Hypertrophic Cardiomyopathy: Evaluation and Management

Diagnostic Evaluation

All patients with suspected HCM require transthoracic echocardiography as the initial diagnostic test, combined with a comprehensive 3-generation family history and physical examination to identify unexplained left ventricular hypertrophy (≥15 mm in any segment, or ≥13 mm with positive family history). 1

Initial Diagnostic Workup

Echocardiography with provocative maneuvers (Valsalva, standing, amyl nitrite) is mandatory when resting LVOT gradient is <50 mmHg to unmask obstruction 1
Exercise echocardiography is required for symptomatic patients without resting/provocable gradients ≥50 mmHg to detect latent LVOT obstruction 1
Cardiac MRI should be obtained when echocardiography is inadequate or when assessing maximum wall thickness, LV apical aneurysm, ejection fraction, and extent of late gadolinium enhancement for risk stratification 1
12-lead ECG and 24-48 hour Holter monitoring to detect nonsustained ventricular tachycardia (≥3 beats at ≥120 bpm lasting <30 seconds) 1
Genetic testing and counseling for patients meeting diagnostic criteria and their first-degree relatives 1

Pharmacologic Management Algorithm

First-Line Therapy: Beta-Blockers

Nonvasodilating beta-blockers (metoprolol, atenolol, propranolol) are the mandatory first-line treatment for all symptomatic HCM patients, titrated to achieve resting heart rate of 60-65 bpm. 1, 2 Do not declare beta-blocker failure until maximally tolerated doses with documented heart rate suppression are achieved 2.

Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers

If beta-blockers are ineffective, not tolerated, or contraindicated, switch to verapamil (up to 480 mg/day) or diltiazem—never combine with beta-blockers due to bradycardia and heart block risk. 1, 2 These agents provide negative inotropic effects and improve diastolic filling 2.

Third-Line Options for Obstructive HCM

Mavacamten (cardiac myosin inhibitor) is now Class I recommended for adults with persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers 1, 2
Disopyramide (combined with AV nodal blocking agent to prevent rapid ventricular response if AF develops) can be added when first-line agents fail 1, 2
Low-dose diuretics may be cautiously used for persistent dyspnea with volume overload, but aggressive diuresis worsens LVOT obstruction by decreasing preload 2

Critical Medications to AVOID

Immediately discontinue all vasodilators in symptomatic patients with LVOT obstruction: 2

Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) - Class III: Harm recommendation 1, 2
ACE inhibitors and ARBs - worsen outflow obstruction 2
Nitrates, hydralazine, alpha-blockers (terazosin, doxazosin) - can precipitate hemodynamic collapse 2
Positive inotropes (dobutamine, dopamine) - increase contractility and worsen obstruction 2

Mavacamten is contraindicated in pregnancy due to teratogenic effects. 1

Sudden Cardiac Death Risk Stratification

The HCM Risk-SCD calculator is the Class I recommended method for estimating 5-year sudden death risk in patients ≥16 years old without prior cardiac arrest or sustained VT. 1 Reassess risk at initial evaluation and every 1-2 years or with clinical status changes 1.

Major Risk Factors for SCD

The following factors should be systematically evaluated: 1

Personal history: Prior cardiac arrest or sustained VT causing syncope/hemodynamic compromise
Syncope: Recent unexplained episodes suspected to be arrhythmic (not vasovagal or LVOTO-related)
Family history: Premature HCM-related sudden death in first-degree relative ≤50 years old
Massive LVH: Maximum wall thickness ≥30 mm (or Z-score ≥6 in children)
LV apical aneurysm: Independent of size
LV systolic dysfunction: Ejection fraction <50%
Nonsustained VT: On ambulatory monitoring

ICD Indications

Secondary Prevention (Class I): ICD implantation is mandatory for patients who survived cardiac arrest due to VT/VF or have spontaneous sustained VT causing syncope/hemodynamic compromise, with life expectancy >1 year 1.

Primary Prevention (Class IIa): ICD placement is reasonable for adult patients with ≥1 major risk factors listed above, after shared decision-making that includes discussion of estimated 5-year sudden death risk, device complications (inappropriate shocks occur in 20-30% over 5 years), and driving/occupational implications 1.

Pediatric Considerations: For children with ≥2 major risk factors, ICD implantation should be considered despite higher complication rates in younger patients 1. Single-chamber devices are preferred to reduce complications 1.

Device Programming: Shock-only programming with extended detection times should be considered to minimize inappropriate shocks 1. Subcutaneous ICD may be considered in patients without pacing indications, ensuring optimal R-wave sensing at rest and exercise 1.

Septal Reduction Therapy Indications

SRT is recommended for patients with obstructive HCM (LVOT gradient ≥50 mmHg at rest or with provocation) who remain severely symptomatic (NYHA class III-IV) despite maximally tolerated guideline-directed medical therapy. 1, 2

Eligibility Criteria

Severe dyspnea or chest pain interfering with daily activities despite optimal medical therapy 2
Dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation 2
Appropriate septal morphology and absence of intrinsic mitral valve disease requiring separate intervention 1

Surgical Myectomy vs. Alcohol Septal Ablation

Surgical myectomy is the preferred SRT when performed at experienced comprehensive HCM centers, achieving >90% relief of obstruction with perioperative mortality <1%. 1, 2 Myectomy is mandatory for patients requiring concomitant cardiac surgery 2.

Consider earlier myectomy for: 2

Severe progressive pulmonary hypertension attributable to LVOTO
Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation
Poor functional capacity on treadmill testing attributable to LVOTO
Children/young adults with very high resting gradients (>100 mmHg)

Alcohol septal ablation is recommended for adult patients when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age 1, 2. Intracoronary ultrasound-enhancing contrast injection is required to identify appropriate septal perforators 1.

SRT is not recommended for asymptomatic patients with normal exercise capacity. 2

Special Clinical Scenarios

Atrial Fibrillation Management

All HCM patients with paroxysmal or persistent atrial fibrillation require oral anticoagulation with direct-acting oral anticoagulants (DOACs), regardless of CHA₂DS₂-VASc score. 1, 2, 3 HCM confers sufficiently increased stroke risk that traditional risk stratification tools do not apply 2.

Acute Hypotension in Obstructive HCM

Phenylephrine (pure alpha-agonist vasoconstrictor) is the preferred agent to reverse acute hypotension—never use vasodilators or positive inotropes. 2 Maximize preload and afterload while avoiding increases in contractility or heart rate 2. Beta-blockade can be added to dampen contractility and prolong diastolic filling 2.

Hypertension Management

Beta-blockers and non-dihydropyridine calcium channel blockers are the preferred antihypertensive agents in obstructive HCM. 2 ACE inhibitors and ARBs have uncertain benefit and are potentially harmful in patients with resting or provocable LVOT obstruction 2.

Obesity and Sleep-Disordered Breathing

Screen all HCM patients for sleep-disordered breathing (affects 55-70% of patients) and refer to sleep medicine if present, as it is associated with greater symptom burden, reduced exercise capacity, and higher prevalence of atrial fibrillation and NSVT. 2 Comprehensive lifestyle interventions for weight loss are recommended, as obesity (present in >70% of adult HCM patients) is independently associated with increased LVH burden and worse outcomes 2.

Activity Restrictions

Avoidance of competitive sports is mandatory for all HCM patients (Class I recommendation). 1 However, the 2024 guidelines represent a paradigm shift: universal restriction from vigorous physical activity or competitive sports is not indicated for most patients (Class III: No Benefit). 1 After comprehensive evaluation and shared decision-making with an expert provider, participation in vigorous recreational activities is reasonable (Class IIa) 1.

Family Screening Protocol

Screen all first-degree relatives with transthoracic echocardiography and ECG, beginning at any age based on family history specifics. 1 For genotype-positive/phenotype-negative individuals, serial clinical assessment, ECG, and cardiac imaging are recommended every 1-2 years in children/adolescents and every 3-5 years in adults 1. Reconfirm reported pathogenicity of detected variants every 2-3 years, as classifications evolve 1.

Referral to Specialized HCM Centers

Consultation with or referral to comprehensive or primary HCM centers is reasonable for: 1

Complex disease-related management decisions
Interpretation of genetic testing results
Primary prevention ICD decision-making when risk assessment is uncertain
All patients requiring septal reduction therapy 1
Challenging treatment decisions where reasonable alternatives exist or strength of recommendation is weak 1

How should I evaluate and manage a patient with hypertrophic cardiomyopathy, including diagnosis, pharmacologic therapy, risk stratification for sudden cardiac death, and indications for implantable cardioverter‑defibrillator (ICD) or septal reduction?

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