Factors Contributing to Increased Left Ventricle Size in Patients With Abnormally Enlarged Hearts
Factors Contributing to Increased Left Ventricle Size in Patients With Abnormally Enlarged Hearts
The human heart is divided into four chambers. One of the four chambers, the left ventricle,
 is the chamber mainly responsible for pumping blood out of the heart into the circulation.
 There is an inherited condition affecting the heart, passed on through genetics, hypertrophic
 cardiomyopathy (HCM). HCM causes the left ventricle to become abnormally enlarged (left
 ventricular hypertrophy LVH).

 Some patients with the abnormal genes that may cause HCM do not have the characteristic LVH.
 Approximately 20 - 40% of patients with the genetic abnormality (missense mutation of genes
 encoding for sarcomeric protein) actually have an enlarged left ventricle. Because of this,
 researchers believe there may be other factors, along with the genetic abnormality that
 contribute to the development of HCM. Researchers are interested in learning more about
 several factors they suspect may play a role in the development of HCM.

 Specifically, researchers plan to study levels of a hormone and the protein it attaches to,
 which may contribute to the development of an abnormally enlarged heart. Insulin-like growth
 factor (IGF-1) and insulin-like growth factor binding protein (IGFBP) work together with
 growth hormone (GH) in the development and maturation of many organ systems. Previous studies
 have suggested that these hormones affect the development and function of the heart.

 Patients participating in this study will undergo a variety of tests including collection of
 blood samples, echocardiogram of the heart, treadmill exercise test, and continuous
 electrical monitoring of heart activity (Holter monitor).
Hypertrophic cardiomyopathy (HCM) is a genetic disease with an autosomal dominant pattern of
 inheritance which is characterized by left ventricular hypertrophy (LVH). HCM is often caused
 by missense mutations of genes that encode for sarcomeric proteins. The LVH varies markedly
 in patients with identical sarcomeric gene mutations, and notably, 20 to 40% of subjects with
 disease mutation do not have LVH as assessed by echocardiography. These findings suggest that
 other factors affect LV wall thickness in HCM. We wish (1) to investigate the potential role
 of IGF-I and its binding protein, IGFBP3, in determining increased LV mass in HCM caused by
 sarcomeric mutations; and (2) to assess myocardial ultrasound backscatter, exercise
 tolerance, and propensity to arrhythmias, in subjects who have inherited sarcomeric mutations
 but who do not have LVH.
INCLUSION CRITERIA

 HCM subjects 5 years or older, with distinct sarcomeric gene mutations and LV wall
 thickness greater than 15 mm in subjects older than 18 years, and greater than 2 SDs in
 subjects 18 years of age or younger, as assessed by MRI.

 Age- and gender-matched blood relatives with sarcomeric gene mutations but without LVH.

 Age- and gender-matched blood relatives without sarcomeric gene mutations.

 EXCLUSION CRITERIA

 History of hypertension (basal systolic and diastolic pressures above 170 mm Hg and 95 mm
 Hg, respectively) or another systemic or cardiac disease that may cause cardiac
 hypertrophy.

 History of recent acute illness or other chronic illness that might affect plasma levels of
 IGF-I and IGFBP3.

 History of thyrotoxicosis, diabetes mellitus or abnormally elevated fasting blood sugar.

 Any conditions which would exclude patients from undergoing MRI scan.