B.16 Hypertophic Cardiomyopathy Flashcards
B.16 Hypertophic Cardiomyopathy
defintiion
Hypertrophic cardiomyopathy (HCM) is a genetic condition characterized by left ventricular hypertrophy that is not caused by other cardiac or causative systemic diseases.
Nonobstructive HCM: Hypertrophic cardiomyopathy without obstruction of the left ventricular outflow tract (LVOT)
Hypertrophic obstructive cardiomyopathy (HOCM): HCM with left ventricular outflow tract obstruction (LVOTO) that is dynami
B.16 Hypertophic Cardiomyopathy
Epidemiology
Second most common cardiomyopathy
Two types are distinguished:
1. Obstructive type/hypertrophic obstructive cardiomyopathy (HOCM): ∼ 70% of cases
- Nonobstructive type: ∼ 30% of cases
Alongside myocarditis, HCM is one of the most frequent causes of sudden cardiac death in young patients, especially young athletes.
B.16 Hypertophic Cardiomyopathy
Etiology
HCM is a genetic condition characterized by otherwise unexplained left ventricular hypertrophy.
Most common hereditary heart disease
Autosomal dominant inheritance with varying penetrance
Autosomal dominant mutations in sarcomeric proteins
– β-myosin heavy chain
– Myosin-binding protein C
– Troponin T
Most commonly caused by mutations of the sarcomeric protein genes (e.g., myosin heavy chain, myosin binding protein C) → disorganization of myocyte architecture characterized by myofibrillar disarray and fibrosis
- MYH7 gene: gene on the long arm of chromosome 14 that codes for the beta-myosin heavy chain, which forms a part of type II myosin in skeletal and cardiac muscle cells
- MYBPC3 gene: gene on the short arm of chromosome 11 that codes for cardiac myosin binding protein C, which prevents the breakdown of thick filaments in cardiac sarcomeres
Other conditions that are associated with left-ventricular hypertrophy include the following:
Chronic hypertension (most common cause of left ventricular hypertrophy)
Aortic stenosis
Friedreich ataxia, Fabry disease, Noonan syndrome
Amyloidosis
B.16 Hypertophic Cardiomyopathy
General Pathophys
HCM is characterized by hypertrophy of the left ventricle ; most commonly occurs with asymmetrical septal involvement, which leads to diastolic dysfunction (impaired left ventricular relaxation and filling) → reduced systolic output volume → reduced peripheral and myocardial perfusion. → cardiac arrhythmia and/or heart failure and increased risk of sudden cardiac death
B.16 Hypertophic Cardiomyopathy
Nonobstructive and obstructive HCM Pathophys
Typical features include:
- Increased LV wall thickness with septal predominance , no dilation of left ventricle
- Myofibrillar disarray, interstitial fibrosis, and myocyte hypertrophy
Concentric hypertrophy: a form of cardiac remodeling characterized by parallel duplication of sarcomeres that leads to thickening of the ventricular wall
Concentric hypertrophy can also occur secondary to the following diseases, then potentially mimicking HCM: - Hypertension and aortic valve stenosis (due to chronic pressure and volume overload): Chronic hypertension → increased afterload → increased myocardial wall tension → changes in myocardial gene expression → sarcomeres laid down in parallel → increased left ventricular thickness → decreased left ventricular size → diastolic dysfunction
- Storage disorders (e.g., Fabry disease, amyloidosis) and hereditary syndromes (e.g., Friedreich ataxia, Noonan syndrome)
B.16 Hypertophic Cardiomyopathy
Hypertrophic obstructive cardiomyopathy (HOCM) Pathophys
Pathomechanism:
Left ventricular outflow tract obstruction→ increased LV systolic pressure → prolongation of ventricular relaxation → increased LV diastolic pressure → exacerbation of HCM with further reduction of cardiac output
Mechanisms of obstruction
- Systolic anterior motion (SAM) of the mitral valve, results in mitral-septal contact during mid-to-late systole
- Venturi effect: accelerated blood flow through ventricular outflow tract creates negative pressure that pulls the mitral valve towards the septum → increased outflow tract obstruction
- Ejection against an elongated and distorted mitral valve causes leaflets to get pulled into the outflow tract → potential secondary mitral regurgitation
Muscular obstruction
Encroachment of the LVOT by the hypertrophic septum
Hypertrophy or anomalous insertion of papillary muscles → increased left ventricular apical pressure → ↑ risk for development of apical ventricular aneurysms
LVOT obstruction is dynamic
The following factors can increase the degree of obstruction: ↑ LV contractility, ↓ preload, and ↓ afterload
Clinically exacerbating factors
Physical exercise/stress
Dehydration
Pharmacologic provocation (e.g., diuretics, ACEIs/ARBs, digoxin, hydralazine)
Valsalva maneuver (strain phase)
B.16 Hypertophic Cardiomyopathy
Symptoms
Symptoms: worsen with exercise, dehydration, and use of certain drugs (e.g., diuretics, hydralazine, ACEIs/ARBs, digoxin)
- Frequently asymptomatic (especially the nonobstructive type)
- Exertional dyspnea
- Angina pectoris
- Dizziness, lightheadedness, syncope
- Palpitations, cardiac arrhythmias
- Sudden cardiac death (particularly during or after intense physical activity)
B.16 Hypertophic Cardiomyopathy
Physical Exam
Systolic ejection murmur (crescendo-decrescendo) - This is caused by dynamic LV outflow tract obstruction due to asymmetrically thickened myocardium.
Increases with Valsalva maneuver, standing, inotropic drugs (e.g., digitalis) - A decrease in preload due to a decrease in venous return to the heart leads to increased force of contraction, which generates stronger forces driving LV outflow obstruction.
Decreases with:
Hand grip, squatting, or passive leg elevation
Drugs that decrease cardiac contractility (e.g., beta blockers)
Possible holosystolic murmur from mitral regurgitation
Sustained apex beat
S4 gallop
Paradoxical split of S2 - Audible during expiration but not inspiration
Pulsus bisferiens: LV outflow obstruction causes a sudden quick rise of the pulse followed by a slower longer rise (biphasic pulse).
B.16 Hypertophic Cardiomyopathy
DX
Echocardiography is the best initial and confirmatory test. Other investigations (e.g., ECG, CXR, cardiac MRI, exercise testing, and screening for coronary artery disease or genetic diseases) can be done on a case-by-case basis.
B.16 Hypertophic Cardiomyopathy
DX Criteria
Both of following are required to make the diagnosis:
- Left ventricular nondilated hypertrophy (usually ≥ 15 mm in adults)
- Absence of other cardiac or systemic diseases that could explain hypertrophy (e.g., long-standing hypertension or aortic stenosis)
B.16 Hypertophic Cardiomyopathy
Transthoracic echocardiography with Doppler
Indications
- Initial assessment of patients with suspected HCM
- Repeat testing in patients with a new cardiovascular event or change in clinical status
Findings in patients with HCM
Wall thickness
- Asymmetrically thickened left ventricular wall, (≥ 15 mm), typically involving the septum
- LV wall thickness ≥ 30 mm is associated with a high risk of sudden death. [5]
Outflow tract abnormalities
- Systolic anterior motion of the mitral valve - Protrusion of the anterior mitral valve cusp toward the septum that can lead to dynamic LV outflow tract obstruction
- Mitral regurgitation
- ↑ LVOT pressure gradient via Doppler echocardiography - The gradient describes the difference between LV and aortic pressures.
Other findings
- Left atrial enlargement - This has been associated with increased, adverse, disease-related events. A transverse size > 48 mm or a chamber volume ≥ 118 mL is associated with a risk of atrial fibrillation or heart failure death.
- Systolic function typically normal - Ejection fraction is typically preserved. Impairment is seen in end-stage HCM.
- Diastolic dysfunction - I.e., decreased ventricular compliance and increased stiffness
B.16 Hypertophic Cardiomyopathy
Transthoracic echocardiography with Doppler Findings more specific to HOCM
Findings more specific to HOCM
- Asymmetrically thickened interventricular septum
- Dynamic LVOT obstruction due to contact between the septum and mitral valve during systole
B.16 Hypertophic Cardiomyopathy
ECG Findings
– LVH, deep Q waves (esp. inferior/lateral leads), ST–T changes
Indication: all patients with suspected HCM
Classic findings: commonly seen in obstructive HCM
ECG signs of LVH (see Sokolow-Lyon criteria)
Deep Q waves, particularly in the inferior (II, III, and aVF) and lateral (I, aVL, V4–6) leads - These suggest septal hypertrophy
Giant inverted T waves in the precordial leads
Other supportive findings
- Nonspecific ST segment and T-wave changes - E.g., diffuse or localized repolarization abnormalities such as T-wave inversion
- P wave changes indicating left atrial enlargement (e.g., P mitrale)
- LBBB - In advanced disease with prominent fibrotic changes of the LV wall
Associated dysrhythmias: Ventricular tachycardia, atrial fibrillation, or atrial flutter - Due to the reentry mechanism enabled by fibrotic changes in corresponding ventricular and atrial walls. Paroxysmal tachycardias may be better visualized on ambulatory ECG.
B.16 Hypertophic Cardiomyopathy
Exercise testing
Provocation tests (e.g., exercise testing) are obligatory if no obstruction is discernible at rest.
Exercise echocardiography
Indications: to confirm and quantify dynamic LVOT obstruction in patients with inconclusive TTE
Findings: LVOT obstruction and/or mitral regurgitation
Treadmill exercise testing
Indications
Assessment of functional capacity and response to therapy
Addition of ECG and blood pressure monitoring for SCD risk stratification
Findings
- Clinical observation for development of symptoms (e.g., dyspnea, palpitations)
- Blood pressure monitoring: hypotension
- ECG tracings with arrhythmias and/or signs of ischemia
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Cardiac MRI
Indications
Evaluation of ventricular morphology if echocardiographic findings are inconclusive
Consider in patients with inconclusive risk stratification for sudden cardiac death.
Evaluation of alternative diagnoses
Advantages
Better visualization of segmental left ventricular hypertrophy located in the anterolateral wall or apex compared to echocardiography
Better detection of apical aneurysms compared to echocardiography
Identification of myocardial fibrosis with late gadolinium enhancement (LGE)
B.16 Hypertophic Cardiomyopathy
asymptomatic Pts TX
No pharmacological or invasive treatment is needed
Lifestyle changes
- Avoidance of dehydration
- Maintaining a healthy body weight
- Avoidance of excessive alcohol intake
- Avoidance of strenuous exercise and situations that will likely cause vasodilation (e.g., environmental factors such as high temperatures)
Automated implantable cardioverter defibrillator (AICD)
An AICD is considered for primary or secondary prevention of sudden cardiac death (SCD) in patients who are at high risk.
Absolute indication: known prior history of ventricular fibrillation, sustained ventricular tachycardia, or cardiac arrest
Relative indications
- Syncope of unknown cause
- Family history of SCD in a first-degree relative
- LV wall thickness ≥ 30 mm
B.16 Hypertophic Cardiomyopathy
Symptomatic Pts TX
Initial therapy: for all symptomatic patients with obstructive or nonobstructive HCM
First-line: Beta blockers (e.g., propranolol OR atenolol OR nadolol
Titrate to goal resting heart rate < 60–65/minute
Second-line: Nondihydropyridine CCBs
Consider in patients who do not tolerate or respond to beta blockers
Verapamil, Diltiazem
Additional therapy: to consider adding to beta-blocker or CCB if symptoms are persistent
Obstructive HCM: Disopyramide
Obstructive HCM, or nonobstructive HCM with LVEF > 50%): Oral diuretics, e.g., furosemide
B.16 Hypertophic Cardiomyopathy
Pharma to avoid
Medications to be avoided in LVOT obstruction - These either increase inotropy, or reduce preload or afterload, all of which can worsen symptoms.
- High-dose diuretics
- Digoxin - Can cause harm in patients who do not have atrial fibrillation
- Spironolactone - No benefit
- ACE inhibitors and ARBs
- Dihydropyridine CCBs (e.g., nifedipine)
- Vasodilators (e.g., nitrates and PDE-5 inhibitors)
- Positive inotropes (e.g., dopamine, dobutamine, norepinephrine)
B.16 Hypertophic Cardiomyopathy
Invasive TX
generally indicated for symptoms that are refractory to medical therapy.
- Septal reduction therapy
Indication: severe symptoms (e.g., dyspnea or chest pain, often NYHA III or IV, exertional syncope or presyncope) due to LVOT obstruction (LVOT gradient ≥ 50 mm Hg)
Procedures
Surgical septal myectomy (Morrow procedure) is preferred for most patients; involves thinning the hypertrophic muscular intraventricular septum to widen the left ventricular outflow tract
Transcoronary ablation of septal hypertrophy (alcohol septal ablation) when surgery is considered too high risk or is contraindicated
Dual-chamber pacemaker: Consider for patients who are poor candidates for septal reduction therapy.
Heart transplant: Consider in end-stage nonobstructive HCM when LVEF ≤ 50%.
B.16 Hypertophic Cardiomyopathy
Complications
Hypotension
Heart failure
Atrial fibrillation
Ventricular dysrhythmias
B.16 Hypertophic Cardiomyopathy
Does the murmur of HCM increase with squatting?
→ ❌ No – it decreases (↑ preload)
B.16 Hypertophic Cardiomyopathy
Is HCM always obstructive?
→ ❌ No – obstruction is dynamic and may be absent
B.16 Hypertophic Cardiomyopathy
Is afterload reduction useful in HCM?
→ ❌ No – reducing afterload worsens obstruction
B.16 Hypertophic Cardiomyopathy
Can HCM present with a normal ECG?
→ ❌ Rarely – ECG is usually abnormal (LVH, Q waves)
