Clinical Treatment of HF

Question 1

GOALS OF MANAGEMENT HF

Answer 1

General goals of any therapy

• 1. ↑ quantity of life (improve survival)
• 2. ↑ quality of life (reduce symptoms)
• 3. Decrease financial / resource burden of disease

HF-specific goals

• Correction of the underlying cause of HF
  
  • o e.g. revascularization for ischemia
  • o not possible to reverse many causes (e.g. infarcted tissue)
• Elimination of precipitating factors
  
  • o e.g. infection, anemia,
• Reduction of congestion (fluid optimization is a major part of HF therapy)
• Improve flow (may be difficult to do medically; mechanical devices/txplt)
• Modulate neurohormal activation
  
  • o Long-term stabilization, positive remodeling, increased survival

Question 2

TREATMENT: DIURETIC

Answer 2

•  Reverses the sodium and fluid retention of HF
•  Classes
  
  •  Loop diuretics are preferred due to potency
  •  Can be augmented with a thiazide diuretic
•  The most common HF therapy
  
  •  90% of HF hospitalizations, 70% only Rx Δ
•  Can be used chronically and acutely
  
  •  Typically PO dose at baseline, adjust to patient need
  • Often used IV in the hospital
    
    • • Congested intestine may not absorb PO as well
    • • With worsening renal function, also need higher dose
•  Typically work at the far end of the Frank-Starling curve, such that significant decreases in pressure produce minimal changes in stroke volume (and thus cardiac output). Thus, symptoms of congestion can be reduced without major effects on blood flow.
•  No survival data; ↑doses signify worse disease

Question 3

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEI)

Answer 3

•  …prils (lisinopril, enalapril, benazepril)
• Use for HFrEF
•  Block conversion of ATI to ATII
•  Effects
  
  •  Direct vasodilation
  •  Decreased aldosterone activation
  • Other effects beyond ATII?
•  Side effects
  
  •  Hypotension
  •  Worsening renal function (afferent vasocontraction)
  • Hyperkalemia (excretion of Na in exchange for K reabsorption)
  •  Cough (kinin potentiation)
  •  Angioedema = swelling under skin, not on surface

Question 4

ANGIOTENSIN RECEPTOR BLOCKERS (ARB)

Answer 4

• Similar efect as ACEI-> use for HFrEF
•  …sartans (e.g. valsartan, candesartan, losartan)  Effect: Block the receptor of angiotensin II
•  Clinical use:
  
  •  In studies have been equivalent to ACEI
  •  Controversial whether use in combination (ARB + ACEI) provides added benefit
  •  Generally used when patients develop cough to ACEI
•  Side effects:
  
  •  ARBs do not produce kinin potentiation (no cough)
  • Otherwise side effects are similar

Question 5

ALDOSTERONE RECEPTOR BLOCKERS

Answer 5

• Chronic excess of aldo- sterone in heart failure contributes to cardiac fibrosis and adverse ventricular remodeling
•  Spironolactone and eplerenone
•  Effect:
  
  •  Block effect of aldosterone on the kidney
  • • ACEI/ARB aldosterone block is incomplete • Produces additional sodium loss (diuretic)
•  Other effects
  
  • • Antifibrotic
•  Side effects
  
  • ** Hyperkalemia (requires close monitoring) **

Question 6

BETA-BLOCKERS

Answer 6

•  …olols (metoprolol, carvedilol, bisoprolol)  Effect:
•  Antagonize effect of sypathetic system (epinephrine/norepinephrine)
  
  • β1 blockade:
    
    • – Negative chronotrope (slow heart rate, less arrhythmia)
    • – Negative inotrope (decreased metabolic demand)
  • [α1 blockade: vasodilation]
•  Side effects:
  
  •  Negative inotrope: short-term loss for long-term gain
    
    • • Fluid retention
    • • Hypotension
    • • Decreased cardiac output, even cardiogenic shock
  •  Bronchoconstriction

Question 7

Adrenergic and RAAS blockers

Answer 7

Question 8

VASODILATORS

Answer 8

•  Arterial vasodilation (antihypertensives)
  
  •  Decrease in LV afterload
  •  Reduced cardiac work
  •  Less mitral regurgitation 
• Venous vasodilation
  
  •  Decrease in preload
•  Pulmonary arterial vasodilation
  
  •  Decrease in RV afterload

Question 9

ELECTRICAL THERAPIES FOR HFrEF

Answer 9

•  Implanted Cardioverter Defibrillators
  
  •  Patients with LVEF <=35% or prior dangerous heart rhythms
  •  Abort sudden cardiac death from ventricular tachycardia / fibrillation
•  Cardiac Resynchronization Therapy / Biventricular Pacemakers (CRT or BiV)
  
  •  Left ventricular lead placed from the RA through the coronary sinus over the epicardium of the LV (3 leads: RA, RV, cor sinus/LV)
  •  For patients with QRS duration > 120 msec (bundle brank block)
  •  Cause the LV lateral wall and septal wall to contract together, which produces a more efficient contraction / ↑ stroke volume, may also improve mitral valve function / ↓ regurgitation
  •  Usually placed with ICD

Question 10

INOTROPES

Answer 10

• All drug increase contractility of heart muscle
•  Examples:
  
  •  Digoxin (PO) - K/Na exchanger
  •  Dobutamine (IV) – β agonist (opposite of beta blocker)
  •  Milrinone (IV) – phosphodiesterase inhibitor (effect is similar to dobutamine) ​
•  Clinical Use
  
  •  IV agents used short term in the ICU to reverse shock
    
    • • Long-term they worsen remodeling, increase mortality
  •  Digoxin has no effect on mortality but may reduce symptoms and hospitalization (also some decrease in heart rate in AFib)
    
    • In high doses causes dig toxicity (mostly arrhythmias)
    • Completely renally cleared, so needs dose adjustment with renal dysfunction

Question 11

END-STAGE HF

Answer 11

HF will progress in most patients. Once standard therapies begin to fail, advanced therapies should be considered:

• Aggressive advanced therapy (typically requires up front risk, and cost; used only in patients with HFrEF)
  
  • o Cardiac transplantation (<2500 organs available per year)
  • o Mechanical circulatory support (ventricular assist devices [LVAD])
  •  As a “bridge to transplantation”, to stabilize patients while waiting
  •  As “destination therapy” – the final therapy
• Palliative advanced therapy (paradigm shift from quantity to quality of life)
  
  • o Hospice
  • o Continuous infusion of inotropic therapy