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Questions and Answers

What is a common symptom associated with mitral valve prolapse?

Rapid heart rate

Severe dyspnea

Mid- or late-systolic click (correct)

Holosystolic murmur

Which condition most urgently requires surgery if left ventricular hypertrophy develops?

Mitral valve stenosis with mild symptoms

Mild mitral regurgitation

Mitral valve prolapse with significant regurgitation (correct)

Asymptomatic with no history of heart disease

What murmur is typically associated with mitral regurgitation?

Holosystolic murmur (correct)

Mid-systolic click

Rumbling diastolic murmur

Early systolic ejection murmur

What is the prognosis for most patients with mitral valve prolapse?

Most have a good prognosis and do not need urgent intervention (A) Signup and view all the answers

Which symptom may indicate the development of significant mitral stenosis?

Worsening cough and dyspnea with exertion (C) Signup and view all the answers

What is a potential consequence of severe mitral regurgitation if left untreated?

Heart failure symptoms (C) Signup and view all the answers

What type of murmur is associated with mitral stenosis?

Opening snap followed by a rumbling diastolic murmur (B) Signup and view all the answers

In the case of mitral valve regurgitation, what sign indicates the need for surgical intervention?

Development of left ventricular hypertrophy or symptoms of congestive heart failure (C) Signup and view all the answers

What is the primary cause of heart failure with reduced ejection fraction (HFrEF)?

Impaired contractility (A) Signup and view all the answers

Which of the following accurately describes heart failure with preserved ejection fraction (HFpEF)?

It involves elevated diastolic pressures. (A) Signup and view all the answers

Which statement best describes the 'forward flow' problems in heart failure?

They refer to impaired perfusion of vital organs. (C) Signup and view all the answers

What is a direct consequence of decreased cardiac output in the pulmonary circulation?

Pulmonary edema and increased vascular resistance. (B) Signup and view all the answers

In heart failure, which ventricle typically fails first as a result of increased afterload?

Left ventricle (D) Signup and view all the answers

What typically happens in the case of cor pulmonale?

The right ventricle fails due to lung disease. (B) Signup and view all the answers

What can lead to abdominal pain in heart failure patients?

Impaired flow to the viscera. (C) Signup and view all the answers

Which of the following best describes the pathophysiological pathways in congestive heart failure (CHF)?

Both forwards and backwards problems can occur. (A) Signup and view all the answers

In which demographic is rheumatic fever most commonly observed?

Less-industrialized countries (C) Signup and view all the answers

What is the most common mitral valve lesion associated with rheumatic heart disease?

Mitral stenosis (D) Signup and view all the answers

Which of the following symptoms is associated with severe aortic stenosis?

Chest pain (D) Signup and view all the answers

What characterizes the murmur associated with aortic stenosis?

Systolic crescendo-decrescendo murmur (C) Signup and view all the answers

Which of the following complications is a common result of aortic regurgitation?

Volume-overload left ventricular hypertrophy (LVH) (D) Signup and view all the answers

What structural change is often associated with aortic stenosis?

Aortic commissures fusion (D) Signup and view all the answers

Which symptom is indicative of severe aortic regurgitation?

Diastolic decrescendo murmur (C) Signup and view all the answers

What consequence can arise from mitral stenosis in the context of rheumatic heart disease?

Long-term valvular incompetence (D) Signup and view all the answers

What is a significant characteristic of concentric hypertrophy associated with heart failure?

Thickened ventricular wall (C) Signup and view all the answers

Which pathway is primarily responsible for increased vasoconstriction and volume retention in heart failure?

Renin-angiotensin-aldosterone system (RAAS) (B) Signup and view all the answers

What effect does increased angiotensin II have in heart failure?

Hypertrophy and connective tissue deposition (D) Signup and view all the answers

What is the main function of B-type natriuretic peptide (BNP) in relation to heart failure?

Aid in vasodilation and natriuresis (C) Signup and view all the answers

In the context of heart failure, what does diastolic dysfunction primarily involve?

Reduced compliance of the ventricles (C) Signup and view all the answers

What is the consequence of long-term beta-adrenergic signaling in heart failure?

Myocyte apoptosis and fibrosis (A) Signup and view all the answers

How does eccentric hypertrophy differ from concentric hypertrophy in heart failure?

Eccentric hypertrophy is associated with decreased ejection fraction (B) Signup and view all the answers

Which signaling molecule is a potent vasoconstrictor and acts as a growth factor for cardiomyocytes in heart failure?

Endothelin-1 (D) Signup and view all the answers

What role does calcium homeostasis play in the pathophysiology of heart failure?

Elevates diastolic calcium levels (A) Signup and view all the answers

What is a common symptom associated with left-sided heart failure?

Dyspnea (C) Signup and view all the answers

How does chronic heart failure lead to disturbances in baroreceptor function?

Elevated pressures and decreased PNS tone (D) Signup and view all the answers

What characterizes the remodeling phase in heart failure at the molecular level?

Increased extracellular matrix deposition (D) Signup and view all the answers

What does the term 'heart failure with preserved ejection fraction' (HFpEF) imply?

Ejection fraction remains normal or relatively high (C) Signup and view all the answers

What is the ejection fraction (EF) threshold that classifies heart failure with reduced ejection fraction (HFrEF)?

EF < 40% (A) Signup and view all the answers

What diagnostic method is most commonly used to assess heart failure?

Echocardiography (C) Signup and view all the answers

Which drug class is primarily used to reduce cardiac remodeling in chronic heart failure?

Beta-blockers (B) Signup and view all the answers

What is the typical effect of chronic hypertension on the left ventricle?

Concentric LV hypertrophy (D) Signup and view all the answers

Which is a common cause of heart failure in patients with ischemic heart disease?

Myocardial hypertrophy (B) Signup and view all the answers

What is the primary mechanism by which statins lower LDL cholesterol levels?

Decrease hepatocyte cholesterol production (A) Signup and view all the answers

Which condition is characterized by the backflow of blood due to ineffectiveness of the valve to close completely?

Regurgitation (D) Signup and view all the answers

What is the most common underlying cause of chronic heart failure?

Coronary artery disease (D) Signup and view all the answers

Which type of calcium channel blocker has a significant effect on cardiac conduction and contractility?

Nondihydropyridine (A) Signup and view all the answers

What is the consequence of digoxin's mechanism of action related to intracellular calcium levels?

Increases intracellular calcium concentrations (B) Signup and view all the answers

Which medication class aids in preventing hypertrophy and myocardial fibrosis by reducing blood pressure?

ACE inhibitors (D) Signup and view all the answers

What pathological process is primarily responsible for aortic stenosis?

Calcification and wear & tear (B) Signup and view all the answers

Which condition is associated with left ventricular hypertrophy due to chronic pressure overload?

Chronic hypertension (A) Signup and view all the answers

What is the effect of nitrates on cardiac preload and afterload?

Decrease both preload and afterload (C) Signup and view all the answers

Study Notes

Mitral Valve Prolapse

Many cases are asymptomatic
Some individuals experience nonspecific symptoms like presyncope, palpitations, or poorly-characterized chest pain
A mid- or late-systolic "click" can be heard at the apex, indicating mitral valve prolapse
A click followed by a systolic crescendo-decrescendo murmur suggests regurgitation
Most individuals with mitral valve prolapse have a good prognosis and do not require surgery urgently
Surgery becomes more urgent if regurgitation develops and left ventricular hypertrophy (LVH) occurs

Mitral Valve Regurgitation

Asymptomatic if regurgitation is minor
Severe regurgitation leads to volume overload and heart failure (CHF) symptoms
A holosystolic murmur, difficult to hear S1, is usually best heard at the apex but can sometimes radiate to the base
Surgery is more urgently needed if LVH is present or the patient experiences CHF symptoms

Mitral Valve Stenosis

Often asymptomatic
Symptoms arise due to elevated atrial pressures and include cough and dyspnea that worsens during exercise or activity
An opening snap followed by a rumbling, diastolic murmur at the apex is characteristic
Symptomatic patients and those with severely reduced mitral valve orifice usually require surgery

Heart Failure

Atherosclerosis is a key underlying etiology of heart failure, accounting for roughly two-thirds of cases
Two major phenotypes of heart failure are systolic dysfunction and diastolic dysfunction

Systolic Dysfunction (Heart Failure with Reduced Ejection Fraction - HFrEF)

Impaired force of contraction (contractility)
Reliance on elevated preload for adequate cardiac output

Diastolic Dysfunction (Heart Failure with Preserved Ejection Fraction - HFpEF)

Elevated diastolic pressures
Maintained force of contraction
Despite elevated diastolic pressures, end-diastolic volume (EDV) may be impaired

Pathophysiologic Pathways in Heart Failure

Two major problems arise as heart failure progresses: forward flow problems and backwards problems

Forward Flow Problems

Impaired cardiac output to tissues impairs function
Major tissues affected include the brain, heart, kidneys, and extremities
Reduced flow to the viscera can sometimes lead to abdominal pain, but it's uncommon

Backwards Problems (Congestion)

Reduced left ventricular cardiac output (CO) leads to congestion in the pulmonary venous circulation, causing elevated pulmonary capillary pressures, pulmonary edema, and thickening of pulmonary arterioles and arteries
Reduced right ventricular (RV) CO results in congestion in the systemic venous circulation, resulting in elevated pressures in systemic capillaries and edema, including hepatic congestion, splenomegaly, and dependent edema

Right Ventricular Failure

Left ventricle "fails first" due to greater afterload
Increased pulmonary congestion increases RV afterload, leading to RV failure
Right ventricle can also be the "first to fail" in cases of lung disease, where areas are hypoxic or poorly ventilated, causing pulmonary vasoconstriction and pulmonary hypertension
This is known as cor pulmonale and common causes include chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea

Comparison of Microcirculation

Pulmonary microcirculation is controlled by oxygen concentrations, constricting in response to decreased oxygen levels

Heart Failure - Ventricular Hypertrophy

The failing heart typically exhibits two hypertrophy patterns: concentric and eccentric

Concentric Hypertrophy

Thought to occur earlier in heart failure development
Thickened ventricular wall without chamber size increase
Increased thickness minimizes wall stress

Eccentric Hypertrophy

Ongoing remodeling, resulting in increased myocyte length
Usually associated with reduced ejection fraction and increased symptoms

Molecular Adaptations in the Failing Heart

Ventricular remodeling alters myocyte structure and surrounding tissue over time
Increased expression of fetal myosin forms that use ATP more efficiently but generate less force
Elevated expression of transforming growth factor-beta (TGF-beta) leads to extracellular matrix deposition
Myocytes enlarge, but the capillary network in the hypertrophic heart is less extensive than in healthy hypertrophy

Signaling Pathways Implicated in Heart Failure

Angiotensin II (AT II) is elevated due to reduced cardiac output to the kidneys and release from stressed cardiac cells
AT II binds to receptors in myocytes and myofibroblasts, causing hypertrophy, myofibroblast proliferation, and increased connective tissue deposition
AT II also increases volume and vasoconstriction, worsening edema and afterload
Beta-adrenergic signaling is initially increased but leads to receptor downregulation, hypertrophy, fibrosis, and eventually apoptosis of myocytes
Other detrimental pathways include endothelin-1 and inflammatory cytokines

Calcium Homeostasis in the Failing Heart

Reduced calcium release per action potential (AP) by ryanodine receptors
Inhibition of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) calcium uptake
These effects result in elevated diastolic calcium levels and impaired calcium spikes during contraction
Beneficial pathways include activation of insulin-like growth factor 1 (IGF-1) and phosphatidylinositol 3-kinase (PI3K) pathways, which drive healthy hypertrophy

CHF Pathophysiology and Neurohormonal Activation

The sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) initially lead to increased heart rate, blood pressure, and contractility, as well as sodium and water retention
Over time, excessive vasoconstriction and volume retention occur, contributing to baroreceptor dysfunction, elevated pressures, reduced parasympathetic nervous system tone, and increased antidiuretic hormone (ADH) release
Excessive SNS activation reduces renal perfusion, leading to chronically elevated renin and AT2 levels to maintain blood flow to the kidneys

Protection Against Fluid Overload

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have similar sodium and water loss promoting effects
BNP is released by stretched ventricles
Over time, individuals with heart failure become resistant to BNP and ANP, decreasing their effectiveness
Neprilysin inhibitors reduce this resistance

Heart Failure - General Clinical Features

Universal symptom of fatigue
Left-sided symptoms include orthopnea, dyspnea, angina, and impaired cognitive function
Right-sided symptoms include dependent edema and right upper quadrant (RUQ) pain

Heart Failure Signs

Pitting edema, hepatosplenomegaly
Elevated jugular venous pressure (JVP), displacement of the apical impulse, S3 or S4 heart sounds
Crackles, wheezing, and pleural effusions depending on the extent of pulmonary edema

New York Heart Association Classification

This staging tool categorizes heart failure based on functional limitation and clinical assessment
Class I: No functional limitations with ordinary physical activity
Class II: Comfortable at rest but limited with mild activity

Heart Failure - Diagnosis

Heart failure is usually diagnosed with echocardiography.
Normal ejection fraction (EF) is greater than 50%.
Heart failure with reduced ejection fraction (HFrEF) is diagnosed when EF is less than 40%.
Heart failure with preserved ejection fraction (HFpEF) is diagnosed when EF is greater than 50% but there is left ventricular hypertrophy, atrial enlargement, and abnormal ventricular wall movement.

Brain Natriuretic Peptide (BNP)

BNP is a natriuretic factor released by the ventricle in response to increased strain.
BNP can be helpful to diagnose both chronic heart failure and acute exacerbations of congestive heart failure.

Chest X-ray

Chest x-ray can identify cardiomegaly and pulmonary edema.
It is less specific or sensitive than echocardiography.

Chronic Ischemic Heart Disease (IHD) → CHF

Chronic IHD is the most common cause of heart failure (60% of cases).
Hypertension is the second most common cause.
Clinical features of CHF due to IHD include myocardial hypertrophy and fibrosis.
Scars from healed old infarcts may be visible.
CHF due to IHD usually presents as HFrEF.

Atherosclerosis

Progression occurs from fatty streak to deposition of oxidized LDL.
Macrophages migrate and activate during the process.
Atherosclerosis leads to calcification, accumulation of cholesterol, and foam cell development.
Increased extracellular matrix deposition under the intima occurs.
A variably-stable fibrous cap is formed with underlying necrotic tissue and immune cells.
Stenosis of the lumen leads to impaired blood flow.

Risk Factors & Development of Atherosclerosis

Smoking, high blood pressure, and oxidative stress increase endothelial damage.
Lipoprotein (a) (Lp(a)) likely increases endothelial damage through increased immune cell recruitment at a developing plaque.
Lp(a) may also inhibit breakdown of clots.
Diabetes and dyslipidemia increase the likelihood of LDL being incorporated into the intima.
Advanced glycation end products (AGEs) in the endothelium likely contribute to LDL oxidation.
AGEs also increase inflammation, leading to oxidative stress.

Chronic Hypertension → CHF

Long-term hypertension can lead to CHF (second most common cause).
Concentric left ventricular hypertrophy is typically observed.
Over time, concentric hypertrophy can progress to eccentric hypertrophy.
Microscopic examination shows hypertrophied cardiomyocytes.
Hypertrophy often does not result in increased capillary density.

Medications for CHF & Angina: Beta-blockers

Beta-blockers are used for angina and CHF.
Most beta-blockers used in IHD or CHF are relatively selective for the beta-1 epi/norepinephrine receptor.
In IHD, beta-blockers reduce cardiac oxygen demand which is effective for prophylaxis of angina and other complications of IHD.
In CHF, beta-blockers reduce and even reverse cardiac remodeling (less fibrosis, hypertrophy, cell death).

Medications for CHF: Cardiac Glycosides (Digoxin)

Digoxin inhibits the sodium-potassium pump.
It increases contractility by increasing intracellular calcium, but also increases vagal tone (resulting in a slower heart rate).

Mechanism of Action of Digoxin

Calcium extrusion from the cytosol is partially determined by the sodium gradient.
Digoxin decreases the sodium gradient, which decreases the activity of the sodium-calcium exchanger.
This results in a slightly increased cytosolic calcium concentration during systole.

Medications for CHF: Diuretics

Diuretics are used for CHF.
They reduce blood volume by increasing water and sodium loss at the kidney tubule.
Loop and thiazide diuretics inhibit sodium reabsorption by inhibiting specific sodium transporters earlier in the nephron.
Spironolactone blocks the aldosterone receptor, leading to loss of sodium and water in the distal nephron.
Angiotensin-converting enzyme (ACE) inhibitors block the angiotensin-converting enzyme, which converts AT1 to AT2.
ACE inhibitors have beneficial impacts on heart remodeling.

CHF Strategies

Heart failure rarely occurs in isolation.
Prevent causes such as IHD, hypertension, and diabetes.
Early adoption of medications that positively impact modeling is essential.
Medications that increase cardiac output should be adopted later in the disease course.

Medications for Angina: Calcium Channel Blockers

Calcium channel blockers cause vasodilation with limited impact on cardiac conduction or contractility.
Dihydropyridine (DHP) calcium channel blockers, such as amlodipine and nifedipine, are notable examples.
Nondihydropyridine calcium channel blockers cause slowing of AV conduction (slows heart rate) and decreased contractility but with variable effects on vasodilation.
Verapamil is the prototype medication for nondihydropyridine calcium channel blockers.

Medications for Angina: Nitrates

Nitrates are converted to nitric oxide.
Nitrates reduce preload through venodilation, which decreases venous return and oxygen demand.
Nitrates reduce afterload through arteriodilatation, which decreases oxygen demand.
Nitrates cause coronary vasodilation, which increases blood supply.

Dyslipidemia Medications: HMG CoA-reductase Inhibitors (Statins)

Statins reduce the hepatocyte's ability to produce cholesterol.
Statins deplete the hepatocyte's "intracellular supply" of cholesterol, which upregulates the LDL receptor on the hepatocyte cell membrane.
This increases the clearance of LDL from the circulation.
Statins also decrease circulating triglyceride levels, improve endothelial function, and reduce oxidative stress and inflammation at the plaque.

Dyslipidemia Medications: PCSK9 Inhibitors

PCSK9 inhibitors block a protease known as PCSK9 on the hepatocyte membrane.
PCSK9 degrades the LDL receptor, so blocking it increases the number of LDL receptors available to clear LDL.

Dyslipidemia Medications: Ezetimibe

Ezetimibe reduces the absorption of dietary and biliary cholesterol in the small intestine.
This leads to a decrease in cholesterol stores in the hepatocyte, which increases LDL receptor expression.

Dyslipidemia Medications: Niacin

Niacin inhibits lipolysis in adipose tissue.
This reduces the release of free fatty acids (FFAs) and decreases VLDL production by the liver.
This leads to decreased circulating LDL and decreased triglyceride synthesis.
Niacin also increases HDL levels but its importance is unknown.

Valvular Pathology

Valves are lined by endocardium with underlying dense irregular connective tissue connected to the fibrous rings.

Causes of Valvular Damage

Congenital disorders can lead to malformation of structures (improper migration, other causes). Examples of congenital disorders include pulmonic stenosis and bicuspid aortic valves.
"Wear and tear" chronic damage often involves a chronic inflammatory or calcific process on top of increased physical stresses. Examples include aortic stenosis and sclerosis, and mitral valve calcification.
Inflammatory processes due to infection or autoimmunity can damage valves. Examples include bacterial endocarditis, rheumatic heart disease, lupus, and ankylosing spondylitis.
Acute impairments in valvular function can be caused by ischemia, impaired papillary muscle function, aortic dissection, and idiopathic mitral valve prolapse.

Stenosis, Prolapse, Incompetence, and Regurgitation

Stenosis is characterized by a narrow orifice or difficulty opening the valve.
Stenosis increases strain across the wall of the heart proximal to the stenosis, which leads to hypertrophy and complications.
Stenosis can also initially result in impaired outflow to structures after the stenosis, causing physiologic adaptations to poor outflow.
Regurgitation is backflow of blood across a valve.
Backflow of blood into the chamber proximal to the regurgitation increases end-diastolic volume (EDV)/preload and impairs outflow distal to the regurgitation, eventually leading to chamber enlargement.
Incompetence (insufficiency) means the valve does not close completely.
Prolapse is excessive movement of the valve backward into the proximal chamber.

Valvular Pathologies

Aortic regurgitation
Bicuspid and calcific aortic stenosis
Mitral valve prolapse and mitral regurgitation
Rheumatic heart disease

Rheumatic Fever & Rheumatic Heart Disease (RHD)

Rheumatic fever (RF) is uncommon in North America but very common in less-industrialized countries.
Most cases of RHD in North America were contracted in the home country of origin.
RF causes life-long consequences even if damaged valves are replaced.
RHD occurs in a significant minority of those with RF.
Clinical features of RF include carditis, migratory polyarthritis, a temporary movement disorder called chorea, a characteristic rash, and subcutaneous nodules.

Chronic RHD - Valvular Disease

The mitral and aortic valves are most often involved in RHD.
Mitral stenosis is the most common mitral valve lesion in RHD.
RHD is the most common cause of mitral stenosis.
Scarring along the valve and shortening of the chordae tendinae can cause valve incompetence.
Aortic stenosis is the most common aortic valve lesion in RHD.
The aortic commissures are often fused, making them resemble a bicuspid aortic valve.
The aortic valve can also be incompetent as well as stenotic.

Aortic Stenosis & Regurgitation

If severe, aortic stenosis can cause chest pain.
If CO is severely impaired, aortic stenosis can cause syncope.
If it is not severe, aortic stenosis is often asymptomatic.
Signs of aortic stenosis include a systolic crescendo-decrescendo murmur, loudest at the 2nd right intercostal space, which radiates to the neck and downwards.
Left ventricular hypertrophy (LVH) is common with aortic stenosis.
Aortic stenosis is a common cause of CHF.
Valve replacement is helpful for aortic stenosis, but it should be done prior to LVH.
Aortic regurgitation is very dangerous if it is acute and severe and can cause flash pulmonary edema.
If significant, aortic regurgitation requires valve replacement.
Aortic regurgitation causes a diastolic decrescendo murmur which can be heard at the left or right intercostal space, and radiates parasternally.
It causes volume-overload LVH.

Review: Valvular Pathology

Valvular pathology affects heart function and overall health.
Understanding the types of valvular lesions, their causes, and their impact on the body is critical for clinical practice.
Early detection and treatment of valvular pathologies are essential for improving patient outcomes.

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