What is the management approach for Hypertrophic Obstructive Cardiomyopathy (HOCM) symptomatology?

Management of Hypertrophic Obstructive Cardiomyopathy (HOCM) Symptomatology

Beta-blockers are the first-line pharmacologic therapy for symptomatic HOCM, titrated to a resting heart rate of 60-65 bpm, with non-dihydropyridine calcium channel blockers (verapamil or diltiazem) as second-line agents when beta-blockers fail or are contraindicated. 1

Initial Pharmacologic Management Algorithm

First-Line Therapy: Beta-Blockers

• Initiate beta-blockers (propranolol, metoprolol, or other non-vasodilating agents) as primary therapy for all symptomatic patients with HOCM, regardless of whether obstruction is present. 2, 1
• Titrate gradually to achieve resting heart rate <60-65 bpm or maximally tolerated doses. 1
• Beta-blockers improve symptoms by reducing myocardial oxygen demand, prolonging diastolic filling time, and decreasing contractility, which reduces left ventricular outflow tract (LVOT) gradients. 2
• Propranolol has been specifically studied in hypertrophic subaortic stenosis, showing improved NYHA functional class in patients with class 2-3 symptoms at doses of 40-80 mg three times daily. 3

Second-Line Therapy: Non-Dihydropyridine Calcium Channel Blockers

• If beta-blockers are ineffective, not tolerated, or contraindicated, substitute with verapamil or diltiazem (never add to beta-blockers due to risk of severe bradycardia and heart block). 1
• Verapamil can be titrated up to 480 mg/day for symptom control in both obstructive and nonobstructive HCM. 1
• These agents improve diastolic dysfunction by enhancing ventricular relaxation and reducing chamber stiffness. 2

Third-Line Therapy: Disopyramide

• Disopyramide is an alternative third-line agent when beta-blockers and calcium channel blockers fail, typically added to existing beta-blocker therapy. 1

Novel Therapy: Cardiac Myosin Inhibitors

• Mavacamten is recommended for adults with persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers (Class I recommendation). 1
• This represents a paradigm shift in medical management, targeting the underlying sarcomeric hypercontractility. 2

Critical Medications to Avoid

Absolutely Contraindicated Agents

• Never use dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) in patients with resting or provocable LVOT obstruction—these cause vasodilation that worsens gradients and can precipitate hemodynamic collapse. 1
• Avoid all vasodilators including alpha-blockers (terazosin, doxazosin), nitrates, and hydralazine in obstructive HOCM. 1
• ACE inhibitors and ARBs are potentially harmful in patients with resting or provocable LVOT obstruction. 1

Cautious Use of Diuretics

• Diuretics should be used cautiously at low doses for congestive symptoms only, as aggressive diuresis decreases preload and worsens LVOT obstruction. 1
• Avoid diuretics and vasodilators entirely in symptomatic patients with LVOT obstruction, though they can be used in asymptomatic patients. 1

Septal Reduction Therapy (SRT)

Indications for SRT

• SRT is recommended for patients with obstructive HCM who remain symptomatic despite guideline-directed medical therapy (GDMT). 1
• Eligibility criteria include: 1
  • Severe dyspnea or chest pain attributable to LVOTO that interferes with everyday activity despite optimal medical therapy
  • Dynamic LVOT gradient ≥50 mmHg at rest or with physiologic provocation

Surgical Myectomy: Preferred Approach

• Transaortic septal myectomy is the most appropriate treatment for the majority of patients with obstructive HCM and severe symptoms unresponsive to medical therapy, achieving >90% relief of obstruction with perioperative mortality <1% in experienced centers. 2, 1
• Myectomy is mandatory for patients requiring concomitant cardiac surgery. 1
• Long-term survival after myectomy approaches that of the general population (99%, 98%, and 95% at 1,5, and 10 years respectively for HCM-related mortality). 2
• The procedure physically enlarges the outflow tract through muscular resection and abolishes systolic anterior motion (SAM) of the mitral valve, eliminating both obstruction and mitral regurgitation. 2

Earlier Myectomy Considerations

• Consider earlier intervention in presence of: 1
  • Severe progressive pulmonary hypertension attributable to LVOTO or associated mitral regurgitation
  • Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation
  • Poor functional capacity attributable to LVOTO on treadmill testing
  • Children and young adults with very high resting LVOT gradients (>100 mmHg)

Alcohol Septal Ablation: Alternative Approach

• Alcohol septal ablation is recommended for adult patients who remain severely symptomatic despite GDMT when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age. 1
• Success depends on variable septal artery anatomy, which may not supply the targeted area in 20-25% of patients. 2
• In patients ≥65 years, survival free from recurrent symptoms favored myectomy over ablation (89% versus 71%, p<0.01). 2
• High-grade atrioventricular block requiring permanent pacemakers occurs in 10-20% of patients following septal ablation. 2
• Acute results show reduction in LVOT gradient from 61.8±29.8 mmHg to 19.4±20.8 mmHg at rest, with further reduction at 3-month follow-up. 4

Operator Experience Requirements

• Operators should have performed at least 20 procedures or work within an HCM program with cumulative volume of at least 50 procedures. 2
• Target mortality rates should be ≤1% and major complication rates ≤3%. 2

When SRT is NOT Recommended

• SRT is not recommended for asymptomatic patients with normal exercise capacity. 1

Management of Acute Hypotension in HOCM

Emergency Protocol

• Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention with phenylephrine as the preferred agent. 1
• Treatment priorities include maximizing preload and afterload while avoiding increases in contractility or heart rate. 1
• Beta-blockade can be useful in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling. 1
• Never use vasodilators or inotropes like dopamine or dobutamine in this setting—they will worsen obstruction and precipitate cardiovascular collapse. 1

Management of Comorbidities

Hypertension Management

• Beta-blockers and non-dihydropyridine calcium channel blockers are preferred antihypertensive agents in obstructive HCM. 2, 1
• Lifestyle modifications and medical therapy for hypertension are recommended in all HCM patients. 2
• In younger patients with nonobstructive HCM due to pathogenic cardiac sarcomere genetic variants who have concomitant hypertension, valsartan may be considered for potential disease progression slowing. 2

Obesity Management

• Counseling and comprehensive lifestyle interventions are recommended for achieving and maintaining weight loss, potentially lowering risk of developing LVOTO, heart failure, and atrial fibrillation. 2, 1
• Obesity is present in >70% of adult HCM patients (body mass index >25 kg/m²) and >30% have body mass index >30 kg/m². 2
• Obesity is independently associated with increased burden of left ventricular hypertrophy, more symptoms, greater likelihood of LVOTO, reduced exercise capacity, and composite outcomes of death, heart failure, atrial fibrillation, ventricular arrhythmias, and stroke (hazard ratios 1.4-1.9). 2

Sleep-Disordered Breathing

• Assessment for symptoms of sleep-disordered breathing is recommended, with referral to sleep medicine specialist if present. 2, 1
• Sleep-disordered breathing affects 55-70% of HCM patients and is associated with greater symptom burden, reduced exercise capacity, older age, hypertension, and higher prevalence of atrial fibrillation and non-sustained ventricular tachycardia. 2, 1

Primary Prevention

• Adherence to ACC/AHA primary prevention guidelines is recommended to reduce risk of cardiovascular events, addressing hypertension, diabetes, hyperlipidemia, inactivity, and tobacco abuse. 2

Pathophysiology of Symptoms

Symptoms in HOCM result from multiple interrelated mechanisms: 2

• Diastolic dysfunction with impaired filling due to abnormal relaxation and increased chamber stiffness, leading to elevated left atrial and LV end-diastolic pressures, pulmonary congestion, and reduced stroke volume
• Myocardial ischemia from supply-demand mismatch despite normal coronary arteries
• LVOT obstruction with elevated LV pressures and concomitant mitral regurgitation
• Atrial fibrillation contributing to hemodynamic compromise

Common Pitfalls to Avoid

• Never combine beta-blockers with non-dihydropyridine calcium channel blockers—this causes severe bradycardia and heart block. 1
• Do not abruptly discontinue beta-blockers, as this precipitates rebound tachycardia and worsening symptoms. 1
• Avoid treating HCM patients with hypertension using standard vasodilator-based regimens without considering the obstructive physiology. 2
• Do not assume all patients with left ventricular hypertrophy and hypertension have hypertensive heart disease—marked LVH disproportionate to blood pressure elevation suggests HCM. 2
• Recognize that many patients with HCM may not require treatment for most or all of their lives and deserve reassurance regarding prognosis. 2

2, 1, 3, 4