Podcast
Questions and Answers
Which type of cardiomyopathy is characterized by genetic deficits in sarcomere proteins and can also be acquired from infectious, inflammatory, or toxic origins?
What distinguishes hypertrophic cardiomyopathy (HOCM) specifically regarding its anatomical effect on the heart?
In the context of atherosclerosis, which factor is NOT directly linked to plaque instability?
What is a common epidemiological characteristic of hypertrophic cardiomyopathy?
Signup and view all the answers
Which underlying mechanism is primarily associated with restrictive cardiomyopathy?
Signup and view all the answers
What is a major feature of hypertrophic cardiomyopathy that poses a danger to patients?
Signup and view all the answers
In dilated cardiomyopathy, which of the following statements is true concerning its clinical presentation?
Signup and view all the answers
Which condition is NOT commonly associated with causing restrictive cardiomyopathy?
Signup and view all the answers
Which of the following is a recognized genetic cause of dilated cardiomyopathy?
Signup and view all the answers
What is the typical finding on echocardiography for dilated cardiomyopathy?
Signup and view all the answers
What is one consequence of the deposition of oxidized LDL in atherosclerosis?
Signup and view all the answers
What best describes the pathogenesis of restrictive cardiomyopathy?
Signup and view all the answers
In atherosclerosis, which factor is considered a systemic contributor?
Signup and view all the answers
Which factor is a contributor to increased endothelial damage in atherosclerosis?
Signup and view all the answers
Which of these factors is typically implicated in the pathogenesis of atherosclerosis?
Signup and view all the answers
What is the role of Lp(a) in the context of plaque development?
Signup and view all the answers
The term 'syncope' in relation to hypertrophic cardiomyopathy refers to what?
Signup and view all the answers
Which condition is associated with an increased likelihood of LDL incorporation into the intima?
Signup and view all the answers
What diagnostic feature is commonly observed in microscopy of dilated cardiomyopathy?
Signup and view all the answers
What happens to the levels of Lp(a) in response to an acute phase response?
Signup and view all the answers
Which of the following best describes the potential pathogenicity of Lp(a)?
Signup and view all the answers
What is the consequence of a variably-stable fibrous cap in atherosclerotic plaques?
Signup and view all the answers
What is the relationship between diabetes and oxidative stress in the context of atherosclerosis?
Signup and view all the answers
What mechanism does Lp(a) potentially use to contribute to unstable plaque development?
Signup and view all the answers
Which of the following factors is noted to increase Lp(a) secretion?
Signup and view all the answers
What is the primary characteristic of an unstable plaque?
Signup and view all the answers
Which component is thought to play a significant role in the adverse effects of Lp(a)?
Signup and view all the answers
What is the role of activated platelets in stabilizing an atherosclerotic plaque?
Signup and view all the answers
How does inflammation affect the stability of atherosclerotic plaques?
Signup and view all the answers
What distinguishes an eroded plaque from a ruptured plaque?
Signup and view all the answers
What consequence does the rupture of an unstable plaque typically have?
Signup and view all the answers
Which symptom is often associated with dilated cardiomyopathy and can lead to heart failure?
Signup and view all the answers
Which factor is commonly linked to the prognosis of restrictive cardiomyopathy?
Signup and view all the answers
Which of the following is NOT a characteristic feature of dilated cardiomyopathy?
Signup and view all the answers
In what way does restrictive cardiomyopathy primarily differ from dilated cardiomyopathy?
Signup and view all the answers
What is a common underlying cause associated with both restrictive and dilated cardiomyopathy?
Signup and view all the answers
What is the primary mechanism by which Lp(a) may contribute to the development of unstable plaques?
Signup and view all the answers
Which of the following factors is NOT associated with enhancing the stability of an atherosclerotic plaque?
Signup and view all the answers
What is a characteristic feature of an eroded plaque compared to a ruptured plaque?
Signup and view all the answers
Which cytokine is indicated to increase the secretion of Lp(a)?
Signup and view all the answers
What typically occurs as a result of ruptured unstable plaques?
Signup and view all the answers
What role do activated platelets play in the context of plaque stability?
Signup and view all the answers
In the worsening of plaque stability, which process is directly influenced by inflammation?
Signup and view all the answers
Which component within Lp(a) is believed to have a significant role in its potentially harmful effects?
Signup and view all the answers
Which symptom is most likely to manifest as the heart condition progresses in patients with dilated cardiomyopathy?
Signup and view all the answers
What is a common consequence of ventricular dilation in dilated cardiomyopathy?
Signup and view all the answers
Which condition is primarily characterized by restricted ventricular filling and normal systolic function?
Signup and view all the answers
Which of the following clinical features is most often associated with restrictive cardiomyopathy?
Signup and view all the answers
In the context of heart failure with preserved ejection fraction (HFpEF), what physiological change is characteristic?
Signup and view all the answers
What is a typical echocardiographic finding in patients with dilated cardiomyopathy?
Signup and view all the answers
Which pathogenesis mechanism is associated with restrictive cardiomyopathy?
Signup and view all the answers
What distinguishes the symptomatology of dilated cardiomyopathy from hypertrophic cardiomyopathy?
Signup and view all the answers
Which myocardial structural change is noted in patients with dilated cardiomyopathy under microscopy?
Signup and view all the answers
Study Notes
Cardiomyopathies
- Cardiomyopathies are diseases affecting heart muscle cells or the extracellular tissue in the myocardium.
-
Dilated Cardiomyopathy:
- Most common cardiomyopathy.
- Can be caused by:
- Genetic Factors: often autosomal dominant mutations affecting sarcomere proteins like dystrophin, titin, actinin, tropomyosin, troponins, and myosin.
- Acquired Factors: Infections, inflammation, toxicity from substances such as alcohol, catecholamines, or cancer therapies, peripartum cardiomyopathy (occurring around childbirth).
- Often presents with heart failure (HFrEF) due to ventricular enlargement and reduced pumping ability.
-
Hypertrophic Cardiomyopathy (HOCM):
- Often characterized by septal overgrowth, resulting in outflow obstruction of the left ventricle.
- Common autosomal dominant disorder (1 in 500 prevalence).
- The “O” in HOCM stands for “obstructive.”
-
Clinical Features:
- Often asymptomatic, making it dangerous as undetected hypertrophy can lead to sudden cardiac death or arrest in athletes.
- As the patient ages, symptoms can develop, including: angina, dyspnea, syncope.
- Can progress to HFpEF and later HFrEF.
-
Restrictive Cardiomyopathy:
- Least common type.
- Characterized by restricted ventricular filling due to reduced diastolic volume.
- Often results from abnormal extracellular material deposition.
-
Causes:
- Autosomal Dominant Mutations: the mechanism is not fully understood.
- Secondary Causes: Amyloidosis (accumulation of proteins in various tissues), hemochromatosis (iron accumulation), and sarcoidosis (granulomatous disease infiltrating the ventricle wall).
- Mortality rate is high due to heart failure, and it rarely resolves on its own.
Atherosclerosis Pathogenesis
- Atherosclerosis is a complex, multifactorial disease involving systemic and local inflammation, dyslipidemia, high lipoprotein A (Lp(a)) levels, metabolic syndrome, diabetes, and hypertension.
-
Progression of Atherosclerosis:
- Fatty Streaks: deposition of oxidized LDL, recruitment of macrophages, foam cell formation, accumulation of cholesterol.
- Fibrous Plaque Formation: increased extracellular matrix deposition under the intima, formation of a fibrous cap containing necrotic tissue and immune cells.
-
Risk Factors:
- Smoking, high blood pressure, oxidative stress increase endothelial damage, which promotes atherosclerosis.
-
Lp(a):
- May contribute to endothelial damage by increasing immune cell recruitment at developing plaques and inhibiting clot breakdown.
-
Diabetes and Dyslipidemia:
- Diabetes: LDL is more readily incorporated into the intima due to the presence of advanced glycation end products.
- Metabolic Syndrome: increased levels of LDL, especially oxidized LDL, leads to increased fatty streak formation, macrophage activation.
-
Lipoprotein A (Lp(a):
- Lipoprotein resembling LDL, but containing a plasminogen-like protein.
-
Pathological Roles:
- Contributes to unstable plaque development.
- Activates monocytes in the arterial wall.
- Induces pro-inflammatory cytokines and adhesion molecules in the arterial wall.
-
Unstable Plaques:
- Prone to rupture due to a weakened fibrous cap.
- Rupture leads to the release of pro-coagulant molecules into the bloodstream.
-
Factors Influencing Stability:
-
Collagen Content:
- Increased collagen content in the fibrous cap enhances stability.
- Platelets release growth factors that stimulate collagen production.
-
Metalloproteinases:
- Macrophages produce metalloproteinases that degrade collagen, weakening the fibrous cap.
- So, inflammation is generally associated with unstable plaques.
-
Collagen Content:
Plaque Types
-
Eroded Plaques:
- Different from ruptured plaques.
- Exhibit a stable fibrous cap, overlying thrombus, and high levels of neutrophil extracellular traps (NETs).
Cardiomyopathies
- Disorders that affect cardiac myocytes or the extracellular tissue of the myocardium
- Three major types:
- Dilated cardiomyopathies
- Hypertrophic cardiomyopathies
- Restrictive cardiomyopathies
- Dilated cardiomyopathies are often caused by genetic deficiencies in sarcomere proteins, or by acquired factors like infections, inflammation, or toxicities
- Hypertrophic cardiomyopathies result from genetic deficiencies in sarcomere proteins
- Restrictive cardiomyopathies are caused by abnormal deposition of extracellular material
Hypertrophic Cardiomyopathy
- Often abbreviated as HOCM
- The septum is often massively overgrown, leading to outflow obstruction of the left ventricle
- One of the more common autosomal disorders (usually dominant) with a prevalence of 1 in 500
- Severity varies in patients
Hypertrophic Cardiomyopathy Pathogenesis
- Sarcomere proteins (i.e. myosin) are implicated
- The mutation tends to be gain-of-function, resulting in impressive hypertrophy
- The myocytes are disorganized in orientation
Clinical Features of Hypertrophic Cardiomyopathy
- Many patients are asymptomatic, making the disease dangerous
- A major cause of “athlete’s heart,” which can result in sudden cardiac death or arrest due to dangerous dysrhythmias
- As patients age, angina, dyspnea, and syncope become more common
Dilated Cardiomyopathy
- Most common cardiomyopathy, though there are many causes
- Causes include: toxicities, peripartum cardiomyopathy, genetic causes, and inflammatory causes
- Genetic causes are most often autosomal dominant, though some (such as dystrophin) can be X-linked
- Mutations can occur in proteins that support the sarcomere (dystrophin, titin, actinin) or in proteins closely associated with contraction (tropomyosin, troponins, myosin)
- Although the heart wall appears thin, the heart is massive (often weighing 2-3x the weight of a healthy heart)
- Ventricles are usually more affected (dilated) than the atria
- Dilation can lead to regurgitation of AV valves
Dilated Cardiomyopathy Clinical Features
- Can be asymptomatic until heart failure symptoms appear, such as fatigue, exercise intolerance, dyspnea, and dependent edema
- The degree of ventricular enlargement can be great enough to cause mitral regurgitation
- Can also manifest as palpitations or syncopal episodes due to development of dysrhythmias
- Many acquired causes of DCM reverse if damage is not long-term and the initial insult is eliminated
- If the inciting cause cannot be remedied, the prognosis is more serious, and DCM is one of the most common indications for heart transplant
Restrictive Cardiomyopathy
- Characterized by restricted ventricular filling
- Reduced diastolic volume in one or both ventricles
- Normal or near-normal ventricular systolic function and wall thickness
- Least common of the three cardiomyopathies discussed
- Carries a high mortality rate
- Usually presents with an isolated diastolic dysfunction, HFpEF picture with normal stroke volume in most cases
Restrictive Cardiomyopathy Pathogenesis
- Some are autosomal dominant mutations, but the pathogenesis is not well understood
- Many are secondary, caused by conditions outside the heart
- Amyloidosis: accumulation of abnormal proteins in various tissues
- Hemochromatosis: accumulation of iron in cardiomyocytes and other tissues
- Sarcoidosis: chronic, granulomatous disease that infiltrates the wall of the ventricle
Atherosclerosis
- A complex disorder that is multifactorial and somewhat unique across individuals depending on environmental and genetic factors
- Contributing factors include:
- Systemic and local inflammation
- Dyslipidemia
- Higher levels of lipoprotein A – Lp(a)
- Metabolic syndrome and diabetes
- Hypertension
Lipoprotein A (Lp(a))
- May increase atherogenesis by:
- Initiating coagulation
- Contributing to the development of unstable plaques
- Activation of monocytes in the arterial wall
- Eliciting secretion of pro-inflammatory cytokines and expression of adhesion molecules in the arterial wall
- Lp(a) secretion is increased when IL-6 levels increase
- May be more harmful when systemic inflammation is present
- Some effects are thought to be due to the OxPL carried by the Lp(a) particle, although this is not yet confirmed
Plaque Types
- Unstable plaque: a plaque with an unstable fibrous cap that is prone to rupture
- Rupture releases pro-coagulant molecules into the bloodstream
- Factors increasing stability: amount of collagen in the fibrous cap
- Activated platelets can release growth factors that stimulate collagen production
- However, activated platelets are often triggered by binding to a rupture in the fibrous cap or activated endothelial cells
- Activated macrophages produce metalloproteinases that degrade collagen, weakening the fibrous cap
- Inflammation tends to decrease stability of atherosclerotic plaques
Unstable Plaques and ACS
- Unstable plaques can lead to acute coronary syndromes (ACS)
- Factors contributing to ACS include:
- Plaque rupture
- Thrombus formation
- Vasospasm
Eroded Plaques
- A different pathophysiological alteration of the plaque
- Have a more stable fibrous cap, an overlying thrombus, and lots of NETS
- NETS = neutrophil extracellular traps
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on the different types of cardiomyopathies, including dilated and hypertrophic cardiomyopathy. Explore the causes, clinical features, and implications of these heart muscle diseases. This quiz will help you understand their significance and presentation in patients.
