genetic deficiency of cystathionine gamma-lyase exacerbates myocardial reperfusion injury and is...

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(3.6%) and 11 (4.3%) deaths (P=1.000), with 1 (1.8%) and 9 (3.5%) being cardiac deaths (P=1.0000) and ME 5 (9.1%) and 45 (17.6%) (P=.1762). In univariate analysis and multivariate Cox analysis, the single or Inoue balloon technique did not predict survival or EFS, and independent predictors for survival were age b50 years (P=.016, HR=0.233), ES 8(Pb .001, HR=0.105), MBV dilation area (Pb .001, HR 16.838) and mitral valve surgery in the FU (P=.001, HR=0.152) and, for events-free survival, prior commissurotomy (P=.012, HR=0.390) and post-MBV MVA 1.50 cm 2 (Pb .001, HR=7.969). Conclusions: Mitral balloon valvuloplasties with single balloon and Inoue balloon were equally efficient with similar survival and EFS in the follow- up. Independent predictors of survival were age b50 years, ES 8 points, MBV dilation area and mitral valve surgery in the follow-up and, of event- free survival. prior commissurotomy and post-MBV MVA 1.50 cm 2 . doi:10.1016/j.carrev.2011.04.317 Single-center multimodality experience with transcatheter aortic valve implantation Danny Dvir, Abid Assali, Eyal Porat, Alexander Sagie, Yaron Shapira, Hana Vaknin, Arnon Koren, Gideon Shafir, Aeyal Raz, Nurit Shor, Roussana Aranbitski, Marina Kupershmidt, Vachislav Bobovnikov, Alexander Battler Ran Kornowski Rabin Medical Center, Petah-Tikva, Israel Background: Transcatheter aortic valve implantation (TAVI) is an alternative for surgery in patients at high surgical risk. We would like to describe our single-center multimodality experience with transfemoral, transaxillary and transapical TAVI procedures using CoreValve and Edwards-Sapien devices. Methods: By November 2010, 67 patients were treated: 32 transfemoral Corevalve, 7 transaxillary CoreValve, 14 transfemoral Edwards and 14 transapical Edwards. This patient group (65% women) was characterized by relatively older age (mean 82.8±4.8 years) and high prevalence of severe comorbidities: 33% diabetes mellitus, 40% postthoracotomy, 44% chronic renal failure, 24% chronic pulmonary disease. The mean calculated logistic euroSCORE was 21.5%±15% and STS score was 8.1%±5.4%. Four TAVI cases (6%) were performed in bioprosthetic valves. Results: Procedural success was reached in 98.5%. Two patients died within 30 days after the procedure, and another patient died after that period (97% 30-day survival and 91.4% 180-day survival). There were no cases with a need for urgent cardiac surgery or cardiac tamponade. Major vascular complications were noted in five patients (7.5%). Two patients suffered from debilitating stroke (3%). Permanent pacemaker implantation was required in 11 patients (16.4%). Significant (grade 2) postprocedural aortic regurgitation was noted in 2 patients (3%), acute renal failure in 2 patients (3%) and blood transfusion in 28 patients (42%). The median length of hospital stay was 6 days. After the procedure, valve gradients decreased from 88/51 to 15/5 mmHg ( Pb .001). At follow-up, symptomatic improvement was evident in 89.6% of patients, and 95.5% of patients were in NYHA class I/II. Conclusions: Our experience with TAVI using the Edwards-Sapien and Corevalve devices suggests that this is an effective and relatively safe procedure for the treatment of severe aortic stenosis in suitable carefully screened patients at high surgical risk. doi:10.1016/j.carrev.2011.04.318 High transvalvular gradient vs. low transvalvular gradient in patients with severe aortic stenosis and poor left ventricular function Itsik Ben-Dor, Michael A. Gaglia Jr., Kohei Wakabayashi, Gabriel Maluenda, Manuel A. Gonzalez, Michael Mahmoudi, Gabriel Sardi, Rafael Romaguera, Ana Laynez, Rebecca Torguson, Okubagzi Petros, Zhenyi Xue, William O. Suddath, Kenneth M. Kent, Joseph Lindsay, Lowell F. Satler, Augusto D. Pichard, Ron Waksman Washington Hospital Center, Washington, DC, USA Background: Left ventricular systolic dysfunction in patients with severe aortic stenosis (AS) is associated with poor outcome. The aim was to compare the outcome of patients with severe AS and low ejection fraction (EF) with high vs. low transvalvular gradients. Methods: A total of 193 patients with severe AS and low EF b40% who were referred to participate in the clinical trial of transcatheter aortic valve implantation (TAVI) were studied. Patients were divided into two groups: group I with low mean transvalvular gradient b40 mmHg (N=103) and group II with high transvalvular gradients 40 mmHg (N=90). Clinical, hemodynamic and follow-up mortality data were collected. Results: Patients with low gradient (b40 mmHg) had significantly lower mean age and higher euroSCORE, renal failure and coronary artery disease compared to patients with high gradient (40 mmHg). The aortic valve area was smaller and the EF and cardiac out were higher in the group with high gradient (40 mmHg) compared to the group with low gradient (b40 mmHg). Patients with low gradient were treated more medically and less with balloon aortic valvuloplasty compared to patients with high gradients. The EF improved immediately and in follow-up after TAVI, surgical aortic valve replacement and BAV (Fig. 1). Conclusion: While the EF improves in all patients with severe AS and left ventricular dysfunction post-TAVI, surgical aortic valve replacement and BAV, patients with severe AS and low transvalvular gradient are at higher risk for worse outcome when compared to patients with high transvalvular gradient. doi:10.1016/j.carrev.2011.04.319 Miscellaneous science Genetic deficiency of cystathionine gamma-lyase exacerbates myocardial reperfusion injury and is rescued by exogenous hydrogen sulfide Shashi Bhushan, Madhav Lavu, Benjamin Predmore, Marah Elston, Juan Pablo Aragon, Saurabh Jha, Susheel Gundewar, David Lefer Emory University, Atlanta, GA, USA Hydrogen sulfide (H 2 S) is a novel gaseous signaling molecule that up- regulates antioxidants and antiapoptogens and promotes cellular survival. In the heart, cystathionine gamma-lyase (CSE) is the primary enzyme for endogenous production of H 2 S. We have previously demonstrated that CSE transgenic mice or mice treated with H 2 S are protected against myocardial ischemia/reperfusion (MI/R) injury and heart failure. We hypothesized that CSE knockout mice (KO) would develop increased infarct size following MI/R compared to wild-type (WT) mice. CSE KO mice (n=12) and WT mice (n=11) at 1214 weeks of age were subjected to 45 min of MI and 24 h of R in vivo, at which time the left ventricular (LV) area-at-risk (AAR) and infarct size (INF) were determined with Evan's blue dye and 2,3,5-triphenyl tetrazolium chloride (TTC) staining (Fig. 1). An additional group of CSE KO mice (n=12) was subjected to MI/R and received Na 2 S (100 μg/kg) at the time of reperfusion. Western blotting for basal cardiac antioxidant enzyme levels was also performed in separate groups of mice (n=6 per group). The results show a significant increase in the myocardial INF/AAR of CSE KO mice compared to WT mice (62%±2% vs. 42%±3%, respectively, Pb .001). This exacerbation of MI/R injury was attenuated by 50% following Na 2 S therapy at reperfusion (29%±4% INF/AAR, Pb .001 vs. CSE KO). However, CSE KO mice failed to demonstrate a significant difference (P=NS vs. WT) in myocardial tissue levels of thioredoxin (TRX), superoxide dismutase (SOD), heat shock protein 90 (HSP-90) or heme oxygenase-1 (HO-1). This study demonstrates that basal H 2 S production from CSE is critical for protecting the heart during ischemia and reperfusion. Future studies will determine the mechanisms by which CSE KO mice have increased susceptibility to MI/R injury. doi:10.1016/j.carrev.2011.04.320 e28 Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1e46

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Page 1: Genetic deficiency of cystathionine gamma-lyase exacerbates myocardial reperfusion injury and is rescued by exogenous hydrogen sulfide

e28 Abstracts / Cardiovascular Revascularization Medicine 12 (2011) e1–e46

(3.6%) and 11 (4.3%) deaths (P=1.000), with 1 (1.8%) and 9 (3.5%) beingcardiac deaths (P=1.0000) and ME 5 (9.1%) and 45 (17.6%) (P=.1762). Inunivariate analysis and multivariate Cox analysis, the single or Inoue balloontechnique did not predict survival or EFS, and independent predictors forsurvival were age b50 years (P=.016, HR=0.233), ES ≤8 (Pb.001,HR=0.105), MBV dilation area (Pb.001, HR 16.838) and mitral valvesurgery in the FU (P=.001, HR=0.152) and, for events-free survival, priorcommissurotomy (P=.012, HR=0.390) and post-MBV MVA ≥1.50 cm2

(Pb.001, HR=7.969).Conclusions: Mitral balloon valvuloplasties with single balloon and Inoueballoon were equally efficient with similar survival and EFS in the follow-up. Independent predictors of survival were age b50 years, ES ≤8 points,MBV dilation area and mitral valve surgery in the follow-up and, of event-free survival. prior commissurotomy and post-MBV MVA ≤1.50 cm2.

doi:10.1016/j.carrev.2011.04.317

Single-center multimodality experience with transcatheter aorticvalve implantationDanny Dvir, Abid Assali, Eyal Porat, Alexander Sagie, Yaron Shapira,Hana Vaknin, Arnon Koren, Gideon Shafir, Aeyal Raz, Nurit Shor,Roussana Aranbitski, Marina Kupershmidt, Vachislav Bobovnikov,Alexander BattlerRan Kornowski Rabin Medical Center, Petah-Tikva, Israel

Background: Transcatheter aortic valve implantation (TAVI) is analternative for surgery in patients at high surgical risk. We would like todescribe our single-center multimodality experience with transfemoral,transaxillary and transapical TAVI procedures using CoreValve andEdwards-Sapien devices.

Methods: By November 2010, 67 patients were treated: 32 transfemoralCorevalve, 7 transaxillary CoreValve, 14 transfemoral Edwards and 14transapical Edwards. This patient group (65% women) was characterized byrelatively older age (mean 82.8±4.8 years) and high prevalence of severecomorbidities: 33% diabetes mellitus, 40% postthoracotomy, 44% chronicrenal failure, 24% chronic pulmonary disease. The mean calculated logisticeuroSCORE was 21.5%±15% and STS score was 8.1%±5.4%. Four TAVIcases (6%) were performed in bioprosthetic valves.Results: Procedural success was reached in 98.5%. Two patients diedwithin 30 days after the procedure, and another patient died after thatperiod (97% 30-day survival and 91.4% 180-day survival). There wereno cases with a need for urgent cardiac surgery or cardiac tamponade.Major vascular complications were noted in five patients (7.5%). Twopatients suffered from debilitating stroke (3%). Permanent pacemakerimplantation was required in 11 patients (16.4%). Significant (grade ≥2)postprocedural aortic regurgitation was noted in 2 patients (3%), acuterenal failure in 2 patients (3%) and blood transfusion in 28 patients(42%). The median length of hospital stay was 6 days. After theprocedure, valve gradients decreased from 88/51 to 15/5 mmHg(Pb.001). At follow-up, symptomatic improvement was evident in89.6% of patients, and 95.5% of patients were in NYHA class I/II.Conclusions: Our experience with TAVI using the Edwards-Sapien andCorevalve devices suggests that this is an effective and relatively safeprocedure for the treatment of severe aortic stenosis in suitable carefullyscreened patients at high surgical risk.

doi:10.1016/j.carrev.2011.04.318

High transvalvular gradient vs. low transvalvular gradient in patientswith severe aortic stenosis and poor left ventricular functionItsik Ben-Dor, Michael A. Gaglia Jr., Kohei Wakabayashi, Gabriel Maluenda,Manuel A. Gonzalez, Michael Mahmoudi, Gabriel Sardi, Rafael Romaguera,Ana Laynez, Rebecca Torguson, Okubagzi Petros, Zhenyi Xue,William O. Suddath, Kenneth M. Kent, Joseph Lindsay, Lowell F. Satler,

Augusto D. Pichard, Ron WaksmanWashington Hospital Center, Washington, DC, USA

Background: Left ventricular systolic dysfunction in patients with severeaortic stenosis (AS) is associated with poor outcome. The aim was tocompare the outcome of patients with severe AS and low ejection fraction(EF) with high vs. low transvalvular gradients.Methods: A total of 193 patients with severe AS and low EF b40% whowere referred to participate in the clinical trial of transcatheter aortic valveimplantation (TAVI) were studied. Patients were divided into two groups:group I with low mean transvalvular gradient b40 mmHg (N=103) andgroup II with high transvalvular gradients ≥40 mmHg (N=90). Clinical,hemodynamic and follow-up mortality data were collected.Results: Patients with low gradient (b40 mmHg) had significantly lowermean age and higher euroSCORE, renal failure and coronary artery diseasecompared to patients with high gradient (≥40 mmHg). The aortic valve areawas smaller and the EF and cardiac out were higher in the group with highgradient (≥40 mmHg) compared to the group with low gradient (b40mmHg). Patients with low gradient were treated more medically and lesswith balloon aortic valvuloplasty compared to patients with high gradients.The EF improved immediately and in follow-up after TAVI, surgical aorticvalve replacement and BAV (Fig. 1).Conclusion: While the EF improves in all patients with severe AS andleft ventricular dysfunction post-TAVI, surgical aortic valve replacementand BAV, patients with severe AS and low transvalvular gradient are athigher risk for worse outcome when compared to patients with hightransvalvular gradient.

doi:10.1016/j.carrev.2011.04.319

Miscellaneous science

Genetic deficiency of cystathionine gamma-lyase exacerbatesmyocardial reperfusion injury and is rescued by exogenoushydrogen sulfideShashi Bhushan, Madhav Lavu, Benjamin Predmore, Marah Elston,Juan Pablo Aragon, Saurabh Jha, Susheel Gundewar, David LeferEmory University, Atlanta, GA, USA

Hydrogen sulfide (H2S) is a novel gaseous signaling molecule that up-regulates antioxidants and antiapoptogens and promotes cellular survival. Inthe heart, cystathionine gamma-lyase (CSE) is the primary enzyme forendogenous production of H2S. We have previously demonstrated that CSEtransgenic mice or mice treated with H2S are protected against myocardialischemia/reperfusion (MI/R) injury and heart failure. We hypothesized thatCSE knockout mice (KO) would develop increased infarct size followingMI/R compared to wild-type (WT) mice. CSE KO mice (n=12) and WTmice (n=11) at 12–14 weeks of age were subjected to 45 min of MI and 24h of R in vivo, at which time the left ventricular (LV) area-at-risk (AAR) andinfarct size (INF) were determined with Evan's blue dye and 2,3,5-triphenyltetrazolium chloride (TTC) staining (Fig. 1). An additional group of CSEKO mice (n=12) was subjected to MI/R and received Na2S (100 μg/kg) atthe time of reperfusion. Western blotting for basal cardiac antioxidantenzyme levels was also performed in separate groups of mice (n=6 pergroup). The results show a significant increase in the myocardial INF/AARof CSE KO mice compared to WT mice (62%±2% vs. 42%±3%,respectively, Pb.001). This exacerbation of MI/R injury was attenuated by50% following Na2S therapy at reperfusion (29%±4% INF/AAR, Pb.001 vs.CSE KO). However, CSE KO mice failed to demonstrate a significantdifference (P=NS vs. WT) in myocardial tissue levels of thioredoxin (TRX),superoxide dismutase (SOD), heat shock protein 90 (HSP-90) or hemeoxygenase-1 (HO-1). This study demonstrates that basal H2S productionfrom CSE is critical for protecting the heart during ischemia and reperfusion.Future studies will determine the mechanisms by which CSE KO mice haveincreased susceptibility to MI/R injury.

doi:10.1016/j.carrev.2011.04.320