. The candidate is a cardiologist who studies physiologic hypotheses regarding valvular heart disease using advanced noninvasive imaging techniques in an environment that fosters strong interactions between clinical and basic scientists. His immediate goal is to develop more effective therapies for ischemic mitral regurgitation (MR). The initial K24 Award has enabled extensive progress toward the following goals: 1) developing novel therapies for ischemic MR that address its fundamental mechanism;2) expanding the scope of the scientific endeavor through new directions and collaborations: and 3) expanding opportunities for training and mentoring through these new research directions and co-mentorships. New directions include understanding the impact of ischemic MR on LV remodeling and the reversibility of such remodeling at a cellular and molecular level (with Dr. Roger Hajjar);applying cell and polymer approaches to ventricular restoration for reversing ischemic MR (with Prof. Philippe Menasche);determining the genetic basis of mitral valve prolapse (MVP), another cause of MR, and applying knowledge from bench to bedside to identify early, potentially treatable forms (with Dr. Susan Slaugenhaupt);and extending concepts from mitral to tricuspid regurgitation (with Dr. Carlos Duran). The candidate has a strong record of mentoring that supports transition to independent careers, as recognized by the Richard Popp Excellence in Teaching Award. Renewed K24 support is critical to build upon and fund interdisciplinary programs in cardiac imaging, LV remodeling and molecular genetics. The research program tests the central hypothesis that ischemic MR can be treated by realigning the leaflets with their ventricular attachments. The K24 renewal will support a new clinical direction, in collaboration with leaders in exercise physiology, to test the hypothesis that ischemic MR, fully appreciated with exercise, strongly predicts functional limitation, LV remodeling, and adverse prognosis following coronary interventions. Relevance: Ischemic MR is a common complication of coronary disease, doubling late mortality. Existing repairs are disappointing;new therapies that target fundamental changes in the LV are needed to reduce the associated remodeling and heart failure. MR in MVP can also cause lasting LV impairment, and discovering its responsible genetic defects has therapeutic promise. Both areas provide growing opportunities to mentor the next generation of successful investigators.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL067434-09
Application #
7781418
Study Section
Special Emphasis Panel (ZHL1-CSR-R (O1))
Program Officer
Scott, Jane
Project Start
2001-07-10
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
9
Fiscal Year
2010
Total Cost
$186,796
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Bartko, Philipp E; Dal-Bianco, Jacob P; Guerrero, J Luis et al. (2017) Effect of Losartan on Mitral Valve Changes After Myocardial Infarction. J Am Coll Cardiol 70:1232-1244
Beaudoin, Jonathan; Dal-Bianco, Jacob P; Aikawa, Elena et al. (2017) Mitral Leaflet Changes Following Myocardial Infarction: Clinical Evidence for Maladaptive Valvular Remodeling. Circ Cardiovasc Imaging 10:
Dal-Bianco, Jacob P; Bartko, Philipp E; Beaudoin, Jonathan et al. (2016) 3D Ultrasound: seeing is understanding-from imaging to pathophysiology to developing therapies in secondary MR. Eur Heart J Cardiovasc Imaging 17:510-1
Dal-Bianco, Jacob P; Aikawa, Elena; Bischoff, Joyce et al. (2016) Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve. J Am Coll Cardiol 67:275-87
Levine, Robert A; Hagége, Albert A; Judge, Daniel P et al. (2015) Mitral valve disease--morphology and mechanisms. Nat Rev Cardiol 12:689-710
Zeng, Xin; Zou, Lin; Levine, Robert A et al. (2015) Efficacy of polymer injection for ischemic mitral regurgitation: persistent reduction of mitral regurgitation and attenuation of left ventricular remodeling. JACC Cardiovasc Interv 8:355-363
Dina, Christian; Bouatia-Naji, Nabila; Tucker, Nathan et al. (2015) Genetic association analyses highlight biological pathways underlying mitral valve prolapse. Nat Genet 47:1206-11
Bertrand, Philippe B; Verbrugge, Frederik H; Verhaert, David et al. (2015) Mitral valve area during exercise after restrictive mitral valve annuloplasty: importance of diastolic anterior leaflet tethering. J Am Coll Cardiol 65:452-61
Durst, Ronen; Sauls, Kimberly; Peal, David S et al. (2015) Mutations in DCHS1 cause mitral valve prolapse. Nature 525:109-13
Dal-Bianco, Jacob P; Levine, Robert A (2015) The mitral valve is an actively adapting tissue: new imaging evidence. Eur Heart J Cardiovasc Imaging 16:286-7

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