Aetiology

Monogenic (Mendelian): ~30–40% of idiopathic DCM, up to ~50–60% with a family history (TTN, LMNA, FLNC)^[1]^[8]

Acquired: common, exclude first: myocarditis, alcohol, tachycardia-mediated, peripartum, chemotherapy, thyroid, nutritional^[1]

Complex (likely polygenic): part of "idiopathic" DCM after exclusion reflects polygenic susceptibility with environmental triggers^[1]

Genetics

Inheritance: Predominantly autosomal dominant (penetrance 30-50% by age 40-50); some X-linked and recessive forms

Genetic yield: ~30-40% in unselected DCM, up to 50-60% with family history

Major genes, arrhythmic risk and ESC 2023 ICD thresholds:^[1]

Gene / protein	% Familial DCM	Penetrance	Arrhythmic risk	Key features	ESC 2023 predictors of SCD, and ICD threshold
LMNALamin A/C	6–8%	>90%	High	Conduction disease before DCM; VT with preserved LVEF; mid-wall septal LGE	Annual SCD rate 5–10%. ESC directs risk estimation to the validated LMNA risk score (lmna-risk-vta.fr; Wahbi 2019), see Risk section, rather than a factor count^[1]
FLNC (truncating)Filamin C	3–4%	60–70%	High	Ring-like/circumferential LGE; VT with mild LV dysfunction	Annual SCD rate 5–10%. ESC predictors: LGE on CMR, LVEF <45%. Consider at a higher LVEF than the standard HFrEF threshold, in specialist risk assessment^[1]
TMEM43Transmembrane protein 43	Rare; founder p.Ser358Leu	–	High	Strongly male-predominant; also classified within the ARVC spectrum, see that page	Annual SCD rate 5–10%. ESC predictors: male sex alone; in females, any of LVEF <45%, NSVT, LGE on CMR, or >200 ventricular ectopics per 24h Holter^[1]
DSPDesmoplakin	2–3%	–	High	LV-dominant or biventricular; ring-like LGE; ARVC overlap	Annual SCD rate 3–5%. ESC predictors: LGE on CMR, LVEF <45%. Consider at a lower threshold than standard HFrEF criteria where VT and LV dysfunction coexist, in specialist risk assessment^[1]
PLN p.Arg14delPhospholamban	<1%*	–	Mod-High	Founder variant (Netherlands); low voltage ECG; variable progression	Annual SCD rate 3–5%. ESC directs risk estimation to the variant-specific PLN risk score (plnriskcalculator.shinyapps.io); listed predictors are LVEF <45%, LGE on CMR and NSVT^[1]
RBM20RNA-binding motif 20	2–3%	>90%	Mod-High	Early onset; >80% atrial fibrillation burden; rapid progression	Annual SCD rate 3–5%. ESC predictors: LGE on CMR, LVEF <45%^[1]
DESDesmin	1–2%	~65% (familial)	Mod-High	AV block / conduction disease in ~40%, often the first sign; ring-like LGE; skeletal (myofibrillar) myopathy in a proportion; phenotype spans DCM, RCM and ACM	Sustained VA ~16% and HF events ~19% in pooled data; risk is carried by males (VA HR 2.3), whose outcomes match LMNA-tv and FLNC-tv. Not among the ESC 2023 tabulated high-risk genotypes; individualise ICD decisions on male sex, NSVT and LVEF ≤50%^[30]^[31]^[33]
SCN5ANav1.5 (Na⁺ channel)	2–3%	30–60%	Moderate	Conduction disease	Standard (LVEF ≤35%)
TTN (A-band truncating)Titin	15–25%	30–40%	Standard	Most common; lower arrhythmic risk; reverse remodelling possible	Standard (LVEF ≤35%)
MYH7β-myosin heavy chain	~5%	70–80%	Standard	–	Standard (LVEF ≤35%)
TNNT2Cardiac troponin T	~3%	High	Standard	–	Standard (LVEF ≤35%)
BAG3BAG cochaperone	2–3%	>80%	Standard	HF progression rather than arrhythmic risk; skeletal myopathy	Standard (LVEF ≤35%)
Dystrophin (DMD)Dystrophin	X-linked	~100% males	Standard	See DMD/BMD section	Standard (LVEF ≤35%)

*PLN p.Arg14del high prevalence in Dutch population. Annual SCD rates and predictors are those tabulated as high-risk genotypes in the 2023 ESC cardiomyopathy guideline; where a validated variant-specific risk score exists (LMNA, PLN), ESC directs that it should be used to guide primary-prevention ICD implantation rather than a count of risk factors. TTN, BAG3, SCN5A, MYH7, TNNT2 and dystrophin are not listed among those high-risk genotypes.^[1]

Pathophysiology: Gene-specific mechanisms → cytoskeletal disruption (TTN, FLNC), nuclear envelope dysfunction (LMNA), sarcomeric dysfunction (MYH7, TNNT2), RNA splicing defects (RBM20) → progressive cardiomyocyte loss, fibrosis, chamber dilatation, and contractile dysfunction

TTN variants: Interpretation challenging; truncating variants in high-expression (A-band) exons are pathogenic; such TTN truncating variants occur in ~1% of the general population

Gene frequencies and penetrance figures derive largely from referral cohorts and vary with variant class and ascertainment; treat them as indicative rather than fixed.

LMNA Cardiomyopathy: Natural History (Hasselberg et al, Eur Heart J 2018^[11])

Single-centre longitudinal study of 79 LMNA genotype-positive patients (mean age 42±16 yrs, EF 45±13%):

LMNA mutations found in 6.2% of familial DCM in Norway
Asymptomatic LMNA carriers: 9% annual incidence of newly documented cardiac phenotype; 61% developed phenotype by 4.4 years follow-up^[11]
Of early-phenotype carriers: 95% had conduction/arrhythmic disease before DCM, AV block (32%), AF (23%), non-sustained VT (39%)
72% overall developed AV block; 37% became pacemaker-dependent
Sustained ventricular arrhythmia predicted by: AV block (log-rank P=0.03) and LVEF <45%, AV block negative predictive value for VA = 100%
Heart transplantation in 19% of this cohort over 7.8±6.3 years, higher than typically seen in other DCM aetiologies^[11]

Clinical implications: Early and regular follow-up of asymptomatic LMNA carriers from point of genetic diagnosis; ECG/Holter at every review; ICD consideration before LVEF falls to standard HFrEF threshold

Prevalence

1 in 250–400 individuals in the general population^[1]

~30–40% of cases are familial/genetic; a pathogenic or likely pathogenic variant is identifiable in ~20–35% of DCM probands^[8]

Most common indication for cardiac transplantation

Wide age range at presentation (childhood to elderly)

Population-level epidemiology (UK Biobank, Shah et al 2022^[8]): Among 18,665 individuals who underwent whole-exome sequencing, ECG and CMR, 7.8% carried ≥1 putative pathogenic variant in 44 DCM genes; over 90% of these carriers had no known history of DCM. Combined clinical/subclinical penetrance was ≤30% across all three variant-filtering strategies. The most common early DCM manifestation was arrhythmia or conduction disease (15.2%), occurring before ventricular dilation or dysfunction, highlighting the importance of ECG surveillance in variant carriers.

Diagnosis

Diagnostic Criteria (2023 ESC): both features are required.

LV systolic dysfunction: LVEF <50%, global or regional^[1]
LV dilatation: LV end-diastolic dimension or volume more than 2 z-scores above the population mean, corrected for body size, sex and age. In adults this corresponds to an LV end-diastolic diameter >58 mm in males and >52 mm in females, or an LV end-diastolic volume index ≥75 mL/m² in males and ≥62 mL/m² in females on echocardiography^[1]
Not explained solely by abnormal loading conditions (hypertension, valve disease, congenital heart disease) or coronary artery disease^[1]

Related definitions:

Isolated left ventricular dilatation: LV dilatation with a normal ejection fraction, in the absence of athletic remodelling or another environmental cause. This is not itself a cardiomyopathy, but may represent an early manifestation of DCM^[1]
Right ventricular involvement: RV dilatation and dysfunction may be present but are not required for the diagnosis. Where dilatation or wall motion abnormality is confined to, or predominantly affects, the right ventricle, consider ARVC instead^[1]
Diagnosis in a first-degree relative: the threshold is lower than in the index patient. Isolated LV dilatation with preserved systolic function, or LV dilatation in the presence of the familial causative variant, is sufficient for a diagnosis of DCM in a relative. Lesser electrocardiographic or imaging abnormalities in the context of a family history are suggestive of disease and warrant close follow-up rather than a diagnosis^[1]

Clinical Presentation:

Heart failure symptoms: dyspnea, fatigue, edema
Arrhythmias: AF, VT, heart block
Thromboembolic events
Sudden cardiac death (particularly in LMNA and FLNC)
May be asymptomatic with incidental finding

Investigations

First-line:

12-lead ECG (may show AF, BBB, Q waves, low voltage)
Transthoracic echocardiography (LVEF, chamber dimensions, valves)
NT-proBNP
24-hour Holter monitoring (arrhythmia burden, heart block)

Advanced imaging:

Cardiac MRI - precise LVEF, LGE pattern (mid-wall suggests genetic/inflammatory)
Consider coronary angiography to exclude ischemic cause

Specialist investigations:

Genetic testing (especially if young onset, family history, or specific features)
Myocardial biopsy (selected cases: suspected myocarditis, infiltrative disease)
Screening for metabolic/storage diseases if indicated

Treatments

1. General measures:

Treat any identified reversible/acquired cause (e.g. alcohol cessation, rate control of a tachyarrhythmia, correction of nutritional deficiency)
Fluid and weight monitoring, dietary sodium advice, routine heart-failure vaccination (influenza, pneumococcal)
Structured exercise-based cardiac rehabilitation where available
Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy:

Foundational medical therapy: RAS inhibitor or ARNI, beta-blocker, MRA and SGLT2 inhibitor^[26]
Ejection fraction bands: HFrEF is LVEF <50%, HFpEF ≥50%^[26]. Foundational medical therapy applies across the HFrEF range, though no randomised trial has tested beta-blockers or ACE-I/ARNI/ARB exclusively at LVEF 41–49%; the doses below are those from the trials that established them^[26]. LVEF <50% is also the diagnostic threshold for DCM itself^[1], so the same figure carries two meanings here — one defines the disease, the other the group treated for heart failure.
Therapy that extends beyond the HFrEF range: an MRA is recommended in symptomatic heart failure independent of LVEF — steroidal in HFrEF, steroidal or non-steroidal in HFpEF (Class I)^[26]. Semaglutide or tirzepatide should be considered at LVEF ≥45% with BMI ≥30 kg/m², regardless of diabetes status, to reduce weight and improve exercise capacity and quality of life — not for mortality or hospitalisation (Class IIa)^[26]. Digoxin/digitoxin, durable mechanical circulatory support and transcatheter edge-to-edge mitral repair also carry stronger recommendations^[26]. These derive from general heart-failure populations and do not extend automatically to a sarcomeric, infiltrative or genetic phenotype; hypertrophic cardiomyopathy and cardiac amyloidosis are managed under their own pathways^[26].
Early disease expression versus an unaffected carrier: in a relative with early disease, first-line heart-failure therapy (ACE inhibitor or ARB, beta-blocker, MRA) may be considered to slow progression of LV dilatation and dysfunction (Class IIb^[1]). In a genotype-positive relative with no phenotype there is no evidence supporting any drug to prevent disease developing, and none should be started; the EARLY-Gene trial is testing this question. Surveillance, not treatment, is the intervention^[1]. A carrier with a structurally normal heart and normal biomarkers is Stage A (at risk); structural change, abnormal function or a raised natriuretic peptide makes them Stage B (pre-heart failure) while still asymptomatic, which describes the disease rather than creating an indication to treat^[26].
ACE inhibitor / ARB / ARNI:
- Ramipril: start 1.25–2.5 mg once daily; uptitrate every 2 weeks → target 10 mg once daily (or 5 mg bd)
- Lisinopril: start 2.5–5 mg once daily → target 20–35 mg once daily^[7]
- Sacubitril/valsartan (Entresto®)^[2]^[12] (PARADIGM-HF), PREFERRED if LVEF ≤40%, tolerating ACEi/ARB:
  - Start 24/26 mg twice daily; leave 36-hour washout after last ACEi dose
  - Double dose every 2–4 weeks as tolerated → target 97/103 mg twice daily
  - Monitor BP and eGFR; hold if systolic BP <90 mmHg or eGFR <30 ml/min/1.73m²
- Candesartan (if ACEi-intolerant), start 4–8 mg once daily → target 32 mg once daily
Beta-blockers (mortality benefit established by MERIT-HF^[17], CIBIS-II^[18] and COPERNICUS^[19]):
- Bisoprolol: start 1.25 mg once daily; uptitrate every 2 weeks → target 10 mg once daily
- Carvedilol: start 3.125 mg twice daily; uptitrate every 2 weeks → target 25 mg twice daily (50 mg bd if >85 kg)
- Metoprolol succinate (CR/XL): start 12.5–25 mg once daily → target 200 mg once daily
- Only initiate when euvolaemic; do not start in acutely decompensated HF
Mineralocorticoid receptor antagonist (MRA) (RALES^[15], EMPHASIS-HF^[16]):
- Eplerenone: start 25 mg once daily → target 50 mg once daily; preferred post-MI or in males (avoids gynaecomastia)
- Spironolactone: start 25 mg once daily → target 25–50 mg once daily
- Monitor K⁺ and eGFR at 1–2 weeks after initiation; hold if K⁺ >5.5 mmol/L or eGFR <30
SGLT2 inhibitor:
- Dapagliflozin 10 mg once daily (DAPA-HF^[13]; NICE TA679^[5])
- Empagliflozin 10 mg once daily (EMPEROR-Reduced^[14]; NICE TA773^[6])
- Fixed doses, no uptitration required; hold if eGFR <20 ml/min/1.73m² (empagliflozin) or <25 (dapagliflozin)
- Interrupt 3–5 days before planned surgery; advise sick-day rules

3. Device therapy:

ICD for primary prevention if LVEF ≤35% after ≥3 months of foundational medical therapy, NYHA II–III, life expectancy >1 year (SCD-HeFT^[20], MADIT-II^[21]; note DANISH^[25] showed no overall mortality benefit of primary-prevention ICD in non-ischaemic cardiomyopathy, so device decisions are individualised, weighing arrhythmic risk markers such as LGE and genotype)
CRT-D if LVEF ≤35%, LBBB morphology, QRS ≥130 ms (greatest benefit QRS ≥150 ms) (COMPANION^[22], CARE-HF^[23], RAFT^[24])

4. Advanced heart failure and/or transplant referral:

Heart transplantation assessment, refer if NYHA III–IV, peak VO₂ <12–14 ml/kg/min despite foundational medical therapy
LVAD as bridge to transplant or destination therapy

5. If the ejection fraction improves (HFimpEF):

Definition. Heart failure with improved ejection fraction requires all three: antecedent HFrEF, a ≥10-point increase in LVEF, and a new LVEF >40%^[27].
Remission, not cure. These patients remain susceptible to recurrent left ventricular dysfunction and need continued medical therapy and longitudinal surveillance^[27]. A normalised ejection fraction is not a reason to stop treatment.
Withdrawal of therapy. TRED-HF randomised 51 patients with recovered DCM to phased withdrawal of heart-failure therapy or continuation. Within 6 months 45.7% of the withdrawal group relapsed, and none of the continuation group did^[28].
Longer term. At a median 6 years, 33 of the 51 (65%) had relapsed; of the 41 who restarted therapy, 18 (44%) relapsed again, and only 5 remained off treatment and asymptomatic. The authors describe a relapsing–remitting course and conclude that heart-failure therapy at robust doses should be continued^[29].
Recovery does not neutralise genotype. In LMNA, FLNC, PLN, DSP and RBM20 the arrhythmic risk exceeds what LVEF predicts^[1], so an improved ejection fraction is not on its own a reason to revisit an ICD decision or to relax surveillance in a high-risk genotype.

Gene-specific considerations:

LMNA: ICD decisions should be guided by the validated LMNA ventricular-tachyarrhythmia risk calculator (Wahbi 2019), which estimates an individual 5-year VTA probability from male sex, NSVT, LVEF <45%, non-missense variant type and first-degree AV conduction block, rather than a simple count of risk factors; the resulting risk estimate should be combined with phenotype, specific variant, competing risks and shared decision-making, not applied as a fixed universal threshold (ESC 2023^[1])
FLNC: truncating variants carry a higher arrhythmic risk that may justify ICD consideration at an LVEF above conventional thresholds when additional risk factors are present, this is a risk-modifying consideration rather than a fixed rule for every truncating-variant carrier
DES: conduction disease is the commonest first manifestation and usually precedes ventricular dysfunction, so keep a low threshold for ambulatory monitoring and pacing assessment; sustained ventricular arrhythmia and heart-failure events are frequent and male sex is the strongest predictor; ask about proximal or distal weakness and check CK (normal in a third) with neurology referral if myopathy is suspected^[30]^[31]^[32]

Related Resources

Complications

Progressive heart failure: the dominant clinical course, advancing to refractory heart failure, LVAD or transplant^[1]
Ventricular arrhythmia and sudden cardiac death: can precede severe systolic dysfunction in arrhythmogenic genotypes (LMNA, FLNC, PLN, DSP)^[1]
Conduction disease and high-grade AV block: especially with LMNA variants, which can demand pacing or ICD before the ejection fraction falls
Atrial fibrillation.
Intracardiac (LV) thrombus and systemic embolism: in low-flow, severely impaired ventricles
Functional mitral regurgitation: from annular dilatation, worsening the heart failure spiral

Risk Stratification

ICD for primary prevention:

LVEF ≤35% despite ≥3 months optimal medical therapy
NYHA Class II-III symptoms
Life expectancy >1 year with good functional status^[3]

High arrhythmic risk genes (consider ICD even if LVEF >35%):

LMNA: ICD decisions should be guided by the validated LMNA ventricular-tachyarrhythmia risk calculator (Wahbi 2019), which computes an individual 5-year VTA probability from male sex, NSVT, LVEF <45%, non-missense variant type and first-degree AV conduction block, combined with phenotype, competing risks and shared decision-making rather than a simple count of risk factors^[1]. Additionally, LMNA variants localising to the IgD domain (C-terminal immunoglobulin-like domain, e.g. p.Arg471His, p.Arg541His) present a distinct apical pseudo-infarct LGE pattern (transmural fibrosis) and independently predict major ventricular arrhythmias (HR 2.39, 95% CI 1.05–5.46; Castrichini et al 2025^[10]); these variants may carry higher thromboembolic risk (emerging variant-specific evidence); individualise anticoagulation with MDT input where apical fibrosis/aneurysm, AF, intracardiac thrombus, or severe LV dysfunction are present
FLNC: Consider ICD if truncating variant with any additional risk factor
DSP: Associated with ARVC phenotype; arrhythmic risk

CMR Late Gadolinium Enhancement (LGE) and Prognosis in DCM (Halliday et al, JACC Imaging 2018^[9])

In 874 DCM patients followed for a median of 4.9 years, 34.3% had nonischemic LGE. Even small LGE amounts predicted substantially higher SCD risk:

LGE 0–2.55%: SCD adjusted HR 2.79 (95% CI 1.42–5.49)
LGE 2.55–5.10%: SCD adjusted HR 3.86 (95% CI 2.09–7.13)
LGE >5.10%: SCD adjusted HR 4.87 (95% CI 2.78–8.53)
Septal + free-wall LGE combined = highest SCD risk (the combination outperforms extent or pattern alone)
Predictive models using LGE presence and location were superior to models based on LVEF alone

CMR with LGE should be performed in all DCM patients, LGE presence, location (septal vs free-wall), and extent all independently inform ICD decision-making beyond LVEF.

Heart transplant referral considerations:

NYHA Class III-IV despite optimal therapy
Peak VO2 <12-14 ml/kg/min
Recurrent hospitalizations for heart failure
Refractory arrhythmias
Seattle Heart Failure Model or HFSS can aid prognostication

Pregnancy Management

Pregnancy in DCM - individualized risk assessment (2025 ESC Pregnancy Heart Team approach)

Pregnancy risk in DCM rises with lower LVEF and worse functional class, and a history of peripartum cardiomyopathy carries a recognised risk of recurrence, but there is no single validated LVEF or NYHA cut-off that makes pregnancy universally contraindicated; risk should be assessed individually by a Pregnancy Heart Team using baseline LVEF, functional capacity, NT-proBNP, arrhythmia history and genotype where known.^[1]^[4]

Medication: ACE inhibitors, ARBs, sacubitril-valsartan and spironolactone are generally stopped before conception (teratogenic); beta-blockers are generally continued. Anticoagulation is switched from warfarin to LMWH if indicated. These are general heart-failure medication principles, not disease-specific to DCM.

Monitoring: surveillance frequency (clinical review, echocardiography, NT-proBNP) should be individualized to the patient's baseline severity and trajectory rather than a fixed universal monthly or fortnightly schedule; the threshold for admission should likewise be set by the treating team based on the individual's trend rather than a fixed absolute LVEF drop.

Delivery: mode and timing of delivery, need for invasive monitoring, and any role for pulmonary-artery catheterisation should be individualized decisions made by the Pregnancy Heart Team based on the patient's haemodynamic status at the time, not applied via a fixed LVEF-based rule.^[4]

Postpartum: the early postpartum period carries a recognised risk of haemodynamic decompensation from autotransfusion and fluid shifts; the intensity and duration of monitoring should be individualized to the patient's severity rather than a fixed universal CCU/HDU admission for all. Pre-existing DCM can also deteriorate postpartum in a pattern that overlaps with peripartum cardiomyopathy, so a low threshold for reassessment if symptoms worsen is reasonable.

Genetic considerations: where a pathogenic variant is identified (e.g. LMNA, FLNC), this should inform counselling about arrhythmic risk in the patient and transmission risk to offspring, but does not by itself dictate a fixed monitoring or delivery protocol.

Contraception and future pregnancy: discuss the full range of options through non-directive counselling; a prior peripartum cardiomyopathy history carries a recognised recurrence risk with a further pregnancy, and this should be discussed with the decision led by the patient.

Follow-up

Based on ESC 2023 Cardiomyopathy & ESC Heart Failure guidelines^[1]^[2].

Advanced / complicated = LVEF <35%, NYHA III–IV symptoms, recurrent arrhythmia, high-risk genotype (LMNA, FLNC, RBM20, PLN, DSP), or a device in situ.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

	Genotype+ / Phenotype−	Uncomplicated / Stable	Advanced / Complicated
Frequency	Every 2–3 yrs (annual if LMNA/FLNC)	Every 1–2 years	Every 3–6 months
Clinical review	Symptoms, BP	Symptoms, NYHA, BP, weight	As above + fluid status, device check
ECG	Each screening visit	Annual 12-lead	Each visit
Echocardiography	Each screening visit (early dysfunction)	Every 1–2 years (LVEF, dimensions)	6-monthly
Holter / ambulatory	If high-risk genotype (LMNA/FLNC)	Every 1–2 years (more often if LMNA/FLNC)	6-monthly
Bloods	NT-proBNP if indicated	Annual (renal function, NT-proBNP)	Each visit
CMR	Consider (early fibrosis)	Baseline; repeat if phenotype changes	As clinically indicated
Family screening	–	Cascade ECG + echo (genotype-guided)	–

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

Key Points

TTN truncating variants require phenotype- and variant-level interpretation; not all TTN variants are pathogenic
Address reversible causes: thyroid, nutritional deficiency, toxins
Screen first-degree relatives (clinical + genetic if variant identified)
Ensure optimal medical therapy before considering devices (wait 3-6 months on foundational medical therapy)^[1]
LMNA carriers - do NOT wait for LVEF ≤35% to consider ICD^[1]
Anticoagulation for AF/flutter, LV thrombus, prior systemic embolism or another standard indication; not routine for low LVEF alone in sinus rhythm^[1]
Excess alcohol should be avoided; complete abstinence is recommended where alcohol-related cardiomyopathy is suspected
Preconception counselling essential - pregnancy contraindicated if LVEF <30% or NYHA III-IV

References & Review Date

Last reviewed: September 2026

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Dilated Cardiomyopathy (DCM)