What is the management approach for patients with symptoms suggestive of Hypertrophic Obstructive Cardiomyopathy (HOCM) where the Brockenbrough-Braunwald sign is observed?

Brockenbrough-Braunwald Sign in Hypertrophic Obstructive Cardiomyopathy

The Brockenbrough-Braunwald-Morrow sign is a diagnostic hemodynamic finding used during invasive cardiac catheterization to confirm left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy when noninvasive imaging is ambiguous or unreliable. 1

What the Sign Represents

The Brockenbrough-Braunwald-Morrow sign demonstrates post-extrasystolic augmentation of the left ventricular outflow tract (LVOT) gradient with simultaneous reduction in aortic pulse pressure following a premature ventricular contraction. 1 This paradoxical hemodynamic response—where contractility increases but aortic pressure decreases—is pathognomonic for dynamic LVOT obstruction in hypertrophic cardiomyopathy. 1

When to Perform Invasive Assessment

Invasive hemodynamic assessment with cardiac catheterization is recommended (Class I, Level B-NR) for symptomatic HCM patients (NYHA class II-IV) when there is uncertainty regarding the presence or severity of LVOTO on noninvasive imaging studies. 1

Specific Clinical Scenarios Warranting Invasive Assessment:

• Poor echocardiographic windows that limit reliable Doppler gradient assessment 1
• Ambiguous Doppler profiles where increased velocity cannot be distinguished between outflow tract obstruction versus mitral regurgitation contamination 1
• Coexistent valvular aortic stenosis requiring differentiation from dynamic LVOT obstruction 1
• Persistent severe symptoms despite optimal medical therapy to fully characterize hemodynamic profile and contribution of other disease states 1

Provocative Maneuvers During Catheterization

When resting gradients are not severe (≥50 mm Hg), provocative maneuvers are used to unmask latent obstruction: 1

• Inducing premature ventricular contractions to assess for the Brockenbrough-Braunwald-Morrow sign 1
• Valsalva maneuver 1
• Low-dose isoproterenol infusion (preferred over dobutamine due to lower false-positive rates) 1
• Upper or lower extremity exercise 1
• Amyl nitrate inhalation 1

Critical caveat: Dobutamine stress protocols can induce gradients even in patients without HCM, leading to significant false-positive rates and should be avoided. 1

Management After Confirming Obstruction

Initial Medical Therapy

Beta-blockers are the first-line treatment for symptomatic patients with obstructive or nonobstructive HCM (Class I, Level B). 1, 2

• Titrate to resting heart rate <60-65 bpm using doses up to generally accepted maximum (e.g., metoprolol up to 400 mg/day) 1, 2
• Monitor for bradycardia, hypotension, and heart block during administration 2

If beta-blockers are ineffective, contraindicated, or not tolerated, verapamil (starting at low doses and titrating up to 480 mg/day) is recommended (Class I, Level B). 1, 3

• Use verapamil with extreme caution in patients with high gradients, advanced heart failure, or sinus bradycardia 1, 3
• Never combine beta-blockers with verapamil or diltiazem due to risk of high-grade atrioventricular block 2, 3
• In patients with severe LVOT obstruction and past history of left ventricular dysfunction, verapamil can precipitate pulmonary edema and severe hypotension 3

Critical Medications to Avoid

Never administer the following in patients with confirmed LVOT obstruction:

• Dihydropyridine calcium channel blockers (nifedipine, amlodipine) are potentially harmful 2
• Vasodilators (ACE inhibitors, ARBs, nitroglycerin) reduce preload and afterload, worsening obstruction 2
• Digoxin for dyspnea in HCM patients without atrial fibrillation is potentially harmful 2

Septal Reduction Therapy

For patients with severe symptoms (NYHA class III-IV) despite optimal medical therapy and resting or provocable gradients ≥50 mm Hg, septal reduction therapy should be considered. 1, 4

Surgical septal myectomy is the gold standard treatment:

• Operative mortality <1% in experienced centers 1, 4, 5
• >90% relief of obstruction and symptom improvement 4, 5, 6
• Major complication rate should be ≤3% 1
• Complete heart block requiring permanent pacemaker occurs in ~2% 1, 5

Alcohol septal ablation is an alternative:

• Procedural mortality 0-4% 1
• High-grade AV block requiring permanent pacemaker in 10-20% of patients 1
• Results are dependent on septal perforator anatomy and may not achieve complete relief in younger patients with severe hypertrophy 4

Pre-Procedural Requirements

Coronary angiography (CT or invasive) is recommended (Class I, Level B-NR) before surgical myectomy in patients at risk of coronary atherosclerosis. 1 Findings of extensive coronary artery disease would inform decision-making regarding combined myectomy with coronary bypass surgery. 1

Critical Operator Requirements

The operator performing invasive hemodynamic assessment must be experienced and use appropriate catheters (end-hole pigtail, halo) while avoiding catheter entrapment. 1 For septal reduction procedures, operators should have performed at least 20 procedures or work within an HCM program with cumulative volume of at least 50 procedures. 1