The left ventricle is a thick-walled muscular pump. Its wall consists of three layers:

1. Endocardium (innermost, lines the cavity)
2. Myocardium (the muscle itself — cardiomyocytes arranged in spiral bundles)
3. Epicardium (outermost, continuous with pericardium)

Cardiomyocytes are connected end-to-end by intercalated discs (containing gap junctions for electrical coupling and desmosomes for mechanical coupling). The cytoskeleton of each myocyte includes:

• Sarcomere proteins (actin, myosin, troponins, titin) → the contractile machinery
• Cytoskeletal proteins (desmin, dystrophin, lamin A/C) → structural scaffolding connecting the sarcomere to the sarcolemma (cell membrane) and nucleus
• Nuclear envelope proteins (lamin A/C) → maintain nuclear shape and gene regulation

In DCM, the fundamental problem is loss of effective myocardial contractility:

1. Cardiomyocytes are damaged, die, or become dysfunctional
2. The ventricle cannot generate adequate systolic pressure
3. The residual volume at end-systole increases → the ventricle dilates (Frank-Starling mechanism initially compensates)
4. Wall stress increases by Laplace's Law: Wall stress = (Pressure × Radius) / (2 × Wall thickness)
   • As radius ↑ and wall thickness stays the same or ↓ → wall stress ↑ dramatically
   • This further impairs contraction and increases myocardial oxygen demand
5. The mitral valve annulus dilates with the LV → functional mitral regurgitation (the valve leaflets are intrinsically normal but can no longer coapt)
6. Eventually, biventricular dilatation may occur

"When visualizing a dilated left ventricle, and a reduced LVEF that cannot be explained by the severity of coronary artery disease, valvular heart disease, congenital heart disease, or hypertension" — that is DCM ^[1].

DCM is a very clinically heterogeneous disease, as it can be caused by an array of different aetiologies ^[1]:

┌─────────────────────────────────────────────┐
│        CAUSES OF DILATED CARDIOMYOPATHY     │
├─────────────────────────────────────────────┤
│ 1. Idiopathic (~50%)                        │
│    └─ 50% of "idiopathic" have +ve FHx      │
│       → Familial DCM (~15-30% of all DCM)   │
│ 2. Infectious (9%) — viral myocarditis      │
│ 3. Ischaemic (7%) — occult CAD              │
│ 4. Toxic — alcohol, anthracyclines, cocaine  │
│ 5. Metabolic/Endocrine                      │
│ 6. Autoimmune                               │
│ 7. Infiltrative — haemochromatosis          │
│ 8. Neuromuscular — Duchenne, Becker, MyD    │
│ 9. Peripartum                               │
│10. Tachycardia-mediated                     │
│11. Others — ESRF on HD, deficiencies        │
└─────────────────────────────────────────────┘

Three key factors in the pathogenesis of DCM ^[1]:

1. Genetic factors → altered gene products (e.g. truncated titin, defective lamin A/C, absent dystrophin)
2. Alterations of the immune system (autoantibodies against cardiac myosin, β-adrenergic receptors, mitochondrial proteins)
3. Viral infection / myocarditis + viral persistence (direct cytopathic effect + immune-mediated damage)

"Not an all-or-none — i.e. genetic factors alone are enough to cause DCM" ^[1]. These factors interact: a genetically predisposed individual may develop overt DCM after a viral trigger, while another with the same mutation may never manifest disease (variable penetrance).

• Idiopathic DCM constitutes ~35–50% of all DCM ^[1][3].
• However, 50% of patients with idiopathic DCM have a positive family history → so not truly idiopathic ^[1].
• Familial DCM = 15–30% of all DCM ^[1][3].
• Diagnostic criteria for familial DCM ^[1]:
  • ≥2 first- or second-degree relatives with DCM, OR
  • A first-degree relative who had sudden death at < 50 y/o with DCM clinically proven following autopsy

Onset of familial DCM: ~20 to 50 years old ^[1].

Genetics:

• > 90% autosomal dominant inheritance ^[1][3]

• 40 genes implicated; most commonly affect myocyte cytoskeletal proteins ^[3]

• Most common gene: Titin (TTN) — 20–25% of familial DCM cases ^[1]
• Lamin A/C (LMNA) — 6% of cases, but more important in Chinese ^[1]
  • LMNA mutations are associated with conduction disease and malignant arrhythmias → higher risk of sudden cardiac death
• Other genes: MYH7, TNNT2, DES (desmin), SCN5A, PLN (phospholamban), RBM20
• May be part of a greater syndrome ^[1]:
  • Duchenne muscular dystrophy (X-linked, dystrophin gene, Xp21) → virtually all boys develop DCM by teens
  • Becker muscular dystrophy (partial dystrophin expression, milder course)
  • Myotonic dystrophy (CTG repeat expansion, DMPK gene)
  • Mitochondrial diseases

Three challenges preventing diagnosis of familial DCM ^[1]:

1. Incomplete family history (many people in HK waive autopsy)
2. Variable age-related penetrance (some present young, some old, some never)
3. Reduced penetrance (carrier with normal echo at one point may develop DCM later)

This is a critically important pathway, especially for exams:

Common viral infections known to cause DCM ^[1]:

• Enteroviruses, especially Coxsackie A/B
• Herpesviruses / adenoviruses / parvovirus B19

The sequence: Viral infection → myocarditis → viral persistence causing chronic cardiac disease → chronic dilated cardiomyopathy ^[1].

Pathophysiology in three phases:

"Idiopathic dilated cardiomyopathy is believed to be a sequelae of myocarditis" — "Usually viral, creating immune response" ^[5].

• Results from direct ethanol toxicity to cardiomyocytes and its metabolite acetaldehyde
• Typically requires > 80 g/day of alcohol for > 5 years (though threshold varies)
• Mechanism: ethanol disrupts mitochondrial function, increases oxidative stress, impairs calcium handling, causes myocyte apoptosis and fibrosis
• Alcohol has a J-curve relationship with cardiovascular disease: mild intake may decrease risk (HDL-raising, anticoagulant effects), but higher levels → direct cytotoxicity ^[6]
• Associated cardiovascular conditions: CAD, atrial fibrillation, alcoholic dilated cardiomyopathy, hypertension ^[6]
• Partially reversible with abstinence (LVEF may improve by 10–15% over 6–12 months)

• Anthracyclines (doxorubicin, daunorubicin, epirubicin) → dose-dependent, cumulative cardiotoxicity
• Mechanism: generation of free radicals → oxidative damage to cardiomyocyte mitochondria and DNA; topoisomerase 2β inhibition in cardiomyocytes; iron-mediated Fenton reaction
• Risk increases significantly above cumulative doxorubicin dose > 400–450 mg/m²
• May present years to decades after chemotherapy — very relevant for childhood cancer survivors ^[4]
• Prevention: dose limitation, dexrazoxane (iron chelator that reduces free radical formation), liposomal formulations

• DCM developing in the last month of pregnancy to 5 months postpartum in a woman without prior cardiac disease
• Incidence: ~1:1000 to 1:4000 pregnancies (varies widely by population; higher in Africa and Haiti)
• Pathophysiology: incompletely understood; likely involves:
  • Abnormal prolactin cleavage → 16-kDa prolactin fragment → antiangiogenic and proapoptotic to cardiomyocytes
  • Autoimmune factors, oxidative stress, genetic susceptibility (TTN mutations found in ~15%)
• ~50% recover LVEF within 6 months; ~25% progress to severe DCM; mortality ~5–10%
• Subsequent pregnancies carry risk of recurrence, especially if LVEF has not normalised

• Sustained rapid heart rate (typically > 100 bpm for weeks to months) → progressive LV dysfunction
• Mechanisms: chronic calcium overload, energy depletion, neurohormonal activation, myocyte remodelling
• Reversible with rate or rhythm control
• Common culprits: uncontrolled AF, atrial flutter, incessant SVT, frequent PVCs (> 15–20% PVC burden)

• Haemochromatosis (iron overload → preferential deposition in ventricle → restrictive then dilated pattern; important in transfusion-dependent thalassaemia in HK)
• Sarcoidosis (granulomatous infiltration of myocardium → conduction disease + DCM)
• HIV cardiomyopathy (direct viral injury + opportunistic infections + ART toxicity)
• Thyroid disease (thyrotoxicosis → high-output state → eventually dilated; hypothyroidism → pericardial effusion + myocardial oedema)
• Nutritional deficiencies: thiamine (wet beriberi), selenium (Keshan disease), carnitine

Four morphological types of cardiomyopathy ^[1][2]:

"Systolic dysfunction is characteristic of dilated cardiomyopathy" ^[1]. "Diastolic dysfunction is characteristic of HCM and RCM" ^[1].

Can also be classified by aetiology as above:

• Primary (genetic/idiopathic/familial) vs. Secondary (acquired)
• When all identifiable causes are excluded → idiopathic DCM

DCM patients who develop heart failure are classified by:

• NYHA Functional Class (I–IV) — based on symptom limitation ^[7]
• ACC/AHA Stages (A–D) — based on structural disease and symptoms ^[7]

DCM may present in several ways ^[3]:

CXR findings of left heart failure correlate with left atrial pressure ^[10]:

Additional CXR findings:

• Cardiomegaly (cardiothoracic ratio > 0.5)
• Pleural effusions (blunting of costophrenic angles)
• Prominent pulmonary arteries (if pulmonary hypertension)

The classic mnemonic for CXR findings of heart failure: Alveolar oedema, B-lines (Kerley B), Cardiomegaly, Diversion (upper lobe), Effusion (pleural).

• The most important mimic to exclude — and in many populations, the most common cause of LV dilatation and systolic dysfunction
• Why it mimics DCM: Extensive myocardial infarction (especially anterior STEMI from LAD occlusion) → loss of functioning myocardium → LV remodelling and dilatation → reduced EF. The end-result looks identical to DCM on echo.
• Key differentiating features:
  • History of angina, prior MI, or CAD risk factors (smoking, DM, hypertension, dyslipidaemia, family history of premature CAD)
  • Regional wall motion abnormalities on echo (DCM tends to show global hypokinesis; ischaemic cardiomyopathy shows segmental akinesis/dyskinesis corresponding to coronary territories)
  • ECG: pathological Q waves in a coronary territory distribution
  • Coronary angiography (or CT coronary angiogram) is the definitive test to rule out significant CAD ^[1][12]

"Diagnosis requires excluding coronary artery disease via catheterization" ^[10]

• Chronic severe mitral or aortic regurgitation → chronic volume overload → LV dilatation → eventually systolic dysfunction
  • MR: volume overload from regurgitant flow → LV dilates to accommodate increased preload → eventually contractile function fails ^[11]
  • AR: combined volume and pressure overload → massive LV dilatation ("cor bovinum") → late systolic failure
• Key differentiating features:
  • Significant murmur on auscultation (though functional MR from DCM also produces a murmur — the question is: did the valve disease come first, or did the dilatation come first?)
  • Echo: structural valve abnormality (flail leaflet, prolapse, calcification, rheumatic changes) vs. structurally normal valve with annular dilatation
  • Severity of regurgitation disproportionate to degree of LV dilatation suggests primary valve disease

In the Cardiology Interactive Tutorial Case 1: "mitral valve prolapse → mitral regurgitation → volume overload of LV → LV enlargement/dilatation and failure" — this is valvular cardiomyopathy, not primary DCM ^[11]

• Chronic poorly controlled hypertension → LV pressure overload → concentric hypertrophy initially (HFpEF) → but if untreated or with superimposed insults → "further worsening of myocardial ischaemia, may result in dilatation" ^[13] → eccentric remodelling → dilated LV with reduced EF
• Key differentiating features:
  • History of long-standing hypertension, often poorly controlled
  • LVH on ECG or echo
  • Evidence of hypertensive end-organ damage (retinopathy, nephropathy, proteinuria)
  • The degree of hypertension should be "sufficient to explain" the observed dysfunction

• Large left-to-right shunts (VSD, AVSD, PDA) → chronic LV volume overload → LV dilatation ^[9][14]
• In children/adolescents: "Unoperated CHD, repaired or palliated CHD with late ventricular dysfunction" ^[14]
• Key differentiating features:
  • History of childhood cardiac diagnosis/surgery
  • Echo: structural abnormality (septal defect, abnormal great vessel connections)

AOS Paeds Q8: the answer is cardiomyopathy, NOT VSD — "VSD less likely to cause RV failure at this age" (10-year-old). The prior chemotherapy history and displaced apex point to anthracycline-induced DCM ^[4].

• Idiopathic DCM constitutes ~35–50% of all DCM ^[1][15]
• 50% of "idiopathic" DCM has a positive family history → familial DCM ^[1]
• Clues for familial aetiology:
  • Young patient (onset 20–50 years old) ^[1]
  • Family history of DCM, premature sudden cardiac death, heart transplant, pacemaker/ICD
  • Lamin A/C (LMNA) mutation: prominent conduction disease (AV block, AF) + arrhythmias, often before significant dilatation — more important in Chinese ^[1]
  • Neuromuscular features (limb-girdle weakness, calf pseudohypertrophy → think dystrophinopathy)
• Key investigation: Genetic counselling + 3-generation family tree + genetic screening ^[12]

• "Idiopathic dilated cardiomyopathy is believed to be a sequelae of myocarditis — usually viral, creating immune response" ^[5]
• Clues: preceding febrile/flu-like illness weeks to months before HF symptoms; younger patient; elevated inflammatory markers
• Coxsackie B is the classic culprit ^[1][12]
• Key investigation: Cardiac MRI (oedema, LGE in non-ischaemic pattern); endomyocardial biopsy is gold standard (Dallas criteria) but has risk of perforation and is reserved for specific scenarios ^[5][12]
• "Majority of myocarditis has no specific treatment — except for immunosuppressive-susceptible myocarditis (giant cell myocarditis, autoimmune myocarditis)" ^[5]

• Clues: heavy alcohol intake (typically 7–8 drinks/day for > 5 years) ^[15]; other features of alcohol excess (liver disease, macrocytosis, elevated GGT)
• "Ethanol has direct cytotoxic effect on the heart" ^[6]
• Partially reversible with abstinence — this is why identifying it matters
• Also a/w AF, hypertension ^[6]

• Clues: history of cancer treatment with doxorubicin or other anthracyclines; may present years to decades after chemotherapy ^[4][15]
• Trastuzumab (anti-HER2) can also cause cardiomyopathy — typically reversible, non-dose-dependent
• Other drugs: cyclophosphamide, 5-FU, tyrosine kinase inhibitors

• Thyrotoxicosis → high-output state → eventually DCM (hyperthyroid cardiomyopathy)
• Hypothyroidism → pericardial effusion + myocardial dysfunction
• Phaeochromocytoma → catecholamine-mediated cardiomyopathy (catecholamine excess is directly toxic to myocytes)
• Acromegaly → LVH → cardiomyopathy with diastolic HF, but can progress to DCM ^[16]
• Nutritional: thiamine deficiency (wet beriberi) — classically in alcoholics and post-bariatric surgery; selenium deficiency (Keshan disease); carnitine deficiency

• SLE, scleroderma, polymyositis → autoimmune myocarditis → DCM ^[15]
• Sarcoidosis → granulomatous myocardial infiltration → conduction disease + DCM; FDG-PET scan is the key investigation ^[12]
• Giant cell myocarditis → rapidly progressive, high mortality; responds to immunosuppression — one of the rare indications for endomyocardial biopsy ^[5]
• Eosinophilic myocarditis → peripheral eosinophilia, responds to immunosuppression

• Haemochromatosis (iron overload) → iron deposition in myocardium → initially restrictive, then dilated pattern. Extremely relevant in HK for transfusion-dependent thalassaemia patients.
  • Clues: bronze skin, diabetes, hepatomegaly, elevated ferritin/transferrin saturation
  • Cardiac MRI T2 mapping* is the key investigation (T2* < 20 ms indicates cardiac iron loading)
• Amyloidosis → usually restrictive pattern, but can have elements of dilatation
  • "Small complex / low QRS voltages on ECG with a very thickened LV wall → CLASSICAL FOR AMYLOIDOSIS" ^[12]
  • 99m Tc-PYP scan for transthyretin amyloidosis ^[12]

• Duchenne muscular dystrophy → virtually all boys develop DCM; X-linked, dystrophin gene ^[1]
• Becker muscular dystrophy → milder, later onset ^[1]
• Myotonic dystrophy → conduction disease + DCM ^[1]
• Clue: proximal muscle weakness, pseudohypertrophy of calves, Gower's sign, elevated CK

• Clues: DCM developing in last month of pregnancy to 5 months postpartum in a previously well woman
• Risk factors: multiparity, older maternal age, African descent, pre-eclampsia, twin pregnancy
• ~50% recover; risk of recurrence in future pregnancies

• Clues: chronic uncontrolled tachyarrhythmia (persistent AF, incessant SVT, high PVC burden > 15–20%)
• Key feature: LVEF improves dramatically after rate/rhythm control — a reversible cause
• Must be suspected in any patient with new DCM + concurrent tachyarrhythmia

LV end-diastolic volume/diameter > 2 standard deviations from normal according to age- and body-surface-area-corrected nomograms + LVEF < 50% ^[1]

In practical terms:

• LV end-diastolic diameter (LVEDD) > 55 mm in adults (but must be indexed to BSA — LVEDDI > 33 mm/m² in men, > 32 mm/m² in women is dilated)
• LVEF < 50% — though in established DCM, LVEF is typically < 30% ^[2]
• ↑LV mass but with normal or ↓ wall thickness ^[3] — this is key: the ventricle is big and heavy (more total muscle), but the wall is thin relative to the chamber size (because it is stretched out). Compare with HCM where wall thickness is disproportionately ↑.

"A diagnosis of DCM is predicated on a dilated left ventricle and a reduced LVEF that cannot be explained by the severity of coronary artery disease, valvular heart disease, congenital heart disease, or hypertension" ^[1]

This means you must have performed adequate investigation to rule out:

1. Coronary artery disease — via coronary angiography or CT coronary angiogram
2. Valvular heart disease — via echocardiography (any MR/TR should be functional/secondary, not primary)
3. Congenital heart disease — via echocardiography and clinical assessment
4. Hypertension — via BP measurement and assessment of end-organ damage

Only when these four conditions are insufficient to explain the observed LV dysfunction can the label "DCM" be applied.

Familial DCM is diagnosed when ^[1]:

• ≥ 2 first- or second-degree relatives have DCM, OR
• A first-degree relative had sudden death at < 50 years old with DCM clinically proven at autopsy

"Heart failure is a clinical diagnosis → made using the Framingham Criteria" ^[8]

Requires the simultaneous presence of at least 2 major criteria, OR 1 major + 2 minor criteria ^[8]:

When the diagnosis of HF is uncertain, natriuretic peptides are invaluable:

• BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro-BNP) are released from ventricular myocytes in response to wall stretch
• BNP > 400 pg/mL is suggestive of HF; BNP < 100 pg/mL has a strong negative predictive value for HF ^[17]
• NT-proBNP thresholds are age-dependent ^[17]:
  • Age < 50: > 450 pg/mL for HF
  • Age 50–75: > 900 pg/mL for HF
  • Age > 75: > 1800 pg/mL for HF
• Why age-dependent? Older patients have higher baseline natriuretic peptide levels due to age-related decline in renal clearance and increased ventricular stiffness.

Blood tests in DCM serve three purposes: (1) confirm/exclude HF, (2) assess end-organ damage and comorbidities, (3) identify the underlying aetiology.

Investigations for cardiomyopathy: ECG, CXR, ECHO, exercise test / Holter monitoring (look for arrhythmias), coronary angiography (to rule out IHD), endomyocardial biopsy ^[2]

The ECG in DCM is usually abnormal, but there are no specific diagnostic features ^[1]. Its role is to:

1. Detect arrhythmias (AF, VT, conduction disease)
2. Provide clues to the underlying aetiology
3. Guide management (LBBB → CRT candidacy)

CXR provides rapid, bedside assessment of cardiac size and pulmonary congestion.

Echo is the single most important investigation in DCM. It confirms the diagnosis, assesses severity, identifies complications, and helps distinguish DCM from its mimics.

Echocardiographic findings in DCM ^{[2][3][15][20]}:

Cardiac MRI (CMR) has become the second most important imaging modality after echo. Its unique advantage is tissue characterisation — it can tell you not just the structure, but what the tissue is made of.

"Cardiac MRI is going to the forefront" ^[5]

This is not optional. You cannot diagnose DCM without assessing the coronary arteries.

"Diagnosis requires excluding coronary artery disease via catheterization" ^[10]

Indications for invasive coronary angiography in the DCM workup ^[22]:

• Angina or risk factors for CAD in the setting of depressed LVEF
• Non-invasive testing results with high-risk features
• For diagnostic purposes, in the individual in whom the results of non-invasive testing are unclear

"Endomyocardial biopsy is gold standard, but has risk for cardiac perforation" ^[5]. "Routine biopsy is NOT indicated in most cases" ^[17].

Why not do it in everyone? Because:

1. The procedure carries a ~1% risk of cardiac perforation (RV free wall is thin)
2. "Majority of myocarditis has no specific treatment, so it just helps you diagnose, but treatment will just be like that for other heart failure" ^[5]
3. Sampling error — inflammation may be patchy, so a negative biopsy does not exclude myocarditis

Indications for EMB ^[17]:

1. New-onset HF < 2 weeks with normal-size or dilated LV and haemodynamic compromise (suspected fulminant lymphocytic myocarditis)
2. New-onset HF of 2 weeks – 3 months with dilated LV and new ventricular arrhythmia, 2nd/3rd degree heart block, or failure to respond to usual care within 1–2 weeks (suspected giant cell myocarditis)
3. Suspected specific infiltrative/inflammatory disease where histology will change management (sarcoidosis, eosinophilic myocarditis, amyloidosis)

Histopathological criteria (Dallas Criteria for Myocarditis) ^[17]:

• Evidence of inflammatory infiltrate of the myocardium
• Infiltrates associated with myocyte necrosis or degeneration of adjacent myocytes not typical of ischaemic damage

Immunohistochemical criteria ^[17]:

• Abnormal inflammatory infiltrate defined as ≥ 14 leucocytes/mm² including up to 4 monocytes/mm² with presence of CD3-positive T-lymphocytes ≥ 7 cells/mm²

Why right heart biopsy? The biopsy is taken from the RV septum — the LV free wall is thicker but harder to access safely, and the septum is at lower risk of perforation than the RV free wall ^[5].

Why? In HFrEF, ↓CO activates the renin-angiotensin-aldosterone system (RAAS) as a compensatory mechanism. While initially helpful (↑BP, ↑Na⁺ retention), chronic RAAS activation is maladaptive: angiotensin II causes vasoconstriction (↑afterload), aldosterone causes Na⁺/water retention (↑preload), both promote myocardial fibrosis and remodelling. Blocking RAAS → ↓afterload, ↓preload, ↓remodelling → improved survival.

Side effects: Hypotension, hyperkalaemia, cough (ACEi only), angioedema (rare but serious), renal impairment ^[26].

Contraindications ^[26]:

• High-grade bilateral renal artery stenosis (why? Both kidneys depend on angiotensin II to maintain GFR via efferent arteriolar constriction → blocking RAAS → GFR crashes → acute kidney injury)
• Azotaemia (significant renal impairment — relative CI; monitor K⁺ and creatinine)
• Pregnancy (teratogenic — causes renal agenesis, oligohydramnios)
• Hyperkalaemia (K⁺ > 5.5 mmol/L)
• Previous angioedema with ACEi (→ use ARB; if angioedema with ARB too → use hydralazine + isosorbide dinitrate)

Why? In HFrEF, chronic sympathetic activation is maladaptive: ↑HR → ↓diastolic filling time → ↓coronary perfusion → ↑myocardial O₂ demand; catecholamines are directly toxic to myocytes; β₁ stimulation promotes arrhythmias and remodelling. Beta-blockers antagonise these effects → proven survival benefit.

Only these three beta-blockers have Level A evidence for mortality reduction in HFrEF. Do NOT substitute with atenolol, propranolol, or short-acting metoprolol tartrate.

For patients with reduced EF: consider bisoprolol / carvedilol / metoprolol succinate ^[27]

Indications ^[26]:

• LVEF ≤ 40% (all HFrEF patients)
• Post-MI with LV dysfunction
• Rate control in AF

Side effects: Bradycardia, hypotension, syncope, fatigue, bronchospasm, impaired glucose tolerance ^[26].

Contraindications ^[26]:

• AV block (2nd/3rd degree), sinus node dysfunction, symptomatic bradycardia
• Bronchial asthma (relative — bisoprolol safest; carvedilol worst due to β₂ blockade)
• Vasospastic angina, severe PAD, Raynaud phenomenon
• Acute decompensated HF (start only when stable and euvolaemic — "start low, go slow")
• Depression (relative)

Why? Aldosterone escapes ACEi/ARB blockade over time ("aldosterone breakthrough"). Aldosterone promotes Na⁺/water retention, K⁺ wasting, myocardial fibrosis, endothelial dysfunction, and baroreceptor dysfunction. MRAs block these effects.

Indications: HFrEF NYHA II–IV, LVEF ≤ 35%, already on ACEi/ARB + BB ^[24].

Side effects: Hyperkalaemia (must monitor K⁺ and renal function), renal impairment, gynaecomastia (spironolactone).

Contraindications:

• K⁺ > 5.0 mmol/L at initiation
• eGFR < 30 mL/min/1.73m²
• Concomitant K⁺-sparing diuretics + K⁺ supplements without monitoring

"SGLT2i interesting since it's an antidiabetic → cardioprotective effects by diuresis" ^[25]

Why? Sodium-glucose co-transporter 2 inhibitors ("gliflozins" — the name tells you: "gli" = glucose, "flozin" = sodium-glucose transport inhibition) were initially developed as antidiabetics but have shown remarkable cardiovascular benefits independent of glycaemic control:

• Osmotic diuresis (↓preload without activating RAAS — unlike loop diuretics)
• Natriuresis (↓Na⁺ reabsorption in proximal tubule)
• ↓Myocardial fibrosis and inflammation
• Improved myocardial energy metabolism (ketone bodies as fuel for failing heart)
• Renoprotective (↓intraglomerular pressure via tubuloglomerular feedback)

"Very safe, rarely causes hypoglycaemia and hypotension" ^[25]

Side effects: Genital mycotic infections (candidiasis — ↑glucose in urine = bacterial/fungal growth), urinary tract infections, volume depletion, euglycaemic diabetic ketoacidosis (rare but important).

Contraindications:

• eGFR < 20 mL/min/1.73m² (updated 2023; previously < 30)
• Type 1 diabetes (risk of DKA)
• Recurrent urogenital infections

Mechanism: Inhibit Na⁺-K⁺-2Cl⁻ co-transporter in the thick ascending limb of the loop of Henle → massive natriuresis → fluid removal → ↓preload → relief of congestion.

Additional mechanisms ^[28]:

• "Preload = fluid removal by diuresis reduces preload"
• "Initial morphine-like effect that induces transient venodilation leading to a fall in cardiac filling pressures and decreased pulmonary congestion prior to onset of diuresis mediated by enhanced release of prostaglandins" ^[28]

Side effects: Hypotension, hypokalaemia, hypomagnesaemia, metabolic alkalosis, ototoxicity (high-dose IV), AKI ^[28].

Key principle: Use the minimum dose required to maintain euvolaemia. Over-diuresis → hypovolaemia → ↓CO → renal hypoperfusion → cardiorenal syndrome.

• Metolazone or hydrochlorothiazide — used as adjuncts to loop diuretics in diuretic-resistant oedema (sequential nephron blockade)
• Block Na⁺-Cl⁻ co-transporter in the distal convoluted tubule

• Indicated as an alternative when ACEi/ARB/ARNI are contraindicated (bilateral renal artery stenosis, severe renal impairment, angioedema) ^[25]
• Particularly beneficial in African American patients (A-HeFT trial) — can be added on top of standard quadruple therapy
• Hydralazine = arteriolar vasodilator (↓afterload); Isosorbide dinitrate = venodilator (↓preload)
• Together they mimic some of the effects of ACEi without affecting RAAS

• Soluble guanylate cyclase stimulator — enhances the NO-sGC-cGMP pathway ^[25]
• Indicated in patients with recent HF hospitalisation despite optimal quadruple therapy (VICTORIA trial)
• Modest additional benefit

• Cardiac glycoside: inhibits Na⁺/K⁺-ATPase → ↑intracellular Ca²⁺ → ↑contractility (positive inotrope) + vagotonic effect → ↓HR
• "Seldom used due to narrow therapeutic index" ^[9]
• No mortality benefit, but ↓HF hospitalisation (DIG trial)
• Role: symptomatic relief in patients with persistent symptoms despite optimal therapy; rate control in AF
• Therapeutic drug monitoring essential (therapeutic range 0.5–0.8 ng/mL; toxicity risk ↑ with hypokalaemia, hypomagnesaemia, renal impairment)

• Selective If channel inhibitor → ↓HR without ↓contractility or ↓BP
• Indicated when: sinus rhythm, HR ≥ 70 bpm despite maximum tolerated beta-blocker, LVEF ≤ 35%, NYHA II–IV
• SHIFT trial: ↓composite of CV death + HF hospitalisation

• Indicated for:
  • AF (CHA₂DS₂-VASc score ≥ 2 in men, ≥ 3 in women → DOAC or warfarin)
  • LV thrombus on echo (warfarin for at least 3–6 months)
  • Very low LVEF with intracardiac stasis (controversial; no routine anticoagulation for sinus rhythm DCM without thrombus) ^[24]

Indications ^[28]:

• Adjuncts to diuretics for patients without adequate response
• Patients with urgent need for afterload reduction (hypertensive emergency, acute MR/AR)

Contraindications ^[28]:

• Hypotension
• Suspected RV infarction
• Hypertrophic obstructive cardiomyopathy (HOCM) — nitrates ↓preload → ↓LV cavity size → ↑LVOT obstruction
• Constrictive pericarditis
• Intake of PDE5 inhibitors (sildenafil, vardenafil, tadalafil) within 24 hours — severe hypotension due to synergistic vasodilation

Inotropes are a bridge (to recovery, to device, or to transplant) — they are NOT a long-term solution. Chronic inotrope use increases mortality due to arrhythmias and myocardial oxygen mismatch.

Why? DCM patients with very low LVEF are at high risk of sudden cardiac death from ventricular arrhythmias (VT/VF). ICDs detect and terminate these arrhythmias with overdrive pacing or defibrillation.

Indications ^[8][15]:

"Shown to reduce sudden cardiac death in patients with HFrEF — as ejection fraction goes down lower, the indication becomes stronger, since the chance of lethal ventricular arrhythmias increases with reducing LVEF" ^[8]

Why 6 months for non-ischaemic DCM? Because some causes of DCM (especially myocarditis, tachycardia-mediated, peripartum) may recover LVEF with medical therapy alone. Implanting an ICD too early means subjecting a potentially recovering patient to device-related risks (infection, inappropriate shocks, lead complications).

Special consideration — LMNA mutations: Patients with LMNA-related DCM have a particularly high arrhythmia burden and may need ICD even with LVEF > 35%. A LMNA risk calculator exists to guide decision-making.

Why? In ~30% of HFrEF patients, the ventricles contract dyssynchronously (typically due to LBBB — the left ventricle depolarises late → the septum and lateral wall do not contract together → mechanical inefficiency → worsening HF). CRT = biventricular pacing: a lead in the RV + a lead in the coronary sinus (pacing the LV lateral wall) → synchronises contraction → ↑cardiac efficiency.

Indications ^[8][15]:

"Cardiac resynchronisation therapy (biventricular pacing) should be considered for patients with ALL of the following:" ^[8]

• NYHA III despite optimal medical therapy (also now recommended for NYHA II)
• Sinus rhythm
• Widened QRS ( > 120 ms) → left bundle branch block
• LVEF ≤ 35% & LVD > 5.5 cm

CRT improves mechanical synchrony resulting in ^[15]:

• Improved coordination and relaxation of cardiac chambers
• Increased LV filling time
• Decreased septal dyskinesia
• Decreased MR

Why mainly LBBB? "Data shows that seems more beneficial for LBBB patients, but not RBBB patients" ^[8]. This is because LBBB causes the most pronounced mechanical dyssynchrony (delayed lateral wall activation). RBBB dyssynchrony is less amenable to correction by biventricular pacing.

CRT device types:

• CRT-P (pacemaker) — biventricular pacing only
• CRT-D (defibrillator) — biventricular pacing + ICD function (most patients who meet CRT criteria also meet ICD criteria)

• A mechanical pump implanted in the LV apex that continuously draws blood from the LV and delivers it to the ascending aorta, bypassing the failing ventricle
• "LVAD is a pump with battery → in public only for patients bridged to transplant, but in private just need to pay" ^[1]

"Common indication of cardiac transplantation" ^[15] — DCM is the leading indication for heart transplant worldwide.

Indications:

• Refractory NYHA IV HF despite optimal medical therapy + devices
• Peak VO₂ < 12–14 mL/kg/min on cardiopulmonary exercise testing
• Recurrent life-threatening arrhythmias not controlled by ICD
• Intractable angina not amenable to revascularisation

Contraindications:

• Active infection / malignancy
• Irreversible pulmonary hypertension (PVR > 5 Wood units → fixed)
• Severe peripheral or cerebrovascular disease
• Active substance abuse / psychiatric illness precluding compliance
• Age (relative — typically < 65–70, but assessed case by case)

"Mechanical circulatory support (e.g. IABP, LVAD, ECMO) for potentially reversible pump dysfunction" ^[9]:

• IABP (intra-aortic balloon pump): inflates during diastole (↑coronary perfusion), deflates during systole (↓afterload). Bridge in cardiogenic shock.
• VA-ECMO (veno-arterial extracorporeal membrane oxygenation): drains venous blood, oxygenates it, and returns it to the arterial system. Used in refractory cardiogenic shock, fulminant myocarditis.
• Impella: percutaneous axial-flow pump placed across the aortic valve.

• The most common sustained arrhythmia in DCM — occurs in 25–40% of patients
• Why? Chronic ↑LVEDP → ↑LA pressure → LA dilatation → structural and electrical remodelling of atrial myocardium → multiple wavelet re-entry → AF
• Consequences:
  • Loss of atrial "kick" → ↓LV filling by ~20–25% → ↓CO → worsening HF symptoms (particularly devastating in a ventricle that is already struggling)
  • Rapid ventricular rate → ↓diastolic filling time → further ↓CO; chronic tachycardia itself worsens DCM (tachycardia-mediated cardiomyopathy superimposed on existing DCM)
  • Thromboembolism → stasis in dilated, fibrillating atria → thrombus formation → stroke, peripheral embolism ^[30]
• Management: Rate control (beta-blocker or digoxin; avoid non-DHP CCBs in low EF), ± rhythm control (amiodarone, catheter ablation), and anticoagulation based on CHA₂DS₂-VASc score

• A major cause of sudden cardiac death in DCM ^[1]

• Non-sustained VT (NSVT): runs of ≥ 3 consecutive ventricular beats lasting < 30 seconds. Very common on Holter monitoring in DCM (up to 40–70% of patients). A marker of increased SCD risk.

• Sustained VT: lasting ≥ 30 seconds or requiring intervention to terminate. Haemodynamically significant → syncope, cardiogenic shock, or degeneration to VF.

• Ventricular fibrillation (VF): disorganised ventricular activity → no cardiac output → cardiac arrest → death within minutes if not defibrillated

• Why? In DCM, the dilated, fibrotic myocardium creates areas of slow conduction interspersed with normal tissue → re-entrant circuits. Myocyte stretch also → afterdepolarisations (triggered activity). Autonomic imbalance (↑sympathetic tone) further lowers the arrhythmia threshold.

"As the ejection fraction goes down lower, the indication for ICD becomes stronger — since the chance of lethal ventricular arrhythmias increases with reducing LVEF" ^[8]

• Prevention: ICD implantation for primary prevention (LVEF ≤ 35%, NYHA II–III, after ≥ 6 months of optimal medical therapy in non-ischaemic DCM) ^[8]; beta-blockers; correction of electrolytes; avoidance of pro-arrhythmic drugs

• AV block (1st, 2nd, or 3rd degree) and bundle branch block (LBBB most common) can occur from fibrosis of the conduction system
• LMNA mutations are particularly associated with progressive conduction disease — AV block may be the first manifestation, even before LV dilatation becomes apparent ^[1]
• LBBB itself causes ventricular dyssynchrony → worsens mechanical efficiency → further ↓EF (this is the rationale for CRT)
• Complete heart block → haemodynamic compromise, syncope; may require permanent pacemaker

• LV apex is the most common site for thrombus formation — the apex is the most distal point from the mitral valve and has the lowest flow velocity, especially when apical wall motion is severely impaired
• LV thrombus can embolise to:
  • Cerebral arteries → stroke (embolic ischaemic stroke — cardioembolic aetiology). This is one of the most devastating complications.
  • Mesenteric arteries → acute mesenteric ischaemia
  • Renal arteries → renal infarction
  • Peripheral arteries → acute limb ischaemia
• Detection: Transthoracic echo (TTE) with contrast enhancement; cardiac MRI has higher sensitivity
• Management: Anticoagulation with warfarin (target INR 2.0–3.0) for at least 3–6 months if LV thrombus is found; DOACs increasingly used but less evidence for LV thrombus specifically

• When AF complicates DCM, the left atrial appendage (LAA) becomes a prime site for thrombus formation
• Stroke risk assessed by CHA₂DS₂-VASc score; most DCM patients with AF will score ≥ 2 and require anticoagulation
• DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) are preferred over warfarin for AF-related stroke prevention (except in mitral stenosis or mechanical valves)

• Less commonly, RV dilatation and stasis → right-sided thrombus → PE
• Also, immobility from severe HF → DVT → PE

• LV dilatation → mitral annulus stretches → the leaflets can no longer coapt (meet in the middle during systole)
• Additionally, papillary muscles are displaced laterally and apically by the dilated LV → this tethers the leaflets and prevents them from closing properly
• The result: a pansystolic murmur at the apex, radiating to the axilla — identical to primary MR in sound, but the mechanism is entirely different
• "Left ventricular dilatation → enlarged MV ring leading to regurgitation" ^[30]
• Consequence: MR creates a volume load on an already failing LV (some blood goes backward into LA during systole → more blood returns in diastole → further LV dilatation → worsens MR → vicious cycle). This is sometimes called the "mitral regurgitation begets mitral regurgitation" phenomenon.
• Management: Treat the DCM (HFrEF therapy → ↓LV size → ↓annular dilatation → ↓MR); CRT can ↓MR by resynchronising contraction; percutaneous edge-to-edge repair (MitraClip) for selected patients with severe functional MR refractory to medical therapy

AOS Paeds Q8: "Murmur could be due to mitral regurgitation secondary to dilation" ^[4] — the key exam point is that functional MR is a consequence of DCM, not the cause.

• Same mechanism on the right side: RV dilatation → tricuspid annular dilatation → leaflet malcoaptation → TR
• Worsens RV volume overload → further RV dilatation → worsens TR → vicious cycle
• Contributes to systemic congestion (hepatomegaly, ascites, peripheral oedema)