Factors Contributing to Increased Left Ventricle Size in Patients With Abnormally Enlarged Hearts

Brief Title

Factors Contributing to Increased Left Ventricle Size in Patients With Abnormally Enlarged Hearts

Official Title

Contribution of Insulin-Like Growth Factor-I (IGF-I) and Its Binding Protein (IGFBP3) to Increased Left Ventricular Mass in Familial Hypertrophic Cardiomyopathy Caused by Distinct Sarcomeric Mutations

Brief Summary

      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).

Detailed Description

      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.

Study Type



Hypertrophic Cardiomyopathy


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

February 1999

Completion Date

August 2002

Eligibility 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.


        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

        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.




N/A - N/A

Accepts Healthy Volunteers



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Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Study Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

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Verification Date

August 2002