HF Treatment Flashcards
HF Treatment goals
o Improve quality of life • Reduce or eliminate symptoms • Reduce or eliminate congestion o Reduce long term mortality o Slow down progression of or reverse cardiac structural abnormalities o Treat all other cardiac risk factors
Identify the pathophysiologic processes that medical therapy may interrupt and sometimes reverse in a patient with systolic heart failure.
• HF = changes on Frank-Starling curve
o Loss of LV contractile force → rightward and downward shift
o Compensation = increased preload (fluid and Na+ retention) to increased CO (moving to right along curve A to B)
o As HF worsens = loss of CO and increase in preload = counterproductive (B to C)
With myocardial injury = activation of RAAS, SNS, and other neurohormonal systems:
1) myocardial toxicity, LVH, fibrosis, apoptosis, myocyte gene reprogramming (blocked by BB, Aldo-I)
2) remodeling and progressive worsening of LV function
3) Peripheral vasoconstriction, hemodynamic alterations, sal and water retention (blocked by ACE-I, ARB, Diuretics)
Identify the basic hemodynamic subtypes of a patient with systolic heart failure
Dry and warm
Optimized output and preload
Wet and warm
Preserved output, but excessive preload; most common problem
Dry and cool
Reduced output and preload
Wet and cool
Reduced output and excessive preload;
Worst prognosis
Diuretics in HF
Acute effects o Sodium excretion and water excretion o Venodilation o Reduction in filling pressures o Helps relieve symptoms Chronic effects o Maintain normal volume state o Work best in combo with Na+ restriction o Work in conjunction with ACE-I and BB • Reduce stimulation of RAAS o Most HF patients need loop diuretics o Do not favorable effect natural history of HF, only relieve symptoms Types diuretics o Loop diuretics = most commonly used o Thiazide diuretics o Aldosterone antagonists o Other K+ sparing diuretics o Carbonic acid inhibitors and aquartics (rarely used)
ACE-I in HF
Effects
o Balanced vasodilators (reduce preload and afterload)
o Reduced angiotensin II levels and enhance kinin actions
o Fluid overload = attenuates effects; volume depletion enhances side effects
o Reduce total mortality, death, hospitalization rates; also beneficial for patients with large acute MI
o Need gradual titration over weeks to achieve high doses for maximum benefits
• Consider symptoms, BP, renal function, electrolyte balance
Side effects:
o Hypotension due to vasodilation
o Hyperkalemia
o Angioedema (rare)
o Cough (common, especially in Asians and women, so switch to ARB)
o Teratogenic
Types
o Sulfhydryl (captopril)
o Dicarboxyl (enalapril, lisinopril, benazepril, ramipril)
o Phosphorus (fosinopril)
o Tissue vs. non-tissue
Beta-blockers in HF
• In HF: chronic adrenergic stimulation = maladaptive
o Toxicity to myocytes
o Increased vasoconstriction
o Increased chance arrhythmias
o Increased O2 consumption
Effects of BBs
o Reduce mortality
• Anti-arrhythmic and anti-ischemic effects
o Reduce HF related hospitalizations
o Increase LV EF (In 50-70% patients)
o Reduce symptoms
o Partially reduce or reverse process of LV remodeling
• Volume reduction
• Mass reduction
• Shape changes back toward ellipsoid
o Intrinsic effect on myocytes not load mediated
Therapy
o Add BBs to ACE-I
• Combined effects of ACE-I and BB is most important therapy for systolic HF
o Add BBs to stable patients at normal volume status
o Begin at low doses, gradually titrate upward
• Dose ratio from low to high usually at least 8:1
o Beneficial effect will not reach maximum for several months
o Drugs used:
• First generation (propranolol) = more difficult for HF patient to tolerate (combined acute negative inotropic effect on β1 and vasoconstriction from unopposed β2 blockage
• Second generation (metoprolol and bisoprolol) better tolerated
• Third generation (carvedilol) alpha-1 block helps counterbalance vasoconstriction
Angiotensin receptor blockers (ARBs) in HF
Selective AT1-receptor blockers
o Blocks vasoconstriction
o Blocks salt/water retention
o Blocks remodeling
Effects
o Effective for HT
o Effective for HF as alternative to ACE-I in patients intolerant of ACE-Is
o Equally effective as ACE-I in HF and post-MI
o Combined therapy with ACE-I and an ARB (maximally inhibits RAAS) = only weakly more beneficial for HF or post-MI patients
Aldosterone antagonists in HF
Physiology:
o Regulated by angiotensin II levels, K+, and catecholamines
o Multiple potentially harmful effects for HF
• Salt and water retention
• K+ depletion
• Vasoconstriction
• Fibrosis
• Inflammation and platelet aggregation
o Aldosterone is not suppressed by ACE-I over long term
Aldosterone antagonist therapy
o More effective to block aldosterone + ACE than block RAAS with ACE-I and ARB
o RALES trial = benefit in HF patients with spironolactone
• Decreased mortality and frequency of hospitalization for cardiac reasons
o EPHESUS trial = benefit of eplerenone in post-MI HF
Side effects:
o Hyperkalemia (leading to increased hospitalizations, renal insufficiency, and mortality)
o Gynecomastia with spironolactone
• Eplerenone has greater specificity for aldosterone receptor, so less incidence of gynecomastia
Therapeutic use:
o Established for post-MI and severe HF patients
• Also used for less severe forms of HF (unproven)
o Monitor serum K+ and renal function closely
o Spironolactone = most commonly used
o Eplerenone used when side effects not tolerable
Digoxin in HF
Physiology:
o A cardiac glycoside
o Chronic positive inotrope: inhibits Na+ and K+ transport across cell membranes → increases intracellular Na+ concentration → increases contractile force
o Hemodynamic effects: decreased RV and RA pressures, increased CO, increased stroke work
Uses
o HF patients in sinus rhythm with persistent symptoms
o HF patients with atrial fibrillation to help control HR by slowing AV node conduction
o Best combination of safety and efficacy at lower levels in blood: 0.5-1.0 ng/ml
Toxicity
o Heart block and bradycardia
o Ectopic and reentrant arrhythmias (SVT and VT)
o Anorexia, nausea, vomiting
o Visual disturbances and confusion
o Multiple drug interactions
o Treat toxicity with Digibind (Ab to eliminate excess)
Vasodilators in HF
Physiology
o Vasodilation reduces preload and afterload → reduced MV regurgitation, increased forward SV → increased cardiac efficiency, reduced O2 consumption, stable BP
Drugs used
o Hydralazine
o Isosorbide dinitrate
o Use vasodilators in patients refractory to standard treatment
Evidence: A-HeFT (Afriacn American HF trial)
o Patients self-identified as African American
o Added vasodilator to standard HF therapy with ACE-I
o Significantly increased survival and decreased mortality
Device Therapy in HF
• To prevent sudden death
Implantable cardiac defibrillator (ICD):
o Indicated for patients with EF < 35%
Combined pacemaker and defibrillator
o Indicated for patients with low EF and abnormal conduction
o Effects:
• Improved quality of life and HF symptoms
• Improved exercise capacity
• Improved EF, shrinks heart to smaller size
• Reduce mortality (some cases)
LV assisit devices
o Patient not responding to medial treatment for cardiogenic shock, pulmonary edema or other decompensated HF
o Bridge to transplantation, transplant candidacy, destination therapy
Inotropic therapy
For ACUTE HF
o HF patients with congestion and low CO (no benefit for patients with good end organ perfusion)
• Diuretics alone not help with CO
o Used if patient not responding to combined used of diuretics and vasodilators
o Used only if systolic dysfunction
o Monitor hospital course closely
Milrinone
o Phosphodiesterase inhibitor → raises cAMP levels
o Causes increased contractility
o Vasodilates arteries and veins = reduces preload
o Net effect: increase in Cl, reduction in PCWP, SVR, and PVR
o Used: patients with congestion and low output and known systolic dysfunction
Dobutamine
o Simulates beta-1 receptors → increased inotrophy
o Also: chronotrophic, hypertensive and arrhythmogenic effects
o Used: patients with severe systolic dysfunction and evidence of poor end organ perfusion
Dopamine
o Simulates beta-1 receptors
o Effects vary by dose
o Higher doses: more vasoconstriction
o Positive inotropic and chronotropic effects
o Used: patients with hypotension and congestion and poor end organ perfusion
