Phenotypic Approach to Cardiomyopathy
Definition
The phenotypic approach to cardiomyopathy — introduced as the core diagnostic framework in the 2023 ESC Guidelines — requires clinicians to first identify the predominant morphological/functional phenotype at presentation, then pursue an integrated multiparametric aetiological diagnosis. This replaces single-modality diagnostic algorithms and mirrors a "cardiomyopathy mindset" in which cardiomyopathy is actively considered as the cause of common presentations (heart failure, arrhythmia, incidental ECG abnormality).
Key Concepts
The Phenotypes (2023 ESC Classification)
- Five recognized phenotypes: HCM (ventricular hypertrophy), DCM (LV dilatation + systolic dysfunction), NDLVC (non-ischaemic scar/fatty replacement without dilatation), ARVC (predominantly RV dysfunction + fibro-fatty replacement), RCM (restrictive physiology + normal wall thickness). (sources/esc-cmp-2023)
- Phenotypes may coexist in the same family and can evolve from one to another over a lifetime — classification should be based on the predominant phenotype at presentation. (sources/esc-cmp-2023)
- Excluded from cardiomyopathy classification: LVNC (reclassified as a phenotypic trait, preferred term "hypertrabeculation"); Takotsubo syndrome (transient — not a cardiomyopathy); channelopathies (insufficient evidence for structural classification). (sources/esc-cmp-2023)
The Diagnostic Pathway
- Step 1 — Phenotype identification: Use multimodality imaging (echo + CMR) to identify ventricular morphology, function, and tissue characteristics (non-ischaemic scar, fatty replacement, infiltration). (sources/esc-cmp-2023)
- Step 2 — Aetiological diagnosis: Integrate personal and family history, 3–4-generation pedigree, ECG and Holter, laboratory tests, and genetic testing to reach a phenotype-based aetiological diagnosis. (sources/esc-cmp-2023)
- Multiparametric approach (Class I, Level C): All patients with suspected cardiomyopathy must undergo clinical evaluation + pedigree + ECG + Holter + lab tests + multimodality imaging. (sources/esc-cmp-2023)
- 3–4-generation family tree (Class I, Level C): Required for all patients to aid diagnosis, identify inheritance pattern, and find at-risk relatives. (sources/esc-cmp-2023)
Genetic Architecture Considerations
- ~40% of HCM and ~30% of DCM have a confirmed monogenic cause. The absence of a rare variant does not exclude cardiomyopathy; polygenic/complex inheritance is increasingly recognized. (sources/esc-cmp-2023)
- Incomplete and age-related penetrance, and variable expressivity, mean phenotype-negative relatives may still be at risk — warranting ongoing surveillance. (sources/esc-cmp-2023)
- Genocopies (conditions that mimic HCM/DCM but have different management): Anderson-Fabry disease, ATTR amyloidosis, RASopathies, glycogen storage disorders. (sources/esc-cmp-2023)
Aetiology-Specific Management
- Reaching a precise aetiological diagnosis is critical because management differs fundamentally by genotype:
- LMNA variants: lower ICD threshold, specific risk calculators.
- Anderson-Fabry disease: enzyme replacement therapy.
- ATTR amyloidosis: tafamidis; avoid calcium channel blockers.
- ARVC/NDLVC desmosomal genes: exercise restriction.
- PRKAG2/Danon: pacemaker/ICD and AV block management. (sources/esc-cmp-2023)
Contradictions / Open Questions
- LVNC reclassification may cause patient anxiety and ambiguity: ESC 2023 reclassifies left ventricular non-compaction (LVNC) as a morphological trait ("hypertrabeculation") rather than a cardiomyopathy. Patients previously diagnosed with "LVNC cardiomyopathy" may find their diagnosis withdrawn, raising uncertainty about surveillance, ICD decisions, and family screening obligations that prior guidelines addressed. Clinicians managing patients given the prior diagnosis face a transition challenge without prospective guidance. (sources/esc-cmp-2023)
- Phenotype-first approach limited by imaging resolution and operator dependence: The ESC 2023 framework requires accurate phenotype identification from multimodality imaging as the first step. LGE quantification, RV function assessment, and LV wall motion characterization all carry interobserver variability. An incorrect phenotype assignment at step 1 propagates through the entire diagnostic and management pathway. (sources/esc-cmp-2023)
- ~60% of cardiomyopathy patients have no confirmed genetic cause: With ~40% of HCM and ~30% of DCM having a monogenic explanation, the majority of cardiomyopathy patients reach the aetiological diagnosis step without a genetic answer. The phenotypic framework guides these patients toward empirical rather than precision management, and cascade genetic testing cannot be offered to their families without a proband variant. (sources/esc-cmp-2023)
Connections
- Related to entities/HCM
- Related to entities/DCM
- Related to entities/NDLVC
- Related to entities/ARVC
- Related to entities/RCM
- Related to concepts/Late-Gadolinium-Enhancement
- Related to concepts/Cascade-Family-Screening
- Related to concepts/Sudden-Cardiac-Death