Classification of Cardiomyopathy¶

Chapter 266 | Part 6: Disorders of the Cardiovascular System · Part 6 – Cardiovascular Disorders

Detailed clinical reference synthesised from Harrison's Principles of Internal Medicine, 22nd Edition

🔑 Key Clinical Points¶

Harrison's defines cardiomyopathy as primary disease of the heart muscle itself, originally excluding myocardial dysfunction resulting from other cardiovascular disease.
Traditional morphologic classification defines three major phenotypes: Hypertrophic (HCM), Dilated (DCM), and Restrictive (RCM).
HCM diagnostic criteria: Septal thickness ≥15 mm in men, ≥13 mm in women; LVEF ≥ normal (usually >0.60); LV chamber volume ≤ normal.
DCM diagnostic criteria: LVEF ≤0.50 (usually ≤0.40); LVEDV >112% normal for age/sex or LVEDD >95% predicted; Persistent LVEF ≤0.30–0.35 is threshold for primary prevention ICD.
RCM is a functional diagnosis based on moderate-severe diastolic dysfunction and/or elevated cardiac filling pressures; wall thickness often increased but can appear normal.
Arrhythmogenic Cardiomyopathy (ACM) includes ACM-LV (dominant in LV, DCM phenotype), ACM-RV (dominant in RV, ARVC), and Biventricular ACM.
Left ventricular noncompaction (LVNC) trait is often assessed by maximum ratio of noncompacted/compacted LV myocardium >2.3.
Storage diseases (GLA/Anderson-Fabry, PRKAG2, LAMP2/Danon's) and amyloidosis can mimic HCM morphology.
Regional variation exists: North American patients have higher comorbidity burden and device use rates compared to South American patients.
Congestive heart failure is a nonspecific syndrome requiring thorough evaluation of possible etiology/ies, not a diagnosis of cardiomyopathy itself.

📑 Table of Contents¶

1. DEFINITION & OVERVIEW
1.1 Phenotypic Classification
1.2 Evolution of Phenotypes
2. EPIDEMIOLOGY
3. ETIOLOGY & PATHOPHYSIOLOGY
3.1 Genetic and Acquired Causes
3.2 Imaging and Tissue Characterization
4. CLINICAL FEATURES
4.1 Symptom Presentation
5. DIFFERENTIAL DIAGNOSIS
5.1 Mimickers and Challenges
6. INVESTIGATIONS & DIAGNOSIS
6.1 Diagnostic Algorithm
6.2 Imaging Modalities
7. MANAGEMENT & TREATMENT
7.1 Therapeutic Considerations
8. PROGNOSIS & COMPLICATIONS
8.1 Complications
9. SPECIAL CONSIDERATIONS
9.1 Demographic Variations
10. KEY PEARLS & CLINICAL TRAPS
10.1 Board Exam Pearls
Figures & Illustrations

📋 Figures in This Chapter¶

#	Type	Description
1	🖼 Figure	Figure / Illustration

1. DEFINITION & OVERVIEW¶

The term cardiomyopathy describes primary disease of the heart muscle itself, originally excluding myocardial dysfunction resulting from other cardiovascular disease.
Common usage often includes diagnoses of ischemic cardiomyopathy, valvular cardiomyopathy, and hypertensive cardiomyopathy.
Traditional morphologic classification defines the three major phenotypes of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM).
A fourth evolving phenotype with predominantly genetic causes is arrhythmogenic right ventricular cardiomyopathy (ARVC), originally termed arrhythmogenic right ventricular dysplasia.
As new phenotype-genotype connections are revealed, the terminology continues to evolve, as arrhythmogenic right ventricular dysplasia may also be termed ACM-RV (arrhythmogenic cardiomyopathy–right ventricle predominant).
If the ACM terminology is expanded to include acquired disease, the granulomatous disease of sarcoidosis and the protozoal myocarditis of Chagas' disease can both cause phenotypes with cardiomyopathy and ventricular arrhythmias that qualify as ACM-RV and ACM-LV.
Reliance upon phenotypic presentation is diminishing as more is learned about the underlying causes of cardiomyopathy.
The catalog is rapidly growing of pathogenic genetic variants that can lead to heritable cardiomyopathies, which new imaging techniques can now sometimes identify prior to clinical disease.
Expanding knowledge of immune response pathways reveals how some aspects of myocardium may also be inherited and how they contribute to infectious and noninfectious inflammation that can cause clinical myocarditis and cardiomyopathy.
Diagnosis and outcomes of clinical cardiomyopathies are further complicated by the frequent two-hit models where the clinical expression of a genetic predisposition to cardiomyopathy may be triggered by acquired conditions such as infections, toxic exposures, pregnancy, or tachycardia.

Table 1 — Table 266-1 Classification of Cardiomyopathies¶

CARDIOMYOPATHY (CM) PHENOTYPE	DIAGNOSTIC CRITERIA	OTHER MORPHOLOGY	COMMON CHALLENGES IN DIAGNOSIS
Hypertrophic cardiomyopathy (HCM)	• Septal thickness in men ≥15 mm, ≥13 mm in women. • 13–14 mm may be diagnostic in relatives of proband with known HCM or with positive genetic test. • LVEF ≥ normal, usually >0.60 • LV chamber volume ≤normal.	• Patterns of LV hypertrophy (LVH) in HCM: – Asymmetric septal hypertrophy – Inverse (sigmoid pattern) septal hypertrophy – Concentric LVH – Apical hypertrophy	• Distinction from athlete's heart and severe chronic hypertension • The storage diseases of GLA (Anderson-Fabry), PRKAG2, and LAMP2 (Danon's), which can mimic HCM morphology • Exclude aortic stenosis • In older patients, exclude amyloidosis, which can also cause asymmetric septal thickening
Restrictive cardiomyopathy (RCM)	• Functional diagnosis based on moderate-severe diastolic dysfunction and/or elevated cardiac filling pressures. • LVEF usually mildly reduced, occasionally normal.	• Usually marked atrial enlargement • Although both ventricles affected, clinical right heart failure often dominates. • Wall thickness often increased but can appear normal.	• Marked wall thickness suggests: – Amyloidosis – Inherited storage diseases – Inborn metabolic diseases • Some sarcomeric variants and storage diseases can appear with RCM as well as HCM phenotypes • Inborn metabolic diseases • Sarcoidosis more often has morphology of regional wall motion abnormalities, DCM phenotype, or right ventricular (RV) involvement with systolic dysfunction
Dilated cardiomyopathy (DCM)	• Early: LVEF ≤0.50 and/or LVEDV >112% normal for age/sex or LVEDD >95% predicted sex/height • LVEF ≤0.40: threshold for traditionally recommended therapies for heart failure with low LVEF • Persistent LVEF ≤0.30–0.35: threshold for primary prevention ICD	• Can involve LV alone or with RV involvement either from primary cause or from secondary RV failure due to chronically elevated pulmonary artery pressures	• Structural heart disease such as coronary artery disease or infarction from other cause, primary valve disease
Arrhythmogenic CM Dominant in LV (ACM-LV)	• Morphologic criteria generally those for DCM. • Ventricular tachyarrhythmias dominate without or before severely reduced LVEF and heart failure. • Primary prevention ICD considered even when LVEF >0.35.	• Suggestive but not necessarily conclusive differences in patterns of late gadolinium enhancement between different variants • Occasional ACM-LV with RCM phenotype	• For frequent PVCs or NSVT, may be difficult to distinguish PVC-related CM from genetic CM causing both the arrhythmias and the CM
Arrhythmogenic CM Dominant in RV (ACM-RV; also termed ARVC)	• Modified task force criteria from 2010 include combinations of major and minor criteria • Biventricular arrhythmogenic CM often diagnosed from LGE in ventricle with less involvement	• Abnormal RV function or structure • Biventricular ACM often diagnosed predominantly RV involvement with ventricular arrhythmias, RV wall motion abnormalities, aneurysms, and dilation	• Cardiac sarcoidosis can cause predominantly RV involvement with ventricular arrhythmias, RV wall motion abnormalities, aneurysms, and dilation
Trait of LV noncompaction (LVNC)	• Often assessed by maximum ratio of noncompacted/compacted LV myocardium >2.3 and other criteria • Implications determined by CM phenotype and genotype	• Can occur with HCM, DCM, some dystrophies, and other syndromic presentations • Increased prevalence in athletic hearts	• Can occur in normal hearts, pregnancy

1.1 Phenotypic Classification¶

Hypertrophic cardiomyopathy (HCM): Left ventricular wall thickness is increased (≥13–15 mm depending on context) and ejection fraction is normal or high.
Dilated cardiomyopathy (DCM): Defined when the left ventricular ejection fraction (LVEF) is ≤0.50, but most clinical presentations are with LVEF ≤0.40.
Restrictive cardiomyopathy (RCM): Typically presents with mildly decreased ejection fraction and variably increased wall thickness and are often defined less by morphology than by evidence of abnormal diastolic physiology on echocardiography or invasive hemodynamic measurement.
Arrhythmogenic cardiomyopathy (ACM): A fourth evolving phenotype with predominantly genetic causes characterized by life-threatening arrhythmias and abnormal right ventricular structure and function, with variable expression in the left ventricle.

1.2 Evolution of Phenotypes¶

DCMs can respond to recommended therapies with 'reverse remodeling' to higher ejection fraction and smaller ventricles.
HCM evolves in ~5% of patients to a reduced ejection fraction (HCM-rEF) with more restrictive physiology.
Mid-range LVEF is often a transition in DCM, either deterioration from normal for age/sex or early DCM or improvement into DCM remission.
Mid-range LVEF includes rare transition to HCM with LV systolic dysfunction (LVEF <0.50) of proband with known HCM or with positive genetic test.

2. EPIDEMIOLOGY¶

Variation in the benefits of beta blockers based on world region remains an area of controversy.
In oral pharmacologic therapy trials of HFrEF, patients from southwest Europe have a lower incidence of ischemic cardiomyopathy and those in North America tend to have more diabetes and prior coronary revascularization.
There is also regional variation in medication use even after accounting for indication.
In trials of HF, disparate effects are noted across populations.
As a recent example, in TOPCAT, the drug spironolactone was effective when used in the U.S. population, whereas patients recruited from Russia and contiguous territories showed no difference.
Whether this represents population differences or trial conduct disparity remains a serious question.
ADHF patients in Eastern Europe tend to be younger, with higher EFs and lower natriuretic peptide levels.
Patients from South America tend to have the lowest rates of comorbidities, revascularization, and device use.
In contrast, patients from North America have the highest comorbidity burden with high revascularization and device use rates.
Given geographic differences in baseline characteristics and clinical outcomes, the generalizability of therapeutic outcomes in patients in the United States and Western Europe may require verification.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

The catalog is rapidly growing of pathogenic genetic variants that can lead to heritable cardiomyopathies, which new imaging techniques can now sometimes identify prior to clinical disease.
Expanding knowledge of immune response pathways reveals how some aspects of myocardium may also be inherited and how they contribute to infectious and noninfectious inflammation that can cause clinical myocarditis and cardiomyopathy.
Diagnosis and outcomes of clinical cardiomyopathies are further complicated by the frequent two-hit models where the clinical expression of a genetic predisposition to cardiomyopathy may be triggered by acquired conditions such as infections, toxic exposures, pregnancy, or tachycardia.
Congestive heart failure should not be considered a diagnosis or an etiology of cardiomyopathy but a nonspecific syndrome requiring thorough evaluation of possible etiology/ies.

3.1 Genetic and Acquired Causes¶

Pathogenic genetic variants leading to heritable cardiomyopathies.
Infectious and noninfectious inflammation contributing to clinical myocarditis and cardiomyopathy.
Two-hit models: genetic predisposition triggered by acquired conditions (infections, toxic exposures, pregnancy, tachycardia).
Storage diseases: GLA (Anderson-Fabry), PRKAG2, LAMP2 (Danon's) can mimic HCM morphology.
Inherited storage diseases and inborn metabolic diseases can appear with RCM as well as HCM phenotypes.

3.2 Imaging and Tissue Characterization¶

Echocardiography remains the initial imaging modality to define morphology and function.
Increasing use of magnetic resonance imaging to provide further information on myocardial tissue characterization.
Patterns of fibrosis indicated by late gadolinium enhancement.
T1 and T2 mapping for evidence of focal and diffuse inflammation.

4. CLINICAL FEATURES¶

Early symptoms of cardiomyopathy often reflect exertional intolerance with breathlessness or fatigue.
Arrhythmias are often presenting events of unrecognized cardiomyopathy.
Cardiomyopathy can also present with embolic events related to atrial fibrillation or apical ventricular thrombi.
Cardiomyopathy may often present first with the syndrome of congestion, with fluid retention and elevated left heart filling pressures causing shortness of breath with minimal activity or even at rest, particularly with orthopnea.
It may be accompanied by elevated right-sided filling pressures causing edema and often abdominal symptoms.
The nonspecific historical term congestive heart failure describes the syndrome of congestion, which is common to diverse cardiac diagnoses such as congenital heart disease, primary pulmonary hypertension, and structural valve disease.

4.1 Symptom Presentation¶

Exertional intolerance with breathlessness or fatigue.
Arrhythmias as presenting events.
Embolic events (atrial fibrillation, apical ventricular thrombi).
Congestion syndrome (fluid retention, elevated left heart filling pressures, orthopnea).
Right-sided failure signs (edema, abdominal symptoms).

5. DIFFERENTIAL DIAGNOSIS¶

Distinction from athlete's heart and severe chronic hypertension.
The storage diseases of GLA (Anderson-Fabry), PRKAG2, and LAMP2 (Danon's), which can mimic HCM morphology.
Exclude aortic stenosis.
In older patients, exclude amyloidosis, which can also cause asymmetric septal thickening.
Structural heart disease such as coronary artery disease or infarction from other cause, primary valve disease.
Cardiac sarcoidosis can cause predominantly RV involvement with ventricular arrhythmias, RV wall motion abnormalities, aneurysms, and dilation.
For frequent PVCs or NSVT, may be difficult to distinguish PVC-related CM from genetic CM causing both the arrhythmias and the CM.

5.1 Mimickers and Challenges¶

Athlete's heart vs. HCM.
Severe chronic hypertension vs. HCM.
Aortic stenosis vs. HCM.
Amyloidosis vs. HCM (in older patients).
Storage diseases (GLA, PRKAG2, LAMP2) vs. HCM.
Structural heart disease (CAD, infarction, valve disease) vs. DCM.
Cardiac sarcoidosis vs. ACM-RV.
PVC-related CM vs. Genetic CM.

6. INVESTIGATIONS & DIAGNOSIS¶

Initial evaluation of possible cardiomyopathy begins with a detailed clinical history and examination seeking clues to cardiac, genetic, and systemic causes of heart disease.
Echocardiography remains the initial imaging modality to define morphology and function.
Increasing use of magnetic resonance imaging to provide further information on myocardial tissue characterization.
Patterns of fibrosis indicated by late gadolinium enhancement.
T1 and T2 mapping for evidence of focal and diffuse inflammation.
Diagnostic criteria for HCM: Septal thickness in men ≥15 mm, ≥13 mm in women; 13–14 mm may be diagnostic in relatives of proband with known HCM or with positive genetic test.
Diagnostic criteria for DCM: LVEF ≤0.50 and/or LVEDV >112% normal for age/sex or LVEDD >95% predicted sex/height.
Diagnostic criteria for ACM-RV: Modified task force criteria from 2010 include combinations of major and minor criteria.
Diagnostic criteria for LVNC: Often assessed by maximum ratio of noncompacted/compacted LV myocardium >2.3 and other criteria.

Table 2 — Diagnostic Criteria for Cardiomyopathy Phenotypes¶

Phenotype	Key Diagnostic Thresholds
HCM	• Septal thickness ≥15 mm (men), ≥13 mm (women) • LVEF ≥ normal (>0.60) • LV chamber volume ≤ normal
DCM	• LVEF ≤0.50 (usually ≤0.40) • LVEDV >112% normal for age/sex • LVEDD >95% predicted sex/height
RCM	• Functional diagnosis (moderate-severe diastolic dysfunction) • Elevated cardiac filling pressures • LVEF usually mildly reduced, occasionally normal
ACM-LV	• Morphologic criteria generally those for DCM • Ventricular tachyarrhythmias dominate • Primary prevention ICD considered even when LVEF >0.35
ACM-RV	• Modified task force criteria from 2010 • Abnormal RV function or structure • LGE in ventricle with less involvement
LVNC	• Maximum ratio of noncompacted/compacted LV myocardium >2.3

6.1 Diagnostic Algorithm¶

Step 1: Detailed clinical history and examination seeking clues to cardiac, genetic, and systemic causes.
Step 2: Echocardiography to define morphology and function.
Step 3: Magnetic resonance imaging for myocardial tissue characterization, patterns of fibrosis (LGE), and T1/T2 mapping.
Step 4: Genetic testing for heritable cardiomyopathies.
Step 5: Evaluation for acquired conditions (infections, toxic exposures, pregnancy, tachycardia) in two-hit models.

6.2 Imaging Modalities¶

Echocardiography: Initial modality to define morphology and function.
Magnetic Resonance Imaging (MRI): Provides further information on myocardial tissue characterization.
Late Gadolinium Enhancement (LGE): Indicates patterns of fibrosis.
T1 and T2 Mapping: Evidence of focal and diffuse inflammation.

7. MANAGEMENT & TREATMENT¶

LVEF ≤0.40: Threshold for traditionally recommended therapies for heart failure with low LVEF.
Persistent LVEF ≤0.30–0.35: Threshold for primary prevention ICD.
Primary prevention ICD considered even when LVEF >0.35 (in ACM-LV).
Regional variation in medication use even after accounting for indication.
In trials of HF, disparate effects are noted across populations.
In TOPCAT, the drug spironolactone was effective when used in the U.S. population, whereas patients recruited from Russia and contiguous territories showed no difference.
Whether this represents population differences or trial conduct disparity remains a serious question.

7.1 Therapeutic Considerations¶

Recommended therapies for heart failure with low LVEF.
Primary prevention ICD for persistent LVEF ≤0.30–0.35.
Device therapy in heart failure (Hussein AA, Wilkoff BL: Cardiac implantable electronic device therapy in heart failure).
Regional variation in medication use and outcomes.
Verification of therapeutic outcomes in patients in the United States and Western Europe may be required given geographic differences.

8. PROGNOSIS & COMPLICATIONS¶

Ventricular tachyarrhythmias dominate without or before severely reduced LVEF and heart failure in ACM-LV.
Life-threatening arrhythmias and abnormal right ventricular structure and function in ACM-RV.
Prognostic scoring systems exist but specific survival curves are not detailed in this text.
Diagnosis and outcomes of clinical cardiomyopathies are further complicated by the frequent two-hit models.

8.1 Complications¶

Ventricular tachyarrhythmias.
Heart failure.
Embolism (atrial fibrillation, apical ventricular thrombi).
Congestion syndrome.

9. SPECIAL CONSIDERATIONS¶

Can occur in normal hearts, pregnancy (LVNC).
Increased prevalence in athletic hearts (LVNC).
In older patients, exclude amyloidosis, which can also cause asymmetric septal thickening (HCM).
Patients from South America tend to have the lowest rates of comorbidities, revascularization, and device use.
ADHF patients in Eastern Europe tend to be younger, with higher EFs and lower natriuretic peptide levels.

9.1 Demographic Variations¶

Pregnancy: LVNC can occur in normal hearts, pregnancy.
Athletic hearts: Increased prevalence in athletic hearts (LVNC).
Age: In older patients, exclude amyloidosis in HCM.
Geographic: South America (lowest comorbidities), North America (highest comorbidity burden).
Eastern Europe: Younger ADHF patients, higher EFs, lower natriuretic peptide levels.

10. KEY PEARLS & CLINICAL TRAPS¶

Congestive heart failure is a nonspecific syndrome requiring thorough evaluation of possible etiology/ies.
Mid-range LVEF is often a transition in DCM, either deterioration from normal for age/sex or early DCM or improvement into DCM remission.
Mid-range LVEF includes rare transition to HCM with LV systolic dysfunction (LVEF <0.50) of proband with known HCM or with positive genetic test.
Reliance upon phenotypic presentation is diminishing as more is learned about the underlying causes of cardiomyopathy.
The catalog is rapidly growing of pathogenic genetic variants that can lead to heritable cardiomyopathies, which new imaging techniques can now sometimes identify prior to clinical disease.
Expanding knowledge of immune response pathways reveals how some aspects of myocardium may also be inherited and how they contribute to infectious and noninfectious inflammation that can cause clinical myocarditis and cardiomyopathy.
Diagnosis and outcomes of clinical cardiomyopathies are further complicated by the frequent two-hit models where the clinical expression of a genetic predisposition to cardiomyopathy may be triggered by acquired conditions such as infections, toxic exposures, pregnancy, or tachycardia.

10.1 Board Exam Pearls¶

HCM thickness criteria: Men ≥15 mm, Women ≥13 mm.
DCM EF threshold: ≤0.50 (usually ≤0.40).
LVNC ratio: >2.3.
ACM-RV: Modified task force criteria from 2010.
Storage diseases mimic HCM: GLA, PRKAG2, LAMP2.
Exclude amyloidosis in older patients with HCM.
Exclude aortic stenosis in HCM.
Distinction from athlete's heart in HCM.

Figures & Illustrations¶

Reproduced from Harrison's 22nd Edition.

Figure 1¶

: Classification of Cardiomyopathy phenotypes including Hypertrophic (HCM), Dilated (DCM),...

Caption: Figure 266-1: Classification of Cardiomyopathy phenotypes including Hypertrophic (HCM), Dilated (DCM), Restrictive (RCM), and Arrhythmogenic (ACM) cardiomyopathy, illustrating diagnostic criteria, morphological features, and common diagnostic challenges for each phenotype.

Generated from Harrison's Principles of Internal Medicine, 22nd Edition.