Cardiology was consulted on a 61-year-old female patient for activity-limiting shortness of breath and premature ventricular contractions. Pertinent medical history included hypertension. Upon review, an echocardiogram from the prior month revealed a left ventricular intracavitary gradient of 98 mmHg; with the Valsalva maneuver, her gradient increased to 188 mmHg. The interventricular septum thickness was 16 mm, and her left ventricular ejection fraction was hyperdynamic. She also had systolic anterior motion of the mitral valve, causing posteriorly directed mitral regurgitation. This suggested hypertrophic cardiomyopathy. She had a baseline bradycardia, with her resting heart rate in the 50s. Her medications included amlodipine and lisinopril. These medications were stopped because they could potentially increase the left ventricular outflow tract (LVOT) obstruction and filling pressure, causing hypotension and worsening symptoms. She was not willing to undergo any invasive procedures and asked about other therapeutic options. She had a normal QTc on her electrocardiogram (ECG), and there was no family or personal history of long QT syndrome.
What is the best therapeutic option for this patient?
The correct answer is: D. Start disopyramide
Based on the American College of Cardiology 2011 guidelines and Dr. Naidu's 2015 article "Diagnosis and Management of Hypertrophic Cardiomyopathy," medical therapy is recommended as first line. Unfortunately, beta-blockers or non-dihydropyridine calcium channel blockers (first line therapy) are not appropriate because of her resting bradycardia. Disopyramide cannot be used alone in a patient with atrial fibrillation (AF) due to the risk of a tachyarrhythmia, specifically from AF with rapid ventricular response from the increased AV conduction effect; luckily, the patient was in sinus bradycardia. She also had a high LVOT gradient both at rest and with Valsalva maneuver.
Surgical myectomy or alcohol septal ablation would be appropriate if she failed medical therapy and remained symptomatic with a LVOT gradient. If a patient is not a candidate for either myectomy or ablation, then DDD pacing is a Class IIb indication.
Due to her baseline bradycardia, beta-blocker or non-dihydropyridine calcium channel blockers were not started. Her QT was not prolonged. She was safely started on disopyramide CR 200 mg by mouth every 12 hours and noted relief of symptoms within 1 day. Disopyramide offers the benefit of a profound reduction in myocardial contraction. Ideally, we would consider starting beta-blocker or non-dihydropyridine calcium channel blocker therapy if her heart rate improved because disopyramide can also enhance atrioventricular nodal conduction during AF. Even though this patient did not have a history of AF, she was at risk due to the hypertrophic cardiomyopathy. Because of the QT prolonging potential of disopyramide, multiple ECGs over 3 days were obtained in the hospital, and all showed that her QTc interval did not increase while on disopyramide. We discussed with her importance of avoiding any other QT prolonging drugs and having an ECG done at least every 6 months. We also connected her with various resources including a handout on what drugs can prolong her QTc. A follow-up stress test demonstrated a resting gradient of 33 mmHg and a provocable gradient of 66 mmHg. She had only chordal systolic anterior motion, and the intracavitary gradient decreased significantly when taking the disopyramide. Also, no significant arrhythmias were noted during her stress echocardiography. Prior to her disopyramide regimen, she was having frequent premature ventricular contractions. In the short term, it was important to evaluate for the typical anticholinergic side effects but also to recheck an ECG as well as reassess for the addition of beta-blocker or non-dihydropyridine calcium channel blocker therapy.
Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733–79.
Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011;58:e212-60.