Introduction to Diseases of the Myocardium

Myocardial disease covers a genuinely broad territory — from a single sarcomeric gene variant causing focal septal hypertrophy in an otherwise healthy 20-year-old, to diffuse amyloid infiltration stiffening every chamber in an 80-year-old, to a transient stress-induced ballooning syndrome that resolves entirely within weeks. This page lays out the current classification framework, defines each recognized phenotype, and outlines the systematic diagnostic approach echocardiography drives — the foundation the rest of this section’s disease-specific pages build on.

What a Cardiomyopathy Actually Is

A cardiomyopathy is defined as a myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease, or congenital heart disease sufficient to cause the observed myocardial abnormality. This definition applies equally to children and adults, and — deliberately — makes no assumption about cause (familial/genetic or acquired) or underlying pathology. It’s a description of what the myocardium looks like and does, not a statement about why.

This matters practically: a dilated, poorly contracting LV from years of uncontrolled hypertension or severe aortic regurgitation isn’t a cardiomyopathy by this definition, because the loading condition sufficiently explains the finding. The same dilated, poorly contracting LV in a patient with normal blood pressure and no significant valve disease is a genuine diagnostic question — and that’s where the cardiomyopathy pathway begins.

The Modern Diagnostic Philosophy: Phenotype First, Then Etiology

Current guidance is explicit that this is a two-step process, not one:

1. Establish and characterize the phenotype using multimodality imaging — abnormal ventricular morphology (hypertrophy, dilation), function (systolic and diastolic, global and regional), and tissue characterization (non-ischemic scar, fatty replacement) on echo, CMR, or both.
2. Identify the underlying etiological diagnosis using personal and family history, physical examination, ECG, Holter monitoring, and laboratory testing — looking for specific red flags that point toward a particular cause, and for arrhythmia or conduction disease, which can itself suggest specific etiologies and carries its own prognostic weight.

Phenotype comes first because it’s what’s directly observable on a study, and because the same phenotype can arise from genuinely different causes that need genuinely different management — while a single cause can also produce different phenotypes in different family members. Re-analysis of clinical data as new information (especially family data) emerges is part of this process, not a sign the first assessment was wrong: most cardiomyopathies have variable expression and incomplete penetrance, so a relative’s “non-diagnostic” finding today can still be a meaningful clue.

Age itself is a diagnostic clue worth weighing deliberately: inherited metabolic disorders and congenital dysmorphic syndromes are disproportionately represented in neonates and infants, while wild-type transthyretin amyloidosis is almost exclusively a disease of adults over 65 — the same broad phenotype (say, increased wall thickness) points toward genuinely different etiologic territory depending on when in life it shows up.

Family History: A Systematic Tool, Not an Afterthought

A three- to four-generation family pedigree is recommended for every patient with suspected or established cardiomyopathy, since it can reveal a Mendelian inheritance pattern, identify at-risk relatives, and provide diagnostic clues independent of imaging. Specific features worth asking about directly: premature deaths (including sudden deaths that may have been recorded as accidental — drowning, an unexplained traffic accident, or even a stillbirth or sudden infant death), unexplained heart failure, cardiac transplantation, pacemaker or defibrillator implantation, and evidence of systemic disease in relatives (stroke at a young age, skeletal muscle weakness, renal dysfunction, diabetes, deafness).

The inheritance pattern itself narrows the differential:

• Autosomal dominant — the most common pattern; affected individuals appear across multiple generations, with transmission possible from either parent, including male-to-male transmission. Incomplete penetrance means not every carrier in a pedigree will appear clinically affected.
• X-linked — suspected when males are the most severely affected and male-to-male transmission is absent.
• Autosomal recessive — the least common pattern, typically arising when both parents of the affected individual are unaffected carriers.
• Matrilineal (mitochondrial) — transmission exclusively through the maternal line, reflecting mitochondrial DNA inheritance.

The Cardiomyopathy Phenotypes

The three-phenotype framework (dilated, hypertrophic, restrictive) has been the clinical mainstay for decades, and remains genuinely useful — but the current classification recognizes five distinct phenotypes, reflecting a genuinely new category defined in the past few years. Overlap between categories does occur — particularly between dilated and restrictive physiology, and, as covered below, restrictive physiology showing up as a late stage of what began as hypertrophic or dilated disease — so a patient’s phenotype label may reasonably change over the course of their disease rather than being fixed at first diagnosis.

Hypertrophic Cardiomyopathy (HCM)

Defined as increased LV wall thickness (with or without RV hypertrophy) or mass not solely explained by abnormal loading conditions — ruling out hypertensive or valvular hypertrophy before the label applies. Subclassified by the presence and dynamics of LV outflow tract obstruction: nonobstructive, obstructive, and latent obstructive (provokable only with maneuvers that reduce preload or increase contractility). Adult prevalence is estimated around 0.2%. See Hypertrophic Cardiomyopathy for the full diagnostic and echocardiographic approach, including its variants and the phenocopies that can mimic it.

Dilated Cardiomyopathy (DCM)

Defined as LV dilation with global or regional systolic dysfunction not solely explained by abnormal loading conditions (hypertension, valve disease, congenital heart disease) or coronary artery disease. RV dilation and dysfunction may accompany it but aren’t required for the diagnosis — and when dilation or wall motion abnormality is instead confined or predominant to the RV specifically, that points toward ARVC rather than DCM.

A genuinely useful and often-overlooked distinction: LV dilation with a normal ejection fraction, in the absence of athletic remodeling or another clear environmental explanation, isn’t itself a cardiomyopathy — the preferred term is isolated left ventricular dilatation — though it may represent an early manifestation of DCM still to declare itself functionally. Adult prevalence is estimated around 0.036–0.4%, a considerably wider range than HCM’s, reflecting genuine variation in diagnostic criteria and case-finding across studies.

Restrictive Cardiomyopathy (RCM)

Defined as restrictive LV and/or RV physiology — impaired diastolic filling — in the presence of normal or reduced diastolic volumes, normal or reduced systolic volumes, and normal wall thickness. Commonly presents with biatrial enlargement; LV systolic function can be preserved, though truly normal contractility is uncommon even when the ejection fraction itself looks preserved.

Two nomenclature points worth getting right: restrictive physiology may only be present at an early stage of disease, with the phenotype evolving toward a hypokinetic, dilated pattern over time — RCM is not always a fixed, lifelong label for a given patient. And restrictive physiology can also appear in end-stage hypertrophic or dilated cardiomyopathy; in that setting, the preferred terminology is “hypertrophic cardiomyopathy with restrictive physiology” or “dilated cardiomyopathy with restrictive physiology” rather than relabeling the case as RCM outright, since the underlying disease process is genuinely different. Restrictive ventricular physiology can also arise from purely endocardial pathology — fibrosis, fibroelastosis, or thrombosis — that impairs diastolic filling without involving the myocardium itself in the same way. RCM overall is rare in adults.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Defined as predominantly RV dilation and/or dysfunction in the presence of histologic involvement (fibro-fatty replacement of cardiomyocytes) and/or electrocardiographic abnormalities, per published (2010 modified Task Force) diagnostic criteria. Adult prevalence is estimated around 0.078%.

A genuine terminology clarification worth understanding: the clinical picture of ARVC has broadened over time from severe RV disease with malignant ventricular arrhythmia to include concealed or subclinical phenotypes and biventricular — or even left-dominant — disease. This broadening spawned a range of overlapping terms: arrhythmogenic left ventricular cardiomyopathy (ALVC), “left- and right-dominant cardiomyopathy,” “arrhythmogenic DCM,” and the catch-all “arrhythmogenic cardiomyopathy” (ACM). The current guideline explicitly declines to adopt ACM as a formal, distinct phenotype, since it lacks a consistent morphologic or functional definition — instead keeping arrhythmia as an important diagnostic red flag and prognostic marker that cuts across several phenotypes, rather than defining one of its own. “ARVC” is reserved for the original, RV-predominant variant (with or without LV involvement); predominant LV disease without significant RV involvement instead falls under the newer NDLVC phenotype below.

Non-Dilated Left Ventricular Cardiomyopathy (NDLVC) — A Genuinely New Category

This is the most significant recent addition to the classification framework, replacing an earlier, less formalized concept (“hypokinetic non-dilated cardiomyopathy”). NDLVC is defined as the presence of non-ischemic LV scarring or fatty replacement — regardless of whether regional or global wall motion abnormality is present — or isolated global LV hypokinesia without scarring, in a ventricle that is neither dilated nor hypertrophied. It can be further characterized by the presence or absence of systolic dysfunction.

This category exists to formally capture patients who, under the older framework, were inconsistently labeled — sometimes called DCM despite having no actual LV dilation, sometimes called ALVC, sometimes called left-dominant ARVC, sometimes called “arrhythmogenic DCM” without ever meeting formal ARVC criteria. A specific and genuinely useful clinical detail: the genotype often correlates with a recognizable pattern of late gadolinium enhancement on CMR. Desmoplakin (DSP), filamin C (FLNC), and phospholamban (PLN) variants tend to produce a characteristic subepicardial, ring-like LGE pattern; titin (TTN), BAG3, lamin A/C (LMNA), Duchenne muscular dystrophy (DMD), RBM20 variants, and myocarditis tend to produce a more heterogeneous pattern, generally with less scar (sometimes none at all) and a lower LV ejection fraction. Epidemiologic data for this phenotype are still being established, given how recently it was formally defined.

Two Entities That Look Like Cardiomyopathies but Aren’t Classified as One

Worth knowing specifically because both are genuinely common enough to encounter, and both are frequently discussed alongside the cardiomyopathies even though the current framework doesn’t formally include them.

Takotsubo Syndrome

Transient LV apical ballooning syndrome, in its classic form, produces transient regional systolic dysfunction, dilation, and edema involving the LV apex and/or mid-ventricle, without obstructive coronary disease on angiography — presenting with abrupt angina-like chest pain, diffuse T-wave inversion (sometimes preceded by ST-segment elevation), and mild cardiac enzyme elevation, most often in postmenopausal women following emotional or physical stress. Because function typically normalizes over days to weeks, with recurrence genuinely rare, the current Task Force does not recommend classifying it as a cardiomyopathy — it’s a reversible myocardial dysfunction syndrome, not a fixed structural disease. A related, reversible pattern of myocardial dysfunction (neurogenic myocardial stunning) is occasionally seen after intracranial hemorrhage or other acute cerebral events.

LV Hypertrabeculation (Formerly “LV Non-Compaction”)

Characterized by prominent LV trabeculae and deep intertrabecular recesses, with a thin compacted epicardial layer and a thicker endocardial (trabeculated) layer — sometimes associated with LV dilation and systolic dysfunction, sometimes occurring in isolation. The current Task Force does not consider this a cardiomyopathy in the general sense, instead treating it as a phenotypic trait that can occur alone or alongside other structural abnormalities. Two genuinely different processes can produce it: a familial form, associated with variants in sarcomeric, Z-disc, cytoskeletal, and nuclear envelope genes, and a purely acquired, sometimes transient phenomenon — increased trabecular prominence seen in athletes, during pregnancy, or after vigorous physical activity, which must reflect increased prominence of otherwise normal architecture, since cardiomyocytes are terminally differentiated and incapable of forming genuinely new structures. Given the lack of solid morphometric evidence for a true “compaction” process in humans, “hypertrabeculation” is the preferred term over “non-compaction,” particularly when the finding is transient or clearly of adult onset.

Classifying by Cause: Genetic, Acquired, and Mixed

Alongside the phenotype-first framework above, it’s useful to keep a second, complementary lens in mind — grouping the primary cardiomyopathies by the general nature of their cause:

• Genetic — HCM, ARVC, and LV hypertrabeculation/NDLVC-associated variants are all predominantly genetic in origin, alongside rarer causes such as glycogen storage disease and mitochondrial myopathies.
• Acquired — myocarditis, peripartum cardiomyopathy, Takotsubo, tachycardia-induced cardiomyopathy, and the cardiomyopathy seen in infants of insulin-dependent diabetic mothers.
• Mixed — DCM and RCM both draw from a genuinely wide range of genetic and acquired causes, which is exactly why identifying the phenotype is only the first step, not the final diagnosis.

A representative (not exhaustive) list of specific causes by phenotype:

Phenotype	Representative causes
Dilated	Genetic; postviral myocarditis; Chagas disease; alcohol; anthracycline chemotherapy; hypo- or hyperthyroidism; pheochromocytoma; thiamine deficiency (beriberi); peripartum; systemic inflammatory disease; Duchenne-Becker muscular dystrophy
Restrictive	Amyloidosis; Gaucher disease; sarcoidosis; hemochromatosis; Fabry disease; hypereosinophilic syndrome; radiation-induced injury; scleroderma
Hypertrophic	Sarcomeric gene variants; Anderson-Fabry disease; Danon disease; transthyretin amyloidosis; RASopathies; Friedreich ataxia; mitochondrial disease

Genetic testing increasingly informs this second step directly — but as the inheritance-pattern discussion above shows, a careful family history can point toward the right etiologic category well before, or even without, genetic confirmation.

How Echocardiography Drives the Diagnostic Pathway

Echocardiography’s role across every phenotype above follows the same basic structure:

1. Establish the diagnosis — confirm the phenotype (hypertrophy, dilation, restrictive physiology, or a non-dilated ventricle with regional dysfunction or scar-suggestive findings) is genuinely present, and isn’t better explained by a loading condition.
2. Define the likely etiology — specific echo findings (wall thickness pattern and distribution, valve involvement, granular or “sparkling” myocardial texture, regional versus global dysfunction) can point toward a specific cause even before genetic or advanced imaging confirmation.
3. Detect associated cardiac abnormalities — secondary valve disease (particularly functional mitral or tricuspid regurgitation from annular and chamber dilation), intracavitary thrombus, and pulmonary hypertension are all common companions to the primary myocardial process and change management in their own right.
4. Identify high-risk features — chamber size and ejection fraction thresholds, specific wall motion patterns, and (where measured) strain abnormalities all carry prognostic weight and inform decisions like defibrillator candidacy.
5. Guide and monitor therapy — from tracking response to guideline-directed medical therapy, to assessing candidacy for cardiac resynchronization therapy, to monitoring the effect of septal reduction therapy in obstructive HCM.

Each disease-specific page in this section works through this structure in full for its own phenotype — the specific chamber measurements, Doppler criteria, and diagnostic thresholds that turn “this looks hypertrophied” or “this looks dilated” into an actual, actionable diagnosis.

Clinical Importance

The move from a strict three-phenotype model to today’s five-phenotype framework, and the explicit decision to keep Takotsubo and LV hypertrabeculation out of the cardiomyopathy category altogether, both reflect the same underlying principle: classification exists to serve diagnosis and management, not the other way around. A patient whose imaging doesn’t neatly fit “dilated,” “hypertrophic,” or “restrictive” isn’t a diagnostic failure — recognizing that non-dilated, non-hypertrophied scarring or dysfunction is now its own genuine category is precisely what lets that patient’s actual disease be named, rather than forced into the nearest available label.