week 13 Pathophysiology of Congestive Heart Failure (CHF)

Cardiac Output (CO)

• Cardiac output (CO) is the blood volume pumped by the heart during 1 minute.

• Stroke Volume (SV) is the blood volume ejected from each ventricle during a single cardiac contraction, ranging from 60-80 ml.

• Heart Rate (HR) ranges from 60-100 beats per minute (bpm).

• CO = SV \,\times HR

• CO range is 3.6 – 8 L/min.

• Cardiac reserve is the heart's ability to increase cardiac output according to the body's needs. Reduced dramatically in HF.

Control of Cardiac Output

• Cardiac Output (CO) is influenced by Heart Rate (HR) and Stroke Volume (SV).

• Heart Rate is controlled by sympathetic and vagal influences.

• Stroke Volume (SV) is influenced by preload (Frank-Starling mechanism), afterload (peripheral vascular resistance), and inotropic state (Ca++, ATP).

• Heart failure (HF) is a chronic progressive condition where the heart loses its ability to pump enough blood. A key feature is reduced SV.

Atrial and Ventricular Pressures

• Ventricular parameters:

  • End Diastolic Volume (EDV) = 110-120 ml

  • End Systolic Volume (ESV) = 40-50 ml

  • Stroke Volume (SV) = 70 ml

• Ejection Fraction (EF) = SV/EDV (normal >60%); can be readily assessed by cardiac echo.

• Measurements:

  • EDV – end diastolic volume of the ventricle

  • ESV – end systolic volume of the ventricle

  • SV – stroke volume

  • LAP – left atrial pressure

  • LVP – left ventricular pressure

  • LVV – left ventricular volume

  • RAP – right atrial pressure

  • RVP – right ventricular pressure

Jugular Venous Pressure (JVP)

• JVP is measured 3 cm from the sternal angle.

• Add 5cm (distance from the right atrium to the sternal angle).

• Normal JVP is approximately 8 cm H2O

Ejection Fraction (EF)

• EF = \frac{SV}{EDV}

• Normal EF is >60%;

Systolic vs. Diastolic Ventricular Dysfunction

• Heart Failure (HF) can result from systolic or diastolic ventricular dysfunction.

• Systolic Dysfunction:

  • Reduced contractility (EF <40%)

  • Normal relaxation/filling

  • Reduced stroke volume

  • Causes include conditions that directly affect myocardial contractility (e.g., ischemic heart disease - IHD) or create more work for the heart (volume overload, pressure overload).

• Diastolic Dysfunction:

  • Normal contractility (EF)

  • Reduced relaxation/filling

  • Normal or reduced stroke volume

  • Causes include conditions that impede heart expansion (pericardial effusion), reduce ventricular compliance (myocardial fibrosis), increase wall thickness (hypertrophic cardiomyopathy), or delay relaxation (IHD, aging).

• Tachycardia aggravates diastolic dysfunction, while a reduction in heart rate generally improves it.

• Ventricular dysfunction does not always mean HF, but HF always implies ventricular dysfunction.

Right vs. Left Ventricular Dysfunction

• Right Heart Failure:

  • Congestion of peripheral tissues.

  • Signs and symptoms: dependent edema, ascites, liver congestion, GI tract congestion, impaired liver function, anorexia, GI distress, weight loss.

• Left Heart Failure:

  • Pulmonary congestion and decreased cardiac output.

  • Signs and Symptoms: activity intolerance, decreased tissue perfusion, impaired gas exchange, pulmonary edema, cyanosis, hypoxia, cough with frothy sputum, orthopnea, paroxysmal nocturnal dyspnea.

Starling Forces in Heart Failure

• In heart failure, there is impaired right ventricular (RV) or left ventricular (LV) function, leading to increased venous pressure. This results in increased filtration and edema.

• Because filtration exceeds reabsorption, this contributes to oedema.

Compensatory Mechanisms in Congestive Heart Failure (CHF)

• Compensatory mechanisms: sympathetic reflexes, RAAS, Frank-Starling mechanisms, and myocardial hypertrophy and remodelling function to maintain cardiac output.

  • Frank-Starling Mechanism: Increased venous return (preload) leads to increased cardiac output.

  • Sympathetic Reflexes: Increase heart rate and cardiac contractility and vascular tone, increasing vascular resistance (afterload).

  • Renin-Angiotensin-Aldosterone Mechanism: Angiotensin II and aldosterone from the adrenal gland lead to salt and water retention, increasing vascular volume.

  • Myocardial Hypertrophy and Remodeling.

Compensatory Mechanism: Baroreflex

• A drop in arterial pressure (AP) leads to decreased baroreceptor firing.

• This inhibits cardiac vagal neurons and activates cardiac and vascular sympathetic neurons in the brainstem cardiomotor center.

• Cardiac vagal activity decreases, while cardiac and vascular sympathetic activity increases.

• Acetylcholine (ACh) release decreases, while noradrenaline (NA) release increases.

• This results in increased heart rate, vasoconstriction, and ultimately a rise in arterial pressure.

Compensatory Mechanism: Bainbridge Reflex

• Increase in right atrial pressure/central venous pressure in systolic ventricular dysfunction activates atrial and pulmonary vein stretch (volume) receptors.

• This leads to decreased cardiac vagal activity and increased cardiac sympathetic activity.

Compensatory Mechanism: RAAS

• A fall in cardiac output leads to a fall in renal perfusion.

• This stimulates the renin-angiotensin-aldosterone system (RAAS), leading to increased blood volume and a rise in arterial pressure.

Compensatory Mechanism: Frank-Starling Reflex

• The Frank-Starling Law describes the relationship between ventricular filling (measured by left ventricular end-diastolic volume, LVEDV) and stroke volume (SV).

• When more blood stretches the ventricles, the ventricles contract more powerfully to pump out more blood.

• The effect of ventricular stretch (change in myocardial fiber length, end-diastolic volume, or filling pressure/preload) produces a change in the force of contraction.

Compensatory Mechanism: Hypertrophy

• Myocardial hypertrophy is classified according to causes and physical appearance:

  • Physiological (symmetric): Following long-term intensive training.

  • Pathological (concentric): Induced by pressure overload.

  • Cardiac dilation (eccentric): Induced by volume overload.

• Signals that trigger hypertrophy: Mechanical stress, Angiotensin II, ANP, endothelin.

Compensatory Mechanism: Myocardial Remodelling

• Myocardial hypertrophy results from an increase in the size of cardiac myocytes (not the number).

• Myocardial remodeling results from the proliferation of non-contractile cells (fibroblasts, macrophages, vascular smooth muscle, and endothelial cells).

• Both are triggered by similar signals.

• Fibroblast proliferation and activation lead to excessive collagen fiber synthesis and myocardial fibrosis.

• This leads to increased myocardial wall stiffness, electrical conduction abnormalities, ventricular diastolic dysfunction, and an increased risk of ventricular arrhythmias.

Congestive Heart Failure (CHF) Burden

• Global pandemic, affecting at least 26 million people worldwide and increasing with aging population.

• Affects 16% of people > 80 years.

• In 2017, USA had 5.7 million cases, projected to be > 8 million by 2030 (46 % increase in prevalence).

• Affects 1 million Australians.

• Most number of hospitalisations for people >65 years old.

• Financially expensive.

• Dramatically reduced quality of life.

Anatomy of CHF

• Heart chambers

  • Left heart

  • Right heart

• Valves

• Coronary vessels

• Great vessels

• Pulmonary circulation

• Systemic circulation

Pathophysiology of CHF

• Example: Myocardial Infarction

  • Loss of heart muscle in the left ventricle leads to decreased cardiac output.

  • This activates compensatory mechanisms like the SNS and renin secretion.

• Left-Sided CHF

  • The heart muscle (left ventricle) weakens and does not fully empty, leading to decreased cardiac output.

  • Blood backs up into the pulmonary circulation, causing pulmonary congestion, shortness of breath, and pulmonary edema.

• Right-Sided CHF

  • Increased resistance for the right ventricle causes it to weaken and not fully empty.

  • Blood backs up into the systemic circulation, causing swelling in ankles, legs, and abdomen (ascites).

Aetiology of Left CHF

• LV infarction

• Hypertension

• Aortic valve stenosis

• Pacemaker

• Thickened left ventricle wall

Effects of Left CHF

• Forward Effects:

  • Decreased cardiac output (fatigue, hypoxia)

  • Decreased renal blood flow (stimulated RAAS)

• Back Effects:

  • Congestion into lungs, pulmonary hypertension, pulmonary oedema (SOB, dyspnoea)

Aetiology of Right CHF

• Pulmonary disease (e.g., from left-sided CHF)

• RV infarction

• Pulmonary valve stenosis

• Thickened right ventricle wall

Effects of Right CHF

• Forward Effects:

  • Decreased oxygenation of blood (fatigue, hypoxaemia, hypoxia)

• Back Effects:

  • Systemic venous congestion (neck, abdomen + organs, lower limbs) and sequelae

Signs and Symptoms of CHF

• Forward effects:

  • Similar with failure on either side

  • Decreased blood supply to tissues, general hypoxia

  • Fatigue and weakness

  • Dyspnoea and SOB

  • Compensation mechanisms: tachycardia, cutaneous visceral vasoconstriction, daytime oliguria

• Back up effects (Left-sided):

  • Related to pulmonary congestion

  • Dyspnoea and orthopnoea (develop as fluid accumulates in lung)

  • Cough (associated with fluid irritating respiratory passages)

  • Paroxysmal Nocturnal Dyspnoea (PND; indicates the presence of acute pulmonary oedema; usually develops during sleep; haemoptysis and rales)

  • Excess fluid frequently leads to infections (pneumonia)

• Back up effects (Right-sided):

  • Related to systemic congestion

  • Dependent oedema in feet, legs, or buttocks

  • Increased pressure in jugular veins (distension)

  • Hepatomegaly, splenomegaly (digestive disturbances)

  • Ascites (fluid in peritoneal cavity; marked abdominal distension)

  • Acute right-sided failure: flushed face, distended neck veins, headache, visual disturbances

Diagnosis of CHF

• Clinical, laboratory, and imaging tests are used to diagnose heart failure.

• Relevant history: Previous myocardial infarction, angina, hypertension, valvular disease, metabolic or autoimmune disease.

• Symptoms: Dyspnoea, fatigue, oedema, orthopnoea, paroxysmal nocturnal dyspnoea.

• Vital signs and clinical examination: Tachycardia, Tachypnoea (RR >18/min), Oxygen saturation <94% on room air, Raised jugular venous pressure, Displaced apex beat, Third heart sound, Murmur, Pulmonary crackles, Peripheral oedema.

• Blood tests: BNP or NT-proBNP, Full blood count, Renal function, Liver function, Thyroid function.

• Heart imaging and electrical activity: Electrocardiogram, Chest X-ray, Transthoracic echocardiogram.

Classification of CHF

• NYHA Classes = severity of symptoms

• AHA Stages = severity of structural changes that affect the ability to pump blood

Case Study

• 77-year-old female

• Class IV (severe symptoms)

• Fatigue, weakness

• Shortness of breath

• Pitting oedema

• On diuretic tablet

• Dual-chamber pacemaker

Management of CHF

• Depends on stage/severity

  • Lifestyle changes: exercise, smoking cessation, reduce alcohol consumption

  • Drugs: ACE-inhibitors, ARBs, Beta-blockers, MRAs, Diuretics, Digoxin

  • Devices and surgeries: Cardiac resynchronization therapy, Pacemakers and defibrillators, Ventricular assist devices, Valve repair and replacement, Heart transplants

Stages of Heart Failure

• Stage A: At Risk for Heart Failure.

  • Patients at high risk for HF, but without structural heart disease or symptoms of HF.

    • Examples: patients with Hypertension, atherosclerotic disease, diabetes, obesity, or metabolic syndrome, patients using cardiotoxins, with FHX CM.

    • Therapy Goals: Treat hypertension, encourage smoking cessation, treat lipid disorders, encourage regular exercise, discourage alcohol intake and illicit drug use, control metabolic syndrome.

    • Drugs: ACEI or ARB in appropriate patients for vascular disease or diabetes.

• Stage B: Structural Heart Disease

  • Structural heart disease, but without signs or symptoms of HF.

    • Examples: patients with Previous MI, LV remodeling including LVH and low EF, asymptomatic valvular disease.

    • Therapy Goals: All measures under Stage A

    • Drugs: ACEI or ARB in appropriate patients, Beta-blockers in appropriate patients.

• Stage C: Heart Failure

  • Structural heart disease with prior or current symptoms of HF.

    • Examples: patients with known structural heart disease and shortness of breath and fatigue, reduced exercise tolerance.

    • Therapy Goals: All measures under Stages A and B, Dietary salt restriction.

    • Drugs for routine use: Diuretics for fluid retention, ACEI, Beta-blockers.

    • Drugs in selected patients: Aldosterone antagonists, ARBs, Digitalis, Hydralazine/nitrates.

    • Devices in selected patients: Biventricular pacing, Implantable defibrillators.

• Stage D: Refractory HF

  • Refractory Symptoms of HF at Rest requiring specialized interventions.

    • Examples: patients who have marked symptoms at rest despite maximal medical therapy.

    • Therapy Goals: Appropriate measures under Stages A, B, C, Decision regarding appropriate level of care.

    • Options: Compassionate end-of-life care/hospice, Extraordinary measures (heart transplant, chronic inotropes, permanent mechanical support, experimental surgery or drugs).

Cardiac Resynchronisation Therapy (CRT)

• CRT uses a pacemaker to restore a normal heartbeat pattern, coordinating the contraction of the two ventricles (RV lead + coronary sinus lead to LV), and occasionally the atria as well (RV + RA lead).

• Pacemaker used when:

  • Heart beats too slow or unevenly.

  • After an ablation procedure.

  • Taking certain heart medications.

• Cardioversion treats tachyarrhythmia.

Implantable Cardioverter Defibrillator (ICD)

• ICDs monitor heart rhythm and detect irregular heartbeats.

• Can deliver electric shocks via multiple leads to fix abnormal rhythm.

• Defibrillation: Non-synchronised random administration of shock during a cardiac cycle.

• Cardioversion: A synchronised administration of shock during the QRS complex of a cardiac cycle.

Ventricular Assist Devices (VADs)

• Also known as mechanical circulatory support devices.

• Implantable mechanical pump used in either the left or right ventricle.

• Most commonly used in the left ventricle (LVAD).

• If used in both chambers = biventricular assist device (BIVAD).

• Can be used while waiting for surgery (e.g., transplant) or as a long-term solution if surgery is not possible.

• Requires open-heart surgery.

• Risks: Surgical risks, clots, bleeding, infection, right CHF, device malfunction.

Coronary Artery Bypass (CAB) Surgery and Balloon Angioplasty and Stenting

• Coronary Artery Bypass (CAB) Surgery:

  • Revascularization procedure that redirects blood around a blockage or partial blockage in a vessel.

  • Uses another healthy vessel (e.g., a leg vein) or a synthetic graft (not a stent) = CABG.

• Balloon Angioplasty and Stenting:

  • Balloon inserted via catheter and directed to narrowing in the vessel.

  • Balloon inflated, then deflated and removed via catheter.

  • Can also be done with a metal stent that expands as the balloon inflates to keep the artery patent for longer

  • Risk = re-stenosis.

Valve Repair and Replacement

• Heart valves (semilunar + atrioventricular, aortic and pulmonic)

• Heart valve repair (valvuloplasty + balloon) can include:

  • Patching holes

  • Reconnecting leaflets

  • Removing excess tissue

  • Separating fused valve leaflets

• Valve surgery can be done via traditional open-heart surgery or minimally invasive procedures:

  • Transcatheter aortic valve replacement (TAVR)

• Valve replacement can be done using a:

  • Mechanical valve (long-lasting, higher chance of clot)

  • Tissue valve (human or animal donor tissue, less durable, immunological issues)

  • Ross procedure (shifting heart valve positions and replacing shifted valve)

Heart Transplantation

• Performed on patients with end-stage heart failure or severe coronary artery disease and involves the replacement of the diseased heart with a healthy donor heart.

• Indications:

  • Irreversible cardiogenic shock

  • Intractable symptomatic heart failure (NYHA Class III-IV) despite maximally tolerated medical therapy

  • Need for permanent mechanical cardiac support (VAD) or total artificial heart (TAH)

• Used when all other medical or surgical options have failed

• Two types of heart transplant:

  • Orthoptic: Diseased heart removed and replaced with donor’s

  • Heterotopic: Donor’s heart attached to old heart, acting as an assist pump

Stroke Volume

• Stroke volume is the difference between the end diastolic volume (EDV) and the end systolic volume (ESV).

• Equals the amount of blood ejected into the aorta or pulmonary arteries with each heartbeat when the ventricles contract.

• Ventricles do not fully empty during systole – i.e. ESV > 0.

• Ejection fraction (EF) = SV/EDV (normally ~60% at rest; reduced in heart failure).

Cardiac Cycle

• Ventricular parameters:

  • EDV=110 -120 ml

  • ESV=40 -50 ml

  • SV=70ml

  • Ejection fraction (EF) = SV/EDV (normal ~60%; reduced in heart failure)

Frank-Starling Law

• The law describes the relationship between ventricular filling (e.g. measured by left ventricular end diastolic volume, LVEDV) and stroke volume (SV):

  • “when more blood stretches the ventricles, the ventricles contract more powerfully to pump out more blood”

  • bigger venous return = bigger cardiac output”
    *“Frank-Starling Relationship : Long on Importance, Short on Mechanism”

Cardiac Afterload

• Cardiac afterload is the pressure that the ventricle must generate to eject the cardiac stroke volume.

• Hypertension represents increased afterload for the left ventricle.

• Atherosclerosis and heart valve stenosis are primary sources of increased afterload because greater pressure is required to drive blood flow through the narrowed blood vessels.

• Above a certain level of afterload the ventricle cannot maintain cardiac output, so that heart failure will occur at higher afterloads.

• This limit is around 160 mm Hg for a healthy left ventricle, but heart failure can occur at substantially lower levels if the heart is weakened by factors such as cardiac ischaemia, myocardial infarcts and cardiomyopathies.

Cardiac Muscle Contractility

• Inotropy refers to the contractility of cardiac muscle.

• Contractile pressure generated by cardiac muscle cells is dependent on the degree of stretch (preload) and inotropy (contractility).

• Sympathetic stimulation or sympathomimetic drugs such as adrenaline increase inotropy and the contractile pressure generated by the heart for any given level of preload.

• Such drugs are referred to as positive inotropes and are used clinically to treat failing hearts.

Cardiac Pressures

• Aorta: 100-140/60-90

• Pulmonary Artery (PA): 15-30/4-12

• Left Atrium (LA): 2-10

• Left Ventricle (LV): 100-140/3-12

• Right Atrium (RA): 2-8

• Right Ventricle (RV): 15-30/2-8

• Pulmonary Capillary Wedge (PCW): 2-10

Relationship of Jugular Venous Pressure to Right Atrial Events

• Jugular venous pressure shows biphasic pulsations.

  • The "a" wave - corresponds to right atrial contraction with the peak signifying the end of atrial systole.

  • The "c" wave - corresponds to right ventricular contraction which causes the tricuspid valve to bulge towards the right atrium.

  • The "x'" descent - due to the right ventricle pulling the tricuspid valve down during ventricular systole. This occurs because the ventricle takes up less space in the pericardium as stroke volume is ejected which allows the relaxed atrium to rapidly fill and enlarge.

  • The "v" wave corresponds to venous filling when the tricuspid valve is closed and venous pressure increases from venous return.

  • The "y" descent corresponds to the rapid emptying of the atrium into the ventricle following the opening of the tricuspid valve.

Starling Forces in Heart Failure

• Normal: Filtration = reabsorption (reabsorption somewhat less, excess fluid removed via lymph)

• Arterial End: P > \Pi, water moves out of capillaries

• Venous End: P < \Pi, water reabsorbed back

• Heart failure:

  • Reduced RV or LV function

  • Increase in venous pressure (venous congestion)

  • Filtration >> reabsorption

  • Depending on RV/LV failure, symptoms of peripheral or pulmonary oedema dominate

Right vs. Left Ventricular Dysfunction: Effects

• Right Heart Failure:

  • Congestion of peripheral tissues.

  • Symptoms: Dependent edema, ascites, liver congestion, GI tract congestion, signs related to impaired liver function, anorexia, GI distress, weight loss.

• Left Heart Failure:

  • Decreased cardiac output, pulmonary congestion.

  • Symptoms: Activity intolerance, signs of decreased tissue perfusion, impaired gas exchange, pulmonary edema, cyanosis, signs of hypoxia, cough with frothy sputum, orthopnea, paroxysmal nocturnal dyspnea.

Important Compensatory Mechanisms in Heart Failure

• Baroreflex

• Bainbridge reflex

• Frank-Starling mechanism

• Renin-Angiotensin-Aldosterone system (RAAS)

• Myocardial hypertrophy and remodelling

Renin-angiotensin-aldosterone system (RAAS)

• Prevents excessive falls in BP during homeostasis

• Acts to increase blood volume (BP)

• Renin secreted when renal perfusion drops

• Also seen when CO drops

• As in heart failure

• Thus, increased blood volume and BP may be observed in HF

• Can increase afterload

Compensatory mechanisms in heart failure: adaptive or maladaptive?

• Myocardial hypertrophy and remodelling can lead to:

  • Increased O2 demand

  • Shortening diastole

  • More work for the heart, increase O2 demand

  • Further stretch of the chambers

  • Anomalies in cardiac mechanical and electrical properties