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ABSTRACT: BACKGROUND/OBJECTIVES: Transradial access (TRA) is being increasingly used for both diagnostic and interventional cardiac procedures. Use of TRA offers many advantages: decreased bleeding, vascular complications, reduced length of hospital stay, and reduced cost. However, the small size of the radial artery limits the size of the equipment that can be used via this approach. We sought to determine whether pre-procedural administration of topical nitroglycerin and lidocaine increases the size of the radial artery. METHODS: Patients undergoing transradial cardiac catheterization were randomized in a double-blind fashion to a topical combination of nitroglycerin+lidocaine or placebo ointment. The primary endpoint was change in radial artery size. Secondary endpoints included radial artery spasm and radial artery patency. RESULTS: 86 patients were enrolled (43 allocated to treatment group and 43 to placebo group). Patients underwent ultrasound of the radial artery at baseline and before the catheterization. Complications were rare: one hematoma (placebo group) and one radial artery occlusion (placebo group). Baseline demographic and clinical characteristics were similar. The baseline radial artery cross-sectional area (CSA) was similar in both groups (4.95±0.24mm(2) in placebo group and 5.14±0.34mm(2) in the treatment group). However, the final CSA decreased to 4.66±0.25mm(2) in the placebo group and increased to 5.78±0.38mm(2) in the treatment group (p=0.02), which corresponded to a decrease in CSA by -5.6±2.1% and an increase in CSA by 16.5±4.2% (p<0.0001), respectively. CONCLUSIONS: Pre-procedural administration of topical mixture of nitroglycerin+lidocaine increases the size of the radial artery in patients undergoing transradial cardiac catheterization. CLINICALTRIALS.GOV IDENTIFIER: NCT01155167.
International journal of cardiology 04/2013; · 7.08 Impact Factor
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ABSTRACT: The cardiosphere (CS) is composed of a heterogeneous population of cells, including CD45(+) cells that are bone marrow (BM)-derived. However, whether the CD45(+) cells are an essential cell component in CS formation is unknown. The current study was undertaken to address this question. Cardiospheres (CSs) were harvested from 1-week post-myocardial infarction (MI) or non-MI hearts of C57BL/6 J mice. The process of CS formation was observed by timelapse photography. To analyze the role of BM-derived CD45(+) cells in CS formation, CD45(+) cells were depleted from populations of CS-forming cells by immunomagnetic beads. We recorded the number of CSs formed in culture from the same amount (10(5)) of intact CS-forming cells, from CD45(+)-cell-depleted CS-forming cells and from CD45(+) cells alone (n=6-9/cell type). CS-forming cells selectively aggregated together to form CSs by 35 h after plating. The depletion of CD45(+) cells from CS-forming cells actually increased the formation of CSs (67±10 CSs/10(5) cells) compared with non-depleted CS-forming cells (51±6 CSs/10(5) cells, P<0.0001). Purified CD45(+) cells from CS-forming cells did not form CSs in culture. Thus, BM-derived CD45(+) cells including BM progenitors are neither necessary nor sufficient for CS formation.
Cell and Tissue Research 10/2012; · 3.11 Impact Factor
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ABSTRACT: BACKGROUND: Tranilast has been shown to inhibit TGFβ1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricular (LV) remodelling post-MI. METHODS: Following coronary artery ligation, Sprague Dawley rats were randomised to receive tranilast (300mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24h until 7 days post-MI, (2) from 7 days to 28 days post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell culture analyses. RESULTS: Tranilast treatment of MI rats from 24h until 7 days post-MI reduced myocardial collagen content, α1 (I) procollagen, TGFβ1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and exacerbated infarct expansion compared with vehicle-treatment. Delaying the commencement of tranilast treatment to 7 days post-MI attenuated myocardial fibrosis, gene expression of α1(I) procollagen, α1(III) procollagen, fibronectin, TGFβ1 and CTGF mRNA transcripts, and monocyte/macrophage infiltration at 28d compared to vehicle-treatment, without detriment to infarct healing. Extended post-MI also preserved LV infarct size. In cultures of rat cardiac fibroblasts, tranilast attenuated TGFβ1-stimulated fibrogenesis. CONCLUSION: Tranilast inhibits myocardial TGFβ1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24h post-MI exacerbated infarct expansion, delaying the commencement of treatment to 7 days post-MI impeded LV remodelling.
Heart Lung & Circulation 09/2012; · 1.20 Impact Factor
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ABSTRACT: Small radial artery diameter (RAD) and vasospasm are barriers to radial artery cannulation. We performed this study to determine if topical nitroglycerin and/or nitroglycerin plus topical lidocaine increases RAD without affecting systemic blood pressure.
This was a randomized, double-blind, placebo-controlled study. In the first visit, to determine the optimal dose of nitroglycerin, subjects were randomized to either 15 or 30 mg nitroglycerin on one wrist and placebo on the other. In visit 2, to assess for any effect of lidocaine on the vasodilator function of nitroglycerin, the same subjects were randomized to 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo, or 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo. In both visits, blood pressure and RAD using ultrasonography were measured for 2 hours.
In visit 1, both nitroglycerin groups significantly increased RAD, with greater increases with 30 mg nitroglycerin (P < .01) and no significant increase in RAD in placebo wrists. In visit 2, increase in RAD was significantly greater with 20 mg lidocaine + 30 mg nitroglycerin vs 20 mg lidocaine + placebo (P < .001), and 40 mg lidocaine + 30 mg nitroglycerin vs 40 mg lidocaine + placebo (P < .001), indicating that lidocaine does not alter the effect of nitroglycerin. There were significant increases in RAD seen as early as 30 minutes. There were no significant change in RAD in lidocaine + placebo-treated wrists and no change in blood pressure in any group.
Topical nitroglycerin and lidocaine significantly increase RAD within 30 to 60 minutes with no effect on contralateral radial artery or blood pressure, indicating a direct, local effect on the radial artery. (Clinicaltrials.gov number NCT00686231).
Journal of critical care 06/2012; 27(5):532.e9-532.e13. · 2.13 Impact Factor
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ABSTRACT: Background and objectives. Clinical trials of bone-marrow (BM)-derived cells for therapy after acute myocardial infarct (MI) have been controversial. The most commonly used cells for these trials have been mononuclear cells (MNC), obtained by fractionation of BM cells (BMCs) via different protocols. In this study, we performed a head-to-head comparison of: 1) whole BMC; 2) fractionated BM (fBM) using the commonly used Ficoll protocol; 3) the extract derived from the fBM (fBM extract) versus 4) saline (HBSS) control for treatment of acute MI. Methods. In total, 155 male C57BL/6J (10-12-week old) mice were included. Echocardiography was performed at baseline and 2 days after permanent ligation of the left anterior descending artery to induce MI. Echocardiography and histology were employed to measure outcome at 28 days post-MI. Results. Whole BMC therapy improved left ventricular ejection fraction (LVEF) post-MI, but fBM or fBM extract was not beneficial compared to control (change of LVEF of 4.9% ±4.6% (P = 0.02), -0.4% ±5.8% (P = 0.86), -2.0% ±6.2% (P = 0.97) versus -1.4% ±5.3%, respectively). The histological infarct size or numbers of arterioles or capillaries at infarct or border zone did not differ between the groups. Conclusions. Clinical studies should be performed to test whether whole BMC therapy translates into better outcome also after human MI.
Annals of medicine 04/2012; · 3.52 Impact Factor
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ABSTRACT: Many patients with pulmonary hypertension (PH) have symptoms of angina without evidence of occlusive coronary artery disease. For the first time, this study addresses the influence of progressively increasing pulmonary artery pressure (PAP) on left anterior descending artery flow in a rat model of PH. The role of pulmonary artery dilatation, septal wall motion abnormality, cardiac output or diastolic blood pressure in determining coronary blood flow (CBF) during PH was determined.
Pulmonary hypertension was induced in 6-week-old female nude rats (n = 44) using monocrotaline. Animals underwent right heart catheterization and echocardiography, and blood pressure measurement was taken at baseline, 21 and 35 days.
A total of 103 echocardiographic studies were carried out at three fixed time points in rats with variable PAP. CBF decreased from 46·6 ± 14·3 to 24·7 ± 12·3 cm s(-1) (P<0·001) over time. Pulmonary artery diameter increased from 2·30 ± 0·19 to 2·83 ± 0·30 mm (P<0·001), and left ventricular (LV) cardiac output decreased from 143 ± 23 to 78 ± 30 ml min(-1) (P<0·001). Using observed solution estimates of 0·00170 (P = 0·0005) and -1·75 (P = 0·006) for these variables, we calculated that CBF increased by 5·90 cm s(-1) (15·6%, CI: 14·5-17·1%) or decreased by -4·86 cm s(-1) (-12·9%, CI: -14·1-11·9%) for every standard deviation increase in LV cardiac output or pulmonary artery diameter, respectively. CBF decreased significantly with increasing PAP. Pulmonary artery diameter and LV cardiac output appear to be independent determinants of coronary flow in PH.
Coronary flow reduction in murine PH has potential to be clinically meaningful and should therefore further studied in a clinical trial.
Clinical Physiology and Functional Imaging 11/2011; 31(6):477-84. · 1.33 Impact Factor
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Andrew J Boyle,
Yerem Yeghiazarians,
Henry Shih,
Joy Hwang,
Jianqin Ye,
Rich Sievers,
Daiwei Zheng,
Jath Palasubramaniam,
Dharshan Palasubramaniam,
Connie Karschimkus,
Robert Whitbourn,
Alicia Jenkins,
Andrew M Wilson
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ABSTRACT: Stem cell homing to the heart is mediated by the release of chemo-attractant cytokines. Stromal derived factor -1 alpha (SDF-1a) and monocyte chemotactic factor 1(MCP-1) are detectable in peripheral blood after myocardial infarction (MI). It remains unknown if they are produced by, and released from, the heart in order to attract stem cells to repair the damaged myocardium.
Murine hearts were studied for expression of MCP-1 and SDF-1a at day 3 and day 28 following myocardial infarction to determine whether production is increased following MI. In addition, we studied the coronary artery and coronary sinus (venous) blood from patients with normal coronary arteries, stable coronary artery disease (CAD), unstable angina and MI to determine whether these cytokines are released from the heart into the systemic circulation following MI.
Both MCP-1 and SDF-1a are constitutively produced and released by the heart. MCP-1 mRNA is upregulated following murine experimental MI, but SDF-1a is suppressed. There is less release of SDF-1a into the systemic circulation in patients with all stages of CAD including MI, mimicking the animal model. However MCP-1 release from the human heart following MI is also suppressed, which is the exact opposite of the animal model.
SDF-1a and MCP-1 release from the human heart are suppressed following MI. In the case of SDF-1a, the animal model appropriately reflects the human situation. However, for MCP-1 the animal model is the exact opposite of the human condition. Human observational studies like this one are paramount in guiding translation from experimental studies to clinical trials.
Journal of Translational Medicine 09/2011; 9:150. · 3.41 Impact Factor
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Randall C Starling,
Yoshifumi Naka, Andrew J Boyle,
Gonzalo Gonzalez-Stawinski,
Ranjit John,
Ulrich Jorde,
Stuart D Russell,
John V Conte,
Keith D Aaronson,
Edwin C McGee,
William G Cotts,
David DeNofrio,
Duc Thinh Pham,
David J Farrar,
Francis D Pagani
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ABSTRACT: The aim of this study was to determine whether results with the HeartMate (HM) II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, California) in a commercial setting are comparable to other available devices for the same indication.
After a multicenter pivotal clinical trial conducted from 2005 to 2008, the U.S. Food and Drug Administration approved the HM II LVAD for bridge to transplantation (BTT). A post-approval study was required by the U.S. Food and Drug Administration to determine whether results with the device in a commercial setting are comparable to other available devices for the same indication.
The study was a prospective evaluation of the first 169 consecutive HM II patients enrolled in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were listed for transplant or likely to be listed. Patients were enrolled from April through August 2008 at 77 U.S. centers and followed for at least 1 year after implant. A comparison group (COMP) included all patients (n = 169 at 27 centers) enrolled in the INTERMACS registry with other types of LVADs (79% HeartMate XVE, 21% Implantable Ventricular Assist Device [Thoratec Corporation]) for the same BTT indication in the same time period. Survival rates, adverse events, and quality of life with the EuroQol EQ-5D visual analog scale were obtained in the INTERMACS registry.
Baseline characteristics were similar, but creatinine and blood urea nitrogen were lower in the HM II versus COMP groups, and there were fewer patients in the highest-risk INTERMACS patient profile Number 1 (24% for HM II vs. 39% for COMP). Adverse event rates were similar or lower for HM II versus COMP for all events. Bleeding was the most frequent adverse event for both groups (1.44 vs. 1.79 events/patient-year). Operative 30-day mortality for HM II was 4% versus 11% for COMP. The percentage of patients reaching transplant, cardiac recovery, or ongoing LVAD support by 6 months was 91% for HM II and 80% for COMP, and the Kaplan-Meier survival for patients remaining on support at 1 year was 85% for HM II versus 70% for COMP. Quality of life was significantly improved at 3 months of support and sustained through 12 months in both groups compared with baseline.
The results in a post-market approval, actual patient care setting BTT population support the original findings from the pivotal clinical trial regarding the efficacy and risk profile of the HM II LVAD. These data suggest that dissemination of this technology after approval has been associated with continued excellent results.
Journal of the American College of Cardiology 05/2011; 57(19):1890-8. · 14.16 Impact Factor
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Andrew J Boyle,
Henry Shih,
Joy Hwang,
Jianqin Ye,
Brian Lee,
Yan Zhang,
David Kwon,
Kristine Jun,
Daiwei Zheng,
Rich Sievers,
Franca Angeli,
Yerem Yeghiazarians,
Randall Lee
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ABSTRACT: Aging is associated with an increased incidence of heart failure, but the existence of an age-related cardiomyopathy remains controversial. Differences in strain, age and technique of measuring cardiac function differ between experiments, confounding the interpretation of these studies. Additionally, the structural and genetic profile at the onset of heart failure has not been extensively studied. We therefore performed serial echocardiography, which allows repeated assessment of left ventricular (LV) function, on a cohort of the same mice every 3 months as they aged and demonstrated that LV systolic dysfunction becomes apparent at 18 months of age. These aging animals had left ventricular hypertrophy and fibrosis, but did not have inducible ventricular tachyarrhythmias. Gene expression profiling of left ventricular tissue demonstrated 40 differentially expressed probesets and 36 differentially expressed gene ontology terms, largely related to inflammation and immunity. At this early stage of cardiac dysfunction, we observed increased cardiomyocyte expression of the pro-apoptotic activated caspase-3, but no actual increase in apoptosis. The aging hearts also have higher levels of anti-apoptotic and autophagic factors, which may have rendered protection from apoptosis. In conclusion, we describe the functional, structural and genetic changes in murine hearts as they first develop cardiomyopathy of aging.
Experimental gerontology 03/2011; 46(7):549-59. · 3.34 Impact Factor
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Rachel Mirsky,
Sarah Jahn,
Juha W Koskenvuo,
Richard E Sievers,
Sarah M Yim,
Carissa Ritner,
Harold S Bernstein,
Franca S Angeli, Andrew J Boyle,
Teresa De Marco,
Yerem Yeghiazarians
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ABSTRACT: Despite advances in the treatment of pulmonary arterial hypertension, a truly restorative therapy has not been achieved. Attention has been given to circulating angiogenic cells (CACs, also termed early endothelial progenitor cells) because of their ability to home to sites of vascular injury and regenerate blood vessels. We studied the efficacy of human CAC therapy in the treatment of pulmonary arterial hypertension at two different stages of disease severity. Cells were isolated from peripheral blood and administered to nude rats on day 14 ("early") or day 21 ("late") after monocrotaline injection. The control group received monocrotaline but no cell treatment. Disease progression was assessed using right heart catheterization and echocardiography at multiple time points. Survival differences, right ventricular hypertrophy (RVH), and vascular hypertrophy were analyzed at the study endpoint. Quantitative PCR was performed to evaluate cell engraftment. Treatment with human CACs either at the early or late time points did not result in increased survival, and therapy did not prevent or reduce the severity of disease compared with control. Histological analysis of RVH and vascular muscularization showed no benefit with therapy compared with control. No detectable signal was seen of human transcript in transplanted lungs at 14 or 21 days after cell transplant. In conclusion, CAC therapy was not associated with increased survival and did not result in either clinical or histological benefits. Future studies should be geared toward either earlier therapeutic time points with varying doses of unmodified CACs or genetically modified cells as a means of delivery of factors to the pulmonary arterial circulation.
AJP Lung Cellular and Molecular Physiology 03/2011; 301(1):L12-9. · 3.66 Impact Factor
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ABSTRACT: The use of large, pulsatile left ventricular assist devices (LVADs) has been limited in women because of their small body size.
We compared the survival outcomes, quality of life, and adverse events in 465 patients (104 women, 361 men) with advanced systolic heart failure in their first 18 months of support with the HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow LVAD for bridge to transplantation.
During the first 18 months, there were no differences in survival between women and men while on LVAD support (73% ± 3% vs 73% ± 5%, p = 0.855) but fewer women (40%) underwent heart transplantation than did men (55%; p = 0.001). More women continued on support after 18 months (p = 0.007). Median duration of support was 238 days for women and 184 days for men (p = 0.003). Mortality was 20% for women and 19% for men (p = 0.89). Adverse events were similar, with the exception of hemorrhagic stroke, which occurred more frequently in women (0.10 vs 0.04 events/patient-year, p = 0.02), and device-related infections, which occurred less frequently in women (0.23 vs 0.44, p = 0.006). Functional capacity and quality of life at 6 months improved significantly in women and men.
Continuous-flow left ventricular assistance as a bridge to transplantation is associated with similar survival rates in women and men. Differences observed in higher stroke rates and fewer infections among women require further study.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 01/2011; 30(5):515-22. · 3.54 Impact Factor
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ABSTRACT: Risk stratification for mechanical circulatory support (MCS) has emerged as an important tool in patient selection and outcomes assessment. Most studies examining risk stratification have been limited to pulsatile devices. We use the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to stratify patients with continuous-flow devices and assess outcomes in less severe, but functionally impaired, heart failure patients.
This study included 101 bridge-to-transplant and destination-therapy patients at 3 centers. Three groups were studied: Group 1, cardiogenic shock (INTERMACS Profile 1); Group 2, inotrope-dependent (INTERMACS Profile 2 or 3); and Group 3, ambulatory advanced heart failure (INTERMACS Profiles 4 to 7). The outcomes of interest were actuarial survival, survival to discharge and length of stay.
Survival at 36 months was better in Group 3 than in Group 1 (95.8% vs 51.1%, p = 0.011), but not between Groups 2 and 3 (68.8 vs 95.8%, p = 0.065). Lengths of stay for Groups 1 to 3 were 44, 41 and 17 days: Groups 1 vs 3, p < 0.001; Groups 2 vs 3, p < 0.001; and Groups 1 vs 2, p = 0.62. Lengths of stay for survivors were 49, 39 and 14 for the 3 groups: Groups 1 vs 3, p < 0.001; Groups 2 vs 3, p < 0.001; and Groups 1 vs 2, p = 0.28.
INTERMACS classification is a useful metric for risk-stratifying candidates for MCS. Less acutely ill but functionally impaired heart failure patients receiving continuous-flow LVADs had longer short- and long-term survival and shorter lengths of stay compared with patients who were more acutely ill.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 12/2010; 30(4):402-7. · 3.54 Impact Factor
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ABSTRACT: Aging is a risk factor for heart failure, which is a leading cause of death world-wide. Elderly patients are more likely than young patients to experience a myocardial infarction (MI) and are more likely to develop heart failure following MI. The poor clinical outcome of aging in cardiovascular disease is recapitulated on the cellular level. Increase in stress exposure and shifts in signaling pathways with age change the biology of cardiomyocytes. The progressive accumulation of metabolic waste and damaged organelles in cardiomyocytes blocks the intracellular recycling process of autophagy and increases the cell's propensity toward apoptosis. Additionally, the decreased cardiomyocyte renewal capacity in the elderly, due to reduction in cellular division and impaired stem cell function, leads to further cardiac dysfunction and maladaptive responses to disease or stress. We review the cellular and molecular aspects of post-infarction remodeling in the aged heart, and relate them to the clinical problem of post-infarction remodeling in elderly patients.
Journal of the American College of Cardiology 12/2010; 57(1):9-17. · 14.16 Impact Factor
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ABSTRACT: Trans-radial cardiac catheterization has lower rates of arterial access site complications. Hydrophilic-coated sheaths designed specifically for trans-radial procedures have resulted in numerous reports of a foreign body reaction to retained material. Although this is a self-limited condition that should be managed expectantly, it is often confused with an infected pseudoaneurysm, resulting in unnecessary surgery. We searched the FDA MAUDE (Manufacturer and User Facility Device Experience) database to determine which brands of sheath have been associated with this complication. In addition, we performed a literature search for all reported cases of this complication. Only one brand of sheath has been associated with this condition. As trans-radial procedures become more common in the US, knowledge of such complications, which appear to be specific to the Cook radial hydrophilic-coated sheaths, is imperative for all radial interventionalists to prevent unnecessary surgical procedures. © 2010 Wiley-Liss, Inc.
Catheterization and Cardiovascular Interventions 11/2010; 76(5):673-6. · 2.29 Impact Factor
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Celina M Yong,
Madan Sharma,
Victor Ochoa,
Freddy Abnousi,
John Roberts,
Nathan M Bass,
Claus U Niemann,
Stephen Shiboski,
Megha Prasad,
Mehdi Tavakol,
Thomas A Ports,
Gabriel Gregoratos,
Yerem Yeghiazarians, Andrew J Boyle
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ABSTRACT: The optimal preoperative cardiac evaluation strategy for patients with end-stage liver disease (ESLD) undergoing liver transplantation remains unknown. Patients are frequently referred for cardiac catheterization, but the effects of coronary artery disease (CAD) on posttransplant mortality are also unknown. We sought to determine the contribution of CAD and multivessel CAD in particular to posttransplant mortality. We performed a retrospective study of ESLD patients undergoing cardiac catheterization before liver transplant surgery between August 1, 2004 and August 1, 2007 to determine the effects of CAD on outcomes after transplantation. Among 83 patients who underwent left heart catheterization, 47 underwent liver transplantation during the follow-up period. Twenty-one of all ESLD patients who underwent liver transplantation (45%) had CAD. Fifteen of the transplant patients with CAD (71%) had multivessel disease. Among transplant patients, the presence of multivessel CAD (versus no CAD) was predictive of mortality (27% versus 4%, P = 0.046), increased length of stay (22 versus 15 days, P = 0.050), and postoperative pressor requirements (27% versus 4%, P = 0.029). Interestingly, neither the presence of any CAD nor the severity of stenosis in any single coronary artery predicted mortality. Furthermore, none of the traditional clinical predictors (age, gender, diabetes, creatinine, ejection fraction, and Model for End-Stage Liver Disease score) were predictive of mortality among transplant recipients. In conclusion, multivessel CAD is associated with higher mortality after liver transplantation when it is documented angiographically before transplantation, even in the absence of severe coronary artery stenosis. This study provides preliminary evidence showing that there may be significant prognostic value in coronary angiography as a part of the pretransplant workup.
Liver Transplantation 11/2010; 16(11):1242-8. · 3.39 Impact Factor
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ABSTRACT: Trans-radial cardiac catheterization has lower rates of arterial access site complications. Hydrophilic-coated sheaths designed specifically for trans-radial procedures have resulted in numerous reports of a foreign body reaction to retained material. Although this is a self-limited condition that should be managed expectantly, it is often confused with an infected pseudoaneurysm, resulting in unnecessary surgery. We searched the FDA MAUDE (Manufacturer and User Facility Device Experience) database to determine which brands of sheath have been associated with this complication. In addition, we performed a literature search for all reported cases of this complication. Only one brand of sheath has been associated with this condition. As trans-radial procedures become more common in the US, knowledge of such complications, which appear to be specific to the Cook radial hydrophilic-coated sheaths, is imperative for all radial interventionalists to prevent unnecessary surgical procedures. © 2010 Wiley-Liss, Inc.
Catheterization and Cardiovascular Interventions 10/2010; 76(5):673 - 676. · 2.29 Impact Factor
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Konstantinos E Hatzistergos,
Henry Quevedo,
Behzad N Oskouei,
Qinghua Hu,
Gary S Feigenbaum,
Irene S Margitich,
Ramesh Mazhari, Andrew J Boyle,
Juan P Zambrano,
Jose E Rodriguez,
Raul Dulce,
Pradip M Pattany,
David Valdes,
Concepcion Revilla,
Alan W Heldman,
Ian McNiece,
Joshua M Hare
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ABSTRACT: The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes.
Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire.
Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I.
MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.
Circulation Research 10/2010; 107(7):913-22. · 9.49 Impact Factor
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Joseph G Rogers,
Keith D Aaronson, Andrew J Boyle,
Stuart D Russell,
Carmelo A Milano,
Francis D Pagani,
Brooks S Edwards,
Soon Park,
Ranjit John,
John V Conte,
David J Farrar,
Mark S Slaughter
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ABSTRACT: This study sought to assess the impact of continuous flow left ventricular assist devices (LVADs) on functional capacity and heart failure-related quality of life.
Newer continuous-flow LVAD are smaller and quieter than pulsatile-flow LVADs.
Data from advanced heart failure patients enrolled in the HeartMate II LVAD (Thoratec Corporation, Pleasanton, California) bridge to transplantation (BTT) (n = 281) and destination therapy (DT) (n = 374) trials were analyzed. Functional status (New York Heart Association [NYHA] functional class, 6-min walk distance, patient activity scores), and quality of life (Minnesota Living With Heart Failure [MLWHF] and Kansas City Cardiomyopathy Questionnaires [KCCQ]) were collected before and after LVAD implantation.
Compared with baseline, LVAD patients demonstrated early and sustained improvements in functional status and quality of life. Most patients had NYHA functional class IV symptoms at baseline. Following implant, 82% (BTT) and 80% (DT) of patients at 6 months and 79% (DT) at 24 months improved to NYHA functional class I or II. Mean 6-min walk distance in DT patients was 204 m in patients able to ambulate at baseline, which improved to 350 and 360 m at 6 and 24 months. There were also significant and sustained improvements from baseline in both BTT and DT patients in median MLWHF scores (by 40 and 42 U in DT patients, or 52% and 55%, at 6 and 24 months, respectively), and KCCQ overall summary scores (by 39 and 41 U, or 170% and 178%).
Use of a continuous flow LVAD in advanced heart failure patients results in clinically relevant improvements in functional capacity and heart failure-related quality of life.
Journal of the American College of Cardiology 04/2010; 55(17):1826-34. · 14.16 Impact Factor
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Juha W Koskenvuo,
Rachel Mirsky,
Yan Zhang,
Franca S Angeli,
Sarah Jahn,
Tero-Pekka Alastalo,
Nelson B Schiller, Andrew J Boyle,
Kanu Chatterjee,
Teresa De Marco,
Yerem Yeghiazarians
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ABSTRACT: Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = -0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model.
The international journal of cardiovascular imaging 02/2010; 26(5):509-18. · 2.15 Impact Factor
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Mark S Slaughter,
Francis D Pagani,
Joseph G Rogers,
Leslie W Miller,
Benjamin Sun,
Stuart D Russell,
Randall C Starling,
Leway Chen, Andrew J Boyle,
Suzanne Chillcott,
Robert M Adamson,
Margaret S Blood,
Margarita T Camacho,
Katherine A Idrissi,
Michael Petty,
Michael Sobieski,
Susan Wright,
Timothy J Myers,
David J Farrar
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ABSTRACT: Continuous-flow left ventricular assist devices (LVAD) have emerged as the standard of care for advanced heart failure patients requiring long-term mechanical circulatory support. Evidence-based clinical management of LVAD-supported patients is becoming increasingly important for optimizing outcomes. In this state-of-art review, we propose key elements in managing patients supported with the new continuous-flow LVADs. Although most of the presented information is largely based on investigator experience during the 1,300-patient HeartMate II clinical trial, many of the discussed principles can be applied to other emerging devices as well. Patient selection, pre-operative preparation, and the timing of LVAD implant are some of the most important elements critical to successful circulatory support and are principles universal to all devices. In addition, proper nutrition management and avoidance of infectious complications can significantly affect morbidity and mortality during LVAD support. Optimizing intraoperative and peri-operative care, and the monitoring and treatment of other organ system dysfunction as it relates to LVAD support, are discussed. A multidisciplinary heart failure team must be organized and charged with providing comprehensive care from initial referral until support is terminated. Preparing for hospital discharge requires detailed education for the patient and family or friends, with provisions for emergencies and routine care. Implantation techniques, troubleshooting device problems, and algorithms for outpatient management, including the diagnosis and treatment of related problems associated with the HeartMate II, are discussed as an example of a specific continuous-flow LVAD. Ongoing trials with other continuous-flow devices may produce additional information in the future for improving clinical management of patients with these devices.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2010; 29(4 Suppl):S1-39. · 3.54 Impact Factor
