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4D-FLOW MRI MAPPING OF REGIONAL AORTIC WALL SHEAR STRESS IMPLICATES HEMODYNAMICS IN HUMAN BICUSPID AORTOPATHY
S140
Canadian Journal of Cardiology Volume 30 2014
Canadian Society of Cardiac Surgeons (CSCS) Oral VALVES / BASIC SCIENCES Saturday, October 25, 2014
Trainee Research Award Finalist e Basic Science
CONCLUSION:
In the BAV aorta, regional WSS corresponds with local histological abnormalities and ECM dysregulation. These novel data strongly implicate local hemodynamics as a mediator of BAV aortopathy. With further validation, 4DMRI could be used to guide personalized resection strategies for patients with BAV aortopathy.
173 4D-FLOW MRI MAPPING OF REGIONAL AORTIC WALL SHEAR STRESS IMPLICATES HEMODYNAMICS IN HUMAN BICUSPID AORTOPATHY DG Guzzardi, P van Ooij, AJ Barker, M Markl, PM McCarthy, SC Malaisrie, JJ Puthumana, DD Belke, ER O’Brien, HE Mewhort, DA Svystonyuk, J Carr, RO Bonow, PW Fedak Calgary, Alberta BACKGROUND:
Patients with congenital bicuspid aortic valves (BAV) are predisposed to progressive dilatation of the ascending aorta (“bicuspid aortopathy”). A possible inherited/genetic etiology has led to aggressive surgical resection strategies to remove fragile tissue prone to complications. We recently demonstrated patterns of altered wall shear stresses (WSS) in the BAV aorta. These observations suggest regional hemodynamics may trigger local aortic extracellular matrix (ECM) degeneration leading to aortopathy. If validated, a more patient-specific and targeted resection strategy based on preoperative regional hemodynamic assessments may be warranted. For the first time, we correlated regional aortic tissue pathology with local hemodynamics using 4D-MRI in BAV patients undergoing ascending aortic resection. METHODS AND RESULTS: BAV patients (N¼11) referred for ascending aortic resection received preoperative 4D-MRI. Regional WSS differences within each patient’s aorta relative to a normal tricuspid aortic valve control population for “elevated” (>1.96 SD) and “normal” WSS were defined. Paired aortic wall samples were collected during surgical resection from the predefined “elevated” and “normal” WSS regions. Aortic tissue was examined for histologic abnormalities consistent with BAV aortopathy (cystic medial necrosis, ECM fragmentation and mucopolyssacharide deposition) and molecular mediators of ECM regulation (TGFb-1, MMP, TIMP). All BAV patients studied had adjacent aortic regions with elevated and normal areas of WSS suggesting hemodynamic heterogeneity. Within the same patients’ aorta, aortic media subjected to elevated WSS demonstrated increased mucopolyssacharide composition (Figure 1C, white arrows) and elastin fragmentation (Figure 1D, black arrows) as compared to adjacent areas with normal WSS. Multiplex protein analyses revealed a 1.49-fold (0.71SD) increase in the profibrotic transforming growth factor b-1 (TGFb-1) in elevated WSS regions as compared to normal (P¼0.045). Mean fold increases in ECM-proteases MMP-1 (1.62 0.84; P¼0.057), MMP-2 (1.49 1.00; P¼0.18), MMP-3 (1.23 0.36; P¼0.18), MMP-7 (1.57 0.75; P¼0.067), and TIMP-2 (1.26 0.33; P¼0.038) were observed in aortic wall subjected to elevated WSS regions as compared to normal WSS regions within the same patients’ ascending aorta.
174 DETERMINANTS OF LATE OUTCOMES IN WOMEN UNDERGOING REPAIR OF MYXOMATOUS DEGENERATION V Chan, E Elmistekawy, A Ahrari, M Ruel, T Mesana Ottawa, Ontario BACKGROUND:
Studies have consistently shown that women have worse perioperative outcomes following mitral surgery compared to men. Few data are available that explain these divergent gender outcomes. However, female patients who undergo coronary artery bypass grafting are known to be referred to surgery with more advanced disease than men. This study was conducted to determine if women with degenerative mitral valve disease present to surgery with more advanced disease than men, and to determine if these differences influence long-term clinical outcomes. METHODS: Seven hundred forty three patients underwent repair of mitral regurgitation due to myxomatous degeneration between 2001 & 2014. Of these, 325 (44%) were female and concomitant coronary bypass grafting was performed in 103 (14%). Mean clinical follow-up was for 2.8 years, and extended to 11.1 years. A total of 1729 postoperative echocardiograms were available for these 743 patients at a mean of 2.9 years following surgery. RESULTS: There were no perioperative deaths. Preoperatively, women had a larger indexed left atrial diameter (27.45.7 versus 25.34.8 mm/m2, p<0.001), larger indexed left ventricle end-systolic dimension (20.55.5 versus 19.54.9 mm/m2, p¼0.01), and higher right ventricular systolic pressure (44.414.4 mm Hg versus 41.713.3 mm Hg, p¼0.03) compared to men. Five-year survival and freedom from recurrent MR 2+ was 88.71.8%, and 90.71.6%, respectively. Although gender was not associated with survival (hazard ratio 1.60.5, p¼0.2), women were more likely to develop recurrent MR 2+ at follow-up compared to men (hazard ratio 1.90.5, p¼0.01).
Canadian Journal of Cardiology Volume 30 2014
Canadian Society of Cardiac Surgeons (CSCS) Oral VALVES / BASIC SCIENCES Saturday, October 25, 2014
Trainee Research Award Finalist e Basic Science
CONCLUSION:
In the BAV aorta, regional WSS corresponds with local histological abnormalities and ECM dysregulation. These novel data strongly implicate local hemodynamics as a mediator of BAV aortopathy. With further validation, 4DMRI could be used to guide personalized resection strategies for patients with BAV aortopathy.
173 4D-FLOW MRI MAPPING OF REGIONAL AORTIC WALL SHEAR STRESS IMPLICATES HEMODYNAMICS IN HUMAN BICUSPID AORTOPATHY DG Guzzardi, P van Ooij, AJ Barker, M Markl, PM McCarthy, SC Malaisrie, JJ Puthumana, DD Belke, ER O’Brien, HE Mewhort, DA Svystonyuk, J Carr, RO Bonow, PW Fedak Calgary, Alberta BACKGROUND:
Patients with congenital bicuspid aortic valves (BAV) are predisposed to progressive dilatation of the ascending aorta (“bicuspid aortopathy”). A possible inherited/genetic etiology has led to aggressive surgical resection strategies to remove fragile tissue prone to complications. We recently demonstrated patterns of altered wall shear stresses (WSS) in the BAV aorta. These observations suggest regional hemodynamics may trigger local aortic extracellular matrix (ECM) degeneration leading to aortopathy. If validated, a more patient-specific and targeted resection strategy based on preoperative regional hemodynamic assessments may be warranted. For the first time, we correlated regional aortic tissue pathology with local hemodynamics using 4D-MRI in BAV patients undergoing ascending aortic resection. METHODS AND RESULTS: BAV patients (N¼11) referred for ascending aortic resection received preoperative 4D-MRI. Regional WSS differences within each patient’s aorta relative to a normal tricuspid aortic valve control population for “elevated” (>1.96 SD) and “normal” WSS were defined. Paired aortic wall samples were collected during surgical resection from the predefined “elevated” and “normal” WSS regions. Aortic tissue was examined for histologic abnormalities consistent with BAV aortopathy (cystic medial necrosis, ECM fragmentation and mucopolyssacharide deposition) and molecular mediators of ECM regulation (TGFb-1, MMP, TIMP). All BAV patients studied had adjacent aortic regions with elevated and normal areas of WSS suggesting hemodynamic heterogeneity. Within the same patients’ aorta, aortic media subjected to elevated WSS demonstrated increased mucopolyssacharide composition (Figure 1C, white arrows) and elastin fragmentation (Figure 1D, black arrows) as compared to adjacent areas with normal WSS. Multiplex protein analyses revealed a 1.49-fold (0.71SD) increase in the profibrotic transforming growth factor b-1 (TGFb-1) in elevated WSS regions as compared to normal (P¼0.045). Mean fold increases in ECM-proteases MMP-1 (1.62 0.84; P¼0.057), MMP-2 (1.49 1.00; P¼0.18), MMP-3 (1.23 0.36; P¼0.18), MMP-7 (1.57 0.75; P¼0.067), and TIMP-2 (1.26 0.33; P¼0.038) were observed in aortic wall subjected to elevated WSS regions as compared to normal WSS regions within the same patients’ ascending aorta.
174 DETERMINANTS OF LATE OUTCOMES IN WOMEN UNDERGOING REPAIR OF MYXOMATOUS DEGENERATION V Chan, E Elmistekawy, A Ahrari, M Ruel, T Mesana Ottawa, Ontario BACKGROUND:
Studies have consistently shown that women have worse perioperative outcomes following mitral surgery compared to men. Few data are available that explain these divergent gender outcomes. However, female patients who undergo coronary artery bypass grafting are known to be referred to surgery with more advanced disease than men. This study was conducted to determine if women with degenerative mitral valve disease present to surgery with more advanced disease than men, and to determine if these differences influence long-term clinical outcomes. METHODS: Seven hundred forty three patients underwent repair of mitral regurgitation due to myxomatous degeneration between 2001 & 2014. Of these, 325 (44%) were female and concomitant coronary bypass grafting was performed in 103 (14%). Mean clinical follow-up was for 2.8 years, and extended to 11.1 years. A total of 1729 postoperative echocardiograms were available for these 743 patients at a mean of 2.9 years following surgery. RESULTS: There were no perioperative deaths. Preoperatively, women had a larger indexed left atrial diameter (27.45.7 versus 25.34.8 mm/m2, p<0.001), larger indexed left ventricle end-systolic dimension (20.55.5 versus 19.54.9 mm/m2, p¼0.01), and higher right ventricular systolic pressure (44.414.4 mm Hg versus 41.713.3 mm Hg, p¼0.03) compared to men. Five-year survival and freedom from recurrent MR 2+ was 88.71.8%, and 90.71.6%, respectively. Although gender was not associated with survival (hazard ratio 1.60.5, p¼0.2), women were more likely to develop recurrent MR 2+ at follow-up compared to men (hazard ratio 1.90.5, p¼0.01).