Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
A heart condition called hypertrophic cardiomyopathy (HCM) causes abnormal thickening of the
 heart muscle, which obstructs the flow of blood out of the heart. The thickened muscle and
 the obstruction of blood flow are believed to cause chest discomfort, breathlessness,
 fainting, and a sensation of heart pounding. Treatment options for children with HCM include
 medicine, heart operation, and cardiac transplantation. However, there is no evidence that
 medicine prevents further thickening of heart muscle; operations carry the risk of death; and
 donor hearts are not always available. Several studies have shown that pacemaker treatment
 reduces the obstruction and improves heart complaints in patients with HCM. This study
 investigates further the efficacy of pacemaker treatment in children.

 Patients will have exercise tests after treatment with beta blocker and verapamil and will be
 eligible for the study if heart complaints or reduced exercise performance continue.

 A pacemaker that treats slow heart rhythms will be inserted. The patient will be sedated and
 local anesthesia will be administered to numb the area. The procedure takes about an hour.

 The study will last two years. Patients will be placed on one of two pacemaker programs for
 the first year and another the second year. At 3- and 6-month follow-up visits, a pacemaker
 check and echocardiogram will be performed. After 1 year, patients will be admitted to NIH
 for 2 to 3 days for exercise tests, echocardiogram, and cardiac catheterization. Also, the
 pacemaker will be changed to the second program. At 15- and 18-month follow-up visits, a
 pacemaker check and echocardiogram will be performed. After 2 years, patients will again be
 admitted for 2 to 3 days for exercise tests, echocardiogram, and cardiac catheterization. A
 pregnancy test will be given to females of child-bearing age before each cardiac
 catheterization and electrophysiology study.

 At the end of the study, the pacemaker will be set to the program that worked better.

 Risks of pacemaker insertion include lung collapse, infection, blood vessel damage, bleeding,
 heart attack, and death. Risks of cardiac catheterization include infection, bleeding, blood
 clots, abnormal heart rhythms, perforation of the heart, need for surgery, and death.
 However, the safety record for both these procedures at NIH has been excellent. The radiation
 exposure exceeds the NIH radiation guidelines for children, but this exposure in adults has
 not been associated with any definite adverse effects.
Studies suggest that DDD pacemaker therapy is effective in improving symptoms and reducing
 intra-ventricular pressures and pressure gradients in children with obstructive HCM during a
 period of rapid body growth when the severity of the disease is expected to worsen. We
 propose a randomized, cross-over study of DDD pacing versus placebo (AAI pacing mode) in
 children who have limited exercise performance and/or symptoms despite medical therapy
 (beta-blocker or verapamil). Study subjects will receive a pacemaker and will be randomized
 to one of two pacing modes (DDD, AAI). After a 1-year follow-up evaluation the children will
 cross-over to the alternative pacing mode, and will be re-evaluated after a further year. All
 children will continue to receive optimum medical therapy (beta-blocker or verapamil) based
 on improvement in symptoms and exercise performance. The subjects will undergo outpatient
 evaluations (exercise tests and echocardiography) 3, 6, 15, and 18 months after pacemaker
 implantation, and inpatient evaluations (exercise tests, echocardiography, and cardiac
 catheterization) 1 year and 2 years after entry into the study. Primary end-points will be
 exercise duration and severity of LV outflow obstruction. The patient, parents, referring
 physician, and individual supervising the exercise tests will be blinded to the pacing mode.
INCLUSION CRITERIA:

 Children of either gender, aged 4 to 18 years.

 Obstructive HCM defined as LV hypertrophy, and an LV intra-cavitary pressure gradient
 measured at cardiac catheterization of greater than or equal to 30 mm Hg at rest or greater
 than or equal to 50 mm Hg following isoproterenol infusion to a heart rate of greater than
 or equal to 100 beats per minute.

 Cardiac symptoms (chest discomfort, dyspnea, lightheadedness or presyncope, syncope,
 cardio-respiratory arrest, palpitations, excessive fatigue); and/or exercise duration which
 is less than 10th percentile predicted for age/gender despite a trial of a beta-blocker
 therapy and a trial of verapamil therapy.

 EXCLUSION CRITERIA:

 Other systemic diseases that prevent assessment by exercise tests and cardiac
 catheterization.

 Chronic atrial fibrillation.

 Positive pregnancy test: A negative urine pregnancy test will be required before each
 cardiac catheterization, electrophysiologic study and thallium study. Pregnant or lactating
 subjects may not participate in the study due to potential teratogenic effects of
 radiation.