Cardiomyopathy Maladaptive Remodeling Module

Toxicology Module cardiomyopathy_maladaptive_remodeling 48 disorders Pathograph 5

A conserved cardiac pathophysiology module representing the maladaptive remodeling pathway that underlies structural and contractile cardiomyopathy (HP:0001638, MONDO:0004994) across dilated, hypertrophic, and secondary forms. A primary cardiomyocyte insult — an inherited sarcomere or cytoskeletal protein defect, or an acquired hemodynamic, metabolic, toxic, or inflammatory stress — impairs contractile performance. The failing myocardium activates neurohormonal axes (renin-angiotensin-aldosterone and sympathetic) that initially compensate but chronically drive myocyte hypertrophy, cardiomyocyte loss, cardiac fibroblast activation, interstitial fibrosis, and chamber dilation or wall thickening. This adverse ventricular remodeling produces progressive systolic and/or diastolic contractile dysfunction, culminating in structural cardiac impairment and heart failure. This module is distinct from electrical/channelopathy disease (covered by cardiac_ion_channel_repolarization); it captures the structural/contractile final common pathway. Individual disorder entries declare conformance via conforms_to, substituting disorder-specific primary lesions (e.g., MYH7/MYBPC3 sarcomere variants in hypertrophic cardiomyopathy, TTN truncations or LMNA/desmosomal defects in dilated cardiomyopathy, infiltrative or toxic injury in secondary cardiomyopathy) while preserving the conserved chain.

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Pathophysiology Nodes

5 shared nodes are defined in this module.

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Cell Types

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Biological Processes

Sarcomere Organization GO:0045214 ABNORMAL Muscle Contraction GO:0006936 ABNORMAL Response to Angiotensin GO:1990776 INCREASED Cardiac Muscle Hypertrophy GO:0003300 INCREASED Cardiac Muscle Hypertrophy in Response to Stress GO:0014898 INCREASED Extracellular Matrix Organization GO:0030198 INCREASED Cardiomyocyte Apoptosis GO:0010659 INCREASED Heart Contraction GO:0060047 DECREASED Heart Contraction GO:0060047 ABNORMAL

Notes

This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "cardiomyopathy_maladaptive_remodeling#Ventricular Remodeling"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to their etiologic context. Key disorder-specific substitutions: the trigger node substitutes the disorder's primary lesion (e.g., MYH7/MYBPC3/TNNT2 sarcomere variants in HCM, TTN/LMNA/desmosomal variants in DCM, amyloid infiltration in cardiac amyloidosis, anthracycline or alcohol toxicity in secondary cardiomyopathy). This module covers the structural/contractile remodeling pathway and is deliberately kept distinct from the electrical/arrhythmia mechanism captured by the cardiac_ion_channel_repolarization module.

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Used By Disorder Entries

arrhythmogenic right ventricular cardiomyopathy via Fibrofatty myocardial replacement → Ventricular Remodeling

Becker Muscular Dystrophy via Dystrophin-Deficient Cardiomyocyte Injury → Primary Cardiomyocyte Insult , Left Ventricular Impairment and Dilated Cardiomyopathy → Structural Cardiac Impairment and Heart Failure

Cardiac Sarcoidosis via Progressive Ventricular Dysfunction and Heart Failure → Structural Cardiac Impairment and Heart Failure

Cardiomyopathy Dilated 100 via VEZF1 Nonsense Variant Abolishes Transcriptional Transactivation → Primary Cardiomyocyte Insult , Impaired Cardiomyocyte Contractile Function and Compensatory Growth → Progressive Contractile Dysfunction , Left Ventricular Dilation and Systolic Dysfunction → Structural Cardiac Impairment and Heart Failure

Cardiomyopathy-Hypotonia-Lactic Acidosis Syndrome via Cardiomyocyte and Skeletal Muscle Energy Deficit → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy and Ventricular Remodeling → Ventricular Remodeling

Carvajal Syndrome via Contractile and Electrical Dysfunction → Progressive Contractile Dysfunction

Chagas disease via Ventricular remodeling and dilated cardiomyopathy → Ventricular Remodeling

Dilated Cardiomyopathy via Myocardial Fibrosis → Ventricular Remodeling

Dilated Cardiomyopathy 1A via LMNA Variant and Nuclear Lamina Assembly Defect → Primary Cardiomyocyte Insult , Cardiomyocyte Loss and Myocardial Fibrosis → Ventricular Remodeling , Left Ventricular Dilation and Systolic Dysfunction → Progressive Contractile Dysfunction , Progressive Heart Failure and End-Stage Disease → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1AA via Alpha-Actinin-2 Z-Disc Dysfunction → Primary Cardiomyocyte Insult , Neurohormonal Activation , Adverse Ventricular Remodeling → Ventricular Remodeling , Left Ventricular Dilation and Systolic Dysfunction → Progressive Contractile Dysfunction , Heart Failure and Sudden Cardiac Death → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1B via Impaired Myocardial Contractility → Progressive Contractile Dysfunction , Left Ventricular Dilation and Systolic Dysfunction → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1D via TNNT2 Variant in Cardiac Troponin T → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1DD via RBM20 Loss-of-Function Variant in the RS Domain → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure and Malignant Ventricular Arrhythmia → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1E via SCN5A Missense Variant in the Cardiac Sodium Channel → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure and Atrial Fibrillation → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1G via TTN Truncating Variant in the A-Band → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1HH via BAG3 Loss-of-Function Variant → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1I via DES Variant in the Desmin Intermediate Filament → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1JJ via Loss of Laminin-Integrin Binding at the Cardiac Basement Membrane → Primary Cardiomyocyte Insult , Neurohormonal Activation , Adverse Ventricular Remodeling → Ventricular Remodeling , Left Ventricular Dilation and Systolic Dysfunction → Progressive Contractile Dysfunction , Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1S via MYH7 Missense Variant Causing Diminished Contractile Function → Primary Cardiomyocyte Insult , Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Heart Failure → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 1Z via Cardiac Troponin C Variant and Thin-Filament Regulatory Defect → Primary Cardiomyocyte Insult , Neurohormonal Activation , Adverse Ventricular Remodeling → Ventricular Remodeling , Left Ventricular Dilation and Systolic Dysfunction → Progressive Contractile Dysfunction , Heart Failure, Ventricular Arrhythmia and Sudden Cardiac Death → Structural Cardiac Impairment and Heart Failure

Dilated Cardiomyopathy 2A via Biallelic TNNI3 Loss of Function → Primary Cardiomyocyte Insult , Left Ventricular Dilation and Systolic Failure → Progressive Contractile Dysfunction

Dilated Cardiomyopathy 2G via Biallelic LMOD2 Loss-of-Function Variant → Primary Cardiomyocyte Insult , Neonatal Ventricular Dilation and Decreased Contractility → Ventricular Remodeling , Neonatal Heart Failure and Death → Structural Cardiac Impairment and Heart Failure

DSP Cardiomyopathy via Desmoplakin Haploinsufficiency — Desmosomal Disruption → Primary Cardiomyocyte Insult , Fibrofatty Myocardial Replacement → Ventricular Remodeling

FLNC-Related Dilated Cardiomyopathy via FLNC Truncating Variant Causing Filamin C Haploinsufficiency → Primary Cardiomyocyte Insult , Myocardial Fibrosis and Ventricular Dilation → Ventricular Remodeling , Sudden Cardiac Death and End-Stage Heart Failure → Structural Cardiac Impairment and Heart Failure

Hypertensive Heart Disease via Left Ventricular Hypertrophy → Ventricular Remodeling , Cardiac Fibrosis → Ventricular Remodeling

Hypertrophic Cardiomyopathy 1 via MYH7 Missense Variant in Beta-Cardiac Myosin Heavy Chain → Primary Cardiomyocyte Insult , Ventricular Hypertrophy, Myocyte Disarray and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction, Outflow Obstruction, Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 10 via MYL2 Variant in Ventricular Regulatory Myosin Light Chain → Primary Cardiomyocyte Insult , Ventricular Hypertrophy, Myocyte Disarray and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction, Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 11 via ACTC1 Missense Variant in Alpha-Cardiac Actin → Primary Cardiomyocyte Insult , Ventricular Hypertrophy, Myocyte Disarray and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction, Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 13 via TNNC1 Missense Variant in Cardiac Troponin C → Primary Cardiomyocyte Insult , Ventricular Hypertrophy, Myocyte Disarray and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction, Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 2 via Cardiac Troponin T Thin Filament Regulatory Defect → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy with Disarray and Fibrosis, Often Disproportionately Mild → Ventricular Remodeling , Diastolic Dysfunction → Progressive Contractile Dysfunction , Progressive Heart Failure → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 20 via Cardiac Z-Disc Destabilization Under Mechanical Load → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy, Sarcomeric Disarray, and Myocardial Fibrosis → Ventricular Remodeling

Hypertrophic Cardiomyopathy 21 via Ventricular Dilation and End-Stage Heart Failure → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 25 via Telethonin Z-Disc Titin-Capping and Stretch-Sensor Perturbation → Primary Cardiomyocyte Insult , Ventricular Remodeling with Sigmoidal Septal Geometry → Ventricular Remodeling , Left Ventricular Hypertrophy with Diastolic Dysfunction → Progressive Contractile Dysfunction , Progressive Heart Failure → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 26 via Filamin C Z-Disc Cross-Linking Defect → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy and Adverse Ventricular Remodeling → Ventricular Remodeling , Impaired Diastolic Relaxation and Myocardial Stiffening → Progressive Contractile Dysfunction , Heart Failure and Sudden Cardiac Death → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 3 via Alpha-Tropomyosin Thin Filament Regulatory Defect → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis → Ventricular Remodeling , Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction → Progressive Contractile Dysfunction , Progressive Heart Failure → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 4 via MYBPC3 Truncating Variant and Premature Termination Codon Generation → Primary Cardiomyocyte Insult , Ventricular Hypertrophy, Disarray and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction, Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 7 via Cardiac Troponin I Inhibitory Dysfunction → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy, Myocyte Disarray and Interstitial Fibrosis → Ventricular Remodeling , Left Ventricular Hypertrophy with Diastolic Dysfunction → Progressive Contractile Dysfunction , Heart Failure and Sudden Cardiac Death → Structural Cardiac Impairment and Heart Failure

Hypertrophic Cardiomyopathy 8 via MYL3 Essential Light Chain Variant — Altered Lever-Arm and Actin Contact → Primary Cardiomyocyte Insult , Cardiomyocyte Hypertrophy, Myocardial Stiffness and Fibrosis → Ventricular Remodeling , Diastolic Dysfunction and Restrictive Physiology → Progressive Contractile Dysfunction

Left Ventricular Noncompaction 10 via MYBPC3 Loss-of-Function Variant and cMyBP-C Depletion → Primary Cardiomyocyte Insult , Neonatal Structural Cardiac Failure → Structural Cardiac Impairment and Heart Failure

Left Ventricular Noncompaction 8 via Left Ventricular Dilation and Systolic Dysfunction → Ventricular Remodeling , Congestive Heart Failure → Structural Cardiac Impairment and Heart Failure

MRPL44 Deficiency via Cardiomyocyte Bioenergetic Failure and Mitochondrial Proliferation → Primary Cardiomyocyte Insult , Progressive Heart Failure → Structural Cardiac Impairment and Heart Failure

Myocardial Infarction via Cardiac Fibrosis and Ventricular Remodeling → Ventricular Remodeling

Myocarditis via Cardiomyocyte Necrosis and Contractile Failure → Primary Cardiomyocyte Insult , Post-Inflammatory Ventricular Remodeling → Ventricular Remodeling , Inflammatory Dilated Cardiomyopathy → Structural Cardiac Impairment and Heart Failure

Myofibrillar Myopathy via Cardiomyocyte Z-Disc Aggregate Pathology → Primary Cardiomyocyte Insult

Naxos disease via Fibrofatty myocardial replacement → Ventricular Remodeling

PRKAG2 Cardiac Syndrome via Progressive Contractile Dysfunction , Advanced Heart Failure and End-Stage Cardiomyopathy → Structural Cardiac Impairment and Heart Failure

Restrictive Cardiomyopathy via Sarcomeric or Cytoskeletal Variant with Increased Myofilament Tension → Primary Cardiomyocyte Insult , Myocardial Fibrosis and Ventricular Remodeling → Ventricular Remodeling , Diastolic Heart Failure and Arrhythmic Risk → Structural Cardiac Impairment and Heart Failure

Taurine transporter deficiency via Cardiomyocyte Atrophy and Ventricular Remodeling → Ventricular Remodeling

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Pathograph

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Pathophysiology

Primary Cardiomyocyte Insult

trigger

The cascade is initiated by an insult to cardiomyocyte contractile function. In inherited cardiomyopathies this is a variant in a sarcomeric or cytoskeletal protein gene that perturbs sarcomere assembly and force generation; in acquired and secondary cardiomyopathies it is a hemodynamic (pressure or volume overload), metabolic, toxic, or inflammatory stress that impairs myocyte contraction. The specific lesion varies, but the downstream response converges on impaired contractile performance that the myocardium must compensate for.

Cardiomyocyte CL:0000746

Sarcomere Organization GO:0045214 ABNORMAL Muscle Contraction GO:0006936 ABNORMAL

Used by disorders

Becker Muscular Dystrophy as Dystrophin-Deficient Cardiomyocyte Injury

Cardiomyopathy Dilated 100 as VEZF1 Nonsense Variant Abolishes Transcriptional Transactivation

Cardiomyopathy-Hypotonia-Lactic Acidosis Syndrome as Cardiomyocyte and Skeletal Muscle Energy Deficit

Dilated Cardiomyopathy 1A as LMNA Variant and Nuclear Lamina Assembly Defect

Dilated Cardiomyopathy 1AA as Alpha-Actinin-2 Z-Disc Dysfunction

Dilated Cardiomyopathy 1D as TNNT2 Variant in Cardiac Troponin T

Dilated Cardiomyopathy 1DD as RBM20 Loss-of-Function Variant in the RS Domain

Dilated Cardiomyopathy 1E as SCN5A Missense Variant in the Cardiac Sodium Channel

Dilated Cardiomyopathy 1G as TTN Truncating Variant in the A-Band

Dilated Cardiomyopathy 1HH as BAG3 Loss-of-Function Variant

Dilated Cardiomyopathy 1I as DES Variant in the Desmin Intermediate Filament

Dilated Cardiomyopathy 1JJ as Loss of Laminin-Integrin Binding at the Cardiac Basement Membrane

Dilated Cardiomyopathy 1S as MYH7 Missense Variant Causing Diminished Contractile Function

Dilated Cardiomyopathy 1Z as Cardiac Troponin C Variant and Thin-Filament Regulatory Defect

Dilated Cardiomyopathy 2A as Biallelic TNNI3 Loss of Function

Dilated Cardiomyopathy 2G as Biallelic LMOD2 Loss-of-Function Variant

DSP Cardiomyopathy as Desmoplakin Haploinsufficiency — Desmosomal Disruption

FLNC-Related Dilated Cardiomyopathy as FLNC Truncating Variant Causing Filamin C Haploinsufficiency

Hypertrophic Cardiomyopathy 1 as MYH7 Missense Variant in Beta-Cardiac Myosin Heavy Chain

Hypertrophic Cardiomyopathy 10 as MYL2 Variant in Ventricular Regulatory Myosin Light Chain

Hypertrophic Cardiomyopathy 11 as ACTC1 Missense Variant in Alpha-Cardiac Actin

Hypertrophic Cardiomyopathy 13 as TNNC1 Missense Variant in Cardiac Troponin C

Hypertrophic Cardiomyopathy 2 as Cardiac Troponin T Thin Filament Regulatory Defect

Hypertrophic Cardiomyopathy 20 as Cardiac Z-Disc Destabilization Under Mechanical Load

Hypertrophic Cardiomyopathy 25 as Telethonin Z-Disc Titin-Capping and Stretch-Sensor Perturbation

Hypertrophic Cardiomyopathy 26 as Filamin C Z-Disc Cross-Linking Defect

Hypertrophic Cardiomyopathy 3 as Alpha-Tropomyosin Thin Filament Regulatory Defect

Hypertrophic Cardiomyopathy 4 as MYBPC3 Truncating Variant and Premature Termination Codon Generation

Hypertrophic Cardiomyopathy 7 as Cardiac Troponin I Inhibitory Dysfunction

Hypertrophic Cardiomyopathy 8 as MYL3 Essential Light Chain Variant — Altered Lever-Arm and Actin Contact

Left Ventricular Noncompaction 10 as MYBPC3 Loss-of-Function Variant and cMyBP-C Depletion

MRPL44 Deficiency as Cardiomyocyte Bioenergetic Failure and Mitochondrial Proliferation

Myocarditis as Cardiomyocyte Necrosis and Contractile Failure

Myofibrillar Myopathy as Cardiomyocyte Z-Disc Aggregate Pathology

Restrictive Cardiomyopathy as Sarcomeric or Cytoskeletal Variant with Increased Myofilament Tension

Downstream

Neurohormonal Activation

Neurohormonal Activation

amplifier

Impaired contractile performance and the resulting fall in cardiac output trigger compensatory activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system. While initially adaptive, chronic neurohormonal activation becomes maladaptive, directly stimulating cardiomyocyte hypertrophy and promoting fibrosis and apoptosis. This axis is the principal amplifier that converts an initial contractile deficit into progressive structural remodeling, and it is the target of the foundational heart-failure pharmacotherapies (ACE inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists).

Response to Angiotensin GO:1990776 INCREASED Cardiac Muscle Hypertrophy GO:0003300 INCREASED

Used by disorders

Dilated Cardiomyopathy 1AA

Dilated Cardiomyopathy 1JJ

Dilated Cardiomyopathy 1Z

Downstream

Ventricular Remodeling

Ventricular Remodeling

central effector

Sustained insult and neurohormonal drive produce adverse structural remodeling of the ventricle. This central effector step combines cardiomyocyte hypertrophy and progressive cardiomyocyte loss (necrosis and apoptosis) with activation of resident cardiac fibroblasts into myofibroblasts that deposit excess collagen, producing interstitial fibrosis. The net geometric result is chamber dilation with wall thinning (dilated pattern) or wall thickening with reduced cavity size (hypertrophic pattern). Although the dominant geometry differs across disorders, expansion of the cardiac fibroblast population and interstitial matrix deposition are conserved features of the remodeling myocardium.

Cardiac Fibroblast CL:0002548

Cardiac Muscle Hypertrophy in Response to Stress GO:0014898 INCREASED Extracellular Matrix Organization GO:0030198 INCREASED Cardiomyocyte Apoptosis GO:0010659 INCREASED

Used by disorders

arrhythmogenic right ventricular cardiomyopathy as Fibrofatty myocardial replacement

Cardiomyopathy-Hypotonia-Lactic Acidosis Syndrome as Cardiomyocyte Hypertrophy and Ventricular Remodeling

Chagas disease as Ventricular remodeling and dilated cardiomyopathy

Dilated Cardiomyopathy as Myocardial Fibrosis

Dilated Cardiomyopathy 1A as Cardiomyocyte Loss and Myocardial Fibrosis

Dilated Cardiomyopathy 1AA as Adverse Ventricular Remodeling

Dilated Cardiomyopathy 1D as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1DD as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1E as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1G as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1HH as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1I as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1JJ as Adverse Ventricular Remodeling

Dilated Cardiomyopathy 1S as Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1Z as Adverse Ventricular Remodeling

Dilated Cardiomyopathy 2G as Neonatal Ventricular Dilation and Decreased Contractility

DSP Cardiomyopathy as Fibrofatty Myocardial Replacement

FLNC-Related Dilated Cardiomyopathy as Myocardial Fibrosis and Ventricular Dilation

Hypertensive Heart Disease as Cardiac Fibrosis

Hypertensive Heart Disease as Left Ventricular Hypertrophy

Hypertrophic Cardiomyopathy 1 as Ventricular Hypertrophy, Myocyte Disarray and Fibrosis

Hypertrophic Cardiomyopathy 10 as Ventricular Hypertrophy, Myocyte Disarray and Fibrosis

Hypertrophic Cardiomyopathy 11 as Ventricular Hypertrophy, Myocyte Disarray and Fibrosis

Hypertrophic Cardiomyopathy 13 as Ventricular Hypertrophy, Myocyte Disarray and Fibrosis

Hypertrophic Cardiomyopathy 2 as Cardiomyocyte Hypertrophy with Disarray and Fibrosis, Often Disproportionately Mild

Hypertrophic Cardiomyopathy 20 as Cardiomyocyte Hypertrophy, Sarcomeric Disarray, and Myocardial Fibrosis

Hypertrophic Cardiomyopathy 25 as Ventricular Remodeling with Sigmoidal Septal Geometry

Hypertrophic Cardiomyopathy 26 as Cardiomyocyte Hypertrophy and Adverse Ventricular Remodeling

Hypertrophic Cardiomyopathy 3 as Cardiomyocyte Hypertrophy with Myofiber Disarray and Interstitial Fibrosis

Hypertrophic Cardiomyopathy 4 as Ventricular Hypertrophy, Disarray and Fibrosis

Hypertrophic Cardiomyopathy 7 as Cardiomyocyte Hypertrophy, Myocyte Disarray and Interstitial Fibrosis

Hypertrophic Cardiomyopathy 8 as Cardiomyocyte Hypertrophy, Myocardial Stiffness and Fibrosis

Left Ventricular Noncompaction 8 as Left Ventricular Dilation and Systolic Dysfunction

Myocardial Infarction as Cardiac Fibrosis and Ventricular Remodeling

Myocarditis as Post-Inflammatory Ventricular Remodeling

Naxos disease as Fibrofatty myocardial replacement

Restrictive Cardiomyopathy as Myocardial Fibrosis and Ventricular Remodeling

Taurine transporter deficiency as Cardiomyocyte Atrophy and Ventricular Remodeling

Downstream

Progressive Contractile Dysfunction

Progressive Contractile Dysfunction

effector

Adverse remodeling degrades pump function. Myocyte loss, fibrosis, and altered chamber geometry impair systolic shortening (reduced ejection fraction in dilated and end-stage disease) and/or diastolic relaxation and filling (stiffened, hypertrophied, or infiltrated myocardium). Increased wall stress further depresses contractile properties of surviving myocardium, creating a self-reinforcing cycle of declining performance that underlies the clinical progression of cardiomyopathy.

Cardiomyocyte CL:0000746

Heart Contraction GO:0060047 DECREASED

Used by disorders

Cardiomyopathy Dilated 100 as Impaired Cardiomyocyte Contractile Function and Compensatory Growth

Carvajal Syndrome as Contractile and Electrical Dysfunction

Dilated Cardiomyopathy 1A as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1AA as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1B as Impaired Myocardial Contractility

Dilated Cardiomyopathy 1JJ as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1Z as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 2A as Left Ventricular Dilation and Systolic Failure

Hypertrophic Cardiomyopathy 2 as Diastolic Dysfunction

Hypertrophic Cardiomyopathy 25 as Left Ventricular Hypertrophy with Diastolic Dysfunction

Hypertrophic Cardiomyopathy 26 as Impaired Diastolic Relaxation and Myocardial Stiffening

Hypertrophic Cardiomyopathy 3 as Diastolic Dysfunction and Left Ventricular Outflow Tract Obstruction

Hypertrophic Cardiomyopathy 7 as Left Ventricular Hypertrophy with Diastolic Dysfunction

Hypertrophic Cardiomyopathy 8 as Diastolic Dysfunction and Restrictive Physiology

PRKAG2 Cardiac Syndrome

Downstream

Structural Cardiac Impairment and Heart Failure

Structural Cardiac Impairment and Heart Failure

consequence

The end state is cardiomyopathy: a structurally and functionally abnormal myocardium that can no longer meet circulatory demand, manifesting as heart failure with its attendant morbidity and mortality and risk of progression to end-stage disease requiring mechanical support or transplantation. While the dominant geometry (dilated, hypertrophic, restrictive) and the triggering lesion differ across disorders, the convergence on maladaptive structural remodeling and impaired pump function defines the shared cardiomyopathy phenotype.

Heart Contraction GO:0060047 ABNORMAL

Used by disorders

Becker Muscular Dystrophy as Left Ventricular Impairment and Dilated Cardiomyopathy

Cardiac Sarcoidosis as Progressive Ventricular Dysfunction and Heart Failure

Cardiomyopathy Dilated 100 as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1A as Progressive Heart Failure and End-Stage Disease

Dilated Cardiomyopathy 1AA as Heart Failure and Sudden Cardiac Death

Dilated Cardiomyopathy 1B as Left Ventricular Dilation and Systolic Dysfunction

Dilated Cardiomyopathy 1D as Heart Failure

Dilated Cardiomyopathy 1DD as Heart Failure and Malignant Ventricular Arrhythmia

Dilated Cardiomyopathy 1E as Heart Failure and Atrial Fibrillation

Dilated Cardiomyopathy 1G as Heart Failure and Arrhythmic Risk

Dilated Cardiomyopathy 1HH as Heart Failure

Dilated Cardiomyopathy 1I as Heart Failure

Dilated Cardiomyopathy 1JJ

Dilated Cardiomyopathy 1S as Heart Failure

Dilated Cardiomyopathy 1Z as Heart Failure, Ventricular Arrhythmia and Sudden Cardiac Death

Dilated Cardiomyopathy 2G as Neonatal Heart Failure and Death

FLNC-Related Dilated Cardiomyopathy as Sudden Cardiac Death and End-Stage Heart Failure

Hypertrophic Cardiomyopathy 1 as Diastolic Dysfunction, Outflow Obstruction, Heart Failure and Arrhythmic Risk

Hypertrophic Cardiomyopathy 10 as Diastolic Dysfunction, Heart Failure and Arrhythmic Risk

Hypertrophic Cardiomyopathy 11 as Diastolic Dysfunction, Heart Failure and Arrhythmic Risk

Hypertrophic Cardiomyopathy 13 as Diastolic Dysfunction, Heart Failure and Arrhythmic Risk

Hypertrophic Cardiomyopathy 2 as Progressive Heart Failure

Hypertrophic Cardiomyopathy 21 as Ventricular Dilation and End-Stage Heart Failure

Hypertrophic Cardiomyopathy 25 as Progressive Heart Failure

Hypertrophic Cardiomyopathy 26 as Heart Failure and Sudden Cardiac Death

Hypertrophic Cardiomyopathy 3 as Progressive Heart Failure

Hypertrophic Cardiomyopathy 4 as Diastolic Dysfunction, Heart Failure and Arrhythmic Risk

Hypertrophic Cardiomyopathy 7 as Heart Failure and Sudden Cardiac Death

Left Ventricular Noncompaction 10 as Neonatal Structural Cardiac Failure

Left Ventricular Noncompaction 8 as Congestive Heart Failure

MRPL44 Deficiency as Progressive Heart Failure

Myocarditis as Inflammatory Dilated Cardiomyopathy

PRKAG2 Cardiac Syndrome as Advanced Heart Failure and End-Stage Cardiomyopathy

Restrictive Cardiomyopathy as Diastolic Heart Failure and Arrhythmic Risk