Lecture 18: CHF Flashcards
Pathophysiology CHF
Abnormal increases in blood volume & interstitial fluid. Symptoms include dyspnea from pulmonary congestion in left HF, and peripheral edema in right HF
Compensation: Chronic activation of SNS & renin-angiotensin-aldosterone pathway is associated with cardiac tissue remodeling. This prompts additional neurohumoral activation -> vicious cycle -> death
Therapeutic strategies for CHF
- Light aerobic exercise
- Low dietary intake of Na+ (2g sodium diet)
- Smoking cessation
- Achieving ideal weight
- 2L fluid restriction
- Treatment of comorbid conditions
- Use of ACE-inhibitors, diuretics, & inotropic agents
- NSAIDS, alcohol, Ca2+-channel blockers should be avoided if possible (may exacerbate HF)
Management of systolic HF
- Diuretics
- Spironolactone
- Inhibitors of angiotensin (ACE-inhibitors / ARBs)
- Direct vasodilators
- beta-adrenoceptor antagonists (Beta-blockers)
- Inotropic agents
Note: CCB least useful
Management of Diastolic HF
- Diuretics
- beta-adrenoceptor antagonists (beta-blockers)
- Calcium-channel antagonists
Management of CHF by stage
Stage C Goals: treat HPT and lipid disorders, encourage lifestyle mods and dietary salt restrictions
Stage C routine drugs: Diuretics, ACEI, beta-blockers
Beta-Blockers in managing CHF (Carvedilol, Metoprolol)
- Studies demonstrate reverse cardiac remodeling & reduction in mortality & hospitalization (30-40% in patients with NYHA II-IV HF)
- HR (negative inotropic effect) & inhibit renin release (1 receptors)
- Prevent deleterious effects of norepinephrine on cardiac muscle fibers remodeling, hypertrophy etc
- Can get initial exacerbation of symptoms (start at low dose & gradually increase over several weeks)
- Recommended in addition to an ACEi for Pt w:
- Symptomatic heart failure
- Asymptomatic Pt w a decr LVEF or Hx of MI
Adverse
- At the beginning of therapy w Beta-blocker, sx may be exacerbated due to their -ve inotropic effects
- Same as all beta-blockers
- Use cautiously in asthmatics and patients with severe bradycardia
- Fluid retention (upon initial treatment) – an increasing dose of concurrent diuretic may help
Diuretics: Clinical applications
Thiazide diuretics : patients with hypertensive heart disease (with congestive symptoms). Often ineffective as monotherapy due to weak diuretic effect
Loop diuretics : more effective diuretics than thiazides (useful if edema present)
ACE inhibitors
- Agents of choice in CHF
- decr vascular resistance & BP -> incr cardiac output (decr afterload)
- decr salt & H20 retention (decr preload)
- decr long-term remodeling of the heart
- ACE inhibitors improve symptoms in patients with HF, decrease incidence of hospitalization & MI, and prolong survival
ARB
- Candesartan, Valsartan
- Potent competitive antagonists of angiotensin I receptor
- DO NOT affect bradykinin levels
Clinical Application In HF
- Substitute for patients who can’t tolerate ACE inhibitors (severe cough or angioedema)
Adverse Effects
- Similar to ACE inhibitors (no cough)
- Teratogenic
Direct vasodilators
- Hydralazine, Isosorbide dinitrate
- incr vasodilation -> decr cardiac preload
- incr arterial dilation -> decr systemic arteriolar resistance & decr afterload
- Concurrent use of two oral vasodilators: hydralazine & isosorbide dinitrate can produce sustained improvement in LVEF
Clinical applications
- Concurrent use of hydralazine & isosorbide dinitrate recommended for use in patients:
- who cannot tolerate ACEI or ARB or,
- in black patients with advanced heart failure as an adjunct to standard therapy
Digoxin
- Cardiac glycoside
- Derived from digitalis (foxglove) plant
- Widely used in treatment of HF
- Very small difference between therapeutic & toxic dose
- Digoxin can decrease the symptoms of heart failure, increase exercise tolerance and decrease rate of hospitalization, but does not increase survival
MOA
- Positively inotropic: Increases force of heart contraction
- Negatively chronotropic: Decreases heart rate
- Inotropic action : incr cytoplasmic Ca2+ concentration that enhances contractility of cardiac muscle and -> increases cardiac output
- reduced sympathetic activity
- reduced peripheral resistance
- decr HR
- enhanced vagal tone -> decr myocardial O2 demand
- [Ca2+]i must be lowered for cardiac muscle to relax
- Na+/Ca2+ exchanger extrudes Ca2+ from myocyte
- Concentration gradient determines net ion movement
- Inhibiting active transport of Na+ decreases Na+ concentration gradient & ability for Ca2+ to leave cell
- Increased cellular Na+ is exchanged for Ca2+
- Ca2+ is retained intracellularly -> incr [Ca2+]i
- If Na+/K+ ATPase is extensively inhibited -> dysrhythmias
Summary
- Effects of digoxin result from direct action on cardiac muscle as well as indirect actions (autonomic effects):
- incr force and velocity of myocardial systolic contraction (+ve inotropic action)
- decr in the degree of activation of SNS & renin- angiotensin system (-ve chronotropic action)
- Slowing of the HR & conduction velocity through AV node (-ve chronotropic action)
Digoxin: Contraindications
- In patients with diastolic or right-sided HF
- In presence of uncontrolled hypertension
- In presence of bradyarrhythmias
- In non-responders or intolerance
Digoxin: PK
Very potent (narrow safety margin)
Widely distributed (including CSF)
t 1⁄2 = ~36-40 h
Accumulates in muscle -> large Vd (loading dose required)
Digoxin: Adverse
- one of the most common Adverse Drug Reactions (ADR)
- Cardiac effects: arrhythmias, characterized by slowing of
- AV conduction (atrial arrhythmias)
- GI effects: anorexia, nausea & vomiting
- CNS effects: headache, fatigue, confusion, blurred vision, alteration of color perception, halos on dark objects
- Precipitating factors for digoxin toxicity:
- Hypokalemia
- **Quinidine, verapamil & amiodarone **
Digoxin: Interactions
- Ca2+ Accelerates overloading of Ca2+ stores facilitates toxic actions of digoxin, esp. arrhythmias
- Mg2+ Opposite to Ca2+ (Mg2+ antagonizes effects of Ca2+
