Cardiology:Cardiomyopathies

🫀 Cardiomyopathies are disorders of the heart muscle that may cause heart failure, arrhythmia, syncope, thromboembolism or sudden cardiac death. The main phenotypes are dilated, hypertrophic, arrhythmogenic, restrictive and non-dilated LV cardiomyopathy. Some are inherited; others result from inflammation, infiltration, storage disease, metabolic disease or toxins.
Clinical priority: Define the phenotype, identify the cause, assess sudden-death risk, treat symptoms and protect family members.

🎯 Learning objectives: By the end of this chapter you should be able to (1) classify a cardiomyopathy by phenotype and then by cause; (2) choose the right first and second-line investigations; (3) recognise the specific diseases that have targeted treatments (ATTR and AL amyloid, sarcoid, Fabry, haemochromatosis, giant-cell and checkpoint-inhibitor myocarditis); (4) explain why obstructive HCM is managed differently from DCM; (5) outline sudden-death risk assessment, ICD/CRT principles and family screening.

3.01 Definition and Clinical Importance

Cardiomyopathy is structural or functional disease of the heart muscle that is not explained solely by coronary artery disease, abnormal loading conditions (hypertension, valve disease) or congenital heart disease. It may be genetic or acquired, and can present at any age from infancy to old age.

• Why it matters: Cardiomyopathies are a leading cause of heart failure in younger adults, the commonest cause of heart transplantation, and an important cause of sudden cardiac death (SCD) in people under 35.
• The diagnostic sequence: A morphological label such as "dilated" or "hypertrophic" is the beginning of a diagnosis, not the end. Work through phenotype → cause → genotype → risk → family.
• Main priorities: Assess haemodynamic stability; establish the phenotype; identify treatable causes; assess arrhythmia and SCD risk; treat heart failure or obstruction; arrange genetic and family evaluation when indicated.
• Ischaemic cardiomyopathy: Commonly used clinically for LV dysfunction due to coronary disease, but it is not a cardiomyopathy in the ESC phenotypic scheme; coronary disease must be excluded before a non-ischaemic diagnosis is made.
• Typical presentations: Exertional dyspnoea, orthopnoea, oedema, chest pain, palpitations, exertional syncope, ventricular arrhythmia, incidental ECG or echo findings, or screening because a relative is affected.

💡 Clinical / MRCP Pearl: Unexpected syncope during exercise or a family history of sudden unexplained death is a major clue to inherited heart muscle disease and warrants urgent specialist risk assessment.

↑ Chapter index

3.02 Classification and Major Phenotypes

The 2023 ESC cardiomyopathy guideline uses a phenotype-first approach based mainly on imaging, followed by an aetiological and genetic diagnosis. The same gene can produce different phenotypes, and the same phenotype can have many causes.

• Dilated cardiomyopathy (DCM): LV (or biventricular) dilatation with global systolic dysfunction not explained by coronary disease or abnormal loading.
• Hypertrophic cardiomyopathy (HCM): Increased LV wall thickness not explained solely by loading conditions; obstructive or non-obstructive.
• Arrhythmogenic right ventricular cardiomyopathy (ARVC): Predominantly RV dilatation/dysfunction with fibrofatty replacement and ventricular arrhythmia.
• Non-dilated LV cardiomyopathy (NDLVC): Non-ischaemic LV scar or fatty replacement, or isolated global hypokinesia, without LV dilatation. Introduced in 2023; it absorbs many "left-dominant arrhythmogenic" cases.
• Restrictive cardiomyopathy (RCM): Non-dilated ventricles with restrictive filling, raised filling pressures and biatrial enlargement; systolic function often preserved early.
• Traits rather than cardiomyopathies: LV hypertrabeculation ("non-compaction") and isolated dilatation are described as morphological traits that need context.
• Syndromes classified by mechanism: Takotsubo syndrome, peripartum cardiomyopathy, myocarditis and toxic, infiltrative or storage disease are described by cause, though each produces one of the phenotypes above.

💡 Clinical / MRCP Pearl: A normal or mildly reduced ejection fraction does not exclude an important cardiomyopathy; fibrosis and ventricular arrhythmia may precede pump failure, especially in NDLVC, ARVC and LMNA/FLNC disease.

↑ Chapter index

3.03 Epidemiology and Inheritance

Inherited cardiomyopathies are commoner than often assumed, and penetrance is typically incomplete and age-dependent.

• HCM: About 1 in 500 adults have the phenotype; the commonest inherited cardiac disease. A sarcomeric variant is found in roughly 30–60% of probands.
• DCM: Around 1 in 250–500; up to a third are familial when relatives are screened. Truncating TTN variants are the single commonest genetic cause.
• ARVC: Roughly 1 in 2,000–5,000; often presents in adolescence or early adulthood, more commonly in males and athletes.
• ATTR amyloid: Wild-type ATTR is common but under-recognised in men over 70 with HFpEF.
• Autosomal dominant: Most sarcomeric, desmosomal and DCM genes (each child has a 50% risk of inheriting the variant).
• X-linked: Fabry (GLA), Danon (LAMP2), Duchenne/Becker (DMD) — males usually more severe, females variably affected.
• Autosomal recessive or mitochondrial: Friedreich's ataxia (FXN); Naxos disease (JUP); mitochondrial disease is maternally inherited.

💡 Clinical / MRCP Pearl: Male-to-male transmission excludes X-linked inheritance — a useful pedigree clue when distinguishing sarcomeric HCM from Fabry or Danon disease.

↑ Chapter index

3.04 Pathophysiology: Core Mechanisms

Different cardiomyopathies produce different haemodynamic and electrical problems; recognising the dominant mechanism guides treatment.

• Systolic pump failure: Myocyte loss, sarcomeric dysfunction and remodelling reduce contractility and stroke volume (DCM, advanced disease).
• Diastolic dysfunction: Hypertrophy, abnormal relaxation or infiltration reduce compliance, so small rises in volume cause large rises in filling pressure (HCM, RCM, amyloid).
• Dynamic outflow obstruction: In obstructive HCM, septal hypertrophy and abnormal mitral–septal interaction produce a variable LVOT gradient and mitral regurgitation.
• Electrical instability: Fibrosis, fibrofatty replacement and cell-to-cell uncoupling create re-entry circuits causing ventricular ectopy, NSVT, VT and VF.
• Conduction disease: Infiltration or scar of the conduction system (sarcoid, amyloid, LMNA, myotonic dystrophy) causes AV block.
• Neurohormonal remodelling: Sympathetic and RAAS activation drive fibrosis, chamber enlargement and functional valve regurgitation — the target of HFrEF therapy.
• Thromboembolism: AF, low output, LV aneurysm or thrombus predispose to stroke and systemic embolism.

💡 Clinical / MRCP Pearl: In several inherited cardiomyopathies, preventing sudden arrhythmic death matters as much as treating symptoms or improving ejection fraction.

↑ Chapter index

3.05 Causes and Aetiological Clues

Look for treatable acquired causes while remembering that inherited susceptibility and an external trigger often coexist.

• Sarcomeric: MYH7 and MYBPC3 (HCM); TTN truncating variants (DCM).
• Desmosomal and arrhythmogenic: PKP2, DSP, DSG2, DSC2, JUP; non-desmosomal high-risk genes include LMNA, FLNC, PLN, RBM20 and DES.
• Inflammatory/infective: Viral and immune myocarditis, giant-cell myocarditis, sarcoidosis, Chagas disease, checkpoint-inhibitor myocarditis.
• Infiltrative/storage: ATTR and AL amyloid, haemochromatosis, Fabry, Danon, PRKAG2, glycogen storage disease.
• Toxic: Alcohol, cocaine, methamphetamine, anabolic steroids, anthracyclines, trastuzumab, radiotherapy.
• Haemodynamic/rate-related: Persistent tachyarrhythmia or high PVC burden; pregnancy-related (PPCM); catecholamine surge (takotsubo).
• Endocrine/nutritional/neuromuscular: Thyroid disease, acromegaly, phaeochromocytoma, thiamine deficiency; Duchenne/Becker, myotonic dystrophy, Friedreich's ataxia.

💡 Clinical / MRCP Pearl: An apparently non-ischaemic DCM may have several contributors — for example a TTN variant unmasked by alcohol, chemotherapy or pregnancy ("two-hit" model).

↑ Chapter index

3.06 Symptoms and Red Flags

Presentations range from asymptomatic family-screening findings to cardiac arrest.

• Heart failure: Exertional dyspnoea, orthopnoea, PND, fatigue, oedema, abdominal congestion, early satiety and reduced exercise tolerance.
• Arrhythmia: Palpitations, light-headedness, syncope or documented VT; AF is common in HCM and amyloid.
• Chest pain: Angina in HCM may reflect microvascular ischaemia or obstruction despite normal coronary arteries; acute pain suggests myocarditis or takotsubo.
• Red flags: Exertional syncope, resuscitated arrest, sustained VT, sudden unexplained death in a relative under 50, new high-grade AV block in a younger adult, rapidly progressive heart failure and shock.
• Extracardiac clues: Bilateral carpal tunnel and spinal stenosis (ATTR); macroglossia, periorbital purpura, nephrotic syndrome (AL); angiokeratomas and neuropathic pain (Fabry); ataxia (Friedreich); myotonia and cataracts (myotonic dystrophy); calf hypertrophy (Duchenne/Becker).

💡 Clinical / MRCP Pearl: Ask specifically about drowning, single-vehicle accidents, sudden infant death and "epilepsy" in relatives — an arrhythmic death may be hidden behind these descriptions.

↑ Chapter index

3.07 History and Examination

A targeted history and examination connect the symptoms to a phenotype and frequently suggest the cause.

• History: Onset and tempo of breathlessness; exertional syncope; palpitations; recent viral illness; chemotherapy or radiotherapy; alcohol, stimulants and anabolic steroids; pregnancies; neuromuscular symptoms; travel or residence in Latin America.
• Family history: A three-generation pedigree documenting sudden death, cardiomyopathy, AF, heart failure, pacemakers, ICDs, transplantation and unexplained accidents.
• General: BP (including postural), pulse character and rhythm, JVP, oedema, ascites, cachexia, skin, eyes and muscles.
• DCM: Displaced diffuse apex, S3, pansystolic murmur of functional MR, signs of congestion.
• HCM: Brisk "jerky" carotid pulse, double apical impulse, S4, ejection systolic murmur at the left sternal edge that varies with manoeuvres.
• RCM/amyloid: Raised JVP (may rise on inspiration — Kussmaul's sign), hepatomegaly, oedema with a relatively normal-sized heart; postural hypotension in amyloid.
• Neurological/systemic: Peripheral or autonomic neuropathy, myopathy, ataxia, hearing loss, angiokeratoma, lymphadenopathy.

💡 Clinical / MRCP Pearl: Physical signs do not quantify sudden-death risk. A patient with few symptoms may have extensive fibrosis or a high-risk genotype.

↑ Chapter index

3.08 Baseline Investigations

Combine structural imaging, electrical assessment and targeted laboratory tests; avoid indiscriminate rare-disease panels.

• ECG: Hypertrophy, repolarisation changes, Q waves, conduction delay, pre-excitation, AF, low voltage and ectopy.
• Blood tests: FBC, U&E/eGFR, LFT, TSH, HbA1c, calcium, phosphate, magnesium, ferritin/transferrin saturation, CK, NT-proBNP, and troponin when injury is suspected.
• Echocardiography: LV and RV size and function, maximal wall thickness, diastolic filling, valves, resting and provoked LVOT gradient, thrombus.
• Ambulatory ECG: 24–48 hours (longer if symptoms are infrequent) for NSVT, AF, conduction disease and PVC burden.
• Cardiac MRI: Volumes, function and tissue characterisation (LGE, T1/T2 mapping, ECV, T2*).
• Coronary assessment: CT coronary angiography or invasive angiography when ischaemia is plausible.
• Exercise testing / CPET: Functional capacity, BP response (abnormal in high-risk HCM), arrhythmias and transplant assessment.
• Targeted tests: Serum free light chains plus serum and urine immunofixation (amyloid); bone scintigraphy (ATTR); alpha-galactosidase A and GLA testing (Fabry); FDG-PET (sarcoid); T. cruzi serology (Chagas); eosinophil count (Löffler).

💡 Clinical / MRCP Pearl: ECG, echo and CMR are complementary. The distribution of LGE on CMR is often the single most useful test for separating ischaemic scar from the various non-ischaemic diseases.

↑ Chapter index

3.09 ECG Patterns Worth Recognising

The ECG often suggests the phenotype, but a normal ECG does not exclude disease.

• HCM: LVH voltage, deep narrow Q waves (inferolateral), lateral T-wave inversion; giant T-wave inversion in V2–V5 in apical HCM.
• DCM: LBBB or nonspecific QRS widening, AF, ectopy; poor R-wave progression.
• ARVC: T-wave inversion in V1–V3 beyond age 14 (without complete RBBB), prolonged terminal activation, epsilon wave; VT with LBBB morphology and often a superior axis.
• Amyloid: Low limb-lead voltage despite thick walls (voltage–mass discordance), pseudo-infarct Q waves, AV block, AF.
• Sarcoid / LMNA / myotonic dystrophy: PR prolongation, high-grade AV block, bundle-branch block, VT.
• Fabry, Danon, PRKAG2: Short PR and/or pre-excitation with LVH.
• Chagas: RBBB with left anterior fascicular block.
• Myocarditis / takotsubo: ST elevation mimicking STEMI; takotsubo evolves to deep widespread T-wave inversion with QT prolongation.

💡 Clinical / MRCP Pearl: LVH with a short PR or delta wave should prompt consideration of a storage disease (Fabry, Danon, PRKAG2) rather than sarcomeric HCM.

↑ Chapter index

3.10 Echocardiography and Dynamic Testing

Echocardiography is the first-line imaging test; it establishes morphology and haemodynamic consequences.

• DCM: Dilated LV with reduced EF (<50%), functional MR, RV dysfunction, possible apical thrombus.
• HCM: Maximal segmental wall thickness, distribution of hypertrophy, systolic anterior motion (SAM) of the mitral valve, MR, LVOT gradient, apical aneurysm.
• LVOT provocation: If the resting gradient is <50 mmHg in a symptomatic patient, measure with Valsalva, standing and, if needed, exercise echocardiography.
• RCM: Non-dilated ventricles, large atria, restrictive mitral inflow (high E/A, short deceleration time), reduced tissue Doppler e′.
• ARVC: RV dilatation, regional akinesia, dyskinesia or aneurysm; assess LV involvement.
• Strain imaging: Reduced global longitudinal strain with relative apical sparing ("cherry-on-top") supports amyloid; serial GLS detects early chemotherapy toxicity.
• Limitations: Echo is poor at tissue characterisation and may miss apical HCM, apical aneurysm and RV disease — CMR fills these gaps.

💡 Clinical / MRCP Pearl: Failing to provoke the LVOT gradient misses clinically important obstruction in about a third of HCM patients whose resting gradient is low.

↑ Chapter index

3.11 Cardiac MRI: Pattern Recognition

CMR is the reference standard for volumes and function and the best non-invasive test for tissue characterisation.

• Ischaemic scar: Subendocardial or transmural LGE in a coronary territory.
• Non-ischaemic DCM: Linear mid-wall septal LGE — a marker of fibrosis and arrhythmic risk.
• HCM: Patchy mid-wall LGE in hypertrophied segments and at RV insertion points; extensive LGE (≥15% of LV mass) is a risk modifier.
• Myocarditis: Oedema (T2) plus subepicardial or mid-wall LGE (T1-based), interpreted using updated Lake Louise criteria.
• Amyloid: Diffuse subendocardial or transmural LGE, difficulty nulling myocardium, markedly raised native T1 and ECV.
• Fabry: Low native T1 (sphingolipid) with basal inferolateral mid-wall LGE.
• Sarcoid: Patchy multifocal LGE, often basal septum and RV side; FDG-PET shows active inflammation.
• DSP/FLNC (NDLVC): Ring-like subepicardial LV LGE.
• Iron overload: Myocardial T2* <20 ms; <10 ms indicates severe loading.

💡 Clinical / MRCP Pearl: Native T1 is high in amyloid but low in Fabry — useful when an older patient with LVH has an equivocal work-up.

↑ Chapter index

3.12 Genetic Testing and Family Screening

Cardiomyopathy care is family medicine as well as individual diagnosis. In England, testing is commissioned through the NHS Genomic Medicine Service and inherited cardiac conditions (ICC) clinics.

• Who to test: Offer phenotype-directed panel testing to the affected individual (proband) with pre- and post-test counselling; the diagnostic yield is highest in HCM, ARVC and familial DCM.
• Cascade testing: When a pathogenic or likely pathogenic variant is identified, offer predictive testing to at-risk relatives; those without the variant can usually be discharged from surveillance.
• Variant of uncertain significance (VUS): Must not be used for predictive testing or to discharge relatives; classification may change with time.
• Clinical screening: First-degree relatives receive ECG and echo (± CMR), typically starting in childhood for HCM and ARVC.
• Surveillance intervals: Genotype-positive, phenotype-negative relatives are typically reviewed every 1–3 years in childhood and adolescence and every 3–5 years in adulthood, sooner for high-risk genes.
• Implications of a result: Insurance (the UK Code on Genetic Testing and Insurance limits use of predictive results), reproductive options (including pre-implantation genetic testing) and psychological support.

💡 Clinical / MRCP Pearl: A negative gene panel does not exclude inherited disease, and an unaffected relative may develop disease later because penetrance is age-dependent.

↑ Chapter index

3.13 Endomyocardial Biopsy

Endomyocardial biopsy (EMB) is reserved for cases where histology changes urgent management.

• Main indications: Unexplained new heart failure with haemodynamic compromise, ventricular arrhythmia or high-grade AV block not responding to treatment — especially suspected giant-cell, eosinophilic or sarcoid myocarditis.
• Infiltration: Amyloid typing when non-invasive criteria are not met; storage disease when genetics are inconclusive.
• Technique: Usually RV septal samples via the jugular or femoral vein; multiple samples reduce sampling error in patchy disease.
• Analysis: Histology, immunohistochemistry, Congo red with mass spectrometry for amyloid, and viral PCR.
• Risks: Perforation and tamponade, tricuspid injury, arrhythmia; complication rates are low in experienced centres.

💡 Clinical / MRCP Pearl: A negative biopsy does not exclude patchy diseases such as sarcoidosis; biopsy of an accessible extracardiac site (lymph node, skin) may give the diagnosis more safely.

↑ Chapter index

3.14 Dilated Cardiomyopathy (DCM)

DCM is LV or biventricular dilatation with global systolic dysfunction (LVEF <50%) not explained by coronary disease or abnormal loading. It is the commonest cardiomyopathy causing heart failure and the leading indication for heart transplantation.

• Presentation: Progressive breathlessness, fatigue, orthopnoea, oedema, AF, ventricular ectopy, thromboembolism or acute decompensation; sometimes found incidentally.
• Genetic: TTN truncating variants (commonest; often responds to therapy), LMNA (conduction disease, AF, high SCD risk), FLNC, RBM20, DSP, BAG3, PLN.
• Acquired: Post-myocarditis, alcohol, chemotherapy, tachycardia, peripartum, endocrine and nutritional causes (each has its own section below).
• Examination: Displaced apex, S3, functional MR murmur, raised JVP and oedema.
• Investigations: Echo confirms the phenotype; exclude coronary disease; CMR for mid-wall LGE; Holter; TFTs, ferritin, CK; genetic testing if familial, young, conduction disease or arrhythmia.
• Red flags for high-risk genotype: AV block or PR prolongation, early AF, raised CK or skeletal myopathy, ventricular arrhythmia out of proportion to EF, family SCD.

💡 Clinical / MRCP Pearl: DCM is not synonymous with irreversible disease. Many patients improve markedly with guideline therapy, control of tachycardia or removal of a toxin.

↑ Chapter index

3.15 DCM: Management and Prognosis

Separate relief of congestion from disease modification and arrhythmic protection.

• Disease-modifying therapy: The four foundational HFrEF drug classes — ACE inhibitor (or sacubitril/valsartan), evidence-based beta blocker, MRA and SGLT2 inhibitor — introduced early and titrated.
• Congestion: Loop diuretic titrated to the lowest dose that maintains euvolaemia.
• Additional options: Ivabradine (sinus rhythm, heart rate ≥75/min, LVEF ≤35%), IV iron for iron deficiency, hydralazine/nitrate where ACE inhibitor/ARB/ARNI cannot be used.
• Cause-specific: Rate or rhythm control of AF; ablation of high-burden PVCs; abstinence from alcohol; withdrawal of cardiotoxins; immunosuppression only for proven immune-mediated disease.
• Devices: ICD and CRT by EF, QRS and NYHA class (NICE TA314); high-risk genotypes such as LMNA may justify an ICD with EF >35%.
• Advanced disease: Early referral for transplant or LVAD assessment; palliative care in parallel with active treatment.
• Recovered EF: Continue therapy — withdrawal frequently leads to relapse (TRED-HF).

💡 Clinical / MRCP Pearl: The UK TRED-HF trial showed that about 40% of patients with recovered DCM relapsed within 6 months of stopping treatment — "recovery" is usually remission.

↑ Chapter index

3.16 Hypertrophic Cardiomyopathy (HCM)

In adults, HCM is diagnosed with LV wall thickness ≥15 mm in any segment unexplained by loading conditions; ≥13 mm is sufficient in first-degree relatives of an affected patient or in a genotype-positive individual. In children, a z-score >2–2.5 is used.

• Genetics: Usually autosomal dominant sarcomeric disease (MYBPC3, MYH7 commonest) with variable expressivity and incomplete penetrance.
• Patterns: Asymmetric septal (commonest), apical (more common in Japanese and East Asian populations), concentric, mid-ventricular with apical aneurysm.
• Obstructive HCM: LVOT gradient ≥30 mmHg at rest or with provocation, present in about two-thirds of patients.
• Non-obstructive HCM: Symptoms from diastolic dysfunction, microvascular ischaemia and arrhythmia.
• End-stage ("burnt-out") HCM: LVEF <50% with wall thinning and dilatation in a minority — high risk of heart failure and SCD.
• Phenocopies to exclude: Hypertension, aortic stenosis, athlete's heart, ATTR amyloid, Fabry, Danon, PRKAG2, Friedreich's ataxia, Noonan syndrome (children), mitochondrial disease.

💡 Clinical / MRCP Pearl: Marked LVH in an older man with carpal tunnel syndrome, low ECG voltage or a raised troponin should not be labelled sarcomeric HCM until ATTR amyloid is excluded.

↑ Chapter index

3.17 HCM: Dynamic LVOT Obstruction

Obstruction in HCM is a dynamic haemodynamic phenomenon, not a fixed narrowing.

• Mechanism: A narrowed outflow tract and abnormal mitral apparatus allow systolic flow to drag the anterior mitral leaflet towards the septum (SAM), narrowing the LVOT and causing posteriorly directed MR.
• Thresholds: Peak gradient ≥30 mmHg defines obstruction; ≥50 mmHg is haemodynamically significant and the usual threshold for septal reduction or myosin inhibitors in symptomatic patients.
• Worse with: ↓ preload (standing, Valsalva, dehydration, diuretics, nitrates), ↓ afterload (vasodilators, dihydropyridines, PDE5 inhibitors), ↑ contractility (inotropes, digoxin, exertion) and tachycardia.
• Better with: ↑ preload (squatting, leg raising, fluids), ↑ afterload (handgrip, phenylephrine), ↓ contractility (beta blockers) and slower heart rates.
• Consequences: Exertional angina, dyspnoea, presyncope, post-exertional or post-prandial syncope, MR and occasionally shock.
• Acute hypotension: Give IV fluid and a pure alpha-agonist (phenylephrine or metaraminol), consider IV beta blocker; avoid inotropes and vasodilators.

💡 Clinical / MRCP Pearl: The HCM murmur gets louder on standing or Valsalva and softer on squatting or handgrip — the opposite of aortic stenosis.

↑ Chapter index

3.18 HCM: Clinical Features and Examination

Exertional symptoms, a family history and an unusual dynamic systolic murmur should prompt echocardiography.

• Symptoms: Exertional dyspnoea (commonest), chest pain, presyncope, syncope, palpitations; many patients are asymptomatic.
• Pulse: Brisk, "jerky" upstroke; may be bisferiens with obstruction.
• Apex: Forceful, sustained, sometimes double impulse (palpable atrial contraction).
• Heart sounds: S4 (absent in AF); reversed splitting of S2 with severe obstruction.
• Murmurs: Harsh crescendo–decrescendo systolic murmur at the left sternal edge not radiating to the carotids; pansystolic MR murmur at the apex.
• ECG: Abnormal in over 90% — LVH, Q waves, T-wave inversion, LA enlargement; giant T-wave inversion in apical HCM.
• Imaging: Echo for gradient, SAM and MR; CMR for apical disease, aneurysm, LGE extent and phenocopies.

💡 Clinical / MRCP Pearl: Exertional syncope in HCM may be due to LVOT obstruction, an abnormal vascular response or VT. Treat it as a high-risk symptom until proven otherwise.

↑ Chapter index

3.19 HCM: Symptom Treatment and Septal Reduction

Management depends first on whether haemodynamically important LVOT obstruction is present.

• First-line (obstructive): Non-vasodilating beta blocker (e.g. bisoprolol, propranolol), titrated to symptoms and heart rate.
• Alternative: Verapamil or diltiazem if beta blockers are not tolerated; caution with very high gradients, hypotension or severe pulmonary hypertension.
• Second-line: Add disopyramide (negative inotrope; QT and anticholinergic monitoring) or mavacamten, a cardiac myosin inhibitor (NICE TA913: add-on for symptomatic NYHA II–III obstructive HCM).
• Septal reduction therapy: Surgical myectomy (preferred if concomitant mitral or other surgery needed) or alcohol septal ablation at an experienced centre, for gradient ≥50 mmHg and limiting symptoms despite medical therapy. Complete heart block requiring pacing is a recognised complication.
• Avoid: Dehydration, high-dose diuretics, nitrates, dihydropyridines, ACE inhibitors and digoxin in symptomatic obstruction.
• Non-obstructive HCM: Beta blocker or verapamil/diltiazem for angina or dyspnoea; cautious diuretics for congestion; HFrEF therapy if EF falls below 50%.
• Advanced disease: Transplant assessment for refractory heart failure (including end-stage HCM).

💡 Clinical / MRCP Pearl: Obstruction can coexist with a normal or high EF. Giving a potent inotrope for hypotension in obstructive HCM worsens the gradient and reduces forward output.

↑ Chapter index

3.20 HCM: Sudden Death Risk and Atrial Fibrillation

Sudden-death prevention and thromboembolism prevention require separate, dedicated assessment.

• Secondary prevention: ICD recommended after VF arrest or haemodynamically significant sustained VT.
• HCM Risk-SCD (ESC): Estimates 5-year SCD risk from age, maximal wall thickness, LA diameter, maximal LVOT gradient, family history of SCD, NSVT and unexplained syncope. <4% low; 4–6% intermediate (ICD may be considered); ≥6% high (ICD should be considered). HCM Risk-Kids is used under 16.
• Risk modifiers: Extensive LGE (≥15% of LV mass), LVEF <50%, apical aneurysm and multiple sarcomeric variants support an ICD in borderline cases.
• Abnormal BP response: Failure of BP to rise during exercise is an additional adverse marker.
• AF: Affects about a quarter of patients; poorly tolerated because the stiff ventricle depends on atrial contraction.
• Anticoagulation: Oral anticoagulation (DOAC first-line) for clinical AF irrespective of CHA₂DS₂-VA score, unless contraindicated.
• Rhythm control: Early cardioversion, amiodarone and catheter ablation are often valuable.

💡 Clinical / MRCP Pearl: An HCM patient with AF needs anticoagulation even with a stroke-risk score of zero — the score underestimates HCM-associated thromboembolism.

↑ Chapter index

3.21 HCM versus Athlete's Heart and Hypertension

A wall thickness of 13–16 mm is a "grey zone" where physiological adaptation and HCM overlap.

• Favours athlete's heart: Symmetrical hypertrophy, LV end-diastolic diameter >55 mm, normal diastolic function (normal e′), no LGE, normal LA size for training load, VO₂max >50 mL/kg/min, regression after 6–12 weeks of detraining.
• Favours HCM: Asymmetric or apical hypertrophy, small LV cavity, SAM or LVOT gradient, reduced e′, LGE, deep T-wave inversion in lateral leads, a family history or a pathogenic variant.
• Ethnicity: Black athletes commonly have greater wall thickness (up to 15 mm) and anterior T-wave inversion in V1–V4 preceded by ST elevation, which can be physiological.
• Sex: Wall thickness >12 mm is unusual in female athletes and should raise concern.
• Hypertensive heart disease: Usually concentric and rarely exceeds 15 mm (higher in Black patients and dialysis); regresses with BP control. Marked asymmetry, SAM or a family history suggests coexisting HCM.
• Aortic stenosis: Concentric LVH with a fixed valvular gradient; remember dual pathology with ATTR amyloid in older patients.

💡 Clinical / MRCP Pearl: Lateral T-wave inversion (V5–V6, I, aVL) is never a normal finding in an athlete and requires imaging including CMR.

↑ Chapter index

3.22 Arrhythmogenic Cardiomyopathy (ARVC)

ARVC is progressive fibrofatty replacement of predominantly RV myocardium, often caused by desmosomal gene variants, producing ventricular arrhythmia, RV dilatation and SCD in young people.

• Presentation: Palpitations, exercise-induced syncope, frequent ectopy, VT or SCD — often before structural abnormalities are obvious; heart failure is a late feature.
• Diagnosis: 2010 Task Force criteria (or the 2020 Padua criteria, which add LV involvement) combine imaging, tissue, ECG, arrhythmia and family/genetic findings into major and minor criteria.
• ECG: T-wave inversion V1–V3 after age 14, epsilon wave, terminal activation delay; >500 PVCs/24 h is a minor criterion.
• Genes: PKP2 commonest; DSP causes left-dominant disease; JUP causes Naxos disease (woolly hair and palmoplantar keratoderma).
• Differentials: Idiopathic RVOT VT (normal ECG and imaging), cardiac sarcoidosis, Brugada syndrome.
• Treatment: Beta blockers; amiodarone, sotalol or flecainide (with beta blocker) for arrhythmia; catheter ablation (often epicardial) for recurrent VT; ICD guided by the ARVC risk calculator or prior arrest/sustained VT.
• Exercise: Avoid high-intensity and competitive sport — endurance exercise accelerates disease and arrhythmia in gene carriers.

💡 Clinical / MRCP Pearl: DSP-related cardiomyopathy may present with recurrent episodes of chest pain, troponin rise and myocarditis-like CMR ("hot phases") — think genetics in recurrent myocarditis.

↑ Chapter index

3.23 Non-dilated LV Cardiomyopathy (NDLVC)

NDLVC describes non-ischaemic LV scar or fatty replacement, with or without wall-motion abnormality, or isolated global hypokinesia without scar, in a non-dilated LV.

• Causes: DSP, FLNC, LMNA, DES, PLN variants; post-myocarditis scar; sarcoidosis.
• Imaging: CMR is essential — ring-like subepicardial or mid-wall LGE with normal or mildly reduced EF.
• Importance: Malignant ventricular arrhythmias can occur despite preserved EF; EF-based ICD criteria underestimate risk.
• Presentation: Palpitations, syncope, VT, family screening, incidental LGE on CMR performed for other reasons.
• Management: Genetic testing, arrhythmia monitoring, genotype-specific ICD decisions, HF therapy if EF falls, and family screening.

💡 Clinical / MRCP Pearl: A young patient with VT, a near-normal echo and ring-like LGE on CMR has NDLVC until proven otherwise — not "idiopathic VT".

↑ Chapter index

3.24 LV Non-compaction (Hypertrabeculation)

Excessive LV trabeculation with deep intertrabecular recesses. The ESC 2023 guideline treats it as a trait ("hypertrabeculation") rather than a separate cardiomyopathy.

• Imaging criteria: Non-compacted to compacted ratio >2.0 in systole on echo (Jenni) or >2.3 in diastole on CMR (Petersen); criteria are non-specific.
• Physiological trabeculation: Common in athletes, pregnancy, sickle cell disease and people of Black African or Caribbean ancestry.
• Pathological context: Matters when accompanied by LV dysfunction, dilatation, a family history or a pathogenic variant (e.g. MYH7, TTN), or with congenital heart or neuromuscular disease.
• Complications: Heart failure, arrhythmia and thromboembolism occur according to the underlying LV function rather than trabeculation itself.
• Management: Treat according to the coexisting phenotype; family screening if familial.

💡 Clinical / MRCP Pearl: "LVNC" on an imaging report should not lead to automatic anticoagulation, sports restriction or ICD implantation without other evidence of risk.

↑ Chapter index

3.25 Restrictive Cardiomyopathy (RCM)

RCM is abnormal myocardial stiffness with impaired ventricular filling and raised venous pressures, often with near-normal LV size and EF early in the disease. It is the least common phenotype but has many specific causes.

• Presentation: Exercise intolerance, prominent right-sided congestion (raised JVP, hepatomegaly, ascites, oedema), AF and thromboembolism.
• Echo/CMR: Biatrial enlargement, non-dilated ventricles, restrictive filling with reduced e′ and cause-specific tissue patterns.
• Infiltrative causes: Amyloid (commonest in the UK), sarcoidosis.
• Storage causes: Haemochromatosis, Fabry, glycogen storage disease.
• Endomyocardial causes: Endomyocardial fibrosis, hypereosinophilic syndrome, radiation, carcinoid (right-sided valves), metastatic disease.
• Idiopathic/familial: Sarcomeric variants (e.g. TNNI3) — rare, more aggressive in children.
• Management: Careful diuresis, rate/rhythm control of AF, anticoagulation for AF, cause-specific therapy and early advanced-HF referral.

💡 Clinical / MRCP Pearl: Preserved EF in RCM does not mean normal output; small stroke volumes make these patients heart-rate dependent and intolerant of both over-diuresis and rate-slowing drugs.

↑ Chapter index

3.26 RCM versus Constrictive Pericarditis

Constrictive pericarditis is a curable mimic of RCM; the distinction is a classic examination and clinical problem.

• History: Constriction follows previous cardiac surgery, radiotherapy, tuberculosis or pericarditis; RCM suggests amyloid, systemic disease or family history.
• Examination: Both may show Kussmaul's sign; a pericardial knock suggests constriction; S3 and MR/TR murmurs are commoner in RCM.
• Imaging: Pericardial thickening (>4 mm) or calcification on CT/CMR favours constriction — though up to a fifth have normal thickness.
• Echo — constriction: Septal bounce, respiratory variation of mitral inflow >25%, preserved or increased medial e′, "annulus reversus", expiratory hepatic vein diastolic flow reversal.
• Echo — restriction: Reduced e′ (typically <6–8 cm/s), little respiratory variation, marked biatrial enlargement.
• Biomarkers: NT-proBNP is usually much higher in RCM than in constriction.
• Catheterisation: Constriction shows equalised diastolic pressures and dynamic respiratory discordance of LV and RV systolic pressures; RCM shows concordance, LVEDP exceeding RVEDP by >5 mmHg and higher pulmonary pressures.
• Treatment: Pericardiectomy for chronic constriction; cause-specific therapy for RCM.

💡 Clinical / MRCP Pearl: Ventricular interdependence (respiratory discordance) is the hallmark of constriction; it is absent in restriction because the problem is in the myocardium, not the pericardial "box".

↑ Chapter index

3.27 Ischaemic Cardiomyopathy

LV systolic dysfunction caused by coronary disease — the commonest cause of HFrEF in the UK. It is not a primary cardiomyopathy but must be excluded in every new presentation.

• Mechanisms: Infarction with scar and remodelling, plus hibernating myocardium (chronically underperfused but viable).
• Clues: Risk factors, previous MI, angina, regional wall-motion abnormality in a coronary territory, Q waves.
• Investigations: CT coronary angiography or invasive angiography; CMR for subendocardial/transmural LGE and viability; stress imaging.
• Revascularisation: CABG improves long-term survival in suitable patients (STICH/STICHES at 10 years); PCI did not reduce death or HF hospitalisation in stable ischaemic LV dysfunction (UK REVIVED-BCIS2 trial).
• Treatment: Full HFrEF therapy, secondary prevention (antiplatelet, statin), ICD/CRT by NICE criteria.

💡 Clinical / MRCP Pearl: Mid-wall LGE indicates non-ischaemic disease even in a patient with coronary risk factors — the two can coexist, so match the scar pattern to the coronary anatomy.

↑ Chapter index

3.28 ATTR Cardiac Amyloidosis

Transthyretin amyloid cardiomyopathy (ATTR-CM) results from deposition of misfolded transthyretin, a liver-produced transport protein. It is either wild-type (age-related, mainly men over 70) or hereditary (variant TTR, autosomal dominant). It typically presents as HFpEF or conduction disease.

• Red flags: HFpEF with LV wall ≥12 mm, intolerance of antihypertensives (previously hypertensive, now hypotensive), disproportionately high NT-proBNP and persistently raised troponin, AF, conduction disease, low-flow low-gradient aortic stenosis.
• Extracardiac clues: Bilateral carpal tunnel syndrome (often 5–10 years earlier), lumbar spinal stenosis, spontaneous distal biceps tendon rupture, peripheral and autonomic neuropathy.
• UK variants: V122I (p.Val142Ile) in about 3–4% of people of African-Caribbean ancestry; T60A (p.Thr80Ala) in people with Irish (especially north-west Irish) ancestry, with mixed cardiac and neuropathic disease.
• Echo/CMR: Thick walls, biatrial enlargement, apical-sparing strain, diffuse LGE, high native T1 and ECV.
• Non-biopsy diagnosis: Bone scintigraphy (DPD, PYP or HMDP) showing Perugini grade 2–3 myocardial uptake plus no monoclonal protein (normal serum free light chain ratio and negative serum and urine immunofixation) is diagnostic. Then perform TTR genotyping.
• Disease-modifying therapy: TTR stabilisers — tafamidis (NICE TA984) and acoramidis (TA1121); TTR silencer — vutrisiran, a subcutaneous siRNA every 3 months (TA1115). Specialist-led, typically via the National Amyloidosis Centre network.
• Supportive care: Loop diuretics; avoid or use cautiously beta blockers, ACE inhibitors and rate-limiting calcium channel blockers; anticoagulate AF regardless of risk score; pacing for conduction disease.

💡 Clinical / MRCP Pearl: Treatments slow progression rather than remove deposits, so outcomes depend on early recognition — ATTR is now a treatable cause of "HFpEF in an older man".

↑ Chapter index

3.29 AL Cardiac Amyloidosis

AL amyloidosis is deposition of monoclonal immunoglobulin light chains produced by a plasma-cell clone. Light chains are directly cardiotoxic, so cardiac AL is rapidly progressive and a haematological emergency.

• Clinical features: Rapidly progressive restrictive heart failure, postural hypotension, nephrotic syndrome, peripheral and autonomic neuropathy, weight loss, macroglossia, periorbital purpura, hepatomegaly.
• Investigations: Serum free light chains and ratio, serum and urine immunofixation, NT-proBNP, troponin, eGFR, urine albumin:creatinine ratio, bone marrow examination.
• Confirm the type: Tissue biopsy (fat pad, bone marrow, kidney or heart) with Congo red apple-green birefringence and amyloid typing (immunohistochemistry or mass spectrometry).
• Staging: Mayo staging uses NT-proBNP and troponin (± light-chain difference); very high NT-proBNP indicates very poor prognosis.
• Treatment: Urgent plasma-cell-directed therapy — daratumumab with cyclophosphamide, bortezomib and dexamethasone (Dara-CyBorD) is standard first-line; autologous stem cell transplant in selected patients.
• Supportive: Cautious diuresis; midodrine for postural hypotension; avoid digoxin (binds amyloid fibrils — toxicity) and poorly tolerated vasodilators.

💡 Clinical / MRCP Pearl: Positive bone scintigraphy does not exclude AL — some AL patients have uptake. Always complete the light-chain screen first; missing AL delays life-saving chemotherapy.

↑ Chapter index

3.30 Cardiac Sarcoidosis

Non-caseating granulomatous inflammation affects the myocardium and conduction system. Clinical cardiac involvement occurs in about 5% of patients with systemic sarcoidosis, but is found in about a quarter at autopsy; it can also occur in isolation.

• Presentation: High-grade AV block in a younger adult, VT, syncope, heart failure or SCD.
• Clues: Known pulmonary sarcoid, bilateral hilar lymphadenopathy, uveitis, erythema nodosum, lupus pernio, hypercalcaemia.
• Imaging: CMR shows patchy multifocal LGE (basal septum, RV side, subepicardial); FDG-PET (after carbohydrate-free dietary preparation) shows active inflammation.
• Tissue diagnosis: EMB has low sensitivity because disease is patchy; biopsy of extracardiac tissue (EBUS lymph node) plus typical cardiac imaging is usually accepted.
• Treatment: Corticosteroids (e.g. prednisolone 30–40 mg daily, tapered) for active disease, with methotrexate as a steroid-sparing agent and anti-TNF therapy for refractory cases.
• Devices: ICD rather than a simple pacemaker is generally preferred when pacing is needed, and recommended after sustained VT or with LVEF ≤35%.
• Monitoring: Serial FDG-PET to guide immunosuppression; rhythm monitoring.

💡 Clinical / MRCP Pearl: Unexplained complete heart block under 60 should prompt CMR and screening for sarcoidosis, LMNA disease and Lyme carditis before a pacemaker is fitted.

↑ Chapter index

3.31 Haemochromatosis and Iron Overload

Myocardial iron loading causes initially restrictive then dilated cardiomyopathy with arrhythmia. It is one of the most reversible cardiomyopathies if treated early.

• Causes: Hereditary haemochromatosis (HFE C282Y homozygosity, common in people of Northern European and Irish ancestry); transfusional iron overload (thalassaemia major, sickle cell disease, myelodysplasia).
• Clinical clues: Diabetes, skin pigmentation, liver disease, arthropathy (2nd/3rd MCP joints), hypogonadism.
• Investigations: Transferrin saturation and ferritin; HFE genotyping; CMR myocardial T2* (<20 ms indicates iron; <10 ms severe, high risk of heart failure).
• Hereditary disease treatment: Venesection to deplete iron stores (target ferritin around 50 µg/L), then maintenance.
• Transfusional overload: Chelation with desferrioxamine, deferasirox or deferiprone; intensified combination chelation for cardiac iron.
• Heart failure care: Standard therapy plus arrhythmia management; cardiac function can recover substantially with iron removal.

💡 Clinical / MRCP Pearl: Deferiprone has the best myocardial iron penetration but causes agranulocytosis — weekly FBC monitoring is required.

↑ Chapter index

3.32 Anderson–Fabry Disease

X-linked lysosomal storage disorder caused by GLA variants and deficiency of alpha-galactosidase A, with accumulation of globotriaosylceramide (Gb3) in the heart, kidneys, nerves and vessels. It accounts for around 1% of patients labelled as HCM.

• Cardiac: Concentric LVH (HCM phenocopy), short PR, conduction disease, AF, VT, chest pain.
• Extracardiac: Childhood acroparaesthesia and neuropathic pain, angiokeratomas ("bathing-trunk" distribution), hypohidrosis, cornea verticillata, proteinuria and CKD, early stroke, hearing loss.
• Females: Can be significantly affected because of X-inactivation; enzyme activity may be normal.
• Diagnosis: Low alpha-Gal A activity in males; GLA genetic testing is essential in females; plasma lyso-Gb3 supports diagnosis and monitoring.
• CMR: Low native T1 and basal inferolateral mid-wall LGE.
• Treatment: Enzyme replacement therapy (agalsidase alfa or beta, pegunigalsidase alfa) or oral migalastat for amenable variants, through specialist lysosomal storage disorder centres.

💡 Clinical / MRCP Pearl: Cornea verticillata also occurs with amiodarone — check the drug history before attributing it to Fabry.

↑ Chapter index

3.33 Danon Disease

X-linked dominant glycogen/autophagic storage disease caused by LAMP2 variants.

• Males: Massive LVH in adolescence, pre-excitation (WPW pattern), skeletal myopathy, raised CK, learning difficulties and retinopathy; rapid progression to end-stage heart failure by the 20s.
• Females: Later onset, often DCM, with fewer extracardiac features.
• Clues: Extreme wall thickness (often >30 mm), very high ECG voltages, raised CK and liver transaminases.
• Management: ICD for SCD risk; early referral for transplantation; gene therapy is under investigation.

💡 Clinical / MRCP Pearl: A teenage boy with massive LVH, pre-excitation and a raised CK has Danon disease until proven otherwise.

↑ Chapter index

3.34 PRKAG2 Syndrome

Autosomal dominant glycogen storage cardiomyopathy caused by variants in the gamma-2 subunit of AMP-activated protein kinase.

• Phenotype: LVH mimicking HCM, ventricular pre-excitation, progressive conduction disease and sinus node dysfunction.
• Presentation: Palpitations, AF, syncope from AV block or rapidly conducted pre-excited AF.
• Management: Pacing for conduction disease, ablation of accessory pathways where relevant, HF therapy, family screening.
• Prognosis: Generally better than Danon disease but frequently requires a pacemaker.

💡 Clinical / MRCP Pearl: LVH + pre-excitation + progressive AV block in a young adult with autosomal dominant inheritance points to PRKAG2.

↑ Chapter index

3.35 Acute Myocarditis

Myocarditis is inflammation of the myocardium. Most viral cases recover, but a minority develop chronic DCM or life-threatening arrhythmia. The ESC 2025 guideline groups myocarditis and pericarditis as inflammatory myopericardial syndromes.

• Causes: Viruses (parvovirus B19, HHV-6, enteroviruses such as Coxsackie B, SARS-CoV-2, influenza); mRNA vaccines (young males, within days of the second dose, usually mild); drugs (clozapine); autoimmune disease (SLE, sarcoid); bacterial (diphtheria, Lyme).
• Presentation: Chest pain mimicking ACS, dyspnoea, palpitations, AV block, VT or cardiogenic shock (fulminant myocarditis), often after a viral prodrome.
• Investigations: ECG, troponin, CRP, NT-proBNP, echo; coronary exclusion as needed; CMR using Lake Louise criteria (oedema plus non-ischaemic LGE).
• High-risk features: Shock, LVEF <50%, sustained VT, high-grade AV block — admit to a centre with mechanical support and consider EMB.
• Management: Monitoring, HF therapy for LV dysfunction, avoid NSAIDs if there is LV dysfunction, treat arrhythmias; immunosuppression only for biopsy-proven immune-mediated (virus-negative) disease.
• Exercise: Restrict strenuous and competitive sport for several months (traditionally 3–6) until reassessment with ECG, Holter, echo and often CMR.

💡 Clinical / MRCP Pearl: Clozapine myocarditis usually occurs within the first 2 months; fever, tachycardia and a rising troponin or CRP during titration should prompt urgent review and stopping the drug.

↑ Chapter index

3.36 Giant-cell Myocarditis

A rare, rapidly fatal autoimmune T-cell myocarditis with multinucleated giant cells and myocyte necrosis.

• Typical patient: Young to middle-aged adult, sometimes with thymoma, inflammatory bowel disease or other autoimmune disease.
• Presentation: Rapidly progressive heart failure over days to weeks, refractory VT and high-grade AV block despite standard therapy.
• Diagnosis: Endomyocardial biopsy — the key indication for EMB.
• Treatment: Combined immunosuppression (high-dose corticosteroid plus ciclosporin or tacrolimus, ± anti-thymocyte globulin) improves survival.
• Support: Temporary mechanical circulatory support, ICD and transplantation; recurrence in the transplanted heart is possible.

💡 Clinical / MRCP Pearl: Heart failure + VT + heart block that fails to respond to standard care within 1–2 weeks is the classic trigger for biopsy to look for giant-cell myocarditis.

↑ Chapter index

3.37 Immune Checkpoint Inhibitor Myocarditis

An immune-related adverse event of PD-1, PD-L1 and CTLA-4 inhibitors (e.g. pembrolizumab, nivolumab, ipilimumab). Uncommon (about 1%) but with mortality of up to a quarter to a half in fulminant cases.

• Timing: Usually within the first 3 months; risk is highest with combination therapy.
• Overlap syndrome: Frequently coexists with myositis and myasthenia-like features (ptosis, diplopia, bulbar weakness, respiratory muscle weakness); CK is often very high.
• Investigations: Troponin (screening is often done before each early cycle), ECG (conduction disease, arrhythmia), echo (EF may be normal), CMR, EMB if uncertain.
• Treatment: Stop the checkpoint inhibitor; IV methylprednisolone 500–1000 mg daily for 3–5 days, then oral steroid taper; second-line agents (e.g. abatacept, mycophenolate, ruxolitinib) for steroid-refractory disease.
• Monitoring: Serial troponin and ECG — conduction disease can progress suddenly.

💡 Clinical / MRCP Pearl: A patient on immunotherapy with ptosis and weakness needs a troponin and ECG — the "myositis–myasthenia–myocarditis" triad has a high mortality.

↑ Chapter index

3.38 Eosinophilic (Löffler) Endomyocarditis

Eosinophil-mediated endomyocardial damage, typically in temperate climates, progressing through necrotic, thrombotic and fibrotic stages to a restrictive cardiomyopathy.

• Causes: Hypereosinophilic syndrome (eosinophils >1.5 × 10⁹/L), EGPA, drug hypersensitivity (DRESS), parasitic infection, eosinophilic leukaemia.
• Features: Heart failure, mural thrombus at the ventricular apices, embolic events, AV valve regurgitation.
• Investigations: FBC film, stool and serology for parasites, ANCA, FIP1L1-PDGFRA testing, echo/CMR (apical obliteration, subendocardial LGE, thrombus), EMB.
• Treatment: High-dose corticosteroids; imatinib for FIP1L1-PDGFRA-positive disease; anti-IL-5 therapy (mepolizumab) in selected cases; anticoagulation for thrombus; surgery for late fibrosis or valve disease.

💡 Clinical / MRCP Pearl: Always look at the eosinophil count in unexplained myocarditis or apical LV thrombus with normal wall motion.

↑ Chapter index

3.39 Endomyocardial Fibrosis

Endomyocardial fibrosis (EMF) is fibrous obliteration of the ventricular apices and inflow tracts, seen mainly in children and young adults in tropical Africa, South Asia and South America. It may represent the late stage of eosinophilic disease.

• Features: Restrictive physiology, right-sided congestion with massive ascites, AV valve regurgitation, giant atria, AF and thromboembolism.
• Imaging: Apical obliteration with preserved systolic function; calcified fibrosis.
• Treatment: Diuretics, AF control and anticoagulation; surgical endocardiectomy with valve repair or replacement in selected patients.
• UK relevance: Consider in migrants from endemic regions presenting with restrictive physiology.

💡 Clinical / MRCP Pearl: Apical obliteration on echo with a normal-sized LV and huge atria suggests endomyocardial disease rather than amyloid.

↑ Chapter index

3.40 Chagas Cardiomyopathy

Chronic infection with Trypanosoma cruzi, transmitted by triatomine ("kissing") bugs, blood transfusion, organ transplantation or vertically. It is the commonest cause of non-ischaemic cardiomyopathy in Latin America.

• Course: Mild acute infection, then a long indeterminate phase; 20–30% develop cardiac disease decades later.
• Cardiac features: RBBB with left anterior fascicular block, AV block, VT, LV apical aneurysm with thrombus, DCM and SCD.
• GI disease: Megaoesophagus and megacolon.
• Diagnosis: Two different positive serological tests in chronic disease.
• Treatment: Benznidazole or nifurtimox in acute, congenital and early chronic disease (limited benefit in established cardiomyopathy); HF therapy, amiodarone, ICD and anticoagulation for aneurysm or thrombus.
• UK relevance: Migrants from Latin America; UK blood services screen at-risk donors.