Heart Failure: Pathophysiology and Epidemiology

Heart Failure Pathophysiology

• Heart failure (HF) is examined, including epidemiology, concepts, definitions, and pathophysiology

Epidemiology of Heart Failure

• HF is the fastest-growing heart disorder, affecting 6.7 million Americans
• HF was a contributing cause in more than 1 in 8 deaths in 2021
• Annual HF incidence increases with age
• 24% of US adults will develop HF in their lifetimes
• It is a common cause of hospitalization for individuals older than 65
• Lifetime HF risk is lower in women, but women account for 50% of the total cases due to longer life expectancy
• Approximately 50% of patients die within 5 years of diagnosis

Heart Failure Characterization and Definitions

• HF can be characterized based on heart function as systolic or diastolic:
• Systolic HF: Heart Failure with Reduced Ejection Fraction (HFrEF)
• Diastolic HF: Heart Failure with Preserved Ejection Fraction (HFpEF)
• HF can be characterized based on heart anatomy as left or right heart failure
• HF is a syndrome with common findings regardless of etiology, not a single disease
• HF is defined as the heart's inability to produce enough cardiac output to meet the body's needs
• Left HF is more common and also the most common cause of right HF
• Isolated right HF is often secondary to lung disease, including COPD
• In late stages, most patients develop biventricular failure

Determinants of Blood Volume

• Extracellular fluid compartment
• Sodium intake contributes to blood volume
• Hormonal regulation of sodium and water retention or excretion by the kidneys allows fine-tuning
• Aldosterone: Regulates sodium, increases water retention/volume
• Vasopressin/ADH: Regulates water, increases volume
• Natriuretic peptides (ANP, BNP): Regulate sodium, increase excretion, decrease water retention/volume

Ejection Fraction (EF)

• Defined as SV/LVEDV
• Expressed as the fraction (%) of blood volume in the left ventricle at the end of diastole that is actually ejected

Relationship Between Stroke Volume (SV), End Diastolic Voume (EDV) and Ejection Fraction (EF)

• End Diastolic Volume (EDV): The amount of blood, in mL, present in the left ventricle at the end of diastole
• Ejection fraction (EF): The percentage of the EDV that gets pumped out with each beat
• Stroke volume (SV): The amount of blood, in mL, pumped out of the ventricle with each beat
• SV depends on both EDV and EF
• If EDV is 100 mL and EF is 70%, the SV will be 70 mL (100 mL x 0.7)

Cardiac Remodeling

• Refers to changes that occur at the molecular and cellular level in response to injury and/or stress
• Changes manifest as alterations in size, shape, function, and cellular/tissue characteristics of the heart
• This usually refers to ventricular changes
• Remodeling looks different based which type of HF is being discussed

Systolic Heart Failure

• Systolic heart failure is impaired ability of the ventricle to contract
• Reduces both stroke volume and EF to ≤ 40% (normal is 55-70%)
• Generally occurs due to a thinned, weakened heart wall
• Often called "heart failure with reduced ejection fraction" or HFrEF
• Remodeling in systolic HF involves the thinning of the ventricle wall, chamber enlargement, myocyte apoptosis, and replacement with fibrotic tissue
• The ventricle dilates and loses its shape/structure for contracting/pumping
• This is a result of chronically increased preload and associated elevated end-diastolic pressures

Etiologies of Systolic HF/HFrEF

• Coronary artery disease/MI
• Hypertension
• Valve disorders
• Aging
• Smoking
• Diabetes
• Toxic damage to heart
• Dilated cardiomyopathy: LV is enlarged, dilated, and weak, one specific cause of systolic HF (≈50% of cases are idiopathic, age 20 to 60 on presentation)
• Idiopathic (one form of HF can occur one month pre- or up to 5 months post-partum)

Diastolic Heart Failure

• Impaired relaxation of the ventricle reduces the amount of filling and end-diastolic volume
• It is often called "heart failure with preserved ejection fraction" or HFpEF
• Contractility and ejection fraction (%) are fairly normal, BUT stroke volume is decreased due to poor filling
• Stiff ventricle results in chronically elevated filling pressures
• Remodeling in diastolic HF is ventricular wall hypertrophy and thickening
• Chamber gets smaller usually a response to chronically increased afterload, such as uncontrolled HTN

Etiologies of Diastolic HF/HFpEF:

• Uncontrolled hypertension
• Aging
• Untreated obstructive sleep apnea (OSA)
• CPAP treatment for OSA can reverse some of the physical changes in the heart caused by OSA
• Ischemic fibrosis- makes ventricle stiff

Heart Remodeling Pathways

• Remodeling of the heart varies depending on the activated pathway
• SNS, RAAS, increased wall tension, preload/afterload, stretch etc

Hypertrophic Cardiomyopathy

• Autosomal dominant disease with variable expressivity
• Commonly presents during the second decade of life or later in adulthood
• Missense mutation of one of the contractile proteins in cardiac sarcomeres- no single gene causes all cases
• Physical cardiac changes are somewhat similar diastolic heart failure/HFpEF
• Classic phenotype:
• Abnormal thickening or enlargement of septum and/or L ventricular wall
• Obstruction of blood flow at left ventricular outflow tract and sarcomere disarray
• Clinical presentation:
• Dyspnea on exertion
• Syncope or near-syncope on exertion
• Fatigue, chest pain, palpitations, and arrhythmia
• Can cause sudden death in young athletes

NYHA Classification

• Based on the patient's functional capacity
• Patients may move back and forth between stages depending on their symptoms
• Class 1: Cardiac disease, but no symptoms and no limitation in ordinary physical activity
• Class 2: Mild symptoms and slight limitation during ordinary activity
• Class 3: Significant limitation in activity due to symptoms, comfortable only when at rest
• Class 4: severe limitations, Symptoms even while at rest

Heart Failure Pathophysiology

• Three main adaptive/injury response mechanisms:
• Frank-Starling mechanism: increased preload via fluid retention
• Attempts to increase contractile force (contractility) and maintain stroke volume
• Neurohumoral adaptation (RAAS activation, SNS stimulation)
• Structural alterations ("remodeling"), including dilation, hypertrophy

Frank-Starling Mechanism

• Healthy heart automatically adjusts its stroke volume to match the end-diastolic volume (EDV) (preload)

SNS Activity

• Increased SNS activity increases contractility in the healthy heart
• Higher contractility increases stroke volume
• At any given EDV, stroke volume increases with increased SNS activity and vice versa

The Failing Heart

• A heart where EDV may chronically be greater than normal
• The one where contractility may be decreased

Limits to Adaptation

• In normal range of EDV, increases will increase SV, until it there is a limit
• Chronically elevated EDV can lead to a flat Starling Curve

Decreased Contractility

• Decreased contractility can shift the Frank-Starling curve downward
• SNS activity increases contractility, shifting the Frank-Starling curve upward with greater stroke volume
• In HF, decreased contractility shifts the curve downwards causing higher preload not to lead to normal SV leading to increased workload of the heart

Maximum Adaptation in HF

• In HF, SNS activation shifts the Frank-Starling curve upward, but generally not enough to attain normal SV
• The SNS also works the heart harder, increasing oxygen demand, worsening HF
• Activating the RAAS can increase preload, but the SNS also works the heart harder

Compensatory Mechanisms in Heart Failure

• Body tries to compensate for for insufficient cardiac output and maintain normal tissue perfusion
• Activate process
• Mechanical stressors on hurt like preload or afterload

Compensation Problems

• Compensation mechanisms stress the already weakened heart and attempt to make it work harder
• Compensatory mechanisms may help in the short-term, but worsen the heart failure long-term
• Ask:
• How is this compensatory mechanism attempting to compensate for insufficient CO?
• Or in some cases, how might it be a response to stress/injury to the heart?
• If this compensatory mechanism is chronically activated, how might that stress the heart further?

Short Term Compensation

• Short-term compensation can bring negative long-term consequences
• Fluid retention
• Increased cardiac sympathetic (β1-adrenergic) stimulation
• Increased vascular sympathetic (α1-adrenergic) stimulation
• RAAS activation
• Vasopressin activation
• ANP and BNP early compensatory response to fluid retention (may fail later)
• Injury process to myocardium leads to inflammation, fibrosis
• Short-term compensatory mechanisms worsen the HF when they are chronically activated
• Pharmacotherapy often aims to block some compensatory systems to preserve heart function

Countering RAAS

• Example: ANP and BNP are released mainly in response to stretch of atria and ventricles induced by increased blood volume
• ANP = Atrial Natriuretic Peptide Synthesized in the atria
• BNP = Brain-type Natriuretic Peptide Synthesized mainly in ventricles, but also the brain
• ANP/BNP cause:
• Vasodilation
• Increased excretion of sodium
• Decreased renin release by the kidneys (diuresis)
• Overall:
• decreases blood volume
• decrease blood pressure.
• As HF worsens, ANP and BNP become less effective at decreasing blood volume
• May see very high levels of ANP or BNP in the blood of HF patients with severe disease

Vicious Cycle

• Vicious Cycle of Compensatory Mechanisms in Heart Failure
• Leads to Worsening HF

Left vs Right

Left HF vs. Right HF

• NOT the same as systolic versus diastolic HF
• A way to think about the consequences of one or both sides of the heart failing
• Focuses on the physical locations of the failure and the affected body systems and vascular circuits

Left Ventricle (LV) Failure

• This is the most common type of HF
• Backward effects: decrease Ejection fraction, Increased Left ventricular preload, Increased Left atrial pressure, Increased Pulmonary pressure
• Forward effects: Decreased Cardiac output, Fluid retention, RAAS Decreased tissue perfusion
  • Leads to Person will have fatigue, activity intolerance
• Dyspnea on exertion
• Orthopnea
• Cough
• Paroxysmal nocturnal dyspnea
• Cyanosis
• Basilar crackles
• FORWARD EFFECTS:
• Fatigue
• Oliguria
• Increased Heart rate
• Faint pulses
• Restlessness
• Confusion
• Anxiety

Right Ventricle (RV) Failure

• Most common cause is LV failure; may also occur alone, secondary to chronic lung disease
• Backward effects:
  • Decreased Ejection fraction and Increased Right ventricular preload, Increased Right atrial pressure, Systemic congestion – Output to left ventricle, ↓Left ventricular cardiac output, Fluid retention, RAAS activation, Decreased tissue perfusion
• Manifestations:
  • Edema, enlarged liver and spleen, JVD forward effects
  • Hepatomegaly Ascites Splenomegaly Anorexia Subcutaneous edema Jugular vein distention
• Forward effects:
  • Fatigue
  • Oliguria
• increased Heart rate Faint pulses
• Restlessness Confusion Anxiety

Over Time

• Fatigue + SOB will severely impact the person's ability to perform ADLs.
• In RHF, congestion affects the systemic circulation
• As severity increases, liver distension, GI discomfort/nausea increase ("backward failure")
• With dependent edema and jugular venous distention ("backward failure")

Diagnosing HF

• History and physical
• Labs, including BNP or NT-pro-BNP
• ECG
• CXR: cardiomegaly
• Echocardiogram: chamber size, structure, function, estimate EF
• Exercise testing

Decompensated HF

• Common cause of hospitalization of people with HF
• Gradual or sudden worsening (exacerbation) of symptoms
• A patient may become acutely decompensated and then return to compensated status with treatment
• Most commonly, patients present with increased dyspnea, edema, and other signs of volume overload May have symptoms at rest
• Common causes of acute decompensation:
• infections
• Not taking medications as prescribed
• Not maintaining dietary fluid and sodium restrictions

Dcompensation and Pulmonary Edema

• Alveolar capillaries have higher and higher pressures inside them and fluid fluid starts to leak into the interstitium. Eventually leaks into the alveolar lumen
• Patient may have a sensation of drowning
• Will experience SOB, hypoxia
• Patient will not be able to tolerate laying flat at all. (Orthopnea.)

Right HF causes

• Increased venous hydrostatic pressure
• Fluid leaks out of the veins causing depend edema
• Retention of sodium and water by the kidneys also contributes

HF Sequelae

• Dilation of atria and ventricles impedes impulse conduction atrial fibrillation and other arrhythmias
• Injury to myocardium leads to inflammation, promoting:
  • Fibrosis to replace apoptotic myocardial cells
• Liver and kidney disease
• Lung disease and pulmonary hypertension But lung diseases (ex: chronic bronchitis) and the pulmonary hypertension it causes can cause HF, esp. RHF
• Can cause depression

Clinical Recommendations

• Recognize that heart failure can involve a vicious cycle of tissue injury, inflammation, fibrosis, and worsening heart function
• Self-care is key!!
• Taking medications
• Watching patients weight
• Restricting salt and water intake
• Noting symptoms
• Doing moderate activity
• Patient-provider collaboration involves the patient