Heart Disease in Sickle Cell Anemia
Condition: Sickle Cell Anemia; Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension; Anemia; Anemia, Sickle Cell
Study type: Observational

Summary: 
      This study will explore what may cause people with sickle cell anemia to have heart problems
      and an increased risk of sudden death.

      People 18 years of age and older with sickle cell anemia may be eligible for this study.
      Candidates are screened with a medical history and physical examination, electrocardiogram
      (EKG), echocardiogram (heart ultrasound), and blood tests.

      Participants undergo the following tests and procedures:

        -  Holter monitoring: The patient wears a small, battery-operated device to record heart
           rate and rhythm over 24 to 48 hours.

        -  QRST surface mapping: An EKG using 64 electrodes is done at rest and during exercise to
           provide a detailed look at the heart and its conduction system.

        -  Chest x-rays are taken to examine the lungs.

        -  Bicycle exercise echocardiography test: Blood pressure, pulse, heart rhythm and oxygen
           use are monitored while the patient exercises on a stationary bicycle. Ultrasound
           pictures are also obtained during the exercise.

        -  Echocardiogram: A heart ultrasound is done to check how well the heart is pumping blood.

        -  Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein and
           advanced to the chambers of the heart, through the heart valve and into the lung artery.
           The pressures in the heart and lung blood vessels are measured while the patient is
           resting and during exercise, with the bed tilted up and down, and after giving 500 mls
           of fluid into a vein.

        -  Blood tests are done to measure a hormone called brain natriuretic peptide, which can
           increase with the development of heart failure, and nitrite, a substance that can affect
           blood vessel dilation. Some blood is stored to test for inflammatory markers and for
           possible future gene and protein analysis.

        -  Cardiac magnetic resonance imaging (cMRI): The patient lies in a donut-shaped magnet
           while pictures of the heart are obtained using a magnetic field and radio waves.
           Earplugs are worn to muffle the loud sounds that occur with electrical switching of the
           magnetic fields. A contrast agent called gadolinium may be injected to enhance the
           quality of the images.

        -  Invasive electrocardiographic (reveal) monitoring: This procedure permits study of the
           heart rhythms over a long time period. A small device is placed just under the skin on
           the left side of the chest. It can be left in for up to 14 months to monitor the
           heartbeat continuously during this time.
    

Detailed description: 
      Sickle cell anemia is an inherited blood disorder primarily affecting groups with origins in
      endemic malarial areas, especially those of African descent. SCA results from one of two
      single amino-acid substitutions in beta-hemoglobin (Hb-S and Hb-C) that increases the
      propensity for hemoglobin to polymerize, thus distorting, sickling and hemolyzing red cells.
      Individuals homozygous for Hb-S (or double heterozygote Hb-S and Hb-C) develop sickle cell
      anemia (SCA), while heterozygotes have sickle cell trait. SCA is characterized by chronic
      anemia and crises of red cell sickling and ischemia that are often painful and affect several
      organs and tissue types. SCA confers considerable disability, morbidity and mortality.

      Annual mortality from SCA has been estimated at approximately 3%. As a significant number of
      these deaths are sudden, a cardiac cause has been suspected. However, no cardiac mechanism of
      sudden death (SD) has been clearly identified. Recently, it has been demonstrated that SCA
      patients with pulmonary hypertension (PAH) have a higher incidence of SD than those with
      normal pulmonary pressures. In many patients, PAH occurs in association with elevated
      pulmonary arterial wedge pressures and normal pulmonary arterial resistance, suggesting that
      the PAH develops as the result of left ventricular (LV) abnormalities. Furthermore, in other
      conditions in which PAH develops, SD occurs only at pressures considerably higher than those
      observed in SCA. These factors suggest that PAH in SCA is a surrogate marker for, rather than
      the cause of SD. Rather, an SCA cardiomyopathic process may provide a unifying mechanism that
      associates moderate degrees of PAH and high risk of SD from cardiac causes.

      We propose to describe the extent of cardiac involvement in SCA. Specifically, we will (1)
      describe the LV volume-pressure relations in SCA patients with and without pulmonary
      hypertension in order to determine how elevated pulmonary pressures are related to dynamic
      filling properties of the LV; and (2) determine whether cardiac arrhythmias are common in SCA
      patients with PAH and if they contribute to SD.

      Improved understanding of the etiology and mechanisms of SD in SCA may allow the development
      and testing of therapies for the primary prevention of SD.
    

Keywords: Cardiac Arrhythmias; Diastolic Dysfunction; Pulmonary Hypertension; Sickle Cell Anemia; Sudden Death; Thalassemia