Due to low enrollment the decision was made to terminate study prior to final data collection for any individual.

The specific aims of this study are to:

• Establish baseline levels of circulating MMP-2 and -9 , TIMP-1and- 2 and TGFB levels in individuals with bicuspid aortic valve and ascending aortic or aortic sinus measurements >40mm.
• Assess the effect on MMP levels during treatment with losartan, an angiotensin II receptor blocking agent.
• In the setting of losartan therapy for one year, evaluate the response of MMP levels in these patients, and clinical outcomes including effects on aortic growth rate

Inclusion Criteria:

• Adults >age 18 years and < 65 years old
• Able to give informed consent
• Presence of a bicuspid aortic valve (functional or true bicommisural)and ascending aorta or sinus of Valsalva >4.0cm
• No contraindications to treatment with Losartan, an Angiotensin II receptor blocker
• Able to safely participate in a 4 week drug washout period if currently taking an angiotensin II receptor blocker or ACE inhibitor.

Exclusion Criteria:

• Unable to safely take losartan due to one or more of the following:

  • Hypersensitivity to losartan or other angiotensin receptor blockers
  • Pregnancy
  • Nursing mothers
  • History of angioedema
  • Hypotension - chronically volume depleted patients
  • Hepatic or renal impairment (Cr>1.5mg/dL)
  • Hyperkalemia (K+>4.8)
  • Renal artery stenosis
  • Severe congestive heart failure (class III-IV)
  • Currently taking potassium supplements or salt substitutes containing potassium
  • Currently taking lithium

• Prior surgical intervention to aorta or aortic valve

• Unable or unwilling to give informed consent and follow up with study activities

• Currently taking an angiotensin receptor blocker or ACE inhibitor specifically for hypertension and are therefore unable to or are unwilling to participate in a 4 week drug washout period.

• Females of child bearing who are unwilling to practice adequate birth control throughout the study.

6 months (study was terminated prior to proposed completion)