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Pathophysiology Nodes

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5 shared nodes are defined in this module.
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Cell Types

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Cardiomyocyte CL:0000746 Cardiac Fibroblast CL:0002548
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Biological Processes

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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
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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

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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence-backed metadata.
Pathograph: causal mechanism network for Cardiomyopathy Maladaptive Remodeling Module Interactive directed graph showing how this shared module's pathophysiology nodes connect.
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Pathophysiology

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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
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
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
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
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