2023 ESC Guidelines for the Management of Cardiomyopathies

Authors, Journal, Affiliations, Type, DOI

• Authors: Elena Arbelo & Juan Pablo Kaski (Co-Chairpersons), Alexandros Protonotarios & Juan R. Gimeno (Co-ordinators), and 26-member multinational ESC Task Force
• Journal: European Heart Journal (2023), vol. 44, pages 3503–3626
• Type: ESC Clinical Practice Guideline
• DOI: 10.1093/eurheartj/ehad194

Overview

The 2023 ESC Guidelines are the first major international guideline to comprehensively address all cardiomyopathy phenotypes — HCM, DCM, ARVC, RCM, and the newly defined NDLVC — within a single framework. The guideline introduces a phenotype-first, aetiology-oriented diagnostic approach and formally creates the Non-Dilated Left Ventricular Cardiomyopathy (NDLVC) category to capture patients with non-ischaemic myocardial scar or fatty replacement who do not fit prior definitions. Multimodality imaging (especially CMR late gadolinium enhancement for tissue characterization) and genetic testing are elevated to central roles throughout. Key therapeutic innovations include Mavacamten (cardiac myosin inhibitor) for obstructive HCM and aetiology-specific therapies for metabolic cardiomyopathies.

Keywords

Guidelines • Arrhythmia • Arrhythmogenic right ventricular cardiomyopathy • Cardiomyopathies • Diagnosis • Dilated cardiomyopathy • Genetics • Genetic counselling • Genetic testing • Hypertrophic cardiomyopathy • Implantable cardioverter defibrillator • Management • Multimodality imaging • Non-dilated left ventricular cardiomyopathy • Pregnancy • Restrictive cardiomyopathy • Risk stratification • Screening • Sports • Sudden cardiac death

Key Takeaways

Section 2–3: Introduction and Phenotypic Definitions

• The guideline rejects the term "arrhythmogenic cardiomyopathy (ACM)" as a distinct cardiomyopathy subtype because it lacks a morphological or functional definition consistent with the existing classification scheme. ARVC remains as a phenotype; predominantly LV disease is categorized under NDLVC or DCM.
• 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, and congenital heart disease sufficient to cause the observed myocardial abnormality."
• Five phenotypes are recognized: HCM, DCM, NDLVC (new), ARVC, and RCM. Phenotypes may coexist in the same family and evolve over a lifetime.
• LVNC (left ventricular non-compaction) is reclassified as a phenotypic trait, not a cardiomyopathy in the general sense; "hypertrabeculation" is preferred terminology.
• Takotsubo syndrome is explicitly excluded from the cardiomyopathy classification due to its transient and reversible nature.

Section 3.2.3: NDLVC — New Category

• NDLVC is defined as: non-ischaemic LV scarring or fatty replacement (regardless of presence of wall motion abnormalities) OR isolated global LV hypokinesia without scarring.
• Replaces "hypokinetic non-dilated cardiomyopathy" and encompasses what was previously classified as DCM without LV dilatation, ALVC, left-dominant ARVC, or arrhythmogenic DCM.
• Key genes: DSP, FLNC (truncating), DES, LMNA, PLN — substantial overlap with DCM and ARVC genetic backgrounds.
• CMR with LGE is the foremost imaging modality in NDLVC; characteristic LGE patterns by genotype (ring-like/subepicardial in DSP, FLNC, PLN; septal mid-wall in LMNA; heterogeneous in TTN, BAG3, DMD, RBM20).

Section 4: Epidemiology

• HCM prevalence: ~0.2% in adults; DCM prevalence: 0.036–0.400%; ARVC prevalence: ~0.078%.
• Special populations — "second hit theory": TTNtv in 13.5% of alcoholic cardiomyopathy patients; TTNtv in 7.5% of cancer therapy-induced cardiomyopathy; TTNtv in 10% of peripartum cardiomyopathy. Rare variants in cardiomyopathy genes in 8–22% of acute myocarditis.

Section 5–6: Integrated Patient Management and Diagnostic Work-up

• Multidisciplinary cardiomyopathy teams are mandatory for all patients (Class I, Level C). Team composition includes cardiologists, specialist nurses, genetic counsellors, psychologists, geneticists, and pathologists.
• Multiparametric diagnostic approach is required: personal/family history + 3–4-generation pedigree + ECG + Holter + laboratory tests + multimodality imaging (Class I, Level C).
• Contrast-enhanced CMR is recommended at initial evaluation (Class I, Level B); should be considered for serial follow-up every 2–5 years.
• CMR tissue characterization (LGE, T1 mapping, T2 mapping, T2* for iron) is diagnostic and prognostically important across all phenotypes. Each phenotype/genotype has characteristic LGE distribution patterns.
• Bone scintigraphy (DPD/PYP/HMDP) is the gold standard for diagnosis of ATTR cardiac amyloidosis (Class I, Level B).
• Genetic testing is recommended in all patients with cardiomyopathy (Class I). Utility: confirms diagnosis, informs prognosis, guides therapy selection, enables reproductive counseling, and enables cascade testing of relatives.
• Cascade genetic testing of first-degree relatives is recommended when a P/LP variant is identified. Relatives negative for a confirmed familial variant can be discharged from surveillance.

Section 7.1: Hypertrophic Cardiomyopathy (HCM)

• Diagnostic criteria: LV wall thickness ≥15 mm in adults (any segment), not solely explained by loading conditions. In relatives: ≥13 mm.
• LVOTO is defined as peak LVOT gradient ≥30 mmHg; treatment threshold ≥50 mmHg.
• Medical management of LVOTO (in order): (1) non-vasodilating beta-blockers (Class I, Level B), (2) verapamil or diltiazem if beta-blockers contraindicated (Class I, Level B), (3) disopyramide added to beta-blockers (Class I, Level B), (4) Mavacamten considered as addition (Class IIa, Level A).
• Septal reduction therapy (SRT) is Class I for LVOTO ≥50 mmHg with NYHA III–IV symptoms refractory to maximal drug therapy. ASA and surgical myectomy have similar outcomes; choice depends on anatomy and center expertise.
• SCD risk stratification: HCM Risk-SCD calculator for adults ≥16 years (Class I, Level B); HCM Risk-Kids for <16 years (Class I, Level B). ICD is Class IIa if 5-year risk ≥6%.
• Additional SCD risk markers (used in shared decision-making): extensive LGE ≥15% on CMR, LVEF <50%, LVOT gradient, NSVT, unexplained syncope, family history of SCD, LV wall thickness ≥30 mm, left atrial diameter.
• Sarcomeric variants alone are NOT recommended to guide ICD decisions independent of risk tools.

Section 7.2: Dilated Cardiomyopathy (DCM)

• DCM: LV dilatation + global or regional systolic dysfunction, not explained by loading conditions or CAD.
• Pharmacological treatment follows standard heart failure guidelines (ACEi/ARB, beta-blocker, MRA, ARNI, SGLT2i).
• Genetic yield: ~30% of DCM. Key genes: TTN (most common), LMNA, RBM20, MYH7, and others.
• ICD primary prevention for LVEF ≤35% after ≥3 months of OMT (as per HF guidelines). For specific high-risk genotypes (LMNA, PLN, FLNC, RBM20, DES, TMEM43), ICD should be considered even with LVEF >35% if additional risk factors are present.

Section 7.3: NDLVC

• SCD risk is genotype-dependent. High-risk genotypes: PLN, TMEM43, DES, DSP, LMNA, FLNC (truncating), RBM20.
• Gene-specific risk-prediction scores exist for LMNA (https://lmna-risk-vta.fr) and PLN p.Arg14del (https://plnriskcalculator.shinyapps.io/final_shiny).
• ICD: recommended in NDLVC + HF symptoms + LVEF ≤35% after OMT (Class IIa, Level A); should be considered in high-risk genotype + LVEF >35% with additional risk factors (Class IIa, Level C).

Section 7.4: ARVC

• ESC 2023 maintains ARVC as a distinct phenotype but does NOT adopt ACM as a new diagnostic category. LV-dominant disease → NDLVC.
• Epsilon waves and SAECG should be used with caution — low sensitivity/specificity, high interobserver variability.
• Beta-blockers are first-line antiarrhythmic therapy. Flecainide should be considered when single-agent therapy fails.
• Exercise restriction remains critical: stopping competitive exercise reduces VA burden and may slow disease progression.

Section 7.5: Restrictive Cardiomyopathy (RCM)

• Defined by restrictive LV/RV physiology + normal or reduced diastolic volumes + normal wall thickness.
• Key causes: sarcomeric variants, DES, FLNC, BAG3, amyloidosis, RASopathies. Often presents with biatrial enlargement.
• Pulmonary vascular resistance study guides transplantation timing.

Section 7.6–7.7: Syndromic, Metabolic, and Amyloid Cardiomyopathies

• Anderson-Fabry disease: enzyme replacement therapy (ERT) is indicated in all symptomatic patients with classical disease at earliest signs of organ involvement. Basal-inferolateral LGE and low native T1 on CMR are characteristic.
• ATTR amyloidosis: tafamidis is the approved therapy for ATTR-CM (both wild-type and hereditary). Bone scintigraphy (DPD/PYP/HMDP) is the non-invasive gold standard for ATTR-CA diagnosis.
• Glycogen storage disorders: ERT is recommended in Pompe disease (GSD IIa); no approved aetiological therapy for PRKAG2 or Danon disease.
• Friedreich ataxia: no specific therapy; idebenone showed no significant benefit in 4 RCTs.

Section 8: Sports, Reproduction, Non-Cardiac Surgery

• Healthy adults should exercise ≥150 min/week of moderate intensity. Cardiomyopathy patients need individualized risk assessment.
• High-intensity exercise and competitive sports should be discouraged in high-risk HCM, ARVC, and NDLVC patients.
• Genotype-positive/phenotype-negative patients or those with mild phenotype and no risk factors may participate in competitive sports.
• Pregnancy and post-partum are associated with increased CV risk in women with cardiomyopathy; multidisciplinary pre-pregnancy counseling is recommended.

Section 14: Key Messages

• Aetiology is fundamental — phenotype-first approach leads to aetiology-based management.
• CMR tissue characterization is of value in diagnosis, monitoring, and risk stratification in all phenotypes.
• ICD in DCM and NDLVC should be considered for certain genetic forms even if LVEF >35%.
• Mavacamten should be considered in HCM + LVOTO who remain symptomatic despite optimal medical therapy.
• Identification and management of comorbidities (hypertension, diabetes, obesity, sports, virus, pregnancy) is integral to cardiomyopathy management.

Key Concepts Mentioned

• concepts/Phenotypic-Approach-to-Cardiomyopathy — core diagnostic framework
• concepts/Late-Gadolinium-Enhancement — tissue characterization for all phenotypes
• concepts/HCM-Risk-SCD — validated SCD risk tool
• concepts/LVOTO — management target in HCM
• concepts/Septal-Reduction-Therapy — myectomy vs ASA
• concepts/Cascade-Family-Screening — systematic relative screening
• concepts/Arrhythmogenic-Cardiomyopathy — ESC 2023 position on ACM terminology
• concepts/Sudden-Cardiac-Death — genotype-driven risk stratification

Key Entities Mentioned

• entities/HCM — most common cardiomyopathy; comprehensive management update
• entities/DCM — genotype-guided ICD thresholds
• entities/NDLVC — new phenotypic category; high SCD risk
• entities/ARVC — maintained as phenotype; LV-dominant disease → NDLVC
• entities/RCM — rare; transplantation-oriented management
• entities/Mavacamten — cardiac myosin ATPase inhibitor; Class IIa, Level A for obstructive HCM
• entities/ATTR-Amyloidosis — tafamidis therapy; scintigraphy diagnosis
• entities/Anderson-Fabry-Disease — ERT; specific CMR pattern
• entities/LMNA — gene-specific ICD risk calculator; highest malignant VA risk
• entities/DSP — ring-like LGE; NDLVC archetype
• entities/PLN — gene-specific risk calculator; NDLVC
• entities/FLNC — high-risk NDLVC genotype
• entities/TTN — most common DCM gene; peripartum CMP association
• entities/PKP2 — ARVC desmosomal gene; gene therapy target

Limitations of the Document

• ACM vs ARVC terminology debate: ESC 2023 rejects ACM as a distinct phenotype; HRS 2019 consensus embraces ACM as umbrella term — direct conflict in nomenclature frameworks.
• ICD thresholds for NDLVC/DCM with LVEF >35% and high-risk genotypes: ESC CMP guidelines (this document) recommend shared decision-making around ~6% threshold; 2022 ESC VA Guidelines suggest ≥10% threshold for LMNA specifically — internal ESC inconsistency.
• LGE quantification in HCM: multiple quantification methods; only 2-SD technique validated against necropsy, but other methods widely used in published studies.
• LV apical aneurysm as ICD indication: AHA/ACC 2020 considers it a major independent SCD risk factor; ESC 2023 recommends against using it as sole indication due to insufficient data.
• Exercise restriction in non-PKP2 ARVC genotypes: data predominantly from PKP2 — generalizability unproven for DSP, TMEM43, PLN, and other genes causing NDLVC overlap.

Wiki Pages Updated

• wiki/sources/esc-cmp-2023.md (created)
• wiki/entities/HCM.md (created)
• wiki/entities/DCM.md (created)
• wiki/entities/NDLVC.md (created)
• wiki/entities/RCM.md (created)
• wiki/entities/Mavacamten.md (created)
• wiki/entities/ATTR-Amyloidosis.md (created)
• wiki/entities/Anderson-Fabry-Disease.md (created)
• wiki/concepts/Phenotypic-Approach-to-Cardiomyopathy.md (created)
• wiki/concepts/Late-Gadolinium-Enhancement.md (created)
• wiki/concepts/HCM-Risk-SCD.md (created)
• wiki/concepts/LVOTO.md (created)
• wiki/concepts/Septal-Reduction-Therapy.md (created)
• wiki/entities/ARVC.md (updated)
• wiki/entities/LMNA.md (updated)
• wiki/entities/DSP.md (updated)
• wiki/entities/PLN.md (updated)
• wiki/entities/TTN.md (updated)
• wiki/concepts/Arrhythmogenic-Cardiomyopathy.md (updated)
• wiki/concepts/Sudden-Cardiac-Death.md (updated)
• wiki/concepts/Cascade-Family-Screening.md (updated)
• wiki/index.md (updated)
• wiki/log.md (updated)