Congestive heart failure

pharmacotherapeutics I -2nd Pharm D

1. Congestive Heart Failure Heart failure is defined as the pathophysiologic state in which impaired cardiac function is unable to maintain an adequate circulation for the metabolic needs of the tissues of the body.

2. Causes

3. Symptoms Congested lungs Dizziness, fatigue, and weakness. Fluid and water retention Severe shortness of breath. Arrythmias . Coughing up foamy, pink mucus.

4. Classification Systolic versus diastolic Systolic- loss of contractility Diastolic- decreased filling or preload Left-sided versus right –sided Left- lungs Right-peripheral Acute versus chronic Acute- MI Chronic- cardiomyopathy

5. Classification of Heart Failure AHA (American Heart Association) Guidelines Stage A – High risk of HF, without structural heart disease or symptoms Stage B – Heart disease with asymptomatic left ventricular dysfunction Stage C – Prior or current symptoms of HF Stage D – Advanced heart disease and severely symptomatic or refractory HF

6. Pathophysiology of CHF Pump fails → decreased stroke volume /CO. Compensatory mechanisms kick in to increase CO SNS stimulation → release of epinephrine/nor-epinephrine Increase HR Increase contractility Peripheral vasoconstriction (increases afterload ) Myocardial hypertrophy: walls of heart thicken to provide more muscle mass → stronger contractions

7. Pathophysiology of CHF Hormonal response: ↓’d renal perfusion interpreted by juxtaglomerular apparatus as hypovolemia . Thus: Kidneys release renin , which stimulates conversion of antiotensin I → angiotensin II, which causes: Aldosterone release → Na retention and water retention (via ADH secretion) Peripheral vasoconstriction

8. Pathophysiology of CHF Compensatory mechanisms may restore CO to near-normal. But, if excessive the compensatory mechanisms can worsen heart failure because . . .

9. Pathophysiology of CHF Vasoconstriction: ↑’s the resistance against which heart has to pump (i.e., ↑’s afterload ), and may therefore ↓ CO Na and water retention: ↑’s fluid volume, which ↑’s preload. If too much “stretch” (too much fluid) → ↓ strength of contraction and ↓’s CO Excessive tachycardia → ↓’d diastolic filling time → ↓’d ventricular filling → ↓’d SV and CO

10. Complications Arrythmias Heart valve problems Liver failure Kidney failure

11. DIAGNOSIS No single test is available to confirm the diagnosis of heart failure. The patient’s volume status should be documented by assessing the body weight, JVP, and presence or absence of pulmonary congestion and peripheral edema. Laboratory testing may assist in identification of disorders that cause or worsen heart failure. The initial evaluation should include a complete blood count, serum electrolytes (including magnesium), tests of renal and hepatic function, urinalysis, lipid profile, chest x-ray, and a 12-lead electrocardiogram (ECG). The echocardiogram also can determine the presence of systolic and/or diastolic dysfunction and the left ventricular ejection fraction (LVEF).

12. Chronic Treatment of Heart Failure Correction of systemic factors Thyroid dysfunction Infections Uncontrolled diabetes Hypertension Lifestyle modification Lower salt intake Alcohol cessation Medication compliance Maximize medications Discontinue drugs that may contribute to heart failure (NSAIDS, antiarrhythmics , calcium channel blockers)

13. Order of Therapy Loop diuretics ACE inhibitor (or ARB if not tolerated) Beta blockers Digoxin Hydralazine , Nitrate Potassium sparing diuretcs

14. Diuretics Bolus administration of diuretics decreases preload by functional venodilation within 5 to 15 minutes and later ( >20 minutes) via sodium and water excretion, thereby improving pulmonary congestion. Loop diuretics Furosemide , buteminide For Fluid control, and to help relieve symptoms Potassium-sparing diuretics Spironolactone , eplerenone Help enhance diuresis Maintain potassium Shown to improve survival in CHF Although chronic diuretic therapy frequently is used in heart failure patients, it is not mandatory and is required only in patients with peripheral edema and/or pulmonary congestion.

15. ACE Inhibitor ACE inhibitors act upon the renin –angiotensin– aldosterone system, and they reduce afterload by reducing the formation of angiotensin II, a potent vasoconstrictor in the arterial system. These drugs also have an indirect effect on sodium and water retention by inhibiting the release of aldosterone and vasopressin, thereby reducing venous congestion and preload. Improve survival in patients with all severities of heart failure. Begin therapy low and titrate up as possible: Enalapril – 2.5 mg po BID Captopril – 6.25 mg po TID Lisinopril – 5 mg po QDaily If cannot tolerate, may try ARB

16. Beta Blocker therapy Formerly, β-blockers have been contraindicated in patients with heart failure. However, the sympathetic neurohormonal overactivity that occurs in response to the failing heart has been identified as a decisive factor in the progression of ventricular dysfunction. The use of β-blockers is, therefore, recommended for all patients with heart failure due to left ventricular systolic dysfunction, irrespective of age and the degree of dysfunction. Certain Beta blockers ( carvedilol , metoprolol , bisoprolol ) can improve overall and event free survival in NYHA class II to III HF, probably in class IV .

17. Cause “reverse remodeling” of the left ventricle. Contraindicated: Heart rate <60 bpm Symptomatic bradycardia Signs of peripheral hypoperfusion COPD, asthma PR interval > 0.24 sec, 2 nd or 3 rd degree block

18. Hydralazine plus Nitrates Nitric oxide is released from the nitrate compound and this in turn activates soluble guanylate cyclase in vascular smooth muscle, leading to the vasodilatory effect. Hydralazine has a direct action on arteriolar smooth muscle to produce arterial vasodilation. Dosing : Hydralazine Started at 25 mg po TID, titrated up to 100 mg po TID Isosorbide dinitrate S tarted at 40 mg po TID/QID Decreased mortality, lower rates of hospitalization, and improvement in quality of life.

19. Digoxin Given to patients with HF to control symptoms such as fatigue, dyspnea , exercise intolerance Shown to significantly reduce hospitalization for heart failure, but no benefit in terms of overall mortality . Digoxin doses should be adjusted to achieve plasma concentrations of 0.5 to 1 ng / mL ; higher plasma concentrations are not associated with additional benefits but may be associated with increased risk of toxicity.

20. Digoxin exerts its positive inotropic effect by binding to sodium- and potassium-activated adenosine triphosphatase ( Na+,K +- ATPase or sodium pump) Inhibition of Na+,K +- ATPase decreases outward transport of sodium and leads to increased intracellular sodium concentrations. Higher intracellular sodium concentrations favor calcium entry and reduce calcium extrusion from the cell through effects on the sodium-calcium exchanger. The result is increased storage of intracellular calcium in the sarcoplasmic reticulum and, with each action potential, a greater release of calcium to activate contractile elements and thus increases contractility of heart.

21. Inotropic agents Acute heart failure may require the use of one or more inotropic agents, particularly the sympathomimetic agents dobutamine and dopamine, in an intravenous continuous infusion. With dopamine, low doses (0–2 μcg /kg/min) have a predominant effect on dopamine receptors within the kidneys to improve urine output, intermediate doses (2–5 μcg /kg/min) affect β1-receptors, producing an inotropic effect, and high doses (10 μcg /kg/min) have a predominant action on α- adrenoreceptors .

22. Other important medication in Heart Failure -- Statins Statin therapy is recommended in CHF for the secondary prevention of cardiovascular disease. Some studies have shown a possible benefit specifically in HF with statin therapy Improved LVEF Reversal of ventricular remodeling Reduction in inflammatory markers (CRP, IL-6, TNF-alphaII)

23. Meds to AVOID in heart failure NSAIDS Can cause worsening of preexisting HF Thiazolidinediones Include rosiglitazone (Avandia), and pioglitazone (Actos) Cause fluid retention that can exacerbate HF Metformin People with HF who take it are at increased risk of potentially lethic lactic acidosis

24. TREATMENT OF ADVANCED/DECOMPENSATED HEART FAILURE