Pathophysiology of Heart Failure

Question 1

Prevalence, Incidence and Mortality of Heart Failure in the US

Answer 1

• prev=~5,000,000
• incidence=550,000
• mortality=250,000

Question 2

Approximate cost of heart failure in US

Answer 2

$37.5 billion

Question 3

Reasons for increasing incidence and prevalence

Answer 3

• Aging population
• Increased survival of initial cardiac disease
• Therapies generally stabilize HF, but do not often cure it.

Question 4

Heart failure syndrome (forward failure) definition

Answer 4

Heart failure is the inability of the hear to pump blood forward at a sufficient rate to meet the metabolic demands of the body.

Question 5

Heart failure syndrome (backward failure) definition

Answer 5

the ability to pump blood at a a sufficient rate to meet metabolic demands only if the cardiac filling pressures are abnormally high

Question 6

Major characteristics of heart failure

Answer 6

• Poor forward blood flow
  
  • Low flow →↓CO
• Backward buildup of pressure
  
  • Congestion→↑filling pressure
  • Typically a response to low flow.
• Decrease in cardiac output and an increase in filling pressure are fundamental to the pathophysiology of heart disease

Question 7

Characteristics of systolic dysfunction that leads to heart failure

Answer 7

• Systolic dysfunction: a problem with squeeze→↓contraction→↓inotropy.
• Hallmark: decreased ejection fraction and ventricular enlargement
  
  • Decreased ejection fraction
    
    • Heart failure with reduced ejection fraction=HFrEF
    • Left ventricular systolic dysfunction=LVSD
  • Ventricular enlargement
    
    • Dilated cardiomyopathy= DCM

Question 8

Primary causes of systolic dysfunction leading to heart failure (3)

Answer 8

• Direct destruction of heart muscle cells
• Overstressed heart muscle
• Volume overloaded heart muscle

Question 9

Causes of direct destruction of heart muscle cells

Answer 9

• myocardial infarction
• viral myocarditis
• peripartum cardiomyopathy
• idiopathic dilated cardiomyopathy
• alcohol.

Question 10

Casues of overstressed heart muscle

Answer 10

• tachycardia-mediated HF
• meth abuse
• catecholamine mediated.

Question 11

Causes of volume overloaded heart muscle

Answer 11

• mitral regurgitation
• high cardiac output

Question 12

Characteristics of diastolic dysfunction leading to heart failure

Answer 12

• problem with filling→↓lusitropy/decrease in relaxation.
• Hallmark: normal ejection fraction and ventricular wall thickening.
  
  • Normal ejection fraction:
    
    • HF with preserved ejection fraction=HFpEF
    • Preserved systolic function=PSF
  • Ventricular wall thickening:
    
    • Left ventricular hypertrophy=LVH
    • Hypertrophic cardiomyopathy=HCM

Question 13

Primary causes of diastolic dysfunction leading to heart failure (3)

Answer 13

• High afterload/pressure afterload
• Myocardial thickening/fibrosis
• External compression

Question 14

Causes of high afterload/pressure afterload

Answer 14

• hypertension
• aortic stenosis
• dialysis (inadequate volume removal)

Question 15

Causes of myocardial thickening/fibrosis

Answer 15

• HCM
• primary restrictive cardiomyopathy

Question 16

Causes of external compression

Answer 16

• pericardial fibrosis/constrictive pericarditis,
• pericardial effusion

Question 17

Main types of compensatory responses to heart failure (3)

Answer 17

• heart failure –> decreased CO –> mechanisms that aim to increase CO/compensate for other effects
• neurohormonal activation
• frank-starling increases in preload
• ventricular remodeling: hypertrophy and dilation

Question 18

Characteristics of neurohormonal compensatory response to heart failure

Answer 18

• ↓filling/↓SV→↓CO
• Juxtaglomerular apparatus in kidney senses lower flow→renin-angiotensin-aldosterone (RAAS) activation
  
  • vasoconstriction –> ↑TPR –> helps maintain BP and perfusion of vital organs
  • ​aldosterone –> ↑Sodium retention
• Carotid sinus/aortic baroreceptors sense lower pressure→autonomic nervous system (sympathetic)/adrenergic activation
  
  • ↑HR
  • vasoconstriction
• ​↑sodium retention + vasoconstriction + ↑HR →↑volume→↑LV filling

Question 19

Characteristics of Frank-Starling compesatory response to heart failure

Answer 19

• decreased output/ejection fraction → higher ESV in LV + filling during diastole → ↑LV filling
• ↑LV filling→ increased preload → ↑SV
• stroke volume is preserved by increasing the end diastolic filling/pressure.

Question 20

Types of ventricular remodeling (compensatory response to heart failure) and long-term consequences

Answer 20

• Long term increases in cardiac workload and increased metabolic demands promote adverse myocardial remodelling.
  
  • Ventricular hypertrophy
  • Ventricular dilation
  • Myocardial damage/apoptosis
  • Myocardial fibrosis
• Overtime remodelling causes:
  
  • Decreased contractile force
  • Decreased dynamic function
  • Increased diastolic stiffness

Question 21

Major characteristics of right-sided heart failure

Answer 21

• Under normal circumstances, the pulmonary vasculature is a low pressure system
• Stresses to the RV can cause it to fail to adequately pump blood through the lungs:
  
  • ↓ Circulating blood flow (forward RV HF)
  • ↑ Venous pressures (backward RV HF)

Question 22

Major causes of right-sided heart failure (4)

Answer 22

• Left heart failure
  
  • Backward HF from LV dysfunction stresses the right side by increasing pulmonary venous pressures.
• Lung disease/pulmonary HTN/RV pressure overload
  
  • “cor pulmonale”→primary lung disease causes HF
  • COPD, primary pulmonary hypertension, sleep apnea
• RV volume overload
  
  • Shunt
  • tricuspid regurgitation
• Damage to the RV myocardium
  
  • Isolated RV infarct (rare)
  • myocarditis