# 28 - 266 Classification of Cardiomyopathy

### 266 Classification of Cardiomyopathy

as useful in Europe, although the usefulness is disputable. 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 cardiomy­
opathy 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 con­
tiguous 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, revascular­
ization, 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 char­
acteristics and clinical outcomes, the generalizability of therapeutic 
outcomes in patients in the United States and Western Europe may 
require verification.
■
■FURTHER READING
Anker SD et al: Empagliflozin in heart failure with a preserved ejection 
fraction. N Engl J Med 385:1451, 2021.
Borlaug BA: The pathophysiology of heart failure with preserved 
ejection fraction. Nat Rev Cardiol 11:507, 2014.
Braunwald E: Heart failure. JACC Heart Fail 1:1, 2013.
Heidenreich PA et al: 2022 AHA/ACC/HFSA guideline for the 
management of heart failure: A report of the American College of 
Cardiology/American Heart Association Joint Committee on Clinical 
Practice Guidelines. Circulation 145:e895, 2022.
Hein AM et al: Medical management of heart failure with reduced 
ejection fraction in patients with advanced renal disease. JACC Heart 
Fail 7:371, 2019.
Hollenberg SM et al: 2019 ACC Expert Consensus Decision Pathway 
on Risk Assessment, Management, and Clinical Trajectory of Patients 
Hospitalized with Heart Failure: A report of the American College 
of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 
74:1966, 2019.
Hussein AA, Wilkoff BL: Cardiac implantable electronic device 
therapy in heart failure. Circ Res 124:1584, 2019.
Kittleson MM et al: 2023 ACC Expert Consensus Decision Pathway 
on Management of Heart Failure With Preserved Ejection Fraction: A 
report of the American College of Cardiology Solution Set Oversight 
Committee. J Am Coll Cardiol 81:1835, 2023.
Kusumoto FM et al: HRS/ACC/AHA expert consensus statement on 
the use of implantable cardioverter-defibrillator therapy in patients 
who are not included or not well represented in clinical trials. Circu­
lation 130:94, 2014.
McMurray JJ et al: Angiotensin-neprilysin inhibition versus enalapril 
in heart failure. N Engl J Med 371:993, 2014.
McMurray JJV et al: Dapagliflozin in patients with heart failure and 
reduced ejection fraction. N Engl J Med 381:1995, 2019.
Obadia JF et al: Percutaneous mitral valve repair or medical ther­
apy for secondary mitral regurgitation. N Engl J Med 379:2297, 
2018.
Packer M, Grayburn PA: Neurohormonal and transcatheter repair 
strategies for proportionate and disproportionate functional mitral 
regurgitation in heart failure. JACC Heart Fail 7:518, 2019.
Packer M et al: Cardiovascular and renal outcomes with empagliflozin 
in heart failure. N Engl J Med 383:1413, 2020.
Solomon SD et al: Angiotensin-neprilysin inhibition in heart failure 
with preserved ejection fraction. N Engl J Med 381:1609, 2019.
Solomon SD et al: Dapagliflozin in heart failure with mildly reduced 
or preserved ejection fraction. N Engl J Med 387:1089, 2022.
Stone GW et al: Transcatheter mitral valve repair in patients with 
heart failure. N Engl J Med 379:2307, 2018.

Teerlink JR et al: Cardiac myosin activation with omecamtiv mecarbil 

in systolic heart failure. N Engl J Med 384:105, 2021.
Velazquez EJ et al: Coronary-artery bypass surgery in patients with 
ischemic cardiomyopathy. N Engl J Med 374:1511, 2016.
CHAPTER 266
Classification of Cardiomyopathy 
Lynne Warner Stevenson, Neal K. Lakdawala, 

Joseph Loscalzo

Classification of 

Cardiomyopathy
The term cardiomyopathy describes primary disease of the heart 
muscle itself, originally excluding myocardial dysfunction resulting 
from other cardiovascular disease. Common usage, however, often 
includes diagnoses of ischemic cardiomyopathy, valvular cardiomyopa­
thy, and hypertensive cardiomyopathy. The traditional morphologic 
classification defines the three major phenotypes of hypertrophic car­
diomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive 
cardiomyopathy (RCM) (Table 266-1).
Left ventricular wall thickness is increased (≥13–15 mm depending 
on context) and ejection fraction is normal or high with HCM. DCM is 
defined when the left ventricular ejection fraction (LVEF) is ≤0.50, but 
most clinical presentations are with LVEF ≤0.40. RCMs typically pres­
ent 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.
Although these phenotypes are helpful to guide initial evalua­
tion of clinical disease, the phenotypes increasingly overlap over 
time as there is increasing recognition that DCMs can respond to 
recommended therapies with “reverse remodeling” to higher ejec­
tion fraction and smaller ventricles, while HCM evolves in ~5% of 
patients to a reduced ejection fraction (HCM-rEF) with more restric­
tive physiology. A fourth evolving phenotype with predominantly 
genetic causes is arrhythmogenic right ventricular cardiomyopathy 
(ARVC), originally termed arrhythmogenic right ventricular dysplasia, 
characterized by life-threatening arrhythmias and abnormal right 
ventricular structure and function, with variable expression in the 
left ventricle. As new phenotype-genotype connections are revealed, 
the terminology continues to evolve, as arrhythmogenic right ven­
tricular dysplasia may also be termed ACM-RV (arrhythmogenic 
cardiomyopathy–right ventricle predominant), in line with ACM-LV, 
in which the arrhythmias and structural changes are predominantly 
in the left ventricle. 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 cata­
log 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 myocardi­
tis 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

TABLE 266-1  Classification of Cardiomyopathies
CARDIOMYOPATHY (CM) 
PHENOTYPE
DIAGNOSTIC CRITERIA
OTHER MORPHOLOGY
COMMON CHALLENGES IN DIAGNOSIS
Hypertrophic cardiomyopathy (HCM)
Mid-range LVEF includes rare 
transition to HCM with LV systolic 
dysfunction (LVEF <0.50)
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.
PART 6
Disorders of the Cardiovascular System
Mid-range LVEF (0.40–0.50)
Restrictive cardiomyopathy (RCM)
Least common cardiomyopathy 
(CM) phenotype
Functional diagnosis based on 
moderate-severe diastolic dysfunction 
and/or elevated cardiac filling 
pressures.
Wall thickness often increased but can 
appear normal.
LVEF usually mildly reduced, 
occasionally normal.
Mid-range LVEF is often a transition 
in DCM, either deterioration from 
early DCM or improvement into 
DCM remission
LV 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
Arrhythmogenic CM Dominant in LV 
(ACM-LV)
Usually DCM, occasionally RCM
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.
Arrhythmogenic CM Dominant in RV 
(ACM-RV; also termed ARVC)
Modified task force criteria from 2010 
include combinations of major and 
minor criteria
Ventricular arrhythmias and evidence of 
both ACM-RV and ACM-LV
Biventricular arrhythmogenic CM
Trait of LV noncompaction (LVNC)
Implications determined by CM 
phenotype and genotype
Often assessed by maximum ratio 
of noncompacted/compacted LV 
myocardium >2.3 and other criteria
Abbreviations: ICD, implantable cardioverter-defibrillator; LGE, late gadolinium enhancement; LV, left ventricle; LVEDD, left ventricular end-diastolic dimension; 
LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction; NSVT, nonsustained ventricular tachycardia; PVC, premature ventricular 
contraction.
be triggered by acquired conditions such as infections, toxic exposures, 
pregnancy, or tachycardia.
CLINICAL PRESENTATION AND 
EVALUATION OF CARDIOMYOPATHY
Early symptoms of cardiomyopathy often reflect exertional intolerance 
with breathlessness or fatigue. Arrhythmias are often presenting events 
of unrecognized cardiomyopathy, which can also present with embolic 
events related to atrial fibrillation or apical ventricular thrombi. Car­
diomyopathy 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 non­
specific historical term congestive heart failure describes the syndrome 

Patterns of LV hypertrophy (LVH) 
in HCM:
• Asymmetric septal hypertrophy
• Inverse (sigmoid pattern) septal 
Distinction from athlete’s heart and severe 
chronic hypertension
The storage diseases of GLA (AndersonFabry), 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
hypertrophy
• Concentric LVH
• Apical hypertrophy
Usually marked atrial enlargement
Although both ventricles affected, 
clinical right heart failure often 
dominates.
Marked wall thickness suggests:
• Amyloidosis
• Inherited storage diseases
• Inborn metabolic diseases
Common etiologies of radiation, 
scleroderma-type connective tissue 
diseases, doxorubicin and other 
medications
Some sarcomeric variants and storage 
diseases can appear with RCM as well as 
HCM phenotypes
Although traditionally listed as restrictive, 
sarcoidosis more often has morphology 
of regional wall motion abnormalities, 
DCM phenotype, or right ventricular (RV) 
involvement with systolic dysfunction
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
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
Abnormal RV function or structure
Biventricular ACM often diagnosed 
from LGE in ventricle with less 
involvement
Cardiac sarcoidosis can cause 
predominantly RV involvement with 
ventricular arrhythmias, RV wall motion 
abnormalities, aneurysms, and dilation
Can occur with HCM, DCM, some 
dystrophies, and other syndromic 
presentations
Can occur in normal hearts, pregnancy 
Increased prevalence in athletic hearts
of congestion, which is common to diverse cardiac diagnoses such as 
congenital heart disease, primary pulmonary hypertension, and struc­
tural valve disease. “Congestive heart failure” should not be considered 
a diagnosis or an etiology of cardiomyopathy but a nonspecific syn­
drome requiring thorough evaluation of possible etiology/ies. Initial 
evaluation of possible cardiomyopathy begins with a detailed clinical 
history and examination seeking clues to cardiac, genetic, and systemic 
causes of heart disease, which help to guide subsequent evaluation 
(Table 266-2).
Echocardiography remains the initial imaging modality to define 
morphology and function, with increasing use of magnetic resonance 
imaging to provide further information on myocardial tissue charac­
terization, patterns of fibrosis indicated by late gadolinium enhance­
ment, and T1 and T2 mapping for evidence of focal and diffuse 
inflammation.