Cardiomyopathies
Cardiomyopathies are diseases of the heart muscle that impair the heart’s structure or function, commonly classified into dilated, hypertrophic, restrictive, and arrhythmogenic forms.
This article explains the different types/classification, causes, signs/symptoms, investigations, and management principles.
Hypertrophic Cardiomyopathy (HCM)
Definition
General definition of cardiomyopathy: [Ref]
- A group of diseases that primarily affect the myocardium, resulting in structural and functional abnormalities
- And could not be explained solely by coronary artery disease, hypertension, valvular disease, or congenital heart disease
HCM definition: presence of increased left ventricular wall thickness or mass (+/- right ventricular hypertrophy), that is NOT solely explained by abnormal loading conditions (e.g. volume overload, hypertension, valvular heart disease) [Ref]
- Hypertrophic obstructive cardiomyopathy (HOCM) is a subtype of HCM that develops left ventricular outflow tract obstruction
Aetiology
Clinical Features
Clinical onset is most commonly in adolescence / young adulthood [Ref1][Ref2]
Patients could be asymptomatic. Symptoms are classically triggered / worsened with exercise: [Ref1][Ref2]
- Dyspnoea
- Angina
- Palpitations
- Syncope
Possible examination findings: [Ref1][Ref2]
- Harsh ejection systolic murmur at the left sternal border
- The murmur increases with manoeuvres that reduce preload (e.g. Valsalva manoeuvre, standing up)
- The murmur decreases with manoeuvres that increase preload (e.g. squatting, leg raise)
- A pansystolic murmur from secondary mitral regurgitation is also possible
- Features of LVH
- 4th heart sound
- Prominent apex beat
- Prominent JVP ‘a’ waveThe pathophysiology involves left ventricular outflow tract obstruction and septal hypertrophy, which can also affect right ventricular filling, leading to increased right atrial pressure during atrial contraction and thus a prominent a wave
- Features of abnormal ventricular contraction pattern
- Double apex beat
- Biphasic pulse (pulsus bisferiens) – sudden quick rise of the pulse followed by a slower, longer rise
- Features of heart failure are possible but not common
A typical presentation of HCM is a young athlete who experiences chest pain / syncope / dyspnoea during exercise or sports like football.
HCM could present as sudden cardiac death during exertion or sports.
Only TWO murmurs get louder with Valsalva manoeuvre (which reduces preload): 1) HCM and 2) mitral valve prolapse.
Most other murmurs become quieter with Valsalva manoeuvre.
Complications
Key complications: [Ref]
- Ventricular arrhythmias and sudden cardiac death – the most common cause of death
- Atrial fibrillation
- Heart failure (diastolic heart failure / HFpEF)
Investigation and Diagnosis
Work-up for suspected HCM: [Ref]
- Clinical examination
- Transthoracic echocardiography – 1st line diagnostic test
- ECG
- Genetic testing + 3-generation family history
Cardiac MR is 2nd line, indicated when an echocardiogram is suboptimal or when further characterisation is required. [Ref]
Imaging Findings
Typical transthoracic echocardiography findings: [Ref]
| HCM / HOCM | Findings |
|---|---|
| HCM |
|
| HOCM | Additional findings in HOCM, in addition to those above:
|
Additional findings that can be demonstrated by cardiac MR: [Ref]
- Myocardial fibrosis/scar detection (via Late Gadolinium Enhancement)
- Distinguish HCM from HCM mimics
- Precise measurement of wall thickness
- Assessment of right ventricular involvement
- Identify uncommon sites of hypertrophy (e.g. apex) and aneurysm
HCM can be diagnosed in adults when maximal left ventricular end-diastolic wall thickness is ≥15 mm at any location, without another cause for hypertrophy
- Age-adjusted reference ranges should be used in children
- In the presence of a known genetic variant / 1st degree relative with HCM, a threshold of ≥13 mm is considered diagnostic
ECG Findings
Typical ECG findings: [Ref]
- Left ventricular hypertrophy (deep S wave in V1 + tall R wave in V5 / V6 exceeding 35mm)
- Deep Q waves in inferior (II, III, aVF) and lateral (V5, V6, I, aVL) leads
- Inverted T waves in precordial leads
Histology Findings
Note that myocardial biopsy for histology is not routinely performed and is not necessary for diagnosis, they are usually performed in post-mortem.
Typical histology findings in HCM: [Ref]
- Myocyte hypertrophy and disarray
- Interstitial fibrosis
Management
All patients: [Ref]
- Advice on lifestyle changes
- Consider ICDImplantable cardioverter defibrillator
Symptomatic management (do not routinely offer if asymptomatic): [Ref]
- 1st line: beta blocker monotherapy
- 2nd line: rate-limiting CCB monotherapy
- 3rd line options:
- Cardiac myosin inhibitor (e.g. mavacamten)
- Disopyramide + beta blocker / rate-limiting CCB
- Septal reduction therapy (e.g. surgical myectomy / alcohol septal ablation) – last resort
The following medications are contraindicated in HCM / HOCM:
- Vasodilators (ACE inhibitors, ARB, dihydropyridine CCBs) – reduction in afterload can worsen LVOT obstruction
- +ve Inotropic agents (e.g. digoxin, dobutamine) – increase in contractility can worsen LVOT obstruction
Lifestyle Changes
Advise on: [Ref]
- Structured exercise program tailored to the patient
- Mild to moderate intensity aerobic exercise is safe and beneficial
- Avoid binge drinking (which may precipitate arrhythmias)
- Avoid dehydration
- Maintain a healthy body weight
Implantable Cardioverter Defibrillator (ICD)
ICDImplantable cardioverter defibrillator is the most important intervention to prevent sudden cardiac death in HCM [Ref]
- Absolute indications include a history of documented VF / sustained VT / cardiac arrest [Ref]
Recommendation beyond the absolute indications listed above is complicated; it depends on the risk of sudden cardiac death, risk factors and extent of hypertrophy. The patient’s preference and individualised factors should also be taken into account.
In exams, it is appropriate just to learn that ICD is the most appropriate management for patients with HCM.
Dilated Cardiomyopathy (DCM)
Definition
General definition of cardiomyopathy: [Ref]
- A group of diseases that primarily affect the myocardium, resulting in structural and functional abnormalities
- And could not be explained solely by coronary artery disease, hypertension, valvular disease, or congenital heart disease
DCM definition: left ventricular dilatation + systolic dysfunction (+/- right ventricular involvement) that is NOT solely explained by coronary artery disease or abnormal loading conditions (e.g. hypertension, valvular heart disease, congenital heart disease) [Ref]
Aetiology
Genetic causes (~35-40%): [Ref1][Ref2]
- Involves mutations in sarcomere and desmosome genes (e.g. TTN, LMNA)
- Variable inheritance pattern
- DCM is associated with muscular dystrophy (Duchenne and Becker) and mitochondrial diseases
| Category | Causes |
|---|---|
| Infection (infectious myocarditis) |
|
| Autoimmune disorder |
|
| Toxin / drugs |
|
| Endocrine conditions |
|
The genetics implicated in DCM are less clear-cut and more heterogeneous compared to HCM. Therefore, it is unlikely that the exam would assess one’s knowledge of the genes involved in DCM. It’s more important to be aware of the acquired causes of DCM.
Clinical Features
DCM typically presents similarly to those with chronic heart failure
Left-Sided Heart Failure Features
Symptoms from pulmonary congestion: (increasing in severity)
- Exertional dyspnoea
- Paroxysmal nocturnal dyspnoea
- Orthopnoea
- Dyspnoea at rest
Symptoms from ↓ cardiac output:
- ↓ Exercise tolerance
- Fatigue
Examination findings:
- Bi-basal fine crepitations on auscultation
- S3 heart sound (due to volume overload)
- Cardiomegaly → displaced apex beat
- Peripheral hypoperfusion → ↑CRTcapillary refill time , cold extremities, pallor
Right-Sided Heart Failure Features
Symptoms from systemic congestion and ↑ CVP
- Peripheral oedema
- Ascites → abdominal distention
- Hepatic congestion → RUQ pain and jaundice
- GI congestion → nausea, loss of appetite
Examination findings:
- JVP elevation
- Congestive hepatomegaly
- Hepatojugular reflex
Complications
Key complications of DCM: [Ref]
- Chronic heart failure (systolic heart failure / HFrEF)
- Arrhythmias (atrial fibrillation and conduction abnormalities are common)
- Thromboembolic events (due to intracardiac thrombi)
- Sudden cardiac death (accounts for ~1/3 of mortality in DCM)
Investigation and Diagnosis
1st line: transthoracic echocardiography
- Left ventricular dilation
- Reduced relative wall thickness to cavity size (due to eccentric hypertrophy)
- ↓ Ejection fraction (due to systolic dysfunction)
Further tests (not routinely performed):
- Cardiac MR – indicated if echocardiographic findings are inconclusive or there is diagnostic uncertainty
- CTCACT coronary angiography / coronary angiography – indicated if there is suspicion of ischaemic aetiology / atypical presentation
- Genetic testing – in early-onset disease and suspected familial DCM
Endomyocardial biopsy is reserved for cases with suspected myocarditis, infiltrative disease, or when the diagnosis remains unclear after noninvasive evaluation
Management
Identify and treat any underlying reversible cause, examples:
- Cessation of substance use (e.g. alcohol, cocaine)
- Treat underlying endocrine disorders
- Treat underlying infections
- NB viral myocarditis is managed supportively
- Antiretroviral therapy for HIV
- Antitrypanosomal therapy for Chagas disease
- Substituting cardiotoxic chemotherapy agents
Otherwise, there are no specific treatments that target DCM itself. Management primarily follows the chronic heart failure (HFrEF) guidelines, which are detailed in this article.
Restrictive Cardiomyopathy (RCM)
Definition
General definition of cardiomyopathy: [Ref]
- A group of diseases that primarily affect the myocardium, resulting in structural and functional abnormalities
- And could not be explained solely by coronary artery disease, hypertension, valvular disease, or congenital heart disease
RCM definition: [Ref]
- Impaired left and/or right ventricular filling due to increased myocardial stiffness and abnormal compliance
- In the presence of normal ventricular wall thickness, normal (or reduced) systolic and diastolic volumes
Aetiology
RCM is idiopathic in many cases. [Ref]
Other causes: [Ref]
| Category | Causes |
|---|---|
| Genetic (familial) |
|
| Infiltrative diseases |
|
| Storage disorders |
|
| Endomyocardial fibrosis |
|
Clinical Features
RCM typically presents with features of biventricular heart failure.
Left-Sided Heart Failure Features
Symptoms from pulmonary congestion: (increasing in severity)
- Exertional dyspnoea
- Paroxysmal nocturnal dyspnoea
- Orthopnoea
- Dyspnoea at rest
Symptoms from ↓ cardiac output:
- ↓ Exercise tolerance
- Fatigue
Examination findings:
- Bi-basal fine crepitations on auscultation
- S4 heart sound (due to atrial contraction against a stiff ventricle)
- Cardiomegaly → displaced apex beat
- Peripheral hypoperfusion → ↑ CRT, cold extremities, pallor
Right-Sided Heart Failure Features
Symptoms from systemic congestion and ↑ CVP
- Peripheral oedema
- Ascites → abdominal distention
- Hepatic congestion → RUQ pain and jaundice
- GI congestion → nausea, loss of appetite
Examination findings:
- JVP elevation
- Congestive hepatomegaly
- Hepatojugular reflex
Complications
- Biventricular heart failure (diastolic heart failure / HFpEF)
- Pulmonary hypertension
- Arrhythmias
- Thromboembolic events (due to intracardiac thrombi)
RCM is widely considered the most difficult type of cardiomyopathy to treat, largely due to it causing diastolic heart failure and the lack of prognostic drugs for diastolic heart failure.
Investigation and Diagnosis
1st line investigation: transthoracic echocardiogram [Ref]
- Diastolic dysfunction
- ↓ Ventricular compliance
- Non-dilated ventricles
- Bi-atrial enlargement
- Absence of significant ventricular hypertrophy
Beyond echocardiogram, the work-up and diagnosis of RCM is otherwise complicated, involving: [Ref]
- Cardiac MR
- Screening for suspected underlying cause
- Endomyocardial biopsy – for definitive histological diagnosis
Management
Management of RCM is highly complex, individualised and cause-dependent [Ref1][Ref2]
- Cardiac transplantation is the preferred definitive therapy for advanced RCM
- Early referral for transplantation assessment is recommended, as irreversible pulmonary hypertension can preclude candidacy for transplant
Monitor and treat complications [Ref1][Ref2]
- Manage heart failure as per diastolic heart failure (HFpEF) guidelines, see this article
- Pulmonary hypertension (serial echocardiography is recommended to assess for pulmonary hypertension)
- Thromboembolic disease (severe atrial dilation might require anticoagulation)
- Arrhythmias (identify and treat accordingly)
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Definition
General definition of cardiomyopathy: [Ref]
- A group of diseases that primarily affect the myocardium, resulting in structural and functional abnormalities
- And could not be explained solely by coronary artery disease, hypertension, valvular disease, or congenital heart disease
ARVC definition: [Ref]
- Predominantly right ventricular dysfunction and/or dilatation
- Due to fibro-fatty replacement of cardiomyocytes
Aetiology
Primarily genetic, most commonly due to autosomal dominant mutations in cardiac desmosome genes
Clinical Features
Clinical features of ARVC are highly variable and often age-dependent:
- Many patients remain asymptomatic
- Sudden cardiac death may be the 1st manifestation, esp. in young individuals and athletes
- Right-sided heart failure features predominate (e.g. raised JVP, peripheral oedema, ascites, hepatic congestion)
Investigation and Diagnosis
Very unlikely that students will be expected to know many details of the diagnosis of ARVC.
Recommended investigation includes: [Ref]
- Transthoracic echocardiogram – typically 1st line
- ECG
- Characteristic epsilon wavesSmall +ve deflections that appear at the end of the QRS complex in V1-V2
- T wave inversion in V1-V3 (in the absence of RBBB)
- Cardiac MR
- Genetic testing
Endomyocardial biopsy is reserved for selected cases
- Typical histology finding: fibro-fatty replacement of the myocardium
Management
Key management points: [Ref]
- Exercise restriction (avoid high-intensity and endurance exercise)
- ICDImplantable cardioverter defibrillator implantation (exact indications are of excessive detail)