Heart Failure Flashcards
- What is the main feature of CHF?
CO (either systolic or diastolic) inadequate to provide O2 that the body needs
- What is systolic failure of CHF?
Mechanical pumping (CONTRACTILITY) and ejection fraction of the heart are reduced. Tx needs inotropic agents to increase amt of calcium. Do not treat with calcium channel blockers as they reduce contractility and SV.
- What is diastolic failure of CHF?
Occurs due to stiffening of the heart muscles and loss of adequate relaxation leading to abnormal ventricular filling. Tx with diuretics (to help with pulm edema, but will decrease EDV therefore SV at a certain pt), calcium channel blockers (improved ventricular relaxation and reducing HR to allowing for more time with filling), B-blockers (similar to calcium channel blockers. Positive inotropes ARE NOT used for tx in diastolic failure because they increase outflow obstruction.
- What is the effect of heart failure on preload?
In both systolic and diastolic heart failure there is an increased preload leading to an increase in SV (due to Frank-Starling curve). At a certain pt when diastolic or systolic dysfunction becomes too severe, the heart is exhausted leading to a decline in SV.
- What are the different classifications of heart failure described by the AHA?
Stage A → high risk for developing heart failure (HTN, diabetes, CAD, hx of cardiomyopathy)
Stage B → asymptomatic heart failure (previous MI, LV dysfunction, valvular disease)
Stage C → symptomatic heart failure (structural heart disease, dyspnea, fatigue, impaired exercise tolerance)
Stage D → refractory end-stage heart failure (marked symptoms at rest despite maximal medical therapy)
- Why does the heart rate increase with heart failure?
SV decreases leading to activation of sympathetics (B1-adrenoceptors) and therefore increase in HR
- What is cardiac remodeling?
During HF, there is a decrease in CO leading to myocardial hypertrophy to maintain cardiac performance. At a certain point there are ischemic changes and diastolic filling impairment. Remodeling refers to the dilation and slow changes of the heart due to increased stress on the heart.
- What are the neurohumoral compensatory responses to HF?
- Sympathetic nervous system activation – low bp is detected by the baroreceptors leading to B1-activation increasing both HR and contractility. A1 receptors are also activated causing increased peripheral resistance.
- RAA activation – decreased CO, decreased blood flow to kidneys stimulating renin release therefore increasing peripheral bp
- Increased release of ADH and ANP
- Define positive inotropy.
Increase in cardiac contractility (force)
- Define positive chronotropy.
Increase in HR
- Define positive dromotropy.
Increase in conduction velocity
- Define positive lusitropy.
Increase in rate of relaxation of the heart
- What is the basis behind long term treatment of HF?
- RAA inhibition
- SNS activation
* These decrease amt of cardiac remodeling. Remodeling is irreversible so surgical intervention is the only tx when drugs stop working.
* *reduce preload, reduce afterload, enhance inotropic state
- What classes of drugs are recommended for stages A-D of HF?
Stage A → ACEI, ARB
Stage B → ACEI, ARB, B-blockers
Stage C → diuretics, ACEI, B-blocker [routine drugs], aldosterone antag, ARB, digoxin or hydralazine/isosorbide dintrate [if symptoms do not improve]
Stage D → specialized therapies, continuous support, continuous IV positive inotropic therapy, cardiac transplantation or hospice care
- What is the role of diuretics for HF patients?
Whenever there is evidence of fluid retention (pulm edema, systemic edema, dyspnea), diuretic therapy is recommended. Diuretics reduce venous pressure and ventricular output. This is not used alone b/c it does not alter the disease progression or survival.
- Thiazide diuretics (ex. hydrochlorothiazide) → preferred over loop diuretics in pts with elevated bp or only mild fluid retention
- Loop diuretics (ex. Furosemide) → necessary to restore and maintain euvolemia in HF, better than thiazides b/c they maintain their effectiveness in presence of impaired renal function
- Aldosterone antagonist (ex. spironolactone) → more useful to prevent cardiac fibrosis and remodeling compared to its diuretic effects
- What are the different categories of angiotensin inhibitors (indirect vasodilators)?
- ACE inhibitors → reduce LVEF (stage A, B, C), reduce peripheral resistance and therefore afterload, reduce sympathetic activity, reduce long-term remodeling of the heart and vessels
- ARBs → use only in pts with stage A, B, C heart failure who are intolerance of ACE inhibitors, Candesartan and valsartan are the only ARBs currently approved for HF
- Renin inhibitors → recently approved to for HTN and is in clinical trials for HF
- What category do Hydralazine and Isosorbide Dinitrate fall under?
Direct vasodilators that concurrently improve LVEF
- What is the MOA of Hydralazine and Isosorbide Dinitrate?
Concurrent use produces sustained improvement in LVEF. These drugs are part of the standard therapy in African Americans with moderately severe to severe HF. They can be used in pts unable to tolerate ACE inhibitors or ARBs due to renal insufficiency or hyperkalemia. These medications are usually given along with a diuretic and B-blocker to counter side effects.
These drugs were combined originally b/c of their complementary hemodynamic actions. Nitrates are venodilators, therefore reducing preload and Hydralazine is a vasodilator that acts primarily on arterial smooth muscle reducing peripheral vascular resistance therefore increasing SV and CO. It is also used to reduce cardiac remodeling. Patients take doses 3 times a day.
Adverse side effects for the combination therapy → Hypotension, reflex tachycardia and Na+ and water retention, headache, dizziness, GI disturbances
- What category of drugs do Carvedilol and Metoprolol fall under?
B-adrenoceptor antagonists (B blockers) – cardioinhibitory drugs
- What is the clinical application, MOA and adverse effects for Carvedilol and Metoprolol?
Clinical application → B blockers use to treat HTN, angina, MI, arrhythmias, HF. B-blockers slow disease progression, reduce mortality in pts with HF, reduce LVEF, pts should receive B-blockers even if symptoms are mild or well-controlled with ACE inhibitors and diuretic therapy, also recommended for pt with asymptomatic reduced LVEF (stage B), slows the HR and reduces myocardial oxygen
Mechanism of action → antiarrhythmic effects, slowing or reversing ventricular remodeling, improving LV systolic dysfunction, decreasing HR and ventricular wall stress, inhibiting plasma renin release, negative inotropic effect therefore need to be started at low dose
Adverse effects → drug withdrawal, CV effect (bradycardia, reduced exercise capacity, HF, hypotension, AV block), disturbed lipid metabolism, hypoglycemia, bronchoconstriction, CNS effects
Contraindicated → reactive airway disease (asthma, COPD), pts with sinus bradycardia and partial AV block
- What category of drugs does digoxin fall under?
Cardiac glycoside, inotropic agent
- What is the clinical application or Digoxin?
Decreases symptoms of HF but DOES NOT increase survival. Indicated for pts with HF and supraventricular tachyarrhythmias. Should be used with other standard HF therapies in pts with symptomatic HF to reduce hospitalizations. Benefits of digoxin in tx with HF has been due to its positive inotropic effect on failing myocardium and efficacy in controlling the ventricular rate response to atrial fibrillation. Digoxin is both positively inotropic (increases contractility of heart) and negatively chronotropic (decreases heart rate).
- Explain the positive inotropic effect of Digoxin.
Digoxin is a selective and potent inhibitor of cellular Na+/K+ ATPase allowing for an increase in myocardial intracellular calcium. Inhibition of the Na+/K+ ATPase in vascular smooth muscle causes depolarization which causes smooth muscle contraction and vasoconstriction. Digoxin binds to phosphorylated form of a-subunit of Na+/K+ ATPase. Extracellular K+ promotes dephosphorylation of the enzyme decreasing affinity of enzyme for digoxin.
- Explain the negative chronotropic effect of Digoxin.
Decreases HR due to increased activation of vagal nerve
**note that at high digoxin concentrations there is an increase in SNS activity increasing the automaticity of the cardiac tissue contributing to development of atrial and ventricular arrhythmias
