What is the management approach for a patient with asymmetric left ventricular hypertrophy?

Management of Asymmetric Left Ventricular Hypertrophy

The management of asymmetric left ventricular hypertrophy depends critically on whether this represents hypertrophic cardiomyopathy (HCM) versus other causes—first exclude secondary causes like hypertension, aortic stenosis, infiltrative diseases, and athlete's heart, then if HCM is confirmed, treatment is stratified by the presence or absence of left ventricular outflow tract obstruction (LVOTO) and symptom severity. 1

Initial Diagnostic Evaluation

Establish the underlying etiology before initiating treatment:

• Any LV wall thickness ≥15 mm in adults that is unexplained by loading conditions requires systematic evaluation to determine the cause 1
• In first-degree relatives of HCM patients or those with pathogenic sarcomere gene variants, a wall thickness of 13-14 mm is sufficient for diagnosis 2
• Exclude infiltrative diseases (amyloidosis, sarcoidosis, Fabry disease, glycogen storage diseases), drug-induced causes (anabolic steroids, tacrolimus, hydroxychloroquine), and physiologic athlete's heart 1
• Transthoracic echocardiography is the first-line imaging modality, with cardiovascular magnetic resonance (CMR) reserved for inconclusive cases or suspected apical involvement 2

Key distinguishing features favoring HCM over hypertensive heart disease:

• Family history of HCM, right ventricular hypertrophy, late gadolinium enhancement at RV insertion points on CMR, maximum LV wall thickness ≥15 mm (≥20 mm in Black patients), severe diastolic dysfunction, or marked ECG repolarization abnormalities 3
• Normal ECG or isolated voltage increase without repolarization changes, and regression of LVH with tight blood pressure control (<130 mmHg over 6-12 months) favor hypertension alone 3

Assessment of Left Ventricular Outflow Tract Obstruction

Determine the presence and severity of LVOTO, as this fundamentally alters management:

• Perform 2D and Doppler echocardiography with Valsalva maneuver in sitting and semi-supine positions, then standing if no gradient is provoked 3
• LVOTO is defined as peak instantaneous Doppler gradient ≥30 mm Hg, but the threshold for invasive treatment is ≥50 mm Hg 3
• In symptomatic patients without provoked gradient at rest, exercise stress echocardiography is recommended to identify latent obstruction 3
• Avoid dobutamine provocation due to lack of specificity 1

Management of Obstructive HCM (LVOTO ≥50 mm Hg)

General Measures

• Avoid dehydration, excess alcohol consumption, and encourage weight loss 3
• Avoid arterial and venous dilators including nitrates and phosphodiesterase-5 inhibitors as they exacerbate LVOTO 3
• Avoid digoxin due to positive inotropic effects 3
• Promptly restore sinus rhythm or achieve rate control in new-onset or poorly controlled atrial fibrillation before considering invasive therapies 3, 1

Pharmacological Therapy

First-line treatment:

• Beta-blockers (non-vasodilating) titrated to maximum tolerated dose are first-line therapy to reduce symptoms 3, 1
• Propranolol has been shown to abolish or reduce resting and provocable LVOTO with symptomatic benefit 3

Second-line treatment:

• Non-dihydropyridine calcium channel blockers (verapamil or diltiazem) are alternatives for patients intolerant or with contraindications to beta-blockers 1

Third-line treatment:

• Add disopyramide (when available) to beta-blockers if LVOT gradient ≥50 mm Hg persists with refractory symptoms, titrated to 400-600 mg daily 3, 1

Novel therapy:

• Cardiac myosin inhibitors (mavacamten) are beneficial for patients with obstructive HCM who do not derive adequate symptomatic relief from first-line drug therapy 3

Invasive Septal Reduction Therapy

For patients with LVOT gradient ≥50 mm Hg and symptoms refractory to maximum medical therapy:

• Extended septal myectomy via transaortic approach is the standard surgical procedure and should be performed at experienced HCM centers 3, 1
• Septal alcohol ablation is an alternative in selected patients but requires careful patient selection and experienced centers 1
• Transapical myectomy may be considered for the rare subgroup with extensive apical hypertrophy to augment LV cavity size 1
• Given significantly improved outcomes at comprehensive HCM centers, referral for invasive procedures is strongly recommended 3

Management of Non-Obstructive HCM (LVOTO <50 mm Hg)

• Beta-blockers or non-dihydropyridine calcium channel blockers may improve dyspnea and chest pain 1
• Do not use beta-blockers or calcium channel blockers in asymptomatic patients without data showing benefit 1
• Focus on management of arrhythmias, reduction of LV filling pressures, and treatment of angina 3
• Use diuretics cautiously to prevent symptomatic hypotension from excessive preload reduction 1

Management of Advanced Heart Failure

For patients who develop systolic dysfunction with LVEF <50%:

• Guideline-directed medical therapy for heart failure with reduced ejection fraction is recommended 1
• Perform diagnostic testing to assess for concomitant causes of systolic dysfunction 1
• Cardiopulmonary exercise testing should be performed to assess heart transplant or mechanical circulatory support candidacy in patients with nonobstructive HCM and advanced heart failure 1

Risk Stratification and Sudden Cardiac Death Prevention

Assess sudden cardiac death risk using established risk markers:

• LV apical aneurysm is a major risk factor for sudden cardiac death and warrants ICD implantation regardless of other risk factors 4
• CMR with late gadolinium enhancement is essential to identify apical aneurysms and myocardial fibrosis, which may represent arrhythmogenic substrate 4
• Integrate presence or absence of established risk markers with individual risk score tools to facilitate shared decision-making regarding ICD placement 3
• Pediatric risk stratification differs from adults and requires specialized expertise 3

Atrial Fibrillation Management

• Patients with HCM and persistent or paroxysmal atrial fibrillation should receive oral anticoagulation with direct-acting oral anticoagulants (or warfarin) as the default treatment option irrespective of CHADS2-VASc score 3

Risk Factor Modification

• Intensive management of cardiometabolic risk factors is essential, as obesity, hypertension, diabetes, and obstructive sleep apnea are highly prevalent in HCM patients and associated with poorer prognosis 3, 1

Exercise and Activity

• Healthy recreational exercise at light (<3 METs), moderate (3-6 METs), and vigorous (>6 METs) intensity levels has not been associated with increased adverse outcomes 3
• Exercise stress testing is particularly helpful in determining overall exercise tolerance and latent exercise-provoked LVOTO 3

Follow-Up and Monitoring

• Regular follow-up with cardiac imaging, preferably CMR every 1-2 years, is recommended for patients with HCM, with more frequent monitoring for those with symptoms or progressive disease 4
• Referral to multidisciplinary HCM centers is important for challenging treatment decisions, particularly for interpretation of genetic testing, primary prevention ICD decision-making, and HCM-specific invasive procedures 3