Pharma Co-therapy Of Heart Failure Quiz

Dobutamine and dopamine are used in acute decompensated heart failure to increase the contractility and vasodilation in order to provide short term support for the patient.

Dobutamine is a beta-one agonist, which will stimulate the heart to increase contractility and inotropic activity--this is its primary reason for use.

Dopamine has dose-dependent effects at different receptors. Between 3-10 mcg/kg/min, dopamine is a beta-one agonist that increases heart rate and contractility, thus increasing cardiac output.

Thus, these agents are used to increase cardiac output, not for acutely treating hypertension, although blood pressure would be lowered by their use, due to the increased cardiac output requiring less vasoconstriction to maintain blood pressure.

This is true, but the focus remains on controlling symptoms and the CV comorbidities/ risk factors such as HTN, CAD, and atrial fibrillation. Controlling blood pressure may be the best option for patients with this condition.

Combined alpha and beta-blockers will prevent the effects of norepinephrine on the vasculature and on decreasing vasoconstriction, in addition to the beta-blocking effects.

Direct acting vasodilators such as hydralazine and the nitrates dilate the arteries and veins to decrease afterload by decreasing blood pressure.

Inotropic agents such as dobutamine and dopamine are used in acute situations to increase the the contractility of the heart.

The monitoring of electrolytes, specifically potassium, is critical for patients on digoxin. Frequently, patients on digoxin are also on diuretics, which can result in hypokalemia. Less potassium means digoxin can bind with greater affinity to the Na+/K+ pump. This results in an increased effect of digoxin. This is definitely clinically significant.

The cardiac index (CI) is a measure of cardiac output (CO) normalized for patient size in meters squared. To ensure adequate perfusion, a goal of greater than 2.2 L/min/m2 is supported. A normal human's cardiac index is 2.8-4.2 L/min/m2, but a heart failure may not achieve such a perfusion level in the acute setting, so the patient will be at goal if the CI is greater than 2.2 L/min/m2. Thus, at 2.0 L/min/m2, this patient is not at goal.

The definition of heart failure is a clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. Basically, the heart is unable to deliver enough blood to oxygenate the circulation. This could be due to a structural impairment, such as left ventricular hypertrophy, or simply a functional impairment. The heart may not be filling appropriately due to elevated resistance, or it may not be ejecting blood properly due to an inability to properly contract. Knowing what is wrong, the pathophysiology, permits you to predict which therapies will be of benefit.

The body has mechanisms for ensuring adequate blood flow to the brain and to the heart. These compensations result in decreased blood flow to the kidneys. Decreasing the blood flow to the kidneys is dangerous, and a vicious cycle that worsens the heart failure.

Due to the decreased filtration, more volume backs up in the body, and this increases the pressure in the veins, which raises the hydrostatic pressure in the capillaries (blood is trying to get through but there's too much blood on the venous side of the capillary), leading to leakage into the interstitial fluid space = EDEMA, which is a hallmark symptom of heart failure.

The reduced blood flow also activates the renin angiotensin aldosterone system, since aldosterone will retain more Na+ and water to fill the vasculature and constrict the vasculature to ATTEMPT TO INCREASE the renal pressure.

The decrease in blood pressure will also activate the sympathetic nervous system, to try to stimulate the heart and constrict the vasculature.

The secretion of vasopressin is also increased in order to stimulate water reabsorption and constrict the vasculature.
In case that was not enough, endothelin, a vasoconstrictor, is also produced in greater quantities.

Keep these pathophysiological changes in mind in order to justify drug therapy that targets each of these facts.

Beta-blockers will slow down the heart rate and allow the heart to spend more time in diastole, where it can fill with blood.

Digoxin will increase the force of contraction of the heart through its special mechanism of knocking out Na+/K+ channels, causing less Na+ into a myocyte (cardiac cell), causing less Ca+ out of a myocyte, which means more Ca+ in the myocyte to contract with each beat.

By decreasing the volume in the vasculature, the diuretic will reduce the preload that the heart must pump.

Inhibitors of the RAAS will decrease the production of aldosterone, thereby lowering the afterload due to less vasoconstriction and the preload due to less Na+ and water retention.

The pulmonary capillary wedge pressure is a measure of the pressure in the lungs. If this pressure is elevated, it may lead to leakage of fluid. A normal human will have a PCWP of less than 12 mmHg, but an acutely decompensated heart failure patient has a goal of less than 18 mmHg. If the patient with heart failure has a PCWP of less than 18 mmHg, the patient is at goal. Therefore, this patient is not at goal.

Diuretic therapy has no mortality (death) benefit observed in studies, but may improve symptoms of fluid retention (morbidity). Use them when necessary, but remember that it is not necessarily increased the life expectancy of the patient.

The targeted therapeutic serum concentration is based off the clinical trial in which the greatest mortality benefit was seen in the range of 0.5-0.9 ng/mL, specifically 0.7 ng/mL. Target your dose to match this serum concentration, but monitor for adverse effects as well.

These are the three beta-blockers that have been proven in trials to result in a decrease in all-cause mortality. These should probably be the beta-blockers you choose for your patient.

Beta-blockers must be tapered when discontinuing, otherwise the patient will experience rebound hypertension. The mechanism is thought to be increased sensitivity and up-regulation of the beta-receptors, since they have been blocked by the beta-blocker. Thus, when the beta-blocker is discontinued, these receptors are now free to be extra sensitive to the effects of norepinephrine/epinephrine and thus hypertension is observed.

Keep in mind that beta-blockers decrease cardiac output. They decrease the heart rate and contractility. This allows the heart to decrease its workload and spend more time in diastole, which increases perfusion. However, this therapeutic mechanism can become dangerous, if the heart rate is decreased excessively, such as in cardiogenic shock.

Hepatotoxicity and hypermagnesemia are not particularly associated with beta-blockers.

This patient has both a CI and PCWP that are not at goal. The patient is cold due to inadequate perfusion, and is wet due to increased pressure in the lungs. The treatment for such a patient, who may be in cardiogenic shock and become hemodynamically unstable, is a combination of diuretics and inotropes, to get rid of the excess fluid and stimulate the heart to increase the cardiac output and cardiac index.

Hopefully you were able to reason your way through this one. Since atrial fibrillation would decrease the filling that occurs during diastole (see your notes on dysrhythmias), it would cause even more harm to a heart that has trouble filling, which is the heart with diastolic dysfunction. Likewise, tachycardia would worsen heart failure due to diastolic dysfunction since the fast heart rate would decrease the time in diastole and therefore decrease the ability of the heart to fill with blood.

The B-CONVINCED study found that the continuation of beta-blockers was not associated with a delayed improvement in dyspnea, and had better adherence 3 months post decompensation. However, the exceptions include to discontinue the beta-blocker and ACE-I/ARB if the patient is in cardiogenic shock (since the patient needs to have an adequate cardiac output) or has kidney dysfunction, and to discontinue the ACE-I/ARB if hyperkalemic.

ACE inhibitors and ARBs are harmful in an acute renal insufficiency case because they can increase the serum creatinine. In such a situation, hydralazine with isosorbide dinitrate may be used. Exogenous nitrate therapy has beneficial effects for HF treatment at the cellular and hemodynamic level by enhancing endothelium dependent vasodilation, improving systolic function and exercise capacity, and inhibiting cardiac remodeling black and non-black HF patients. Both Vasodilator-Heart Failure Trials I and II showed improved ejection fraction and exercise tolerance with this therapy in whites and in blacks.

Please keep in mind that systolic dysfunction and diastolic dysfunction are not entirely separate entities. Patients may present with signs and symptoms of both type of heart failure, and the end result is a decrease in cardiac output.

In diastolic dysfunction, the contractility of the ventricle is not necessarily decreased, as it is in systolic dysfunction.

However, the filling is slightly decreased, due to increased resistance from thickened walls in the heart.

The ventricle is not dilated, but it is more difficult to fill due to the stiff walls, so it fills less.

The preload is not increased since the heart fills with slightly less amount of blood, and the pressure caused by the slightly less amount of blood is greater, due to the inability to expand.

Likewise, the ejection fraction is not decreased, since the heart ejects the same fraction, but was filled with less blood. For example, instead of ejecting 40ml out of 50ml, the heart with diastolic dysfunction is now ejecting 32ml out of 40ml. The ejection fraction in each case is identical at 0.8, but the heart is ejecting 8ml less with diastolic dysfunction.

It is often difficult to tell if the mortality benefit may be a class effect, but the selected drugs (candesartan, valsartan, and losartan) have a proven mortality benefit as evidenced by clinical trials.

The contractility of the left ventricle is reduced and the heart cannot pump as well during systole, hence the term systolic dysfunction.

The rate of filling of the ventricles during diastole is not slowed, since the filling is not dependent on the ability of the heart to constrict. The filling during DIASTOLE is slowed in DIASTOLIC dysfunction, usually due to a stiffening of the walls of the ventricular chambers, which increases the pressure when the blood enters.

The ventricle is dilated as a result of not ejecting the blood that filled the chambers.

The preload is increased since the ventricle is dilated and the heart can fill with more blood.

The ejection fraction is decreased since the heart fills with more blood, but the ventricle cannot contract enough to eject all the blood.

A myocardial infarction may contribute to heart failure due to the death of viable cardiac muscle cells. Fewer muscle cells means a reduced ability for the heart to do its job: pumping blood!

Untreated hypertension can lead to atherosclerosis, and increased resistance. This means the heart must work harder on each beat to overcome the resistance to pump blood into the circulation. Over time, the heart will wear out.

A stroke does not affect the heart's ability to pump, and diabetes has no direct link to causing heart failure.

As a side note, the thiazolidinediones (TZDs), pioglitazone and rosiglitazone, are used to treat diabetes and have been shown to worsen and cause new onset heart failure by increasing fluid retention, and should be avoided in patients with advanced (Stage III or IV) heart failure.

Even though furosemide has only 50% bioavailability and bumetanide and torsemide have greater than 90% bioavailability, current practice is to give the same dose in mg as the patient is on at home, but to give those mg IV.

Digoxin has no proven mortality benefit, but may be used to decrease symptoms and hospitalizations. These are the findings from trials that have evaluated digoxin. Digoxin is also indicated for treating atrial fibrillation. By increasing the contractility of the heart, digoxin increases cardiac output, which allows for a decreased heart rate and thus less chance of arrhythmia.

Acetaminophen is a safe option for OTC pain relief in heart failure patients. Recommend this option over the use of an NSAID.

Diltiazem and verapamil and both non-dihydropyridine calcium channel blockers, and slow down conduction in the AV node, which could be dangerous for a heart failure patient with already decreased cardiac output. If a calcium channel blocker is to be used for controlling hypertension or ischemic symptoms, then a dihydropyridine such as amlodipine or nifedipine should be used.

All NSAIDs should be avoided as they can lead to fluid retention and have negative effects on the kidney. They decrease the production of prostaglandins, which decreases pain but also vasodilation, thus resulting in vasoconstriction.

Pioglitazone (Actos) is a thiazolidinedione (TZD) and should be avoided as it can cause a worsening of heart failure. Rosiglitazone (Avandia) is another TZD and as such should be avoided.

Terazosin is an alpha-one antagonist and is beneficial due to reducing afterload and preload.