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CLINICAL REFERENCE & EXAM MASTERY SERIES

Hypertrophic Cardiomyopathy
A Comprehensive Mastery Study Module for ERMP & USMLE Step 2 CK / Step 3

Scope: Genetics · Pathophysiology · Diagnosis · Risk Stratification · Management · Special Populations

Design: Chapter-based mastery format with Key Points, Clinical & Exam Pearls, Pitfalls, Algorithms, and Rapid Revision
Sheets
Context: Integrated Ethiopian epidemiology & resource-adapted practice (STG-aligned)
References: Harrison's Principles of Internal Medicine 22e · 2024 AHA/ACC HCM Guideline · 2023 ESC Cardiomyopathy
Guideline · Ethiopian STG

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 MODULE MAP

Table of Contents

Chapter 1 — Definitions, Classification & Epidemiology incl. Ethiopian/African data

Chapter 2 — Genetics & Pathophysiology sarcomere biology, LVOT obstruction, SAM

Chapter 3 — Clinical Presentation & Physical Examination dynamic murmur maneuvers

Chapter 4 — Diagnostic Workup ECG, echocardiography, CMR, genetic testing

Chapter 5 — Risk Stratification for Sudden Cardiac Death HCM Risk-SCD, ICD criteria

Chapter 6 — Management medical therapy, mavacamten, septal reduction, ICD

Chapter 7 — Special Populations & Complications athletes, pregnancy, pediatrics, AFib

Chapter 8 — Bedside Clinical Reasoning worked case vignette

Chapter 9 — Ethiopian Context & Resource-Limited Practice epidemiology, STG-aligned approach

Closing — Key Study Points & Master Rapid Revision Sheet final synthesis

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 CHAPTER 1

Definitions, Classification & Epidemiology

ONE-LINE SUMMARY

HCM is a primary myocardial disease, usually caused by sarcomeric gene mutations, defined by unexplained left ventricular hypertrophy
not accounted for by loading conditions.

1.1 Definition

Hypertrophic cardiomyopathy (HCM) is defined echocardiographically or by cardiac MRI as a maximal left ventricular (LV) wall thickness
≥15 mm anywhere in the myocardium (or ≥13 mm in a first-degree relative of an affected individual) that cannot be explained solely by
abnormal loading conditions such as hypertension or aortic stenosis. It is the most common inherited cardiovascular disease, with a
phenotypic prevalence of roughly 1 in 500 in the general population, though genotypic prevalence may be higher.

CORE CONCEPT
HCM is a disease of the sarcomere. Even in the absence of overt hypertrophy, a pathogenic sarcomeric variant carrier is at risk and
requires surveillance — the genotype can precede the phenotype, especially in adolescents.

1.2 Classification by Morphology

Pattern Description Approx. Frequency

Disproportionate thickening of the basal/mid interventricular

Asymmetric septal hypertrophy ~70%
septum

Concentric hypertrophy Diffuse symmetric thickening of the LV wall ~10%

Apical hypertrophy (Yamaguchi Confined to the LV apex; classic "spade-shaped" LV on ~10%, more common in East Asian
variant) ventriculography populations

Hypertrophy at mid-LV level causing mid-cavity gradient +/- apical

Mid-cavitary obstruction Uncommon
aneurysm

1.3 Classification by Hemodynamics

• Obstructive HCM (oHCM): resting LV outflow tract (LVOT) gradient ≥30 mmHg — present in about two-thirds of patients.
• Labile/latent obstructive HCM: resting gradient <30 mmHg but ≥30 mmHg with Valsalva, exercise, or amyl nitrite provocation.
• Non-obstructive HCM: gradient <30 mmHg at rest and with provocation — roughly one-third of patients.

1.4 Epidemiology

Global phenotypic prevalence is estimated at 1:500, with most carriers of pathogenic variants remaining undiagnosed. HCM is the leading
cause of sudden cardiac death (SCD) in young athletes in Western case series, though this ranking varies by country and screening
practice. Onset can occur at any age; a bimodal presentation is recognized, with one peak in adolescence/young adulthood and another in
the fifth-to-sixth decade, sometimes with a "burnt-out" phase resembling dilated cardiomyopathy.

TRIAL & REGISTRY EVIDENCE

Large contemporary registries (SHaRe registry) have re-estimated annual SCD event rates at closer to 0.5%/year with modern risk
stratification and ICD use, considerably lower than historical tertiary-referral-center estimates that shaped early risk perception.

EXAM TRAP
HIGH-YIELD Do not confuse HCM with hypertensive heart disease or athlete's heart. A key discriminator is the pattern of hypertrophy
(asymmetric septal in HCM vs. concentric in hypertension), family history, ECG voltage out of proportion to wall thickness, and abnormal
diastolic function/strain on echo.

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RAPID REVISION — CHAPTER 1

• HCM = LV wall thickness ≥15 mm (or ≥13 mm in relatives) unexplained by loading conditions.
• Most common inherited cardiac disease; prevalence ~1:500.
• Obstructive (resting LVOT gradient ≥30 mmHg) vs. non-obstructive; ~2/3 have some obstruction with provocation.
• Apical variant (Yamaguchi) more common in East Asian populations; classic "ace of spades" LV.
• Leading cause of SCD in young athletes in many Western series.

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 CHAPTER 2

Genetics & Pathophysiology

ONE-LINE SUMMARY

Sarcomeric gene mutations cause myocyte disarray, hypercontractility, and impaired relaxation, culminating in dynamic LVOT obstruction
via systolic anterior motion of the mitral valve.

2.1 Genetics

HCM is most commonly an autosomal dominant disease with variable penetrance and expressivity. The two most frequently implicated
genes are MYH7 (beta-myosin heavy chain) and MYBPC3 (myosin-binding protein C), together accounting for roughly 70% of genotype-
positive cases. Other sarcomeric genes include TNNT2, TNNI3, TPM1, MYL2, and ACTC1. Approximately 30-40% of clinically diagnosed
patients have no identifiable pathogenic variant on current panels ("genotype-negative HCM").

CORE CONCEPT
Genetic testing serves two purposes: confirming the diagnosis/informing family cascade screening, and — increasingly — guiding
eligibility for mavacamten and clarifying phenocopies (Fabry disease, PRKAG2, Danon disease, amyloidosis, RASopathies) that mimic
HCM but require different management.

2.2 Mechanisms of LVOT Obstruction

Basal septal hypertrophy narrows the LVOT. During systole, the resulting Venturi effect plus abnormal papillary muscle position pulls the
anterior mitral leaflet toward the septum — systolic anterior motion (SAM) of the mitral valve. SAM causes both dynamic outflow
obstruction and a posteriorly-directed mitral regurgitation jet (typically mid-to-late systolic). Obstruction is dynamic and worsens with
reduced preload, reduced afterload, or increased contractility.

M E C H A N I S M C A S C A D E — LV O T O B S T R U C T I O N

Basal septal hypertrophy

|
v
Narrowed LV outflow tract --> increased systolic flow velocity (Venturi effect)
|
v
Anterior mitral leaflet drawn toward septum --> Systolic Anterior Motion (SAM)
|
v
+----------------------+----------------------+
| |
v v
Dynamic LVOT gradient Posteriorly directed MR jet
| |
v v
Worsens with: decreased preload (Valsalva, standing,
diuretics), decreased afterload (vasodilators), or
increased contractility (exercise, inotropes, digoxin)
|
v
Improves with: increased preload (squatting, leg raise,
fluid), increased afterload (handgrip, phenylephrine),
beta-blockade / negative inotropes

2.3 Diastolic Dysfunction & Microvascular Ischemia

Myocyte disarray and interstitial fibrosis impair ventricular relaxation, elevating filling pressures despite a preserved or hyperdynamic
ejection fraction — the dominant mechanism of exertional dyspnea. Small-vessel (microvascular) disease from abnormal intramural

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coronary arterioles causes angina-like chest pain even with angiographically normal epicardial coronaries, and contributes to myocardial
fibrosis and, in a minority, progression to a "burnt-out" dilated phase with reduced EF.

Mnemonic — "SAM causes MR, ACHE": Septal hypertrophy → Anterior leaflet pulled → MR (posterior jet); worse with Afterload down,
Contractility up, Hypovolemia, Exercise.

CLINICAL PEARL
Any maneuver or drug that decreases LV preload or afterload, or increases contractility, will increase the LVOT gradient and murmur
intensity in oHCM — this is the opposite of aortic stenosis, where the murmur behaves in the reverse direction with most maneuvers
except handgrip.

EXAM TRAP
HIGH-YIELD Nitrates, digoxin, and inotropes (dobutamine) are relatively contraindicated in obstructive HCM because they worsen the
gradient. Similarly, aggressive diuresis or vasodilation in a hypotensive HCM patient can dangerously worsen obstruction — the reflex
response of giving fluids/vasopressors and stopping inotropes is often correct, unlike in most other forms of shock.

RAPID REVISION — CHAPTER 2

• MYH7 and MYBPC3 = the two most common genes (~70% of genotype-positive cases); autosomal dominant, variable
penetrance.
• SAM of the anterior mitral leaflet is the key mechanical link between septal hypertrophy, LVOT obstruction, and posterior MR jet.
• Gradient worsens with: ↓preload, ↓afterload, ↑contractility. Improves with: ↑preload, ↑afterload, β-blockade.
• Diastolic dysfunction (not systolic) drives most exertional symptoms.
• Avoid nitrates, digoxin, and inotropes in obstructive HCM.

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 CHAPTER 3

Clinical Presentation & Physical Examination

ONE-LINE SUMMARY

Presentation ranges from asymptomatic murmur discovery to exertional dyspnea, angina, syncope, or sudden death — the murmur's
dynamic response to bedside maneuvers is the diagnostic key.

3.1 Symptoms

• Dyspnea on exertion — most common symptom, from diastolic dysfunction and dynamic obstruction.
• Angina — from microvascular ischemia and increased oxygen demand from hypertrophy, even without epicardial CAD.
• Palpitations — atrial fibrillation, ventricular ectopy, or non-sustained VT.
• (Pre)syncope — exertional syncope is a major red flag for SCD risk; suggests critical obstruction or arrhythmia.
• Sudden cardiac death — may be the first manifestation, particularly in young athletes; usually due to ventricular fibrillation.

3.2 Physical Examination

The hallmark finding is a harsh crescendo-decrescendo systolic murmur, loudest at the lower left sternal border/apex, that increases
with maneuvers reducing preload or afterload and decreases with maneuvers increasing preload or afterload. A double or triple apical
impulse and a rapid "spike-and-dome" carotid upstroke (bisferiens pulse) may be present. A prominent S4 reflects reduced compliance.

Bedside Maneuver Table

Maneuver Physiologic Effect oHCM Murmur Aortic Stenosis Murmur

Valsalva (strain phase) ↓ venous return / preload ↑ increases ↓ decreases

Standing abruptly ↓ preload ↑ increases ↓ decreases

Squatting ↑ preload & afterload ↓ decreases ↑ increases

Passive leg raise ↑ preload ↓ decreases ↑ increases

Sustained handgrip ↑ afterload ↓ decreases ↓ decreases

Amyl nitrite ↓ afterload ↑ increases ↑ increases

EXAM TRAP
HIGH-YIELD Handgrip is the one maneuver where both oHCM and AS murmurs decrease — it is not useful for distinguishing the two.
Valsalva and standing are the classic discriminators tested on exams.

CLINICAL PEARL
A murmur that clearly changes intensity with position/Valsalva in a young patient with a family history of SCD should prompt an
echocardiogram even if the resting exam seems otherwise benign.

RAPID REVISION — CHAPTER 3

• Classic murmur: crescendo-decrescendo, LLSB/apex, increases with ↓preload/afterload maneuvers.

• Valsalva/standing ↑ oHCM murmur, ↓ AS murmur — the key bedside discriminator.
• Squatting/leg raise ↓ oHCM murmur, ↑ AS murmur.
• Exertional syncope = red flag symptom, mandates urgent risk assessment.
• Double apical impulse + bisferiens pulse + S4 are classic associated findings.

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 CHAPTER 4

Diagnostic Workup

ONE-LINE SUMMARY

Echocardiography confirms the diagnosis and quantifies obstruction; ECG is abnormal in the vast majority and may precede echo
changes; CMR and genetic testing refine risk and etiology.

4.1 Electrocardiogram (ECG)

ECG is abnormal in over 90% of patients with HCM and can be abnormal before hypertrophy is echocardiographically detectable. Common
findings include left ventricular hypertrophy voltage criteria, deep and narrow "dagger-like" Q waves in the inferolateral leads (from septal
hypertrophy), left atrial enlargement, and repolarization abnormalities. In the apical variant, giant negative T waves in the precordial leads
are classic.

CORE CONCEPT
ECG changes disproportionate to the degree of hypertrophy (or present in a family member of a known HCM patient) should prompt
echocardiographic screening — ECG can be the earliest clue in genotype-positive, phenotype-negative relatives.

4.2 Echocardiography

Transthoracic echocardiography is the primary diagnostic tool. Key measurements include maximal wall thickness, LVOT gradient at rest
and with Valsalva (and with exercise if resting/Valsalva gradients are non-diagnostic but suspicion remains high), presence and severity of
SAM-related mitral regurgitation, left atrial size (a major risk marker), and systolic/diastolic function.

Echo Parameter Clinical Significance

Max wall thickness ≥30 mm Independent major risk factor for SCD

Resting/provoked LVOT gradient ≥50 mmHg Threshold commonly used for considering septal reduction therapy if symptomatic

Left atrial diameter/volume Marker of chronic filling pressure elevation and AF risk

Systolic anterior motion (SAM) Mechanistic driver of obstruction and posterior MR jet

Apical aneurysm Associated with high arrhythmic risk; look for in mid-cavity obstruction

4.3 Cardiac MRI (CMR)

CMR offers superior spatial resolution for apical and other segments poorly seen on echo, and uniquely detects late gadolinium
enhancement (LGE), a marker of myocardial fibrosis. Extensive LGE (generally ≥15% of LV mass) is an emerging major risk factor
incorporated into some risk models and society guidance for ICD decision-making, particularly in patients who otherwise appear lower-risk.

4.4 Genetic Testing & Family Screening

Genetic testing is recommended for the proband to enable cascade testing of first-degree relatives. If a pathogenic/likely pathogenic variant
is identified, relatives who test negative can be reassured and released from further routine surveillance, while positive relatives enter
periodic clinical screening (ECG/echo) even before phenotypic expression, particularly through adolescence.

EXAM TRAP
COMMON MISTAKE A "negative" genetic test in the proband does not exclude HCM — it simply means no pathogenic variant was
identified on current panels (~30-40% of cases). It does not permit cascade "genetic" testing logic in relatives; clinical (ECG/echo)
screening of first-degree relatives is still required in genotype-negative families.

RAPID REVISION — CHAPTER 4

• ECG abnormal in >90%; may precede echo findings — screen relatives with ECG + echo.

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• Echo confirms diagnosis; assess resting + Valsalva (+/- exercise) gradient, SAM, LA size, apical aneurysm.
• Wall thickness ≥30 mm and LA enlargement are major risk markers.
• CMR adds LGE assessment — extensive fibrosis is an emerging major SCD risk factor.
• Genetic testing enables cascade family screening; a negative proband test does not exclude disease.

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 CHAPTER 5

Risk Stratification for Sudden Cardiac Death

ONE-LINE SUMMARY

ICD decisions integrate major clinical risk markers, the HCM Risk-SCD calculator (Europe), and increasingly CMR fibrosis burden and
apical aneurysm — not any single factor in isolation.

5.1 Major Risk Factors for Sudden Cardiac Death

Risk Factor Notes

Personal history of cardiac arrest or sustained VT Secondary prevention — ICD essentially always indicated

Family history of SCD in a close relative attributable to HCM Especially if age <50 at time of death

Unexplained syncope Particularly if exertional or recent

Maximal LV wall thickness ≥30 mm Independent major factor, especially in younger patients

Non-sustained VT on ambulatory monitoring Especially if frequent, prolonged, or fast

Abnormal blood pressure response to exercise Failure to rise or a fall in systolic BP with exertion

LV apical aneurysm Associated with high arrhythmic and thromboembolic risk regardless of other scores

Extensive LGE on CMR (≥15% of LV mass) Increasingly used to reclassify risk, especially in "low risk" patients by score alone

5.2 Risk Calculators & Guideline Approaches

The HCM Risk-SCD model (endorsed by ESC) generates a 5-year SCD risk estimate from age, wall thickness, LA diameter, LVOT
gradient, family history of SCD, NSVT, and unexplained syncope, stratifying patients into low (<4%), intermediate (4-6%), and high (≥6%)
risk categories to guide shared decision-making about ICD implantation. The American (AHA/ACC) approach is more qualitative, relying on
the presence of major risk factors (above) rather than a single numeric threshold, but both approaches converge on very similar clinical
decisions in most patients.

TRIAL & GUIDELINE EVIDENCE

The 2024 AHA/ACC/HRS/other multisociety HCM guideline continues to endorse shared decision-making incorporating major risk
markers plus emerging CMR/LGE data, rather than mandating any single calculator, reflecting incomplete external validation of numeric
risk scores across all populations.

COMMON PITFALL
Relying solely on a single risk factor (e.g., only wall thickness) or solely on a calculated percentage without considering additional
qualitative red flags (apical aneurysm, extensive LGE) can under- or over-estimate true risk. Risk assessment is holistic and should be
reassessed periodically (every 1-2 years or with clinical change), not a one-time calculation.

RAPID REVISION — CHAPTER 5

• Secondary prevention (prior cardiac arrest/VT) = automatic ICD indication.

• Major risk factors: family SCD history, unexplained syncope, wall thickness ≥30 mm, NSVT, abnormal BP response to exercise,
apical aneurysm, extensive LGE.
• HCM Risk-SCD gives a 5-year numeric estimate (ESC); AHA/ACC uses a qualitative major-risk-factor approach.
• Reassess risk periodically — it is not a single static number.

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 CHAPTER 6

Management

ONE-LINE SUMMARY

Symptomatic obstructive HCM is treated first with negative inotropes (beta-blockers, non-dihydropyridine CCBs, disopyramide, or a
cardiac myosin inhibitor); refractory cases proceed to septal reduction therapy; SCD risk is separately managed with ICD.

6.1 First-Line Medical Therapy for Obstructive Symptoms

• Beta-blockers (e.g., metoprolol, bisoprolol, atenolol, or nadolol) — first-line for symptomatic oHCM; reduce heart rate, contractility, and
myocardial oxygen demand, improving the gradient and filling time.
• Non-dihydropyridine calcium channel blockers (verapamil, diltiazem) — alternative/add-on, especially if beta-blockers are
contraindicated or insufficient; use verapamil cautiously in patients with very high resting gradients or hypotension, since vasodilation
can worsen obstruction.
• Disopyramide — a negative inotrope added to a beta-blocker or CCB for refractory obstructive symptoms; requires QT monitoring and
has anticholinergic side effects.

DOSING NOTES
DOSING Beta-blockers are typically titrated to resting heart rate ~60-65 bpm and symptom control; verapamil is usually started at low
dose and up-titrated cautiously with attention to blood pressure and AV conduction; disopyramide requires baseline and follow-up QTc
monitoring and is generally combined with an AV-nodal blocking agent to prevent enhanced AV conduction during atrial fibrillation.

6.2 Cardiac Myosin Inhibitors

Mavacamten is a first-in-class oral cardiac myosin inhibitor that reduces excessive actin-myosin cross-bridge formation, decreasing
hypercontractility and LVOT gradient. It is approved for symptomatic obstructive HCM (NYHA II-III) as an alternative to or in combination
with standard therapy, based on pivotal trial evidence showing improved gradients, symptoms, and reduced need for septal reduction
therapy. It requires REMS-style monitoring (baseline and serial echocardiograms) due to a dose-dependent risk of excessive reduction in
ejection fraction, and has relevant drug interactions via CYP2C19/CYP3A4. Aficamten is a related next-generation myosin inhibitor with a
shorter half-life, studied with a similar mechanism and monitoring paradigm.

TRIAL EVIDENCE

The pivotal randomized trial of mavacamten in obstructive HCM demonstrated significant improvement in the composite endpoint of peak
oxygen consumption and NYHA functional class compared with placebo, establishing the drug class as a new pillar of oHCM therapy
alongside beta-blockers and septal reduction.

6.3 Septal Reduction Therapy

Indicated for patients with severe drug-refractory symptoms (NYHA III-IV, or II with exertional syncope/near-syncope) and a resting or
provoked LVOT gradient ≥50 mmHg.

Modality Key Features

Surgical septal Gold standard at experienced centers; allows direct visualization, concomitant mitral valve repair if needed; very low mortality
myectomy (<1%) in high-volume centers

Alcohol septal Percutaneous, catheter-based induced septal infarction; preferred in older patients or those with high surgical risk; higher rate
ablation of complete heart block requiring permanent pacemaker

EXAM TRAP
HIGH-YIELD Septal reduction therapy is for symptom relief in drug-refractory obstructive disease — it has not been shown to reduce
SCD risk and does not replace a separate ICD risk assessment.

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6.4 Non-Obstructive HCM & Heart Failure Progression

Non-obstructive HCM with preserved EF and diastolic dysfunction is managed with beta-blockers or non-dihydropyridine CCBs for
symptom control and diuretics used cautiously (excess preload reduction can worsen filling in a non-compliant ventricle, or worsen
obstruction if latent obstruction is present). In the minority who progress to a "burnt-out" phase with reduced EF, management follows
standard guideline-directed medical therapy for HFrEF, and such patients may become candidates for transplantation evaluation.

RAPID REVISION — CHAPTER 6

• First-line for symptomatic oHCM: beta-blockers ≥ non-DHP CCBs ≥ add disopyramide.

• Mavacamten/aficamten: myosin inhibitors, reduce gradient and hypercontractility; monitor EF via serial echo.
• Septal reduction (myectomy preferred; ASA as alternative) for drug-refractory symptoms + gradient ≥50 mmHg — symptom
therapy only, not SCD prevention.
• Avoid nitrates, digoxin, pure vasodilators, and inotropes in obstructive disease.
• Burnt-out HCM (reduced EF) is managed as HFrEF.

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 CHAPTER 7

Special Populations & Complications

ONE-LINE SUMMARY

Athletic participation, pregnancy, pediatric screening, and atrial fibrillation each require tailored, guideline-specific modification of the
standard HCM approach.

7.1 Athletes & Exercise

Contemporary guidelines have moved away from blanket disqualification: shared decision-making is now favored, allowing many genotype-
positive/phenotype-negative individuals and select low-risk HCM patients to participate in some competitive sports after individualized risk
assessment, in contrast to older uniformly restrictive recommendations. High-risk features (prior arrest, high-risk genotype/phenotype
combination) still generally warrant restriction from high-intensity competitive sport.

7.2 Pregnancy

Most women with HCM tolerate pregnancy well, but obstructive physiology can be aggravated by the preload reduction of normal labor/
delivery hemodynamics and by neuraxial anesthesia-induced vasodilation. Beta-blockers are generally continued through pregnancy;
vaginal delivery is preferred in most cases with attention to avoiding excessive preload/afterload reduction; high-risk patients (severe
obstruction, prior arrhythmia) warrant a multidisciplinary cardio-obstetric delivery plan.

7.3 Pediatric & Adolescent Screening

First-degree relatives of an HCM proband should undergo serial clinical screening (ECG + echo) starting around age 12-, particularly
through the growth spurt of adolescence when phenotypic expression often first appears, continuing periodically into adulthood even if
genetically negative in a genotype-negative family, or until a genetic result clarifies risk.

7.4 Atrial Fibrillation

AF is the most common sustained arrhythmia in HCM (lifetime prevalence up to 20-25%) and is poorly tolerated because the loss of atrial
contraction (the "atrial kick") critically reduces filling of a non-compliant, hypertrophied ventricle. Rate or rhythm control strategies are
individualized; regardless of CHA2DS2-VASc score, anticoagulation is recommended for essentially all HCM patients who develop
AF, since HCM itself confers a markedly elevated stroke risk independent of the standard scoring system.

EXAM TRAP
HIGH-YIELD Unlike in the general population, CHA2DS2-VASc is not used to decide whether to anticoagulate in HCM + AF —
anticoagulation is essentially mandatory once AF is diagnosed, regardless of calculated score.

7.5 Infective Endocarditis

Routine antibiotic prophylaxis is not recommended for HCM in general; it is reserved for the same high-risk cardiac conditions as in the
general population (e.g., prior IE, prosthetic material) undergoing specific high-risk dental procedures, per standard IE prophylaxis guidance
— HCM with LVOT obstruction/SAM-related turbulent flow alone is not, by itself, an indication.

RAPID REVISION — CHAPTER 7

• Sports eligibility: individualized shared decision-making, not blanket restriction.

• Pregnancy: continue beta-blockers; favor vaginal delivery; avoid excessive preload/afterload drop.
• Screen first-degree relatives with serial ECG/echo through adolescence.
• AF + HCM = anticoagulate regardless of CHA2DS2-VASc score.
• No routine IE prophylaxis for HCM alone.

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 CHAPTER 8

Bedside Clinical Reasoning

ONE-LINE SUMMARY

Working through a case builds the pattern recognition needed to catch HCM before it presents as sudden death.

8.1 Case Vignette

A 19-year-old competitive runner presents after a syncopal episode during a race. He recovered spontaneously within a minute. He reports
occasional exertional chest tightness over the past few months. His uncle died suddenly at age 34 during a football match; cause was
never formally established. On exam, there is a systolic murmur at the left sternal border that increases in intensity when he stands up from
a squat.

Step-by-step reasoning
1. Recognize the red flags: exertional syncope + family history of unexplained SCD in a young relative + dynamic murmur = HCM until
proven otherwise.
2. Bedside exam clue: murmur that increases with standing (↓preload) is characteristic of dynamic LVOT obstruction, not fixed valvular
disease like AS (which would decrease).
3. Initial workup: 12-lead ECG (expect LVH criteria +/- deep Q waves) and transthoracic echocardiogram (assess wall thickness, LVOT
gradient at rest and with Valsalva, SAM, mitral regurgitation, LA size).
4. Immediate management while awaiting workup: restrict from competitive exercise/training pending evaluation; avoid dehydration,
and avoid starting any vasodilator or inotropic agent.
5. If HCM confirmed: begin risk stratification for SCD (family history of SCD already present, personal syncope already present — these
alone are major risk factors warranting strong consideration of ICD), start a beta-blocker for symptom control, and initiate genetic
testing/cascade family screening.
6. Disposition: refer to a comprehensive HCM center for risk stratification, ICD discussion, and long-term follow-up; counsel on sports
participation via shared decision-making.

CLINICAL PEARL
In any young patient with exertional syncope, always ask specifically about family history of sudden, unexplained, or "unexplained car
accident/drowning" deaths in relatives under 50 — these are often unrecognized HCM or channelopathy deaths and are among the most
powerful historical clues on the wards and on exams.

RAPID REVISION — CHAPTER 8

• Exertional syncope + family SCD history + dynamic murmur = urgent HCM workup.
• Get ECG + echo first; avoid vasodilators/inotropes/dehydration while pending.
• Presence of syncope + family SCD history already constitutes 2 major SCD risk factors on presentation.

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 CHAPTER 9

Ethiopian Context & Resource-Limited Practice

ETHIOPIA-FOCUSED

ONE-LINE SUMMARY
HCM in Ethiopia is likely markedly under-diagnosed given limited access to echocardiography and genetic testing outside major referral
centers, so a high index of clinical suspicion and judicious use of available low-cost tools (history, exam, ECG) is essential.

9.1 Epidemiological Considerations

Robust population-based prevalence data for HCM specific to Ethiopia are limited; most available information comes from hospital-based
case series at tertiary cardiac referral centers (e.g., Addis Ababa) rather than community screening studies, consistent with the broader
pattern across much of sub-Saharan Africa where echocardiography access outside major cities is restricted. This likely means true
community prevalence is undercounted, and many cases are identified only after presenting with heart failure, syncope, or sudden death
rather than through pre-symptomatic screening.

RESOURCE-LIMITED REALITY
PRACTICAL In many Ethiopian settings, echocardiography, cardiac MRI, and genetic testing are concentrated in a small number of
referral hospitals. A careful history (exertional syncope, family history of sudden death), a thorough dynamic murmur exam, and a 12-lead
ECG remain the most widely available and highest-yield tools to raise suspicion before referral.

9.2 Practical, Resource-Adapted Approach

• History & exam first: given limited echo access outside referral centers, a careful family history of sudden unexplained death and a
dynamic bedside murmur exam (Valsalva/squat-to-stand) can appropriately triage which patients most urgently need referral for
echocardiography.
• ECG as a screening bridge: ECG is inexpensive, widely available even at many district hospitals, and abnormal in the great majority
of HCM patients — an important lower-cost bridge to referral when echo is not locally available.
• Medication availability: beta-blockers (e.g., propranolol, atenolol, bisoprolol) are generally accessible and remain the practical first-
line therapy; verapamil is also broadly available. Disopyramide, mavacamten, and septal reduction therapy (myectomy/ASA) require
referral to specialized cardiac centers, which may necessitate travel to Addis Ababa or referral abroad.
• Family screening: given limited genetic testing infrastructure, clinical (ECG + echo where available) cascade screening of first-degree
relatives is the practical mainstay rather than genetic cascade testing.
• Sports/occupational counseling: in settings where formal pre-participation cardiac screening programs are not universal, clinicians
should proactively ask about family history of sudden death in young patients presenting with any exertional symptoms, since this may
be the only opportunity for detection before a sentinel event.

9.3 Alignment with Ethiopian Standard Treatment Guidelines

The Ethiopian STG approach to cardiomyopathy emphasizes accessible first-line pharmacologic management (beta-blockers as initial
therapy) and timely referral to higher-level cardiac centers once a structural cardiomyopathy is suspected or confirmed, consistent with the
resource-adapted approach above; specialized interventions (septal reduction, ICD implantation, mavacamten) require referral beyond the
primary/general practice level.

RAPID REVISION — CHAPTER 9

• Ethiopian HCM data are mostly hospital-based/referral-center derived; true community prevalence likely under-recognized.
• History + dynamic murmur exam + ECG are the practical, widely available triage tools before echo referral.
• Beta-blockers/verapamil are the practical first-line, broadly accessible therapy.
• Disopyramide, mavacamten, ICD, and septal reduction therapy require specialized-center referral.
• Clinical (not genetic) cascade screening of relatives is the practical mainstay.

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 MODULE SYNTHESIS

Key Study Points & Master Rapid Revision Sheet

KEY STUDY POINTS — THE MODULE IN 10 LINES

1. HCM = unexplained LV wall thickness ≥15 mm (≥13 mm in relatives); most common inherited cardiac disease (~1:500).
2. MYH7 and MYBPC3 mutations account for ~70% of genotype-positive disease; ~30-40% remain genotype-negative.
3. SAM of the anterior mitral leaflet mechanically links septal hypertrophy to dynamic LVOT obstruction and posterior MR.
4. Gradient worsens with ↓preload/afterload or ↑contractility; the murmur behaves oppositely to aortic stenosis with Valsalva/standing.
5. ECG is abnormal in >90% and can precede echo changes — use it to screen relatives.
6. SCD risk stratification integrates major clinical risk factors, HCM Risk-SCD (ESC), and CMR-LGE burden — not one factor alone.
7. First-line therapy: beta-blockers → non-DHP CCB → add disopyramide or a myosin inhibitor (mavacamten/aficamten); avoid nitrates/
digoxin/inotropes in obstructive disease.
8. Septal reduction therapy (myectomy preferred; alcohol ablation alternative) relieves drug-refractory obstructive symptoms — it does
not replace SCD risk assessment.
9. AF in HCM mandates anticoagulation regardless of CHA2DS2-VASc score.
10. In resource-limited settings, history, dynamic exam, and ECG remain the highest-yield tools before specialist echo/genetic referral.

Master Comparison — HCM vs. Aortic Stenosis (High-Yield Recap)

Feature Obstructive HCM Aortic Stenosis

Valsalva/standing Murmur increases Murmur decreases

Squat/leg raise Murmur decreases Murmur increases

Handgrip Murmur decreases Murmur decreases

Carotid upstroke Bisferiens (spike-and-dome) Parvus et tardus

Radiation Does not radiate to carotids typically Radiates to carotids

O N E - PA G E M A N A G E M E N T A L G O R I T H M

Confirmed HCM (echo/CMR)

|
+-- Assess SCD risk (family Hx SCD, syncope, wall >=30mm,
| NSVT, abnormal exercise BP, apical aneurysm, LGE>=15%)
| |
| +-- Any major risk factor / prior arrest --> ICD
| +-- Low risk --> routine surveillance (1-2 yearly)
|
+-- Assess LVOT obstruction (resting + Valsalva +/- exercise)
|
+-- Obstructive + symptomatic
| |
| +-- Beta-blocker (first line)
| +-- Add/switch non-DHP CCB if needed
| +-- Add disopyramide or myosin inhibitor if refractory
| +-- Gradient >=50 + NYHA III-IV (or II+syncope)
| --> Septal reduction therapy (myectomy > ASA)
|
+-- Non-obstructive + symptomatic
--> Beta-blocker / non-DHP CCB, cautious diuresis

End of Module — Hypertrophic Cardiomyopathy Comprehensive Mastery Study Guide

References: Harrison's Principles of Internal Medicine, 22nd Ed. · 2024 AHA/ACC/HRS Multisociety HCM Guideline · 2023 ESC Guidelines for Cardiomyopathies
· Ethiopian Standard Treatment Guidelines

Hypertrophic Cardiomyopathy Mastery Module | Page 16 of 16