - the jugular vein dumps into the superior vena cava which empties into the right atrium - if backed up due to heart failure, blood pools in the jugular vein. When a patient has right heart failure, it is likely that they also have left heart failure. About 6 million Americans have heart failure, and approximately 50% of CHF patients die within five years of diagnosis.

Phosphodiesterase inhibitors

Phosphodiesterase inhibitors exert their effects by inhibiting the phosphodiesterase enzyme that breaks down cAMP in cardiac cells. cAMP is a common second messenger in many cells, and drugs that inhibit the phosphodiesterase enzyme allow cAMP concentrations to increase in the cardiac cells. In these cells, cAMP then acts on membrane calcium channels to allow more calcium to enter the cell. These drugs cause a cAMP-mediated increases in intracellular calcium, which subsequently increases the force of contraction within the myocardial cell (increased contractility). These drugs also have some vasodilation properties, and some of their beneficial effects in CHF may be due to their ability to decrease cardiac preload and after load in some patients (decreased vascular resistance). Milrinone is a phosphodiesterase inhibitor that is given acutely because long term use of this drug results in increased risk for mortality.

Aldosterone antagonist

Spironolactone is an aldosterone antagonist that acts as a diuretic by blocking aldosterone receptors. Spironolactone is a potassium sparing diuretic - it gets rid of fluid by blocking aldosterone, so sodium/water are not reabsorbed.

Stages of heart failure

Stage A: at high risk for development of heart failure (i.e. high blood pressure, high cholesterol, etc.) Stage B: have structural changes (i.e precipitating factors), but no signs or symptoms have appeared. Stage C: have structural changes and have had signs or symptoms. Stage D: advanced heart disease that requires specialized interventions.