What is obstructive hypertrophic cardiomyopathy and what are the left ventricular outflow tract (LVOT) gradients?

Obstructive Hypertrophic Cardiomyopathy and LVOT Gradients

Obstructive hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy (typically ≥15 mm wall thickness) with a left ventricular outflow tract (LVOT) gradient ≥30 mmHg at rest or with provocation, in the absence of another cardiac or systemic disease capable of producing such hypertrophy. For clinical management purposes, a peak instantaneous LVOT gradient of ≥30 mmHg is considered obstructive, with gradients ≥50 mmHg representing the conventional threshold for considering surgical or percutaneous intervention in symptomatic patients. 1

Definition and Pathophysiology

• HCM is characterized by asymmetric left ventricular hypertrophy with a nondilated and hyperdynamic chamber, often with systolic cavity obliteration 1
• Obstructive HCM refers specifically to the subset of HCM patients who develop dynamic LVOT obstruction, which occurs in approximately two-thirds of patients (either at rest or with provocation) 1
• The obstruction is caused primarily by systolic anterior motion (SAM) of the mitral valve leaflets and mid-systolic contact with the ventricular septum 1
• The mechanical impedance to outflow occurs in the presence of high-velocity ejection, likely attributable to a drag effect or possibly a Venturi phenomenon 1

LVOT Gradient Classifications

Based on the 2011 ACCF/AHA guidelines, LVOT gradients in HCM are classified as follows:

1. Basal (Resting) Obstruction:

   • LVOT gradient ≥30 mmHg at rest 1
   • Approximately one-third of HCM patients have obstruction under basal conditions 1

2. Labile (Provocable) Obstruction:

   • LVOT gradient <30 mmHg at rest but ≥30 mmHg with physiologic provocation 1
   • About one-third of HCM patients have this form 1

3. Nonobstructive HCM:

   • LVOT gradient <30 mmHg both at rest and with provocation 1
   • Approximately one-third of patients have this form 1

Clinical Significance of LVOT Gradients

• The peak instantaneous LVOT gradient (not the mean gradient) is what influences treatment decisions in HCM 1
• LVOT obstruction contributes significantly to heart failure symptoms and is a major determinant of clinical outcomes 1
• Higher LVOT gradients (≥50 mmHg) are associated with increased risk of sudden cardiac death, with a 2.4-fold increase in risk compared to non-obstructive HCM 2
• The magnitude of obstruction shows a direct relationship with risk of adverse events, with each 20 mmHg increase in gradient associated with a 36% increase in risk of sudden death or appropriate ICD discharge 2

Important Clinical Considerations

• LVOT obstruction is dynamic and varies considerably with loading conditions, contractility, and daily activities 1
• Factors that increase obstruction include:
  • Increased myocardial contractility
  • Decreased ventricular volume
  • Decreased afterload 1
• Significant day-to-day variability exists in LVOT gradients, with a 95% confidence interval of ±32 mmHg for resting gradients and ±50 mmHg for provoked gradients 3
• Provocable gradients can be assessed using exercise testing with Doppler echocardiography, which is particularly helpful in patients with exertional symptoms but no resting obstruction 1
• Dobutamine provocation is no longer recommended for assessing LVOT gradients in HCM 1

Clinical Implications

• Management strategies are largely dependent on the presence or absence of symptoms caused by obstruction 1
• Marked gradients ≥50 mmHg (either at rest or with provocation) represent the conventional threshold for surgical or percutaneous intervention if symptoms cannot be controlled with medications 1
• In asymptomatic patients with LVOT obstruction and no other risk factors, the annual rate of sudden death is low (0.37%), suggesting that aggressive interventions to reduce LVOT obstruction may not be warranted in this group 2
• The presence of LVOT obstruction is associated with more severe hypertrophy and poorer systolic and diastolic left ventricular function 4