Heart Function in HIV-Negative Children Exposed to HIV and HAART

• Left Ventricular Mass Index [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  left ventricular mass index measured by 2D echocardiography
  
  
• Fractional Shortening [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Fractional shortening measured by M-mode cardiography
  
  

• Global Strain Rate [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Myocardial deformation (a measure of heart contractility) measured by speckel tracking echocardiography
  
  
• Systolic Myocardial Velocity During Systole (S') [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Systolic myocardial velocity during systole measured by tissue Doppler echocardiography
  
  
• Early to Late Diastolic Filling Ratio [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Early to late diastolic filling ratio measured by tissue Doppler echocardiography
  
  
• Myocardial Wall Velocity During Early Diastole [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  Myocardial wall velocity during early diastolemeasured by tissue Doppler imaging
  
  

Significance:

Approximately 700,000 children annually are born to HIV-infected mothers throughout the world, but with the advent of perinatal highly active antiretroviral therapy (HAART), the majority of children are born uninfected in Westernized nations and those uninfected are increasing in developing nations. Uninfected children exposed to HIV and HAART in utero, have subclinical left ventricular dysfunction (LVD) at birth which may predispose them to heart failure, conduction abnormalities and myocardial infarction later in life. The impact of this LVD on future cardiac risk is unclear as it is unknown if LVD in these children persist, worsen or resolve in pre-pubescence.

Study objectives:

The objective of this study is to characterize left ventricular function in HIV-negative pre-pubertal children born to HIV+ women and exposed to HIV and HAART in utero and compare them to age and gender matched healthy children born to HIV-negative women. Through this objective we will determine if LVD in HIV-negative children born to HIV+ women and exposed to HAART in utero persists, worsens, or resolves during pre-pubescence. If LVD persists or worsens in pre-pubescence, these data will lead to future studies examining mechanisms of and treatments for LVD in these children and will significantly impact the clinical monitoring and care of these children. If LVD resolves during pre-pubescence, then these data will provide important information that clinical cardiac monitoring may not be critical in this population.

Methods:

We plan to examine left ventricular function in 30 HIV-negative children born to HIV+ women and exposed to HAART in utero and compare them to 30 healthy age and gender matched children born to HIV-negative women. Left ventricular function will be examined by 2-D, Doppler and Tissue Doppler imaging echocardiography using a General Electric Vivid 7® ultrasound machine. Left ventricular measures will include left ventricular structure and dimensions, systolic and diastolic flow rates, wall velocities during systole and diastole and systolic and diastolic strain and strain rates (sensitive measures of myocardial contractility). Echocardiographic measures will take place in the Cardiovascular Imaging Laboratory (CVIL) at Washington University School of Medicine by a certified cardiac ultrasonographer and data will be processed, analyzed and interpreted by the ultrasonographer, a consulting cardiologist and the principal investigator.

Outcomes:

Primary outcomes will include measures of left ventricular function: left ventricular mass, left ventricular end diastolic dimension, fractional shortening, systolic and diastolic wall velocities (tissue Doppler imaging) and systolic and diastolic strain and strain rates (2-D speckle tracking methodology).