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Hypertrophic Cardiomyopathy

Learning Objectives

By the end of this rotation, the resident should be able to:

Guideline anchors used in this topic

  • AHA/ACC-HCM-2024 = AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for Management of HCM
  • ESC-CM-2023 = ESC Guidelines for Management of Cardiomyopathies
  • Sports-2025 = AHA/ACC Scientific Statement on Sports Participation
  • HCM-Risk-Kids = Norrish et al., JAMA Cardiology 2019 (pediatric SCD risk model)
  • PACES-CIED-2021 = PACES Expert Consensus on Pediatric CIEDs

Recognize & Diagnose HCM

  1. Apply pediatric diagnostic criteria: LV wall thickness Z-score >2 (high pretest probability: genotype+ or strong family history) or >2.5 (lower pretest probability) not explained by loading conditions (AHA/ACC-HCM-2024)
  2. Identify age-dependent etiologies and recognize that pediatric HCM is more etiologically heterogeneous than adult HCM (higher proportion of syndromic/metabolic causes)
  3. Recognize phenocopy "red flags" that prompt broader workup:
    • Pre-excitation (WPW pattern) → PRKAG2 or Danon (LAMP2)
    • Infant onset + hypotonia → Pompe/metabolic
    • Short stature, facial features, pulmonary stenosis → Noonan/RASopathy
    • Neuropathic pain, angiokeratomas, renal disease → Fabry
    • Skeletal myopathy, cognitive features → Danon disease
  4. Order and interpret initial workup including ECG (LVH, repolarization abnormalities, Q waves), echo (wall thickness, LVOT gradient with provocation, SAM, diastolic function), and recognize when cardiac MRI adds value (morphology, LGE, apical involvement)

Risk Stratify for Sudden Cardiac Death

  1. Identify the four pediatric "major" ICD-anchoring risk factors per 2024 guideline:
    • Family history of HCM-related SCD (especially ≤50 years)
    • Nonsustained VT on ambulatory monitoring (≥3 beats at ≥120 bpm; weight frequency, duration, rate)
    • Massive LV hypertrophy (no established pediatric Z-score threshold—interpret in context)
    • Unexplained syncope (recent, not vasovagal, not clearly LVOTO-related)
  2. Recognize additional risk modifiers when ICD decision is borderline: extensive LGE on CMR, LV systolic dysfunction (LVEF <50%), LV apical aneurysm, genotype-positive status
  3. Apply pediatric 5-year SCD risk estimates (HCM Risk-Kids) to inform shared decision-making for ICD discussions, understanding model limitations (validated ages 1–16; excludes syndromic HCM)

Order Surveillance Appropriately

  1. Know follow-up testing cadence for diagnosed HCM patients:
    • 12-lead ECG: every 1–2 years
    • 24–48 hour ambulatory ECG monitoring: every 1–2 years (NSVT surveillance)
    • SCD risk reassessment: every 1–2 years
  2. Order exercise stress testing in pediatric HCM regardless of symptom status to assess functional capacity and obtain prognostic information (AHA/ACC-HCM-2024)

Initiate Management Safely

  1. Apply stepped medical therapy for symptomatic obstructive HCM:
    • First-line: nonvasodilating beta-blockers
    • Alternative: verapamil or diltiazem if beta-blockers not tolerated
    • Escalation: disopyramide, or referral for septal reduction therapy
  2. Avoid medications that worsen LVOT obstruction (pure vasodilators, high-dose diuretics) in obstructive disease
  3. Recognize cardiac myosin inhibitors (mavacamten, aficamten) are approved for adults only with symptomatic obstructive HCM; discontinue if LVEF <50%
  4. Know ICD indications:
    • Secondary prevention: prior cardiac arrest or sustained VT → ICD recommended
    • Primary prevention in pediatrics: ICD reasonable when ≥1 conventional risk factor; use shared decision-making and consider pediatric complication burden

Genetic Testing & Family Screening

  1. Recommend genetic testing for all patients with HCM phenotype (with genetic counseling); yield ~30–60%
  2. Apply guideline-based family screening intervals for first-degree relatives:
    • Genotype-positive families OR early-onset disease: start when HCM diagnosed, repeat every 1–2 years in children/adolescents
    • All other children/adolescents: start no later than puberty, repeat every 2–3 years
    • Adults: repeat every 3–5 years
  3. Recognize that genotype-negative relatives in genotype-positive families do not require ongoing clinical screening (unless variant is later downgraded)
  4. Apply genotype-positive/phenotype-negative (G+P−) guidance: serial ECG + echo at intervals (1–2 years children, 3–5 years adults); competitive sports is reasonable; ICD is NOT recommended for primary prevention (AHA/ACC-HCM-2024)

Sports Participation

  1. Explain the modern shared decision-making approach: universal restriction from vigorous activity or competitive sports is NOT indicated for most HCM patients (Sports-2025)
  2. Counsel that ICD placement solely to permit sports participation should NOT be done
  3. Reassure G+P− individuals that competitive sports participation of any intensity is reasonable

Communication & Coordination

  1. Deliver clear family-facing explanation of HCM: what it means, inheritance pattern (autosomal dominant), and why surveillance matters even when asymptomatic
  2. Coordinate comprehensive HCM center referral for complex decisions (ICD, septal reduction therapy) given higher pediatric expertise requirements
  3. Develop emergency action plans for schools and athletic programs for at-risk patients

Key Guidelines

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy JACC. 2024;83(23):2324-2405 PMID: 38727647 | DOI: 10.1016/j.jacc.2024.02.014

2023 ESC Guidelines for the Management of Cardiomyopathies Eur Heart J. 2023;44(37):3503-3626 PMID: 37622657 | DOI: 10.1093/eurheartj/ehad194

2025 AHA/ACC Scientific Statement: Sports Participation in Athletes with Cardiovascular Abnormalities JACC. 2025;85:1059-1108 PMID: 39800560 | DOI: 10.1016/j.jacc.2024.12.012

HCM Risk-Kids: Pediatric SCD Risk Prediction Model Norrish G, et al. JAMA Cardiol. 2019;4(9):918-927 PMID: 31411652 | DOI: 10.1001/jamacardio.2019.2861

2021 PACES Expert Consensus on Cardiovascular Implantable Electronic Devices in Pediatric Patients Heart Rhythm. 2021;18(11):1888-1924 PMID: 34246768 | DOI: 10.1016/j.hrthm.2021.07.038

Definition

  • Adults: LV wall thickness ≥15 mm not explained by loading conditions
  • Children: Body-size-adjusted LV wall thickness Z-score:
    • Z-score >2 may be sufficient with high pretest probability (genotype+ or strong family history)
    • Z-score >2.5 better threshold for early disease in asymptomatic children without family history
  • Sarcomeric gene mutations in ~60% of familial cases (MYH7, MYBPC3 most common)
  • Distinguish HCM phenotype (clinical diagnosis) from HCM genotype (pathogenic/likely pathogenic variant)
  • Phenocopies must be excluded: Fabry, PRKAG2, Noonan/RASopathy, Danon (LAMP2), Pompe, mitochondrial

Pediatric-Specific Considerations

  • Pediatric HCM is more etiologically heterogeneous than adult HCM (higher proportion of syndromic/metabolic causes)
  • Phenotype may evolve through adolescence → requires longitudinal surveillance
  • SCD risk stratification differs from adults; must account for growth and different risk marker weights
  • Guideline endorsed by PACES (Pediatric and Congenital Electrophysiology Society)
  • Complex decisions (ICD, septal reduction) best handled at comprehensive HCM centers with pediatric expertise

Risk Factors for SCD in Pediatric HCM

Pediatric "Major" ICD-Anchoring Risk Factors (2024 Guideline)

Risk Factor Notes
Family history of HCM-related SCD First-degree relative, especially ≤50 years
Nonsustained VT (NSVT) ≥3 beats at ≥120 bpm; weight frequency, duration, rate
Massive LV hypertrophy No established pediatric Z-score threshold—interpret in context
Unexplained syncope Recent, not vasovagal, not clearly LVOTO-related

Blood Pressure Response to Exercise

Abnormal BP response is clinically relevant (ischemia, functional limitation) but is not one of the four major pediatric ICD decision anchors in the 2024 guideline framing.

Additional Risk Modifiers (Consider When Borderline)

Factor Notes
Extensive LGE on CMR Risk threshold not defined in children; useful when ICD decision uncertain
LV systolic dysfunction LVEF <50%; uncommon in children but important
LV apical aneurysm Uncommon in children; risk not well studied
Genotype-positive status Associated with higher SCD risk in pediatrics; included in HCM Risk-Kids
Left atrial size / LVOTO Contribute to pediatric 5-year risk models

Diagnostic Evaluation

Initial Workup

  • 12-lead ECG: LVH, repolarization abnormalities, Q waves
  • Echocardiogram: Wall thickness, LVOT gradient (rest + provocation if <50 mmHg), SAM, diastolic function, LA size
  • 24–48 hour ambulatory ECG: NSVT surveillance
  • Exercise stress test: Recommended even if asymptomatic in pediatric HCM—functional capacity, BP response, symptoms, arrhythmias
  • Cardiac MRI: Morphology, LGE (fibrosis), apical involvement; particularly helpful when ICD decision is borderline

Follow-up Cadence (Diagnosed Patients)

Test Interval
12-lead ECG Every 1–2 years
24–48 hour ambulatory ECG Every 1–2 years
SCD risk reassessment Every 1–2 years
Exercise stress test Per institutional protocol (often annually if active in sports)

Genetic Testing

  • Recommended for ALL patients with HCM phenotype (with genetic counseling)
  • Sarcomeric gene panel (MYH7, MYBPC3 most common)
  • ~30–60% yield in probands
  • If pathogenic/likely pathogenic variant found: cascade testing for first-degree relatives
  • If only benign/likely benign variants: cascade genetic testing is NOT useful
  • Reassess variant classification over time (reclassification can change management)

Family Screening

First-Degree Relatives (2024 Guideline Intervals)

Clinical Scenario When to Start Repeat Interval
Genotype-positive families OR early-onset disease When HCM diagnosed in family member Every 1–2 years (children/adolescents)
All other children/adolescents Any time after HCM diagnosis, no later than puberty Every 2–3 years
Adults Any time after HCM diagnosis in family Every 3–5 years

Genotype-Negative Relatives in Genotype-Positive Families

High-Yield Board Point

If the proband has a pathogenic/likely pathogenic variant and a first-degree relative tests genotype-negative, that relative does NOT require ongoing clinical screening (unless the variant is later reclassified/downgraded).

Management

General Principles

  • Education: symptom triggers, hydration, avoidance of stimulants and dehydration
  • Treat comorbidities (hypertension, obesity) thoughtfully—avoid worsening LVOTO
  • Avoid medications that worsen LVOT obstruction in obstructive disease: pure vasodilators, high-dose diuretics

Medical Therapy (Symptomatic Obstructive HCM)

  • Beta-blockers (nonvasodilating): First-line
  • Verapamil/diltiazem: Alternative if beta-blockers not tolerated
  • Disopyramide: Add for refractory symptoms with LVOTO
  • Cardiac myosin inhibitors (mavacamten, aficamten):
    • Approved for adults only with symptomatic obstructive HCM
    • Discontinue if LVEF drops <50%
    • Aficamten (Myqorzo) FDA-approved December 2025 for adults

ICD for SCD Prevention

Secondary prevention (Class I): - Prior cardiac arrest or sustained VT → ICD recommended

Primary prevention in pediatrics (Class IIa): - ICD is reasonable when ≥1 conventional pediatric risk factor present - Use shared decision-making: discuss benefits, pediatric complication burden (higher than adults), growth considerations - Consider 5-year SCD risk estimates (HCM Risk-Kids) and CMR findings when borderline - Options: transvenous vs subcutaneous ICD depending on size/anatomy

Septal Reduction Therapy

For refractory symptomatic LVOT obstruction (gradient ≥50 mmHg): - Surgical myectomy: Preferred in pediatric patients at experienced centers - Alcohol septal ablation: Generally avoided in children - Refer to comprehensive HCM centers for these decisions

Sports Participation (2025 Update)

Paradigm Shift

  • Shared decision-making is now the central approach
  • Universal restriction from vigorous activity or competitive sports is NOT indicated for most patients
  • Risk lower than previously estimated for many patients
  • Absolute disqualification is rare

Key Guidance

  • HCM patients MAY participate in competitive sports after comprehensive evaluation, shared decision-making, and close surveillance
  • ICD placement solely to permit sports participation should NOT be done
  • Regular follow-up during participation; emergency action plan in place

Genotype-Positive / Phenotype-Negative (G+P−)

High-Yield: G+P− Sports Guidance

Competitive sports participation of any intensity is reasonable for genotype-positive/phenotype-negative individuals. ICD is NOT recommended for primary prevention in G+P−.

Board Pearls

Pearl: Four pediatric ICD-anchoring risk factors

Family history of HCM SCD, NSVT, massive LVH (no Z-score threshold defined), unexplained syncope. Abnormal BP response is NOT a major anchor.

Pearl: G+P− = sports OK, no primary prevention ICD

Genotype-positive/phenotype-negative individuals can participate in competitive sports of any intensity. ICD is not recommended for primary prevention.

Pearl: Genotype-negative relatives stop screening

In genotype-positive families, relatives who test genotype-negative do NOT require ongoing clinical screening (unless variant is downgraded).

Pearl: Exercise stress testing is recommended even if asymptomatic

In pediatric HCM, stress testing provides functional capacity and prognostic information—don't skip it because the child "feels fine."

Pearl: Phenocopies have red flags

Pre-excitation (WPW) → PRKAG2/Danon; infant hypertrophy + hypotonia → Pompe; short stature + dysmorphism → Noonan. Always consider phenocopies in pediatric HCM.

Self-Assessment

Q1: A 14-year-old with HCM has an IVS thickness of 28 mm (Z-score +6), no syncope, no NSVT, and normal exercise BP response. Father died suddenly at age 35 from HCM. What is the most appropriate recommendation?

Answer **Answer**: Discuss ICD implantation for primary prevention **Rationale**: This patient has **family history of HCM-related SCD** (father at age 35)—one of the four major pediatric ICD-anchoring risk factors. While the LVH is severe, there is **no established Z-score threshold** for "massive LVH" in pediatrics. Per 2024 guidelines, patients with ≥1 conventional risk factor warrant ICD discussion (Class IIa). The discussion should use shared decision-making, consider a 5-year SCD risk estimate (HCM Risk-Kids), and weigh pediatric device complication rates. **Key learning point**: Family history alone is sufficient to make ICD "reasonable"—don't wait for multiple risk factors.

Q2: Which of the following conditions should be excluded before diagnosing sarcomeric HCM?

Answer **Answer**: Fabry disease, PRKAG2 syndrome, Noonan/RASopathy, Danon disease (LAMP2), Pompe disease, mitochondrial disease **Rationale**: These are HCM phenocopies with different natural histories, treatments, and genetic counseling implications. Red flags include: pre-excitation pattern (PRKAG2, Danon), infant onset with hypotonia (Pompe), short stature/facial features (Noonan), neuropathic pain (Fabry). Fabry is treatable with enzyme replacement, making its exclusion particularly important.

Q3: A 10-year-old is found to carry a pathogenic MYBPC3 variant after cascade testing (father has HCM). Echo and ECG are normal. What is the appropriate guidance regarding sports participation and ICD?

Answer **Answer**: Competitive sports participation of any intensity is **reasonable**. ICD is **NOT recommended** for primary prevention. **Rationale**: This is a **genotype-positive/phenotype-negative (G+P−)** individual. Per the 2024 AHA/ACC guideline and 2025 sports statement: - G+P− individuals can participate in competitive sports of any intensity - ICD is not recommended for primary prevention in the absence of phenotype - Serial surveillance (ECG + echo every 1–2 years) is indicated to detect phenotype development **Key learning point**: G+P− status is **not** the same as HCM phenotype—don't restrict sports or recommend ICD based on genotype alone.

References

  • Ommen SR, et al. JACC. 2024;83(23):2324-2405. PMID: 38727647 — 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR HCM Guideline
  • Arbelo E, et al. Eur Heart J. 2023;44(37):3503-3626. PMID: 37622657 — 2023 ESC Cardiomyopathies Guideline
  • Martinez MW, et al. JACC. 2025;85:1059-1108. PMID: 39800560 — 2025 Sports Participation Scientific Statement
  • Norrish G, et al. JAMA Cardiol. 2019;4(9):918-927. PMID: 31411652 — HCM Risk-Kids
  • Shah MJ, et al. Heart Rhythm. 2021;18(11):1888-1924. PMID: 34246768 — 2021 PACES CIED Expert Consensus