This distinction is exam-favourite: a patient with HCM may never develop HF; a patient with HF may have no cardiomyopathy (e.g., pure valvular disease). ^[1]

^[1]

The deck's prevalence and percentage estimates are lecture-era approximations. Contemporary guidelines emphasize that clinically recognized prevalence depends strongly on the population and diagnostic method. ^[9]

• Definition: Dilated LV and reduced LVEF not explained by the severity of CAD, VHD, CHD, or hypertension. ^[1]
• "Idiopathic" should be used only after a systematic search for ischaemic, toxic, inflammatory, endocrine/metabolic, infiltrative, neuromuscular, pregnancy-related, and genetic causes. A negative family history does not exclude genetic DCM because penetrance is age-dependent and relatives may be unrecognized. ^[9]

^[1]

The lecture's diagram presents a useful but simplified viral myocarditis → DCM model:

1. Viral entry (Coxsackie B most classic) → direct cardiomyocyte damage
2. Immune activation → inflammatory infiltrate, cytokine release
3. Ongoing autoimmune injury → even after virus cleared
4. Myocyte death and fibrosis → LV dilatation → systolic dysfunction → HF / SCD

Viral persistence, immune injury, and host susceptibility do not occur in a single obligatory sequence. Myocarditis can heal completely or progress to scar/DCM. Return to strenuous exercise is now based on clinical recovery, ventricular function, biomarkers, rhythm monitoring, and CMR rather than a calendar rule alone; the deck's 3–6 month restriction is a traditional starting framework. ^[9]

The deck's 15–30% familial estimate and its “≥2 relatives” definition are historical teaching aids, not a gate for genetic assessment. ^[1]

• Onset: 20–50 years old
• A single proband with DCM can justify a three-generation pedigree, specialist genetic counselling/testing, and clinical screening of first-degree relatives when an inherited cause is plausible. ^[9]
• Inheritance: familial DCM is often autosomal dominant, but X-linked, recessive, mitochondrial, and syndromic/neuromuscular forms occur; do not use the deck's “> 90% AD” figure as a universal prior
• Most common genes: Titin (TTN, 20–25%) and Lamin A/C (LMNA, ~6%)

Challenges in diagnosing familial DCM: ^[1]

1. Incomplete family history (autopsy often waived)
2. Variable age-related penetrance (some present young, some old, some never)
3. Concomitant cardiac conditions (e.g., hypertension may mask underlying CM)

Key investigations: ^[1]

• Echo: LV end-diastolic volume/diameter > 2SD from normal (corrected for age and BSA); LVEF < 50%
• ECG: No specific features but usually abnormal — AF, AV block, LBBB common
• Cardiac MRI: Late gadolinium enhancement (LGE) pattern; myocardial oedema
• CT coronary angiogram: Exclude CAD as cause
• FDG-PET scan: For sarcoidosis
• Endomyocardial biopsy: If inflammatory/infiltrative CM suspected
• Blood tests: BNP/NT-proBNP, TFT, iron studies, autoimmune screen
• Idiopathic DCM → genetic counselling (3-generation family tree; genetic screening)

Core treatment follows contemporary HFrEF guidance, then adds aetiology- and genotype-specific risk assessment. ^[9][11]

• Pharmacological: ARNI (or ACEI/ARB), beta-blocker, MRA, SGLT2 inhibitor, diuretics
• Device therapy: secondary-prevention ICD after sustained VT/VF or cardiac arrest when appropriate; primary-prevention ICD after adequate guideline-directed therapy is individualized using LVEF, CMR scar, genotype, arrhythmic history, competing mortality, and patient preference. It is not a reflex based on LVEF alone. CRT follows standard electrical/mechanical criteria. ^[9][11]
• Specific therapies: treat the demonstrated cause. Immunosuppression is not routine DCM therapy; it is reserved for selected, usually biopsy-defined inflammatory conditions under specialist care.
• Exercise: prescribe individually after rhythm, ventricular function, genotype, and—after myocarditis—evidence of resolution are assessed. ^[9]
• End-stage: LVAD / heart transplant for intractable ventricular arrhythmias or HF

Definition: Increased LV wall thickness at end-diastole that cannot be explained by abnormal loading conditions. ^[1]

• The deck quotes 1:500–1:1000; imaging/genotype studies suggest a broader phenotype may be present in up to ~1:200, while clinically recognized disease is less common ^[9]
• One of the leading causes of SCD in young athletes and classically the most common identifiable structural cardiac cause; the leading cause varies between contemporary cohorts ^[15][16]
• Autosomal dominant inheritance with variable penetrance

Adults: LV wall thickness ≥15 mm, OR ≥13 mm if positive family history or genetic test ^[1] Children: BSA-adjusted z-score ≥2.5 SD above mean, OR ≥2 SD if FHx+/genetic test+ ^[1]

The 2020 AHA/ACC Guidelines state that conditions mimicking HCM morphologically but with different pathophysiology should NOT be called HCM. ^[1]

These include: Fabry disease, cardiac amyloidosis (especially ATTR), glycogen storage diseases, Noonan syndrome, and athlete's heart. Their pathophysiology, natural history, and treatment are fundamentally different. This is a common exam trap. ^[1]

Variable ages at onset and clinical presentations even with the same disease-causing mutation. ^[1]

Four interrelated processes: ^[1]

1. LVOT obstruction — Asymmetric septal hypertrophy + systolic anterior motion (SAM) of the anterior mitral valve leaflet (AMVL) → dynamic obstruction that worsens with ↑contractility, ↓preload, ↓afterload
2. Diastolic dysfunction — Stiff, hypertrophied ventricle impairs relaxation and filling
3. Myocardial ischaemia — ↑O₂ demand from hypertrophy, ↓supply from compressed intramyocardial coronaries, and ↓diastolic filling time
4. Mitral regurgitation — SAM distorts the MV → posteriorly directed MR jet

LVOTO contributes to symptoms and adverse outcomes, but a gradient alone does not determine prognosis or mandate treatment. ^[9][10]

Key investigations: ^[1]

• 3-generation family history / genetic testing
• Echo: Measure LVOT gradient (resting / provocated / exercise)
  • ≥30 mmHg = haemodynamically obstructive; ≥50 mmHg at rest or provocation is the usual threshold for considering LVOTO-directed therapy only when symptoms are attributable to obstruction ^[10]
• ECG: LVH with strain (asymmetric/symmetric); precordial TWI (apical HCM); low voltage (think amyloidosis)
• Holter: Non-sustained ventricular tachycardia (NSVT) — key SCD risk factor
• Cardiac MRI: Extensive late gadolinium enhancement (LGE) → ↑SCD risk

Major risk factors to know: ^[1]

• History of cardiac arrest / sustained VT
• Family history of SCD from HCM
• Unexplained syncope
• LV wall thickness ≥30 mm
• NSVT on Holter
• Extensive LGE on MRI
• LV apical aneurysm
• LVEF < 50% (end-stage HCM)

The lecture's fixed 2020 flowchart should be read as a shared-decision framework, not a scorecard. Prior cardiac arrest/sustained VT is a secondary-prevention indication. For primary prevention, age, symptoms, family history, maximal wall thickness, LV systolic function, apical aneurysm, NSVT burden, LGE, and validated adult/paediatric risk estimates are integrated with device complications and patient preference. ^[9][10]

Comprehensive management algorithm: ^[1]

The deck teaches the classic RV-predominant phenotype. Modern ACM recognizes right-dominant, biventricular, and left-dominant disease; scar/fatty replacement and ventricular arrhythmia may precede major chamber dysfunction. ^[9]

• Familial disease is often autosomal dominant with age-dependent penetrance, but genotype and phenotype are heterogeneous; the deck's “1/3 familial” estimate is cohort-dependent
• Genes: mostly encode desmosome, intercalated disc, and ion channel proteins
• High prevalence in certain Italian regions
• Presents with ventricular arrhythmias of LBBB morphology (origin from RV) / SCD in the young
• Disease progression related to exercise — exercise accelerates fibrofatty infiltration

Diagnosis requires a combination of criteria from multiple categories: ^[1]

The deck reproduces a 2019 HRS factor-count framework; do not apply it as a universal bedside checklist. ^[1]

• History of VT/SCA
• LVEF ≤35%
• Major risk factors: NSVT, inducible VT at EPS, LVEF ≤49%
• Minor risk factors: Male sex, > 1000 PVCs/24h, RV dysfunction, proband status, ≥2 desmosomal variants
• Contemporary decisions integrate prior cardiac arrest/sustained VT, syncope, ventricular function, arrhythmia burden, genotype, validated ACM/ARVC risk estimates where applicable, device harms, and patient preference. Appropriate ICD therapy does not prove every treated rhythm would have been fatal. ^[9][11]

Key management principles: ^[1]

• Genetic counselling
• Arrhythmia management: beta-blocker/antiarrhythmic drugs, catheter ablation, and ICD each have phenotype- and risk-specific roles; ablation reduces VT burden but does not substitute for an indicated ICD
• Ventricular dysfunction: treat congestion and LV/RV failure using phenotype-appropriate HF therapy. Routine nitrate preload reduction is not an RV-failure treatment and can worsen hypotension/low output; use diuresis and vasodilators only for a defined haemodynamic indication.
• Thromboembolic risk: anticoagulate AF according to stroke-risk guidance and treat intracavitary thrombus/prior thromboembolism appropriately
• Exercise: frequent high-intensity endurance exercise and competitive sport are generally discouraged in clinically affected/high-risk ACM because of arrhythmia and disease-progression risk; prescribe lower-intensity activity individually rather than “no exercise.” ^[9]
• Intractable VA/HF: LVAD / heart transplant

↑Myocardial stiffness → extremely impaired ventricular filling and diastolic dysfunction = "restrictive physiology." ^[1]

• The least common form of cardiomyopathy
• Mostly acquired; idiopathic RCM carries relentless symptomatic progression and high mortality
• Autosomal dominant forms exist (sarcomere subunit mutations)
• Presents as HFpEF but arrhythmias are possible

Functional resemblance to constrictive pericarditis — differentiating the two is mandatory because constriction is surgically treatable. ^[1]

The lecture devotes several slides to causes, which include:

• Infiltrative: Amyloidosis (AL and ATTR), sarcoidosis, haemochromatosis
• Storage: Fabry disease, glycogen storage diseases
• Endomyocardial: Endomyocardial fibrosis, hypereosinophilic syndrome (Löffler endocarditis), carcinoid, radiation
• Idiopathic
• Genetic/Familial: Sarcomere mutations (overlap with HCM)

Multimodality imaging is essential: ^[1]

• Echo, right heart catheterization, cardiac MRI
• Nuclear imaging: DPD/PYP/HMDP bone-tracer scintigraphy/SPECT can establish ATTR cardiac amyloidosis non-invasively only after AL amyloidosis is excluded with serum free light chains plus serum/urine immunofixation. FDG-PET, not routine gallium-67 scanning, is the contemporary metabolic imaging approach for suspected active cardiac sarcoidosis. ^[9]
• FDG-PET for sarcoidosis
• Endomyocardial biopsy — targeted to cases where tissue diagnosis is likely to change management; a negative biopsy can miss patchy disease
• Blood tests (serum free light chains, troponin, BNP); other biopsies (fat pad, rectal)

Treatment may be available for specific conditions: ^[1]

• Fabry disease: Enzyme replacement therapy
• ATTR-cardiac amyloidosis: Tafamidis
• Sarcoidosis: Immunosuppression
• AL amyloidosis: Chemotherapy directed at plasma cell clone
• Haemochromatosis: Phlebotomy/chelation

LQTS is a disorder characterized by: (1) QT prolongation on ECG and (2) a propensity to ventricular tachyarrhythmias. ^[1]

• Usual presentations: syncope, seizures, or SCD; can remain asymptomatic
• Ion channelopathy
• Congenital: Autosomal dominant (Romano-Ward) or autosomal recessive (Jervell & Lange-Nielsen — with sensorineural deafness)
• Acquired: Much more common — drugs, electrolytes, medical conditions

• The QT interval = beginning of QRS complex to end of T wave → represents the total ventricular electrical cycle (depolarization + repolarization)
• Since repolarization dominates, QT prolongation ≈ prolonged repolarization
• QT varies with heart rate — the deck shows Bazett QTc = QT / √RR, but Bazett overcorrects at fast rates and undercorrects at slow rates. Measure QT manually in a lead with a clear T-wave end, check QRS width, and use serial/alternative correction (often Fridericia) when rate is extreme. A single sex-specific “normal” cut-off is not itself a diagnosis; repeated QTc ≥480 ms without a secondary cause is a major diagnostic threshold, while QTc ≥500 ms is an important risk marker. ^[11]

Prolonged repolarization occurs due to: ^[1]

• Reduced repolarizing (outward) K⁺ currents: IKs, IKr → delays phase 3 repolarization
• Enhanced inward current, classically persistent late Na⁺ current in LQT3, keeps the action potential depolarized longer

This prolonged repolarization creates heterogeneity of refractoriness across the myocardial wall (transmural dispersion of repolarization). Early afterdepolarizations (EADs) can trigger polymorphic VT = Torsade de Pointes (TdP).

TdP is the classic arrhythmia of LQTS — the QRS axis appears to twist around the baseline. It may terminate spontaneously but can recur or degenerate into VF; never use the deck's historical 95% figure to reassure an unstable patient.

Pause-dependent TdP is characteristic of acquired LQTS: a long pause (e.g., after a PVC) → exaggerated repolarization → EAD → "short-long-short" sequence → TdP. ^[1]

^[1][4]

Three categories of acquired causes: ^[1]

Electrolyte imbalance:

• Hypokalaemia, hypocalcaemia, hypomagnesaemia

Medical conditions:

• AV block, severe sinus bradycardia, DM, hypothyroidism, CVA, subarachnoid haemorrhage, starvation, obesity, alcoholism

Drugs (HIGH YIELD — frequently tested):

^[1]

Four-pronged approach: ^[1]

1. Clinical syndrome recognition — symptoms, family history, ECG findings, arrhythmias
2. Dynamic assessment when needed — repeat resting ECG and exercise/recovery testing can reveal abnormal QT adaptation. Epinephrine challenge is a specialist, protocol-dependent test; isoproterenol challenge is not a routine LQTS diagnostic test.
3. Exclusion of reversible causes — electrolytes, TFT
4. Genetic assessment — a pathogenic/likely pathogenic variant can establish the molecular diagnosis and guide cascade testing; a variant of uncertain significance does not. A negative panel does not exclude clinically diagnosed LQTS. ^[11]

Scoring system: ^[1]

Components include: QTc value, T-wave morphology, Torsade de Pointes, syncope (with/without stress), congenital deafness, family history of definite LQTS, unexplained SCD in family member < 30 y/o.

Important caveats:

• (a) No medications/disorders accountable for changes
• (b) Bazett's formula used
• (c) Mutually exclusive criteria
• (d) Resting HR below 2nd centile for age
• (e) Same family member cannot be counted in both categories A & B

The deck's 2017 sequence is updated below using the 2022 ESC ventricular-arrhythmia guideline. ^[11]

Key prognostic points: ^[1]

• The deck's fixed fatality and age-40 percentages are historical cohort estimates, not individual counselling numbers.
• Risk varies with genotype, QTc, sex/age, symptoms, prior arrest, treatment/adherence, and modifiers such as QT-prolonging drugs and hypokalaemia.
• Most patients do well with accurate diagnosis and optimized therapy, but an ICD also carries inappropriate-shock, lead, infection, and psychological burdens. ^[11]

Brugada syndrome is a clinical electrical disorder characterized by a type 1 right-precordial ECG pattern plus an appropriate clinical/genetic context and susceptibility to polymorphic VT/VF. A Brugada ECG pattern is not automatically the Brugada syndrome. ^[11]

• Mean age: mid-late 30s (range 4–70 years)
• Clinical events are much more often recognized in males, but the deck's 8–10:1 ratio is cohort-dependent and women can carry the substrate and experience serious events
• Pathogenic SCN5A loss-of-function variants explain only a minority of cases; many are gene-elusive and should not be described as simple monogenic autosomal-dominant disease
• Patients often show periodic normalization of ECG
• Manifests during fever / use of Na channel blockers

The deck illustrates the repolarization hypothesis: reduced inward Na⁺ current can accentuate RV-outflow epicardial action-potential differences, producing the coved ST pattern and re-entry substrate. Contemporary understanding also includes conduction delay and localized RVOT structural substrate; these mechanisms are complementary rather than settled alternatives. ^[11]

^[1]

Key clinical points: ^[1]

• Malignant tachyarrhythmias usually occur at rest and at night (vagal influence → ↓Na⁺ current further compromised)
• SCD from VF can be the first and only event
• The deck's fixed 40% recurrence figure came from a selected high-risk cohort and must not be applied to an incidental asymptomatic pattern
• LQT/Brugada overlap syndrome exists
• Possible overlap with ARVC

Diagnostic approach: ^[1]

• Type 1 ECG pattern: document spontaneous/fever-associated versus drug-provoked pattern and the lead position
• Latent/intermittent Brugada: repeat standard and high-right-precordial ECGs. Sodium-channel-blocker challenge is a monitored specialist procedure after excluding contraindications and phenocopies; a provoked type 1 pattern without other findings does not by itself diagnose Brugada syndrome. ^[11]
• Brugada-like ECG: Must exclude RBBB, septal hypertrophy, ARVC
• Brugada ECG phenocopies: Myocardial ischaemia, PE, pericardial disease, metabolic disorders, mechanical compression of RVOT

The deck's 2017 table is updated below using the 2022 ESC ventricular-arrhythmia guideline. ^[11]

Catheter ablation is disease- and mechanism-specific; it is not a universal “treatment of choice” across cardiomyopathies and channelopathies. ^[11]

Most monogenic FH is autosomal dominant and caused by pathogenic variants in LDLR, APOB, or gain-of-function PCSK9. LDLRAP1-related FH is autosomal recessive; polygenic severe hypercholesterolaemia can mimic FH. ^[12][13]

• Heterozygous FH (HeFH): ~1:200 to 1:500
• Homozygous FH (HoFH): ~1:160,000 to 1:1,000,000
• A clinical FH diagnosis remains possible when no causal variant is found; conversely, genetic results require correct variant classification
• Increased risk of premature atherosclerotic coronary heart disease

The lecture presents a powerful conceptual graph of cumulative LDL exposure:

The exact ages and “160 mmol-years” line are illustrative—not deterministic treatment thresholds. The robust inference is that earlier and greater LDL-C exposure brings ASCVD forward, while early intensive treatment shifts risk later. Smoking, hypertension, diabetes, CKD, and elevated Lp(a) further modify risk; female sex is not simply a risk-raising arrow as drawn on the slide. ^[12]

Dutch Lipid Clinic Network Criteria — a scoring system incorporating: ^[1][5]

• Family history (premature CAD, elevated LDL in relatives)
• Clinical history (premature CAD in proband)
• Physical examination — tendon xanthomata, corneal arcus (in young patients — in elderly, arcus senilis is normal)
• LDL-C level
• Genetic testing (a pathogenic/likely pathogenic variant supports a molecular diagnosis; a VUS does not)

Exclude secondary causes and repeat a markedly abnormal lipid profile. Use an accepted clinical scheme such as DLCN or Simon Broome, refer likely cases for FH/genetic expertise, and perform cascade testing of biological relatives when the diagnosis is established. Absence of xanthomata does not exclude FH. ^[13]

Children diagnostic thresholds shown in the deck (lecture-era): ^[1]

These isolated cut-offs are not a universal paediatric algorithm. Interpret repeated LDL-C against age, family phenotype/genotype, secondary causes, and local paediatric FH guidance.

Historical Hong Kong data shown in the deck: ^[1]

• PWH study (1990–2000): 252 subjects clinically diagnosed as HeFH → estimated prevalence 1:4000 (likely underdiagnosed)
• HK West Cluster: In 143,400 statin-naïve subjects, 1/10 had LDL ≥4.0; 1/50 had LDL ≥5.0; 1/390 had LDL ≥6.5

Pharmacological treatment: ^[1]

• First-line: High-intensity statins (atorvastatin 40–80 mg or rosuvastatin 20–40 mg)
• Add-on: Ezetimibe (inhibits intestinal cholesterol absorption via NPC1L1)
• Escalate to goal/risk: add a PCSK9 monoclonal antibody (alirocumab/evolocumab) when required; inclisiran or bempedoic acid may be options according to indication, access, tolerance, and local guidance. Niacin is not routine contemporary LDL-lowering therapy. ^[12]
• HoFH: refer early to a specialist centre; LDL apheresis and receptor-independent therapy such as evinacumab may be required in addition to maximally tolerated conventional therapy. ^[12][13]
  • Case example from lecture: 50-year-old HeFH man — LDL dropped from 4.24 to 0.59 mmol/L with alirocumab added to atorvastatin + ezetimibe, with resolution of xanthelasmata

Normally, the LDL receptor on hepatocyte surfaces binds LDL, internalizes it (endocytosis), delivers LDL for lysosomal degradation, and the receptor is recycled back to the cell surface. PCSK9 binds the LDL receptor and targets it for lysosomal degradation (instead of recycling) → fewer LDL receptors on the surface → less LDL clearance → higher LDL levels.

PCSK9 inhibitors block this interaction → LDL receptors are recycled → more receptors remain on the surface → more LDL is cleared. The slide's left panel also shows why statins and PCSK9 inhibition are complementary: statin-driven SREBP2 activity increases both LDLR and PCSK9, while the antibody prevents PCSK9 from diverting receptors to lysosomes. Efficacy depends on residual LDL-receptor function, so LDLR-null HoFH responds poorly; ANGPTL3 inhibition with evinacumab is relatively LDLR-independent. ^[1][12]

^[6]

From GC 115: Heart failure can occur during pregnancy in a woman with well-compensated cardiac disease due to: ^[7]

• Physiological ↑cardiac output
• Antenatal anaemia
• Beta-adrenergic tocolytics
• Stress during labour/delivery
• Excessive IV fluids

This is relevant for HCM and DCM patients who may decompensate during pregnancy.

From Ryan Ho Critical Care: structural heart disease and primary electrical disorders belong in the differential of otherwise unexplained arrest, especially in a young person. The deck's “~15% of all arrests” figure is source- and population-dependent and should not be memorized as universal. ^[8][11]