Valvular Heart Disease

JACC  March 11, 2008 

ABSTRACTS - Valvular Heart Disease   A271

ACC.POSTER CONTRIBUTIONS

9:00 a.m.

1006

Adult Cardiothoracic Surgery/Valvular Surgery I Sunday, March 30, 2008, 9:00 a.m.-12:30 p.m. McCormick Place, South Hall 9:00 a.m. 1006-81

Minimally Invasive Approach for Aortic Valve Replacement In The Elderly Is Associated With Lower Mortality: A Case Matched Study

Charles F. Schwartz, Eugene A. Grossi, Juan B. Grau, Greg H. Ribakove, Gregory A. Crooke, F. Gregory Baumann, Patricia Ursomanno, George Gogoladze, Alfred T. Culliford, Stephen B. Colvin, Aubrey C. Galloway, NYU School of Medicine, New York, NY

Development and Validation of a Prediction Model for Strokes Following Mitral Valve Surgery

Donald S. Likosky, Lawrence Dacey, Yvon Baribeau, Anthony DiScipio, Bruce Leavitt, Felix Hernandez, Jr., Richard Cochran, Reed Quinn, Robert Helm, David Charlesworth, David Malenka, Elaine Olmstead, Cathy Ross, Gerald O’Connor, Northern New England Cardiovascular Disease Study Group, Lebanon, NH Background: Prediction models for strokes in the setting of isolated coronary artery bypass graft (CABG) surgery have been developed. Similar models do not exist for more complex procedures. A pre-operative risk prediction model for stroke was developed and validated for patients undergoing mitral valve surgery without or without CABG. Methods: We performed a regional observational study of 1,778 consecutive patients undergoing mitral valve surgery in northern New England between January 1, 2000 and June 30, 2006. We developed a pre-operative stroke risk prediction model using logistic regression analysis, and validated it using bootstrap resampling techniques. We assessed the model’s fit and discrimination. Results: The regional stroke rate was 2.59% (46 strokes). The final regression model included: age, diabetes, hypertension, renal failure or creatinine >2mg/dl, urgent or emergency, acute or chronic regurgitation, presence of peptic ulcers, and vascular disease. The model significantly predicted (χ2 [10 d.f.] = 38.84, p < 0.0001) the occurrence of stroke. The model had satisfactory calibration (Hosmer-Lemeshow χ2 = 0.13, p=0.99), and discriminated well: ROC = 0.74 (0.63, 0.84). Conclusion. We developed a robust risk prediction model for strokes in the setting of mitral procedures using readily obtainable pre-operative variables. The risk prediction model performs well, and enables a clinician to estimate rapidly and accurately a patient’s preoperative risk of stroke.

Valvular Heart Disease

Background: Significant aortic valve disease is present in 7.2% of septo and octogenarians; these ages representing 9% of the US population. We hypothesized that a minimally invasive approach for aortic valve replacement (AVR) would have benefits for elderly patients (pts). Propensity case matching was used to compare the outcomes of AVR performed with standard sternotomy (SS) versus a minimally invasive (MIN) approach in a single institution’s geriatric population. Methods: Between 1/93 and 4/07, 964 pts 70 years of age or older underwent isolated AVR. Mean age was 78.8 years; 420 (43.6%) were 80 years or older. MIN was performed on 580 pts (60.2%), with either a right anterior mini-thoracotomy (91.2%) or a partial upper sternotomy (8.8%). SS was performed on the 384 pts (39.8%). Data were collected prospectively with the New York State Cardiac Surgery Instrument; EUROSCOREs were calculated. “Greedy” propensity matched-pairs analysis was used to construct a control cohort from SS patients. Matching variables included age, gender, ejection fraction, history of stroke, congestive heart failure, urgent operation, diabetes, previous cardiac surgery, renal disease, and myocardial infarction. Results: A total of 546 pts were case matched. Hospital mortality was significantly lower with MIN (5.5%; 15/273) vs SS (10.3%; 28/273); p=0.04. Univariate analysis also revealed (likelihood ratio; p-value) increased mortality associated with congestive heart failure (19.2; <0.01), history of stroke (3.7;0.05), ejection fraction <30% (20.2;<0.01) and previous cardiac surgery (7.3;.01). In pts with fewer co-morbidities (EUROSCORE < 6), overall mortality for both groups was low (1.6%; 1/64). In higher risk patients (EUROSCORE > 7) MIN was associated with lower mortality (6.1%;15/246 vs 11.4%;27/236 for SS; p=0.04). Pts length of stay was significantly shorter with MIN vs SS approaches (median 7 vs 9 days; p<.01). Conclusions: This demonstrates that use of a minimally invasive approach for AVR in the elderly is associated with lower hospital mortality and shorter hospital stay. Additionally, AVR in elderly pts without significant co-morbidities can be performed at low risk with either approach.

1006-95

9:00 a.m. 1006-82

Seven Years of Clinical Results with a Tissue Engineered Pulmonary Valve in Eleven Consecutive Patients to Replace The Pulmonary Valve during Ross Operation

Pascal M. Dohmen, Alexander Lembcke, Sebastian Holinski, Axel Pruss, Wolfgang Konertz, Dept. of Cardiovascular Surgery, Charite, Berlin, Germany Background: The Ross procedure is limited by the durability of the valve prostheses used to reconstruct the right ventricular outflow tract. This study was performed to collect prospective safety and effectiveness data of a tissue engineered heart valve to reconstruct the right ventricular outflow tract during Ross procedure. Methods: From May 2000 till June 2002, eleven consecutive patients received a tissue engineered heart valve. Four weeks prior to the Ross operation a piece of forearm or saphenous vein was harvested, to isolate, characterize and expand endothelial cells. A cryopreserved pulmonary allograft was decellularized, coated with fibronectin and seeded with autologous vascular endothelial cells, using a specially developed bioreactor. Followup was performed by clinical evaluation, transthoracic echocardiography, and multi-slice computed tomography. Results: Patients mean age was 39.6 ± 10.3 years. Cell seeding density was 1.1 x105 ± 0.5 x105 cells/cm² with a viability of 93.2 ± 2.1 %. All patients survived surgery. No fever of unknown origin was seen postoperatively and leucocyte count did not increase. Currently all patients are in NYHA class I. Transthoracic echocardiography evaluation of the tissue engineered heart valve showed a mean pressure gradient of 6.5 ± 1.0 mmHg at 7 years. Multi-slice computed tomography showed no calcification up to 7 years. Conclusions: Tissue engineered heart valves showed excellent hemodynamic performance during intermediate-term follow-up. Decellularization of heart valves and seeding with autologous vascular endothelial cells may prevent degeneration of tissue valves.

9:00 a.m. 1006-96

Preoperative Wall-Stress-Adjusted Ejection Fraction Change With Exercise Best Predicts Survival After Aortic Valve Replacement for Chronic Severe Aortic Regurgitation

Jeffrey S. Borer, Phyllis G. Supino, Edmund M. Herrold, Clare Hochreiter, Frans V. Beltran, Paul D. Kligfield, Mary J. Roman, Karl H. Krieger, Leonard N. Girardi, O. W. Isom, Weill Cornell Medical College, New York, NY Background: Data from our prospective long-term natural history study in pts with aortic regurgitation (AR) previously showed that, among asymptomatic pts who have nl LV ejection fraction (EF) at rest and remain unoperated, a contractility index (change[Δ] in LVEF from rest to exercise, adjusted for Δ end-systolic wall stress [ESS] from rest to exercise [“ΔEF-ΔESS”]) predicts cardiac events (heart failure, subnl LVEF at rest or sudden death). Methods: To determine whether contractility also predicts death late after aortic valve replacement (AVR), in 66 consecutively studied pts with isolated, pure severe AR who underwent AVR (age 49±15 yrs at AVR, 86% male), we prospectively defined preAVR ΔEF-ΔESS (from combined echocardiographic and radionuclide cineangiographic data) and related this to late post-AVR survival. Pre-AVR ΔEF-ΔESS values were stratified in terciles according to our previously-published cutpoints that segregated outcomes in unoperated pts; survival durations of pts in terciles were compared to each other and to US census survival data. Results: During 12±7 yr endpoint-free follow-up, 22 pts died (1 mo to 16.1 yrs, av 6.4 yrs after index study, average annual risk 3.1%). Log rank Kaplan-Meier comparisons indicated prognostic value of pre-AVR ΔEF-ΔESS for postop survival (p=.01); average annual risks were 1.5% (highest contractility tercile pre-AVR), 2.6% (mid) and 6.1% (lowest). Though overall post-AVR survival was lower (p<.01) than for age- and sex-matched US census cohort, survival in the highest contractility tercile was indistinguishable from that of census cohort (NS). By multivariate Cox regression analysis, predictive value of pre-AVR ΔEF-ΔESS was independent of age, gender, preop heart failure symptoms, echocardiographic LV diastolic and systolic dimensions, fractional shortening and radionuclide cineangiographic LVEF at rest, exercise, and ΔLVEF from rest to exercise (p<.02, all). Conclusions: In AR, non-invasive contractility measurement is independently predictive and superior to other clinical and objective measures for postAVR survival prediction; decisions concerning prophylactic AVR are properly based on this parameter.

A272   ABSTRACTS - Valvular Heart Disease

JACC  March 11, 2008

ACC.POSTER CONTRIBUTIONS 1013

Adult Cardiothoracic Surgery/Valvular Surgery II Sunday, March 30, 2008, 1:00 p.m.-4:30 p.m. McCormick Place, South Hall

Valvular Heart Disease

vs. elective 37.2

3.42 2.31-5.10 <0.0001

surgery

10 year

Utility of N-AcetylCysteine to Prevent Acute Kidney Injury After Cardiac Surgery: A Randomized Controlled Trial

A. Selcuk Adabag, Areef Ishani, Suresh Koneswaran, Deborah J. Johnson, Rosemary F. Kelly, Herbert B. Ward, Edward O. McFalls, Hanna E. Bloomfield, Yellaprada Chandrashekhar, VA Medical Center, Minneapolis, MN, University of Minnesota, Minneapolis, MN Background Acute kidney injury (AKI) after cardiac surgery is associated with postoperative complications, prolonged hospitalization and death. Ischemia, inflammation and increased oxygen free-radical generation has been suggested to underlie AKI in this context. Accordingly, we tested whether prophylactic perioperative administration of the antioxidant and free-radical scavenger N-acetylcysteine (NAC) prevents postoperative AKI in patients with preexisting chronic kidney disease (CKD) undergoing cardiac surgery (clinical trials.gov identifier NCT00211653). Methods In this prospective, randomized, placebo-controlled, double-blinded clinical trial, 102 patients with CKD who underwent heart surgery at the Minneapolis Veterans Affairs Medical Center were randomized to either NAC (n=50) 600 mg p.o twice daily or placebo (n=52). Study medication was administered for a total of 14 doses (3 preoperative). The primary outcome variable was maximum change in creatinine from baseline within 7 days after surgery. Secondary outcomes were AKI (i.e >0.5 mg/dl or >25% increase in creatinine from baseline), hemodialysis, operative mortality and length of stay in the intensive care unit and the hospital. Results Creatinine increased in both groups (0.45+0.7 mg/dl in NAC vs. 0.55+0.9 mg/dl in placebo p=0.53) and peaked on postoperative day 5. AKI occurred in 41 (40%) patients (22 NAC vs. 19 placebo (p=0.44) by postoperative day 5, but persisted in only 14 (7 NAC vs. 7 placebo; p=0.94) by day 30. In multivariable analysis perioperative NAC was unassociated with AKI (relative risk 1.2, 95% CI, 0.8 to 1.9; p=0.34). Five patients (3 NAC vs. 2 placebo; p=0.68) underwent hemodialysis and 5 patients (2 NAC vs. 3 placebo; p=1.0) died perioperatively, including 2 who had undergone hemodialysis. There was a trend towards shorter length of stay in the intensive care unit among NAC patients vs. placebo (4.9+7 vs. 6.5+9 days respectively, p=0.06), however total hospital length of stay was similar (13.2+13 vs. 16.7+17 days respectively, p=0.12). Conclusion The risk of AKI following cardiac surgery is high in patients with preexisting CKD. However, this risk is not altered by prophylactic administration of NAC.

1:00 p.m. 1013-82

Emergent

Age per

1:00 p.m. 1013-81

Factors Associated With Non-use of IMA During CABG Wald Variable OR 95% CI P value Variable Chisquare

29.9

1.36 1.22-1.52 <0.0001

Previous cardiac interventions

Left ventricular

Wald Chisquare

OR

95% CI

P value

6.9

1.46 1.10-1.93 0.0088

6.3

0.99 0.98-1.00 0.0122

increment Female 19.5 Chronic

1.67 1.32-2.08 <0.0001 Hypercholesterolemia 6.1

0.75 0.60-0.94 0.0135

Lung

19.4

1.38 1.20-1.60 <0.0001 Serum creatinine

5.8

1.11 1.02-1.22 0.0163

12.3

0.94 0.90-0.97 0.0005

4.9

1.52 1.05-2.19 0.0268

7.5

1.55 1.13-2.11 0.0061

-

-

ejection fraction

Disease Body mass index <28

Poor Left descending artery target

Kg/M2 Family history of coronary

-

-

artery disease

1:00 p.m. 1013-95

DOES CORONARY ARTERY BYPASS SURGERY COMBINED WITH AORTIC VALVE REPLACEMENT INCREASE THE RISK OF SURGERY IN PATIENTS > 80 YEARS OLD?

Andrew Maslow, William Feng, Carl Schwartz, Paula Casey, Suzanne Dahlberg, George Cooper, Arun Singh, Rhode Island Hospital, Providence, RI Backround: This study compares outcomes in patients > 80 years old undergoing aortic valve replacement (AVR) to those who underwent AVR with coronary artery bypass grafting (CABG). Methods: A retrospective review from a single institution was performed to evaluate the early and late outcomes for 261 patients; 145 had AVR (Group I) and 116 had AVR/CABG (Group II). The median age and followup was 82 years (80-98) and 5.3 yrs resp. Survival was estimated using the Kaplan-Meier method. Categorical data were compared using Fisherâ[[Unsupported Character - €]]™s exact test and continuous data were compared using the Kruskal-Wallis test. Results: The overall perioperative mortality (30 days and/or in-hospital) was 6.1% (16/261). Perioperative outcomes and long-term outcome (Figure I) were not significantly different between groups I and II (p=0.58). For Group I, the median survival was 3.2 yrs. Two and 5 yr survivals were 0.83 and 0.60 resp. For Group II, the median survival was 3.4 yrs. Two and 5 yr survivals were 0.77 and 0.54 resp. Multivariate predictors of operative survival included prolonged cardiopulmonary bypass (p=0.003) and aortic cross clamp time (p=0.006), postop respiratory failure (p=0.002), and sepsis (p<0.0001). Conclusion: Elderly patients undergoing AVR or AVR/CABG have acceptable outcomes, which were not different between those patients who underwent AVR alone and those who underwent AVR with CABG.

Understanding Clinical factors Associated With the Lack of Use of Internal Mammary Artery Conduit in Patients Undergoing Coronary Artery Bypass Surgery

Rajendra H. Mehta, Emily Honeycutt, Linda K. Shaw, Michael H. Sketch, Jr., Duke University Medical Center, Durham, NC, Duke Clinical Research Institute, Durham, NC Background: The use of internal mammary artery (IMA) to bypass an occlusive coronary artery has been associated with better long-term patency and improved survival in patients undergoing coronary artery bypass surgery (CABG). Thus, IMA use is considered an important quality of care indicator for CABG procedure by many organizations comparing and providing public report cards of institutional healthcare quality. Yet many patients do not receive IMA conduit. Factors associated with the non-use of IMA are less known Methods: We analyzed 8229 patients undergoing CABG at Duke University Medical Center (1986-2003). Multivariable Logistic Regression modeling was used to identify baseline and angiographic variables associated with non-use of IMA during CABG. Results: IMA was used in 93.8% of CABG patients and was independently associated with decreased adjusted short- (OR 0.62, 95% CI 0.39-0.98) and long- (HR 0.81, 95% CI 0.69-0.94) term mortality. Baseline factors associated with non-use of IMA are shown in table in descending order of their model chisquare (c index =0.69). Note that OR>1 = greater non-use of IMA graft and OR<1 = more use of IMA graft. Conclusions: IMA graft is not used in 1 of every 16 patients undergoing CABG even at an exerienced tertiary center. Our study provides insight into the patient factors associated with non-use of IMA. Improving use of IMA in patients with these clinical risk factors associated with its non-use has the potential for improving IMA use and thereby outcomes of these patients

1:00 p.m. 1013-96

Functional Polymorphism in the COMT Gene Predisposes to Perioperative Vasoplegia

Anja Haase-Fielitz, Michael Haase, Rinaldo Bellomo, Duska Dragun, Charite University Medicine, Virchow-Klinikum, Berlin, Germany Background: With over one million operations a year, cardiac surgery with cardiopulmonary bypass is perhaps the most common major surgical procedures worldwide. Functional polymorphism of the catecholamine-O-methyltransferase (COMT) gene may affect catecholamine metabolism and contribute to the large variations in vasomotor tone and

JACC  March 11, 2008 

ABSTRACTS - Valvular Heart Disease   A273

clinical outcomes seen in cardiac surgical patients. Methods: In a blinded, prospective, observational study, we determined the COMT genotypes, measured catecholamine levels and obtained clinical and outcome data from 170 consecutive patients undergoing elective cardiopulmonary bypass surgery in a tertiary and in a private hospital. We validated the findings on duration of vasoplegia in an additional analysis now including 260 patients. We hypothesized that the COMT LL genotype might predispose to prolonged vasoplegia and to altered catecholamine metabolism compared to the COMT HH genotype. Results: COMT LL carriers had a significantly longer median duration of vasoplegia compared to HH carriers (21.5 [2-50.5] hours versus 9.0 [0-28.5] hours; P=0.019). Multivariable regression analysis and validation analysis confirmed this finding. LL genotype carrier state was associated with vasoplegia lasting longer than 48 hours (OR, 4.4; 95% CI, 1.3-14.9; P=0.015). Length of stay in intensive care (P=0.043) and in hospital (P=0.018) was longer in COMT LL carriers. Post-operative plasma epinephrine (P<0.001) and pre- and postoperative dihydroxyphenylglycol levels (P=0.030; P=0.090) were higher in COMT LL genotype carriers compared to HH carriers. Conclusions: The COMT LL genotype appears to alter catecholamine metabolism in cardiac surgical patients and to predispose to prolonged vasoplegia, longer stay in intensive care and longer stay in hospital. Preoperative risk assessment of cardiac surgical patients should include information on genetic background. (ClinicalTrials.gov, NCT00334009)

9:00 a.m. 1020-82

Long-Term Follow-Up After Valve-Sparing Aortic Root Remodeling: A Consecutive Series of 55 Yacoub Procedures

Christian D. Etz, Fabian A. Kari, Vivian M. Abascal, Stefano Zoli, Robert Brenner, Randall B. Griepp, Konstadinos A. Plestis, Mount Sinai School of Medicine, New York, NY Background: We report on a contemporary series of remodeling aortic valve (AV) sparing procedures (Yacoub) for aortic root aneurysms. Methods: 55 patients (pts, median age: 47 [4-73] yrs) underwent a remodeling AV sparing procedure (4/98-2/06) for aortic root dilation. The etiology of the aortic aneurysm was degenerative in 29 pts (53%), Marfan`s-Syndrome in 11 pts (20%), annuloaortic ectasia in 6 pts (11%), acute dissection in 3 pts (5%), sinus of valsalva dilation in 2 pts (4%), aortitis and atherosclerosis in 1 pt (4%); in 18 pts (33%) the repair involved the proximal arch. Results: There was no hospital mortality and no permanent neurologic deficits postoperatively. The median ICU- / hospital stay was 1.5 (1-8) / 6 (3-13) days. During a mean follow-up of 4.1±1.8 yrs, 2 pts died for causes other than cardiac; none of the pts developed stroke or intracranial hemorrhage. 4 pts (7%) developed moderate - but none severe - AV insufficiency. One pt required AV replacement 3 months after AV remodeling. At the latest follow-up, 91% of the pts were in functional class I and 11% in class II. A Kaplan-Meier survival curve is shown in Figure 1:

ACC.POSTER CONTRIBUTIONS 1020

Adult Cardiothoracic Surgery/Valvular Surgery III Monday, March 31, 2008, 9:00 a.m.-12:30 p.m. McCormick Place, South Hall 9:00 a.m. 1020-81

Comparison of Clinical Outcomes of Mitral Valve Repair in Patients With Myxomatous Degenerative Versus Rheumatic Mitral Regurgitation

Background: With cumulative experiences of mitral vale repair (MVP) for both myxomatous degenerative (group A) and rheumatic (group B) mitral regurgitation (MR), their outcomes need to be clarified. Methods: Clinical data of 381 patients (group A/B = 276/105) who underwent MVP from 2000 to 2005, were reviewed. Clinical and echo follow-up duration was 3.2±1.9 and 2.7±1.9 yrs, respectively. Remnant or recurred MR was defined as MR ≥ grade 3/4 on echo and events included death of all causes, redo MV surgery, and any admission due to heart failure, arrhythmia, or endocarditis. Results: Group A was older (50±14 vs. 40±12 yrs, p<0.05), more prevalent of hypertension (29.7 vs. 7.6 %, p<0.001), and showed higher preoperative left ventricular ejection fraction (62±9 vs. 58±9 %, p<0.001), while female gender (39 vs. 76 %, p<0.001) and atrial fibrillation (20 vs. 46 %, p<0.001) were more prevalent in group B with higher incidence of concomitant aortic valve surgery (3.5 vs. 14.3 %, p<0.01) and maze operation (18 vs. 43 %, p<0.001). Immediate postoperative repair result was successful in both groups (99 vs. 98 %) and 5-year MR-free survival rates were 90±3, and 79±6 %, respectively (p=0.13). During clinical follow-up, there were 9 redo MV surgery (7/2 in group A/B) and 5 deaths (3/2 in group A/B). Five-year event-free survival rates were similar between two groups (81±4 vs. 76±7 %, p=0.78). Conclusions: MVP for rheumatic MR showed excellent and comparable immediate and mid-term results compared with myxomatous degenerative MR.

Conclusions: The Yacoub procedure is associated with excellent operative outcome and an intermediate survival comparable to the normal population. Freedom from reoperation and absence of neurologic complications in 215 pt-yrs follow-up suggest that AV-sparing in this population may yield a better outcome than would occur in pts with composite replacement requiring oral anti-coagulation.

9:00 a.m. 1020-95

Should the Maze Procedure Be Utilized for Elimination of Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy?

John M. Stulak, Hartzell V. Schaff, Joseph A. Dearani, Steve R. Ommen, Rick A. Nishimura, Mayo Clinic College of Medicine, Rochester, MN Background: In many pts with hypertrophic obstructive cardiomyopathy (HOCM), left atrial function is critically important for adequate left ventricular filling, and symptoms may be precipitated by occurrence of atrial fibrillation (AF). The benefit of the maze procedure on symptomatic status of pts with HOCM is controversial. Methods: We compared outcome of 37pts (23 male, 11 chronic AF) with HOCM and AF who underwent concomitant maze and septal myectomy (maze group) with 105 pt (59 male, 11 chronic AF) with HOCM and AF who underwent septal myectomy alone (control group) between January 1993 and March 2007. Results: All pts underwent extended septal myectomy with relief of LV outflow tract gradient (62±6 to 1±2 mmHg). In the maze group, procedures for AF included classic biatrial maze in 19 (cut and sew in 13) and other lesion sets in 18. AF freedom at last FU tended to be higher in the maze group for both pt with paroxysmal (91% vs 75%, p=0.1) and chronic AF (38% vs 17%, p=0.058). Freedom from anticoagulation was greater in pt with chronic AF after maze procedure (37% vs 0%, p=0.004. Early mortality (maze: 2.6%, no maze: 1.9%, p=0.8), need for new permanent pacemakers (maze: 14%, no maze: 10%, p=0.52), and late NYHA functional class (maze: 1.25, no maze: 1.32, p=0.6) were similar between groups. Conclusions: Concomitant maze procedure at the time of septal myectomy appears effective and reduces need for anticoagulation in patients with chronic AF. The addition of a maze in pt with HOCM did not increase morbidity or mortality.

Valvular Heart Disease

Jeong-Hoon Kim, In Hyun Jung, Jon Suh, Sang-Hyun Kim, Jae-Won Lee, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song, Asan Medical Center, Seoul, South Korea

A274   ABSTRACTS - Valvular Heart Disease

JACC  March 11, 2008 9:00 a.m.

1020-96

Early and Midterm Results in Patients With Tetralogy of Fallot With Hypoplastic Pulmonary Annulus Using Transannular Patch Versus Valved Conduits

1:00 p.m. 1027-82

Aortic Valve Bypass Surgery for the High-Risk Patient with Aortic Stenosis

Sumit Narang, Amit Banerjee, Deepak Kumar Satsangi, Mohammed Abid Geelani, Vikas Saini, G B Pant Hospital, Delhi, India, University of Chicago Hospital, Chicago, IL

James S. Gammie, Leandra Krowsoski, John W. Brown, James M. Brown, Robert S. Poston, John S. Gottdiener, Patrick N. Odonkor, Bartley P. Griffith, University of Maryland Medical Center, Baltimore, MD

Background: Tetralogy of Fallot (TOF) is a complex congenital anomaly. It is most common congenital cyanotic heart disease. Patients greater than 4 years of age and with very small pulmonary annulus (Z < -5) usually have high right ventricular/left ventricular pressure ratio (PRV/PLV > 0.65) just after correction. They have multiple complications immediately post operatively. Over long term, these patients have high incidence of developing severe right ventricular dysfunction with frank right sided failure with significant deterioration of New York Heart Association (NYHA) functional class needing pulmonary valve replacement. This study is a prospective study to compare the results early and midterm of transannular versus bovine jugular vein valved conduit right ventricular outflow tract (RVOT) reconstruction in patients greater than 4 years of age with hypoplastic pulmonary annulus (Z < -5). Methods: 65 patients with TOF and small pulmonary annulus, Z value < -5 were recruited in study. Pulmonary annulus was measured intraoperatiely using Hegar’s dilator. Patients randomly assigned to either transannular patch plasty (Group A) or RVOT reconstruction using Contegra bovine jugular vein valved conduit (Group B). Results: Three patients in Group A died of low output failure while one patient in Group B died of low output failure. Group A patients with transannular patch plasty had significantly greater duration of intensive care unit stay (5.4 ± 0.6 Vs 3 ± 0.5 days ), prolonged inotropic requirement (Dopamine: 4.2 ± 0.7 Vs 2.4 ± 0.5 days; Adrenaline: 2.8 ± 0.5 Vs 1.2 ± 0.4 days), prolonged chest drainage (8 ± 3 Vs 3 ± 1days) at mean 18 months follow up. Twenty patients of Group B were NYHA I and only 5 patients in Group A were NYHA I. Conclusions: TOF patients of more than 4 years of age with small pulmonary annulus (Z < -5), who present late for correction represent a difficult group. The use of these conduits in these patients will reduce post operative morbidity and improve quality of life. Right ventricular function and patients’ clinical condition will also be much preserved at the time of reintervention, when required.

Background: Aortic Valve Bypass (AVB) (apicoaortic conduit) surgery treats aortic stenosis (AS) by bypassing, rather than replacing, the stenotic aortic valve. With growing evidence that a substantial number of higher-risk symptomatic AS patients are not referred for surgery, we have refocused efforts on this uncommonly performed procedure. Methods: We reviewed consecutive AVB procedures performed between 4/2003 and 5/2007 at a single institution. A conduit containing a porcine valve was constructed from the left ventricular apex to the mid descending thoracic aorta. All patients underwent predismissal echocardiography. Results: We performed AVB surgery on 27 high-risk patients. This represents 6.6 % (27/410) of aortic valve operations during this time period. Mean age was 81 years (62-87 years). Indications for AVB included reoperation with patent bypass grafts in 18 (67 %) patients and a porcelain aorta in 5 (18.5%). Myocardial ischemic time was zero minutes for all patients. Cardiopulmonary bypass (CPB) was used for 19 of 27 (70 %) patients: median CPB time was 19 minutes. In-hospital mortality was 11 percent (3/27) and was limited to the first two years of the series. There were no postoperative strokes or new postoperative pacemakers. Echocardiography demonstrated preserved ejection fraction (pre vs. post EF: 51 vs. 53 %, p = ns) and excellent relief of AS (mean aortic valve gradient 9.7 +/- 5.5 mmHg). Conduit flow was 72 +/- 9 percent (56 - 83 percent) of total cardiac output. Conclusions: AVB surgery is an alternative approach to conventional aortic valve replacement for the high-risk patient with AS. It is a beating-heart operation that can be performed without CPB. AVB effectively relieves left ventricular outflow obstruction and is associated with a low risk of stroke. Blood flow is consistently distributed between the native left ventricular outflow tract and the AVB conduit. Outcomes have improved as experience has informed our technical approach.

1:00 p.m.

ACC.POSTER CONTRIBUTIONS

1027-95

Valvular Heart Disease

1027

Adult Cardiothoracic Surgery/Valvular Surgery Monday, March 31, 2008, 1:00 p.m.-4:30 p.m. McCormick Place, South Hall 1:00 p.m. 1027-81

Survival Benefit Of Aortic Valve Replacement In Patients With Severe Asymptomatic Aortic Regurgitation With Normal Left Ventricular Ejection Fraction

Rami Turk, Padmini Varadarajan, Unnati Sampat, Ashvin Kamath, Sumit Kandhar, Ramdas G. Pai, Loma Linda University School of Medicine, Loma Linda, CA Background: Aortic valve replacement (AVR) in patients with asymptomatic severe aortic regurgitation (AR) and LV ejection fraction (EF) and LV dimensions is currently a class III recommendation in the ACC/AHA guidelines. Methods: Our echocardiographic database was screened for patients with severe AR from 1993 to 2007. Detailed chart reviews were done to gain clinical, demographic and therapeutic data. Mortality data was obtained from social security death index. Results: A total of 139 patients had asymptomatic severe AR. Mean age 57+17, Males 66%, LVEF was 61+14%, diabetes in 9% and CAD 24%. Mean duration of follow up was 4.8 years. AVR was associated with a significant survival benefit (hazard ratio 0.42, 95% CI .20 - 0.85, p=0.02) in this group. AVR remained an independent predictor of improved survival after adjusting for age, gender, hypertension, diabetes, CAD and LVEF (HR 0.32, 95% CI 0.13 -0 .77, p = 0.01). Eighty-five patients were found to have asymptomatic severe AR with an LVEF over 50%, an LV diastolic diameter <70 mm and an LV systolic diameter <50 mm. In this group, the patients who underwent AVR had a significant survival benefit (HR 0.09, 95% CI 0.01-0.55, p = 0.01) after adjusting for age, gender, hypertension, diabetes, and CAD. Conclusions: 1) AVR is associated with a better survival in patients with asymptomatic AR, especially in the subset of patients with normal ejection fraction and LV end-systolic dimension <50 mm. 2) We suggest that ACC/AHA guidelines be reconsidered in view of these findings.

Evaluation of Costs and Quality of Life of Octogenarians Undergoing Valve Surgery

sandro gelsomino, roberto lorusso, giuseppe de cicco, carlo rostagno, giuseppe bille’, pierluigi stefàno, gian franco gensini, Experimental Surgery,cardiac surgery, FLORENCE, Italy, Civic Hospital, brescia, Italy Background:This study analyzes quality of life (QoL)and costs of octogenarians undergoing cardiac valve procedures Methods:The RANDSF-36 Health Survey,the Zung’s Self-Rating Depression Scale(SDS) and the Spielberger State-Trait Anxiety Inventory (STAI)Questionnaires were administered at admission and at postoperative outpatients visit or by telephone interview.Costs were obtained from Hospital’s accounting Departments and originally calculated in EURO,converted to 2007 value using yearly inflation factors obtained from the consumer price Index and then changed to UDS (1Euro=1.34829 USD,currency rate,May 29,2007). Median follow-up was 32 months (IQR,12-44) The study population consisted of 1073 octogenarians (mean age 83±2years;52% female) undergoing isolated aortic valve replacement(n=293),isolated mitral valve replacement (n=89), multiple valve replacement (n=119) or combined valve replacement and coronary artery bypass grafting(n=572)between 2002and 2007at single Institution. Five hundred randomly selected patients undergoing valve procedure during the same period were controls Results:The value of the eight-SF-36-scales improved significantly in elderly patient with higher improvement in role physical (p<0.001)and role emotional (p<0.001)but with lower results in vitality(p=0.04)and mental health(p=0.04).Trait anxiety did not change (35 ±8vs.36±9,p=ns), whereas state-anxiety improved(41±6,vs.37 ± 6,p=0.01).Finally, depression significantly worsened after operation(35 ±8vs.47 ±10,p=0.001).However, either QoL or emotionalbehavioural status were significantly poorer in older patients (p<0.001). Total direct costs were $5340 higher in the octogenarians(p<0.001).Cost effectiveness were $35/QoL vs.$16.8/QoL (p<0.001) Conclusions:Despite of improvements of perioperative techniques and postoperative results , octogenarians cannot be indiscriminately referred to the cardiac surgeon.The high cost-benefit ratio in this growing minority of patients must be carefully considered and subject who can really benefit from valve procedure must be carefully selected.

1:00 p.m. 1027-96

Mitral Valve Repair With Artificial Chordae: Is Prolapse Localization An Independent Risk Factor In Degenerative Disease?

Loris Salvador, Giuseppe Minniti, Elena Cavarretta, Tommaso Regesta, Salvatore Mirone, Francesco Cesari, Emanuele Di Angelantonio, Fabio Patelli, Stefano De Castro, Carlo Valfrè, Santa Maria dei Battuti Hospital, Cardiac Surgery Dept., Treviso, Italy Background: Many authors reported that mitral valve (MV) repair feasibility and durability depend on prolapse localization (anterior, posterior or bi-leaflet). We sought to evaluate if in the MV repair with artificial chordae implant, the prolapse localization is an independent risk factor for mortality, repair failure and recurrent mitral regurgitation (MR). Methods: From 1986 to 2006, 608 patients underwent MV repair; 47(53±14y) patients had anterior, 315 (58±11y) posterior and 246(52±11) had bi-leaflets prolapse. In all patients Gore-tex® chordae were used in association with posterior anuloplasty (99%)

JACC  March 11, 2008 

ABSTRACTS - Valvular Heart Disease   A275

and quadrangular resection ±sliding (57.4%). Clinical and echocardiographic follow-up was complete (median 5.7y, IQR 2.2-9.8). Results: There were 34 (5,6%) late deaths and 24 (3,9 %) reoperations. Cumulative survival at 15 years was 84% (95% CI 75-90). According to prolapse localization, survival at 15 years was 82% (95% CI 58-93), 86% (95% CI 75-92) and 89% (95% CI 81-94) for anterior leaflet (AL), posterior leaflet (PL) and bileaflet (BL), respectively; overall freedom from MV reoperation and recurrent MR was 92% and 85% at 15 years (95% CI 88-95 and 95% CI 78-91), with no significant differences between AL, PL and BL. Based on Cox regression, prolapse localization was not identified as an independent risk factor for long term survival, freedom from reoperation and recurrent MR. Conclusions: This series shows that MV repair with Gore-tex® chordae has excellent long-term performance. Even in case of complex lesions, involving the anterior or both leaflets, the use of Gore-tex® chordal replacement can guarantee homogenous longterm results, independently from prolapse localization.

1034

Adult Cardiothoracic Surgery/Valvular Surgery V Tuesday, April 01, 2008, 9:00 a.m.-12:30 p.m. McCormick Place, South Hall 9:00 a.m. Mitral Valve Tenting Predicts Persistent Functional Mitral Regurgitation After Aortic Valve Replacement in Patients With Aortic Valve Stenosis

Yoshiki Matsumura, A. Marc Gillinov, Manatomo Toyono, Tetsuhiro Yamano, Nozomi Wada, James D. Thomas, Takahiro Shiota, Cleveland Clinic, Cleveland, OH

1034-95

Surgical Therapy Versus Slow Thrombolytic Therapy and Fast Thrombolytic Therapy in Patients With Prosthetic Valve Thrombosis

9:00 a.m. Left atrial reverse remodelling after left ventricular reconstruction without mitral valve repair- CMR study

clara alexandrescu, F. Civaia, Laura Iacuzio, B. Alexandrescu, F. Bourlon, Francoise Montiglio, V. Dor, Cardio Thoracic Center, Monte- Carlo, Monte-carlo, Monaco Background: Left ventricular reconstruction (LVR) has been demonstrated to improve the systolic function and to improve the survival. Until now, few data on the evolution of the diastolic function after LVR were reported. Left atrial (LA) enlargement has been proposed as a marker of the left ventricle (LV) diastolic function. We explored early outcome of the left atrial remodelling after LVR. Methods: 30 consecutive patients with severe ischemic cardiomyopathy (24 men, 6 women, mean age 64,6 ± 10,9 years) and completed MRi evaluation were enrolled. They underwent LVR alone (n= 17 patients) or LVR and mitral valve repair for ischemic mitrale regurgitation (n=13 patients). CABG was performed in all patients. The MRI was performed 2 months before intervention and within the first month after surgery with standard measurements for myocardial mass, LV volumes index and LV ejection fraction (EF). LA volume was calculated using the area-length method and the influence of the body surface area on LA volume was corrected. The literature normal value for the LA volume index (LAVol I) was considered 22 ± 6 ml/m² for all ages. Results:The left ventricle end-diastolic volume index (LVEDVol I) significantly decreased early after intervention (108,3± 25,8ml/m²versus 71, 1± 19ml/m², p< 0.001). Also EF

Background: Prosthetic valve thrombosis (PVT) still remains the most dreaded complication despite improvement in design of prosthetic valves. This study has compared surgery with slow thrombolytic therapy (TT) and with fast TT as first line therapy for PVT. Methods: 28 patients (Group A) presenting between July 2004 - July 2005 who were treated with surgery on first line of treatment. Surgery was used as first line therapy of treatment for all patients presenting with left side PVT during that period. Between August 2005 - February 2007, 32 patients (Group B) were treated with slow TT (2.5 lac over 20 minute followed by 1 lac per hr for 24 to 72 hours). 22 patients (Group C) with PVT were treated with fast TT (2.5 lac over 20 min followed by 15 lac over 90 minutes same as for acute myocardial infarction). Diagnosis of PVT was made on transesophageal echocardiography. Patients were randomized for thrombolytic protocol according to the day of their presentation with those presenting on treating unit A day treated with slow TT protocol and those presenting on treating unit B day treated with fast TT protocol. Results: Mortality in Group A was 36% vs 22% in Group B and 18% in Group C. Hemorrhagic complications occurred in 22% in Group C vs 6% in Group B. 1 patients (4.5%) in Group C had hemorrhagic stroke, while no patient in Group B had hemorrhagic stroke. Ischemic stroke occurred in 9% in Group B as compared to 4% in Group C. Transient Ischemic Attack occurred in 3% in Group B vs 14% in Group C. Complete response occurred in 53% in Group B vs 36% in Group C. 1 patient in Group A developed infective mediastinitis and died. 1 patient in Group A developed non infective sternal dehiscence managed conservatively. 2 patients in Group A developed renal failure, 1 died and 1 maintained on chronic dialysis. Conclusions: We conclude that TT should be the first line in patients with PVT except those with PVT less than 5 mm and non obstructive in which primary anticoagulation control is major line of management. Also we conclude that patients who are very critically ill should be given fast thrombolytic protocol while patients who are in lower risk group should be treated with slow dose protocol.

9:00 a.m. 1034-96

Extended Durability and Safety of Percutaneous SeptalSinus Shortening

Jason H. Rogers, Gary R. Caputo, Igor F. Palacios, Jose A. Condado, David Rahdert, Reginald I. Low, UC Davis Medical Center, Sacramento, CA, Ample Medical, Inc., Foster City, CA Background: The long-term durability and safety of emerging percutaneous mitral repair devices remains unknown. We have shown percutaneous septal sinus shortening (the PS3 System) to have immediate and short term efficacy for functional mitral regurgitation. We conducted chronic implants in an ovine model to assess durability and safety at up to one year. Methods: The PS3 System (consisting of interatrial septal and great cardiac vein anchors connected by an adjustable suture bridge) was placed in eight healthy adult sheep as previously described using standard interventional techniques with fluoroscopic and intracardiac echocardiographic (ICE) guidance. The mitral annular septal-lateral dimension in systole (SLS) was acutely reduced by ≥10%. At the time of abstract submission, animals were sacrificed at 3 months (n=2), 6 months (n=3), and 12 month sacrifice is planned (n=3). ICE was performed in all animals pre-implant, post-implant, and at sacrifice. All animals had complete terminal histopathologic characterization, and cardiac computed tomography (CT) was performed in 4 animals. Values are reported as mean±SD. Results: At 3 and 6 months after implantation, ICE and CT showed the PS3 Systems to be intact without erosion, and histopathologic assessment revealed each component correctly deployed in its respective target site without evidence of thrombus or infection. There were no significant complications noted at the site of entry of the bridge into the great cardiac vein (GCV). The GCV was patent in all animals. In the 6 month cohort (n=4), there was sustained overall reduction in SLS after implant. SLS pre-implant was 25.9±0.8 mm, SLS post-implant was 21.1±1.2 mm, and SLS at 6 months was 23.1±2.6 mm (p=NS, post-implant vs. 6 months). Conclusions: The PS3 System appears to provide an overall stable and complicationfree reduction in the mitral annular septal-lateral dimension. There was no evidence of erosion, thrombosis or perforation in this ovine model. One-year follow-up including histopathologic and imaging data will be presented.

Valvular Heart Disease

Background: Moderate functional mitral regurgitation (FMR) in patients with aortic valve stenosis (AS) is often not corrected at the time of aortic valve replacement (AVR) because FMR is expected to improve after isolated AVR. However, some patients have persistent moderate FMR even after AVR. The purpose of this study was to determine whether persistence of FMR after AVR could be predicted by preoperative echocardiographic analysis. Methods: Pre and postoperative echocardiograms were reviewed in 59 patients (aged 71±11 years) who underwent isolated AVR for severe AS (aortic valve area: 0.66±0.16 cm2) with greater than moderate FMR. FMR was defined as mitral regurgitation without morphological abnormalities of the mitral apparatus. Patients with poor image quality, significant aortic regurgitation (grade >2+), and other cardiac surgery such as mitral valve (MV) repair and coronary artery bypass graft were excluded. The left ventricular (LV) volume and ejection fraction (EF) were measured by the Simpson method. The severity of FMR was assessed by using the standard methods recommended by ASE. In patients with MV tenting, defined as the tenting height (TH) of greater than 6 mm, TH, tenting area (TA), and mitral annular diameter were measured in the long axis views at the midsystolic frame. Results: 37 patients had the MV tenting (63%, Group A) and 22 did not have it (37%, Group B) before AVR. Patients in Group A had significantly larger LV volume (P<0.001), lower EF (P<0.001), and severer FMR (P=0.001) than those in Group B. FMR in 28 of 37 (76 %) patients improved to 1+ or less after isolated AVR in Group A, while 22 of 24 (91%) patients in Group B. In Group A, 9 patients with persistent FMR after AVR had significantly severer MV tenting in comparison with those without persistent FMR (TH; 1.2±0.3 vs. 0.9±0.2 cm, TA; 1.9±0.3 vs. 1.4±0.4 cm2, both P<0.005). The sensitivity and specificity in predicting persistent FMR after AVR were 67% and 96% for TH >1.15cm, and 67% and 93% for TA >1.85cm2, respectively. Conclusions: MV tenting predicts persistent FMR after AVR in patients with severe AS. MV repair is strongly recommended at the time of AVR in patients with significant FMR and MV tenting, defined as TA of larger than 1.85cm2.

1034-82

9:00 a.m.

Sumit Narang, Amit Banerjee, Deepak Kumar Satsangi, Mohammed Abid Geelani, Vikas Saini, G B Pant Hospital, Delhi, India, University of Chicago Hospital, Chicago, IL

ACC.POSTER CONTRIBUTIONS

1034-81

improved after LVR (EF presurgery=32, 6%, to EF postsurgery 42,5%, with p< 0.001). Left atrial enlargement was noticed in preoperative MRI assessment (LAVol I 53 ± 24,4 ml/m²).In the group of the patients undergoing LVR alone, EDVol I decreased after intervention (103,3 ± 26,2 ml/m² to 66.5 ± 18,4 ml/m², p< 0.001). Moreover, significantly statistic left atrial reverse remodelling was observed in these patients (46,8 ± 15ml/m² to 37,1 ± 102 ml/m², p= 0.05). Conclusions: These data showed that the left atrial enlargement was significant, in the group undergoing left ventricular reconstruction. Reverse remodelling of left atrium was noticed as early, one month after LVR alone.

A276   ABSTRACTS - Valvular Heart Disease

JACC  March 11, 2008

ACC.ORAL CONTRIBUTIONS

10:30 a.m.

816

Emerging Insights Into the Pathogenesis of Valvular Heart Disease Tuesday, April 01, 2008, 10:00 a.m.-11:30 a.m. McCormick Place, Room S404

MCP-1 blockage inhibits lipoprotein accumulation and valvular calcification in ApoE-/- mice

Valvular Heart Disease

Haimei Wang, Sorel Goland, Kevin Burton, Lawrence Czer, Alfredo Trento, Cedars-Sinai Medical Center, Los Angeles, CA Objective: monocyte chemoattractant protein-1 (MCP-1) has a role in the recruitment of monocytes to sites of injury. In calcified valve lesions, valve endothelial cells can be induced by oxidized lipid to express high levels of MCP-1. This study was designed to determine if MCP-1 blockage can prevent lipid deposition and valve calcification. Methods: ApoE-/- mice, fed a high fat diet for 10weeks either received IV injection of anti-MCP-1 neutralizing antibody or its control. All animals were received subcutaneously implanted bioprosthetic valve leaflets. Native valvular function was evaluated by Doppler echocardiography. Atherosclerosis lesions in aortic roots were examined in tissue section with Oil Red O staining. Calcium and lipid content in explanted leaflets were quantified. Effect of MCP-1 blockage on the adhesion of valve endothelial cells was evaluated in an adhesion assay in which oxidized-LDL induced pig valve endothelial cells were treated with MCP-1 antibody (500ng/ml). CCR2 gene expression in Oxidized-LDL induced cells was determind by real time PCR. Result: Lesions in aortic roots were significantly reduced in MCP-1 antibody treated mice compared to control mice (Ratio of lesion area: 1.76±0.75% vs. 33.5±19% p=0.02). Endothelial cells treated with anti-MCP-1 had reduced adhesion compared to control cells (p=0.05). Calcium and lipid contents were significantly reduced in explanted bioprosthetic valve tissue in mice treated MCP-1 antibody compared to control mice (p<0.05). Aortic velocities were significantly higher in control mice compared to treated mice (0.58±0.03 vs. 0.51±0.06cm/s, p=0.05). CCR2 gene expression was significantly increased in valve endothelial cells by oxidized-LDL treatment. Conclusion: our study demonstrated that MCP-1 antibody effectively reduced lipid deposition and calcification in both native aortic valves and bioprosthetic valve in ApoE-mice, we also showed that MCP-1 receptor CCR2 was in abundance by oxidizedLDL. Collectively our study suggests that MCP-1 blockage may be beneficial for treatment of valvular diseases.

10:15 a.m. 816-4

Bicuspid Aortic Valves Are Associated With Increased Inflammation and Neovascularization in Severe Aortic Stenosis

Luis Astudillo, Elias Zias, Purushothaman K-Raman, Meerarani Purushothaman, Patrick Lento, John T. Fallon, Valentin Fuster, Pedro R. Moreno, Mount Sinai School of Medicine, New York, NY

10:00 a.m. 816-3

816-5

PON1 genotype Correlates with Increased Risk of Aortic Stenosis Progression

Luis Moura, Jose Zamorano, Sandra Ramos, Miguel Brito, Luisa Veiga, F. RochaGonzalves, Nalini M. Rajamannan, San Pedro Hospital, Mastonishos, Portugal, Northwestern University, Chicago, IL Background: Paraoxonase 1 (PON1) is known to be an important regulator of oxidative stress. Normal PON1 activity protects LDL-cholesterol (LDL) from oxidation. Furthremore, it has an inverse association with coronary artery disease and stroke with an higher risk of these syndromes associated with lower PON1 activity. Given the vascular risk factors in calcific valvular aortic stenosis (AS) and the hypothesis that oxidized LDL is a key mediator of atherosclerosis, we postulated that PON 1 polymorphisms might be associated with valvular disease progression. Methods: Over 200 subjects 80 controls age control group without aortic stenosis) compared to 200 patients enrolled in RAAVE study were genotyped for 2 nucleotide polymorphisms (SNP), in the paraoxonase gene 1 on chromosome 7. (Enrollment criteria for RAAVE: ejection fraction > 50%, peak velocity > 2.5 cm2 with an echo performed at baseline and every 6 months for 18 months. 61 pts received rosuvastatin (20 mg/day) according to the NCEP guidelines. 60 pts did not. There was no difference between the baseline characteristics of the two groups except on lipid levels, with the same degree of AS (1.21±0.38cm2 versus 1.23±0.37 cm2; p=0.636). Results: Compared with patients without AS, the genotype distribution of patients with AS differed significantly (p=0.037), with more prevalence of one SNP in the paraoxanase 1 gene. A glutamine (Gln)/arginine (Arg) polymorphism at amino acid residue 192 in PON 1 was significantly associated with AS progression (p=0.043), in multivariate analysis, including age, sex, LDL, hypertension, diabetes, CRP and statin treatment as covariates). The odds ratios were 2.15 (95% CI: 1.49 to 3.19) for Gln/Arg heterozygotes and 1.87 (95% CI: 1.1 to 2.5) for Arg/Arg homozygotes compared with Gln/Gln homozygotes. Conclusions: These results suggest that Gln192Arg genotype in PON 1 marked increase the risk factor for aortic stenosis from the patients of RAAVE, as compared to age matched controls without AS. This SNP may represent a loss of function mutation in these patients with aortic stenosis. PON1 polymorhphism provides genetic evidence that oxidative stress plays a role in the cellular biology of progressive aortic stenosis.

Background. The pathogenesis of bicuspid aortic stenosis (AS) is considered to be similar to tricuspid AS, only that it occurs at an earlier stage. However, we postulated that the hemodynamic and rheological effects will induce a more aggressive inflammatory process, with increased macrophage and neovessel content when compared to tricuspid AS. Methods. Immunohistochemistry on 22 aortic stenotic valves obtained at the time of aortic valve replacement was performed for quantification of macrophage/T cell infiltration (CD68+CD3), and neovessel content (CD-34). Bicuspid (n=12) patients were 15 yrs younger than tricuspid (n=10) patients (61 ± 8 vs 75 ± 8 yrs; P=0.0001). Other variables including risk factors were similar in both groups. Results. Total number of macrophages and T cells was increased in bicuspid AS when compared to tricuspid AS (414 ± 329 vs 101 ± 99; P=0.009) (Figure A). The number of neovessels was also increased in bicuspid AS when compared to tricuspid AS (275 ± 100 vs 153 ± 42; P=0.009) (Figure B). Macrophages and T cells correlated with neovessel content in bicuspid AS (R=0.85; P<0.0001) but not in tricuspid AS (R=0.4; P=NS). Conclusions. The pathogenesis of bicuspid AS involves increased inflammation and neovascularization, probably related to hemodynamic and rheological effects. Aggressive medical therapy to decrease macrophage and neovessel infiltration may provide improved benefit in bicuspid AS at an earlier period. Clinical trials are needed to confirm this hypothesis.

10:45 a.m. 816-6

Risk Factors for Incident Aortic Valve Calcification in the Multi-Ethnic Study of Atherosclerosis

David S. Owens, Ronit Katz, Junichiro Takasu, Richard Kronmal, Matthew J. Budoff, Kevin D. O’Brien, University of Washington, Seattle, WA, Los Angeles Biomedical Research Institute at Harbor-UCLA, Los Angeles, CA Background: Prior, cross-sectional studies have identified several risk factors (RFs) for aortic valve calcification (AVC). However, RFs associated with the development of new, incident AVC have not been reported previously. Methods: AVC was detected by serial CT scanning in 5,141 participants of the Multi-Ethnic Study of Atherosclerosis; RFs for incident AVC were then identified using logistic regression. Results: After a mean follow up of 2.4 +/- 0.9 years, 211 (4.1%) subjects developed incident AVC (mean rate 1.7% per year), but this was highly age-dependent (Figure 1). RFs associated with incident AVC after full adjustment included 10 years of age [odds ratio 1.94 (95% CI 1.65, 2.27), p<0.001], male gender [1.38 (1.03, 1.86), p=0.03], use of antihypertensive medication [1.37 (1.00, 1.86), p=0.048], the ratio of total cholesterol to HDL [1.19 (1.05, 1.35), p<0.01], use of lipid lowering medications [1.67 (1.19, 2.35), p<0.01], impaired fasting glucose [1.41 (1.01, 1.96), p=0.04], and diabetes [1.67 (1.10, 2.51), p=0.02]. Chinese ethnicity was associated with a significantly lower rate of incident AVC [0.42 (0.23, 0.77), p<0.01], while CRP, fibrinogen and creatinine showed no association. Conclusions: In this ethnically diverse, pre-clinical cohort, the rate of incident AVC increased with age. RFs for incident AVC included traditional atherosclerosis RFs, while inflammatory markers and renal dysfunction showed no association. Ethnicity may influence risk for AVC beyond traditional RFs.

JACC  March 11, 2008 

ABSTRACTS - Valvular Heart Disease   A277 11:00 a.m.

816-7

Atorvastatin Attenuates Bioprosthetic Heart Valve Calcficiation in a Rabbit Model via a Stem Cell Mediated Mechanism

Nalini M. Rajamannan, Linnea Arterburn, Roger Bares, Amy Flores, Frank Caira, Northwestern University, Chicago, IL Background: Bioporsthetic Heart Valve Calcification is the major cause of structural valve failure. It is estimated that 20-30% of implanted bioprosthetic heart valves will have some degree of hemodynamic dysfunction at 10 years. The mechanism of valve degeneration is unknown. Recent studies have implicated elevated lipids as risk factors for the development of valve deterioration. We tested the hypothesis that bioprosthetic valve calcification is a stem cell mediated atherosclerosis process.Method: We tested two models of prosthetic valve calcification. First, we tested valves removed at the time of surgical valve replacement (n=23) and compared them to controls (n=23) for stem cell markers and bone matrix formation by immunohistochemistry and RTPCR. We also measured calcification burden with MicroCT Scanco) We then implanted normal bioprosthetic valves in rabbits( n=10 control), (n= 10, 0.5% cholesterol), and (n=10, 0.5% cholesterol + Atorvastatin) for three months. Result: The human valves from surgery demonstrated four-fold increase in stem cell marker cKit by RNA gene expression and protein expression (p<0.05). There was an increase in osteoblast marker osteopontin and heavy calcium burden by MicroCT. Finally, there was an increase in the angiogensis markers, VEGF, CD34 and CD68. The bioprosthetic valve tissue explanted from the cholesterol diets demonstrated severe atherosclerosis four fold with islands of stem cell atherosclerosis positive for ckit, macrophage and osteopontin expression. Control valves demonstrated a 1fold increase in atherosclerotic stem cell markers. The atorvastatin treated valves had no evidence of stem cell markers or atherosclersosis. (p<0.05) Conclusion: In conclusion, bioprosthetic valve calcfication is a mesenchymal stem cell mediated atherosclerotic calcification process. A rabbit model of experimental hypercholesterolemia provides the prrof of principal that cholesterol mediates this stem cell niche. Furthermore, atorvastatin in this model attenuates this process providing the first evidence that this may slow the progression of stem cell mediated bioprothetic valve calcification.

11:15 a.m. 816-8

Nikolaos Tzemos, Erik Lyssegen, Candice Silversides, Michael Jamorski, Samuel Siu, University Health Network, University of Toronto, Toronto, ON, Canada Background: Bicuspid aortic valve (BAV) in young patients is associated with proximal aortic dilation. We hypothesize that aortic dilation will be part of a systemic vascular disorder mediated through changes in systemic endothelial function, aortic stiffness and plasma matrix metalloproteinase’s (MMP-2 and MMP-9). Methods: Thirty-two male patients (mean age 31±4) with non-stenotic BAV disease were prospectively studied; 16 patients with dilated aortic roots and 16 patients without dilated aortic roots. None of the patients had any risk factors for coronary artery disease. Sixteen healthy volunteers matched for age were used as comparison group. All subjects undergone endothelial function [flow mediated vasodilation (FMD)], aortic stiffness (carotid-femoral pulse wave velocity) assessments, and peripheral blood sampling for MMP-2, MMP-9 and their tissue inhibitors TIMP1 and TIMP2. Three dimensional echocardiography and cardiac magnetic resonance (CMR) was used to assess aortic dimensions, cardiac chamber volumes and function. Results: Patients were matched for severity of aortic stenosis, left ventricular mass and function, blood pressure. Patients with dilated aortas had larger aortic root dimensions (38±5 mm vs. 31±6 mm, p=0.01) and ascending aorta dimensions (33±6 vs. 46±4mm, p=<0.01). Similarly, those patients with dilated aortic roots exhibited blunted FMD to hyperemia (8±1 vs. 6±1 % percentage change, p<0.001) and had higher pulse wave velocities (9.4±1 vs. 7±0.5 m/s, p<0.001). Plasma levels of MMP-2 and TIMP2 were also higher in patients with dilated aortic roots (1606±278 vs. 1085±160 ng/mL, p=<0.001) and (178±100 vs. 124±60 ng/mL, p=0.36) respectively. Conversely, MMP-9 and TIMP1 were similar in patients with and without dilated roots. There were no differences in all parameters between patients with BAV-normal size root and the control group. Conclusions: Young patients with non-stenotic BAV disease and dilated proximal aortas have systemic endothelial dysfunction, increased aortic stiffness and excess of plasma MMP-2. These findings suggest that aortic dilation may be a manifestation of a systemic vascular disorder and offers potential new therapeutic targets.

Valvular Heart Disease

Aortic dilation is linked to systemic endothelial dysfunction, increased aortic stiffness and excess plasma matrix metalloproteinases in patients with nonstenotic bicuspid aortic valve