Molecular Mechanisms of Mitral Regurgitation-Aim 2

NCT01052532 | Completed

• 1 other identifier: F0400105007
• Study Type: observational
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that MR in humans is characterized by adrenergic overdrive, reactive nitrogen species, and an antifibrotic phenotype that relate to the severity of adverse LV remodeling prior to surgery and outcome after valve repair.

Conditions

Mitral Regurgitation

Keywords

Mitral Regurgitation; LV remodeling; Reactive nitrogen species; Cardiac MRI; Adrenergic overdrive

Outcome Measures

Primary Outcomes (1)

• Plasma levels of MT1MMP, MMP-1,-2 and -9, bradykinin type-2 receptor, AT1 and AT2 receptor, collagen type II and III and collagen breakdown products

  12 months

Study Arms (1)

Mitral Regurgitation pre&post operation

Patients with severe Mitral Regurgitation without evidence of ischemia are tested prior to surgery and after valve repair.

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Ptaients scheduled for Mitral valve repair from c ardiology clinic / Hospital

You may qualify if:

• years old or older.
• Severe MR by echo or catheterization without evidence of ischemia requiring surgery documented by cardiac catheterization and/or maximal stress test with myocardial perfusion imaging.

You may not qualify if:

• Significant obstructive coronary artery disease and/or myocardial ischemia on graded exercise test with myocardial perfusion.
• Previous myocardial infarction.
• Hypertrophic cardiomyopathy, congenital or pericardial disease.
• Aortic valve disease (\> trace aortic regurgitation or mean gradient \> 10 mmHg)
• Mitral stenosis (mean gradient \> 5 mmHg, valve area \< 1.5 cm2).
• Renal failure with creatinine \> 2.5 mg/dl.
• Renal artery stenosis.
• Severe comorbidity such as liver disease, malignancy, collagen vascular disease, or chronic steroid requirement.
• Pregnancy (negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential (not post-menopausal or surgically sterilized).
• Severe claustrophobia.
• Presence of a pacemaker or non-removable hearing aid.
• Presence of metal clips in the body.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-2180, United States

Location

Related Publications (23)

• 1. Dell'Italia LJ. Mitral Regurgitation. In Hurst The Heart. Eds. O'Rourke, Sclhant, Alexader, Fuster. 11th Edition, Chapter 57 pp 1169-1695, 2004.

  BACKGROUND

• Olson LJ, Subramanian R, Ackermann DM, Orszulak TA, Edwards WD. Surgical pathology of the mitral valve: a study of 712 cases spanning 21 years. Mayo Clin Proc. 1987 Jan;62(1):22-34. doi: 10.1016/s0025-6196(12)61522-5.

  PMID: 3796056 BACKGROUND

• Borer JS, Bonow RO. Contemporary approach to aortic and mitral regurgitation. Circulation. 2003 Nov 18;108(20):2432-8. doi: 10.1161/01.CIR.0000096400.00562.A3. No abstract available.

  PMID: 14623790 BACKGROUND

• Wisenbaugh T, Essop R, Rothlisberger C, Sareli P. Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation. Am J Cardiol. 1992 Feb 1;69(4):348-53. doi: 10.1016/0002-9149(92)90232-n.

  PMID: 1734647 BACKGROUND

• Rothlisberger C, Sareli P, Wisenbaugh T. Comparison of single dose nifedipine and captopril for chronic severe mitral regurgitation. Am J Cardiol. 1994 May 15;73(13):978-81. doi: 10.1016/0002-9149(94)90148-1. No abstract available.

  PMID: 8184862 BACKGROUND

• Wisenbaugh T, Sinovich V, Dullabh A, Sareli P. Six month pilot study of captopril for mildly symptomatic, severe isolated mitral and isolated aortic regurgitation. J Heart Valve Dis. 1994 Mar;3(2):197-204.

  PMID: 8012639 BACKGROUND

• Marcotte F, Honos GN, Walling AD, Beauvais D, Blais MJ, Daoust C, Lisbona A, McCans JL. Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation with normal left ventricular function. Can J Cardiol. 1997 May;13(5):479-85.

  PMID: 9179087 BACKGROUND

• Host U, Kelbaek H, Hildebrandt P, Skagen K, Aldershvile J. Effect of ramipril on mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1997 Sep 1;80(5):655-8. doi: 10.1016/s0002-9149(97)00445-1.

  PMID: 9295005 BACKGROUND

• Tischler MD, Rowan M, LeWinter MM. Effect of enalapril therapy on left ventricular mass and volumes in asymptomatic chronic, severe mitral regurgitation secondary to mitral valve prolapse. Am J Cardiol. 1998 Jul 15;82(2):242-5. doi: 10.1016/s0002-9149(98)00325-7.

  PMID: 9678300 BACKGROUND

• Dujardin KS, Enriquez-Sarano M, Bailey KR, Seward JB, Tajik AJ. Effect of losartan on degree of mitral regurgitation quantified by echocardiography. Am J Cardiol. 2001 Mar 1;87(5):570-6. doi: 10.1016/s0002-9149(00)01433-8.

  PMID: 11230841 BACKGROUND

• Gaasch WH, Aurigemma GP. Inhibition of the renin-angiotensin system and the left ventricular adaptation to mitral regurgitation. J Am Coll Cardiol. 2002 Apr 17;39(8):1380-3. doi: 10.1016/s0735-1097(02)01766-7. No abstract available.

  PMID: 11955859 BACKGROUND

• Stewart JA Jr, Wei CC, Brower GL, Rynders PE, Hankes GH, Dillon AR, Lucchesi PA, Janicki JS, Dell'Italia LJ. Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog. J Mol Cell Cardiol. 2003 Mar;35(3):311-9. doi: 10.1016/s0022-2828(03)00013-0.

  PMID: 12676546 BACKGROUND

• Nemoto S, Hamawaki M, De Freitas G, Carabello BA. Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation. J Am Coll Cardiol. 2002 Jul 3;40(1):149-54. doi: 10.1016/s0735-1097(02)01926-5.

  PMID: 12103269 BACKGROUND

• Dell'italia LJ, Balcells E, Meng QC, Su X, Schultz D, Bishop SP, Machida N, Straeter-Knowlen IM, Hankes GH, Dillon R, Cartee RE, Oparil S. Volume-overload cardiac hypertrophy is unaffected by ACE inhibitor treatment in dogs. Am J Physiol. 1997 Aug;273(2 Pt 2):H961-70. doi: 10.1152/ajpheart.1997.273.2.H961.

  PMID: 9277516 BACKGROUND

• Perry GJ, Wei CC, Hankes GH, Dillon SR, Rynders P, Mukherjee R, Spinale FG, Dell'Italia LJ. Angiotensin II receptor blockade does not improve left ventricular function and remodeling in subacute mitral regurgitation in the dog. J Am Coll Cardiol. 2002 Apr 17;39(8):1374-9. doi: 10.1016/s0735-1097(02)01763-1.

  PMID: 11955858 BACKGROUND

• Nagatsu M, Zile MR, Tsutsui H, Schmid PG, DeFreyte G, Cooper G 4th, Carabello BA. Native beta-adrenergic support for left ventricular dysfunction in experimental mitral regurgitation normalizes indexes of pump and contractile function. Circulation. 1994 Feb;89(2):818-26. doi: 10.1161/01.cir.89.2.818.

  PMID: 8313571 BACKGROUND

• Tallaj J, Wei CC, Hankes GH, Holland M, Rynders P, Dillon AR, Ardell JL, Armour JA, Lucchesi PA, Dell'Italia LJ. Beta1-adrenergic receptor blockade attenuates angiotensin II-mediated catecholamine release into the cardiac interstitium in mitral regurgitation. Circulation. 2003 Jul 15;108(2):225-30. doi: 10.1161/01.CIR.0000079226.48637.5A. Epub 2003 Jul 7.

  PMID: 12847066 BACKGROUND

• Hankes GH, Ardell JL, Tallaj J, Wei CC, Aban I, Holland M, Rynders P, Dillon R, Cardinal R, Hoover DB, Armour JA, Husain A, Dell'Italia LJ. Beta1-adrenoceptor blockade mitigates excessive norepinephrine release into cardiac interstitium in mitral regurgitation in dog. Am J Physiol Heart Circ Physiol. 2006 Jul;291(1):H147-51. doi: 10.1152/ajpheart.00951.2005.

  PMID: 16772522 BACKGROUND

• Tsutsui H, Spinale FG, Nagatsu M, Schmid PG, Ishihara K, DeFreyte G, Cooper G 4th, Carabello BA. Effects of chronic beta-adrenergic blockade on the left ventricular and cardiocyte abnormalities of chronic canine mitral regurgitation. J Clin Invest. 1994 Jun;93(6):2639-48. doi: 10.1172/JCI117277.

  PMID: 7911128 BACKGROUND

• Mehta RH, Supiano MA, Oral H, Grossman PM, Montgomery DS, Smith MJ, Starling MR. Compared with control subjects, the systemic sympathetic nervous system is activated in patients with mitral regurgitation. Am Heart J. 2003 Jun;145(6):1078-85. doi: 10.1016/S0002-8703(03)00111-X.

  PMID: 12796766 BACKGROUND

• Mehta RH, Supiano MA, Oral H, Grossman PM, Petrusha JA, Montgomery DG, Briesmiester KA, Smith MJ, Starling MR. Relation of systemic sympathetic nervous system activation to echocardiographic left ventricular size and performance and its implications in patients with mitral regurgitation. Am J Cardiol. 2000 Dec 1;86(11):1193-7. doi: 10.1016/s0002-9149(00)01201-7.

  PMID: 11090790 BACKGROUND

• Oral H, Sivasubramanian N, Dyke DB, Mehta RH, Grossman PM, Briesmiester K, Fay WP, Pagani FD, Bolling SF, Mann DL, Starling MR. Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation. Circulation. 2003 Feb 18;107(6):831-7. doi: 10.1161/01.cir.0000049745.38594.6d.

  PMID: 12591752 BACKGROUND

• Siwik DA, Colucci WS. Regulation of matrix metalloproteinases by cytokines and reactive oxygen/nitrogen species in the myocardium. Heart Fail Rev. 2004 Jan;9(1):43-51. doi: 10.1023/B:HREV.0000011393.40674.13.

  PMID: 14739767 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, myocyte tissue

MeSH Terms

Conditions

Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Louis J Dell'Italia, M.D

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 20, 2010
• Study Start: June 1, 2005
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: December 2, 2010

Record last verified: 2010-12

Locations

US (1)