[show abstract][hide abstract] ABSTRACT: Study's purpose: Plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) and S100A12 are increased in young children after cardiac surgery and correlate with the time spent on cardiopulmonary bypass (CPB). This study was performed to investigate whether plasma levels of sRAGE and S100A12 are affected by the use of CPB. Levels of S100A12 and sRAGE, along with of interleukin-6, tumor necrosis factor-α, myeloperoxidase, and C-reactive protein were measured in 25 adults undergoing non-urgent coronary artery bypass grafting with and without the use of CPB. Significant finding: Plasma levels of S100A12, sRAGE, IL-6, TNF-α and MPO 4h after cardiac surgery were elevated compared to baseline; this increase was equally observed in patients undergoing traditional coronary artery bypass grafting on cardiopulmonary bypass (n = 16), and in patients undergoing robot-assisted coronary artery bypass grafting off pump (OPCAB, n = 9). Patients with prolonged hospitalization of 7 days or longer had significantly higher S100A12 and sRAGE 4 hours post surgery compared to patients hospitalized ≤ 6 days.
Increased sRAGE and S100A12 after cardiac surgery is associated with prolonged length of hospitalization in patients after coronary artery bypass grafting; however, we did not observe an intrinsic effect of cardiopulmonary bypass on S100A12 or sRAGE plasma levels in our small pilot study. Further studies are required to confirm the value of sRAGE and S100A12 in predicting postoperative complications after cardiac surgery in a larger study.
American journal of cardiovascular disease. 01/2013; 3(2):85-90.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to determine the relevance of S100A12 expression to human thoracic aortic aneurysms and type A thoracic aortic aneurysm dissection and to study mechanisms of S100A12-mediated dysfunction of aortic smooth muscle cells.
Transgenic expression of proinflammatory S100A12 protein in murine aortic smooth muscle causes thoracic aneurysm in genetically modified mice.
Immunohistochemistry of aortic tissue (n = 50) for S100A12, myeloperoxidase, and caspase 3 was examined and S100A12-mediated pathways were studied in cultured primary aortic smooth muscle cells.
We found S100A12 protein expressed in all cases of acute thoracic aortic aneurysm dissection and in approximately 25% of clinically stable thoracic aortic aneurysm cases. S100A12 tissue expression was associated with increased length of stay in patients undergoing elective surgical repair for thoracic aortic aneurysm, despite similar preoperative risk as determined by European System for Cardiac Operative Risk Evaluation. Reduction of S100A12 expression in human aortic smooth muscle cells using small hairpin RNA attenuates gene and protein expression of many inflammatory- and apoptosis-regulating factors. Moreover, genetic ablation of the receptor for S100A12, receptor for advanced glycation end products (RAGE), in murine aortic smooth muscle cells abolished cytokine-augmented activation of caspase 3 and smooth muscle cell apoptosis in S100A12-expressing cells.
S100A12 is enriched in human thoracic aortic aneurysms and dissections. Reduction of S100A12 or genetic ablation of its cell surface receptor, the receptor for advanced glycation end products (RAGE), in aortic smooth muscle resulted in decreased activation of caspase 3 and in reduced apoptosis. By establishing a link between S100A12 expression and apoptosis of aortic smooth muscle cells, this study identifies novel S100A12 signaling pathways and indicates that S100A12 may be a useful molecular marker and possible target for treatment for human aortic diseases.
Journal of the American College of Cardiology 07/2012; 60(8):775-85. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intra-aortic balloon pumps are traditionally inserted through the femoral artery, limiting the patient's mobility. We used alternate approaches of intra-aortic balloon pump insertion to provide temporary and minimally invasive support for patients with decompensating, end-stage heart failure. The present study describes the outcomes with closed-chest, transthoracic intra-aortic balloon pumps by way of the subclavian artery.
During a 3-year period, 20 patients underwent subclavian artery-intra-aortic balloon pump in the setting of end-stage heart failure. The balloon was inserted through a polytetrafluoroethylene graft sutured to the right subclavian artery in 19 patients (95%) and to the left subclavian artery in 1 patient (5%). The goal of support was to bridge to transplantation in 17 patients (85%) and bridge to recovery in 3 patients (15%). The primary outcome measure was death during subclavian artery-intra-aortic balloon pump support. The secondary outcomes included survival to the intended endpoint of bridge to transplantation/bridge to recovery, complications during subclavian artery-intra-aortic balloon pump support (eg, stroke, limb ischemia, brachial plexus injury, dissection, bleeding requiring reoperation, and device-related infection), emergent surgery for worsening heart failure, and ambulation during intra-aortic balloon pump support.
The duration of balloon support ranged from 3 to 48 days (mean, 17.3 ± 13.1 days). No patients died during subclavian artery-intra-aortic balloon pump support. Of the 20 patients, 14 (70%) were successfully bridged to transplant or left ventricular-assist device. Two patients (10%) required emergent left ventricular-assist device for worsening heart failure.
An intra-aortic balloon pump inserted through the subclavian artery is a simple, minimally invasive approach to mechanical support and is associated with limited morbidity and facilitates ambulation in patients with end-stage heart failure.
The Journal of thoracic and cardiovascular surgery 04/2012; 144(4):951-5. · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The goal of this study was to quantify the net increase in resource use associated with complications after isolated mitral valve surgery.
Deidentified patient-level claims data on a random sample of mitral valve operations performed in the United States from January 1, 2006, to December 31, 2007, were obtained from the National Inpatient Sample (n = 16,788). Patients with major concomitant cardiac procedures were excluded from the analysis for a net sample size of 6297 patients. Risk-adjusted median total hospital costs and length of stay were analyzed by major complications, including pneumonia, sepsis, stroke, renal failure requiring hemodialysis, cardiac tamponade, myocardial infarction, gastrointestinal bleed, and venous thromboembolism.
There were a total of 1323 complication events that occurred in 1089 patients. The most common complication was pneumonia (n = 346, 5.5%), which was associated with a $29,692 increase in hospital costs and a 10.2-day increase in median length of stay (P < .001). The most costly complication was cardiac tamponade, which resulted in an increase in hospital cost of $56,547 and an increase in length of stay of 19.3 days (P < .001). There was a stepwise association between the hospital costs and length of stay and the number of complications per patient (P < .001). There was also a significant association between the discharge location and the occurrence of a complication, with 25% more patients who underwent routine home discharge when there were no complications (P < .001).
In patients undergoing isolated mitral valve surgery, postoperative complications were associated with significant increases in mortality, hospital costs, and length of stay, as well as with discharge location. With growing national attention to improving quality and containing costs, it is important to understand the nature and impact of complications on outcomes and costs.
The Journal of thoracic and cardiovascular surgery 04/2012; 143(4):864-72. · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The vast majority of reports describing beating heart robotic myocardial revascularization (total endoscopic coronary artery bypass) contain very small numbers of patients undergoing single-vessel bypass. We present a large series of patients undergoing multivessel total endoscopic coronary artery bypass.
We performed a retrospective clinical review of 106 patients undergoing total endoscopic coronary artery bypass (72% multivessel) at 1 institution by 1 experienced cardiac surgeon/physician assistant team. These results were compared with the expected clinical outcomes from conventional coronary artery bypass grafting calculated using the Society of Thoracic Surgeons risk calculator.
Of the 106 patients, 1% underwent quadruple total endoscopic coronary artery bypass, 8% triple, 63% double, and 28% single. The emergent conversion rate for hemodynamic instability was 6.6%. The postoperative renal failure rate (doubling of baseline serum creatinine or dialysis required) was 7.5%. Overall, 23 patients (21.7%) exhibited at least 1 major morbidity/mortality (4 deaths). The number of vessels bypassed (single/double/triple/quadruple) correlated positively with the surgical/operating room time, the lung separation time, vasoactive medication use, blood use, a postoperative ventilation time longer than 24 hours, intensive care unit length of stay, and hospital length of stay. An increased surgical time was significantly associated with major morbidity (P = .011) and mortality (P = .043). A comparison with the Society for Thoracic Surgeons expected outcomes revealed a similar hospital length of stay but an increased incidence of prolonged ventilation (P = .003), renal failure (P < .001), morbidity (P = .045), and mortality (P = .049).
Our results suggest that addressing multivessel coronary artery disease using total endoscopic coronary artery bypass offers no obvious clinical benefits and might increase the morbidity and mortality.
The Journal of thoracic and cardiovascular surgery 12/2011; 143(5):1056-61. · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Mitral repair is recommended for patients with significant organic mitral regurgitation (MR). The nonresectional dynamic mitral valve repair (NVR) method involves a complete flexible ring and artificial chordal insertion but without leaflet resection or annular plication. The aim of this study was to compare changes in mitral annular structure and function after the NVR technique with those after a resectional mitral valve repair (RVR) method, which involves leaflet resection and annuloplasty with a partial flexible ring.
Patients with organic severe MR undergoing mitral valve repair with either technique underwent three-dimensional transesophageal echocardiography before and after surgery. The mitral annulus was tracked offline and measured throughout the cardiac cycle. Mitral leaflet mobility was also measured.
Fifteen patients underwent repair with NVR, and 13 underwent repair with RVR (age, 56 vs 61 years, respectively). Both operations reduced mitral annular area significantly (maximum area reduction, from 18.5 ± 4.6 to 6.6 ± 1.7 cm(2) and from 20.1 ± 4.8 to 6 ± 1.5 cm(2) with the NVR and RVR techniques, respectively; P < .001). In contrast to RVR, patients who underwent NVR maintained dynamic changes in mitral annular area, circumference, and anterior-posterior diameter during the cardiac cycle. Mitral leaflet mobility was reduced with both techniques, but posterior leaflet mobility was restricted with RVR.
The size of the mitral annulus is reduced after repair with either surgical approach. Compared with resectional valve repair, more dynamic changes in the structure of the mitral annulus are maintained during the cardiac cycle with the NVR technique early postoperatively, along with more preserved motion of the posterior leaflet.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 09/2011; 24(11):1233-42. · 2.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Functional mitral regurgitation (FMR) is primarily due to abnormalities of the ventricular muscle in the presence of normal mitral leaflets. Present surgical treatment options address the mitral valve annulus and leaflets but not the ventricular muscle. We discuss the evolution of a concept that describes a ventricular solution to this problem, and report preliminary clinical results from the first five subjects implanted with the latest version of this device.
Evaluation of safety and efficacy of the latest version of the BACE™ (Basal Annuloplasty of the Cardia Externally) Device was done first in sheep with rapid ventricular pacing to induce severe MR. The BACE Device was implanted around the base of the heart and chambers on the device filled with normal saline through the subcutaneous ports under echocardiogram until there was no evidence of MR. Once MR was effectively reduced, the chest was closed and the animals recovered, with clinical and echocardiographic analysis through six months of follow-up. Human studies were done with in a similar manner, with subjects that were already undergoing concomitant open-chest coronary artery bypass graft (CABG) surgery. Five subjects with ischaemic MR and triple vessel coronary artery disease were first implanted with the BACE Device, applied epicardially on a beating heart without use of cardiopulmonary bypass, before coronary artery bypass grafting was done.
In five sheep, epicardial application of the BACE Device effectively reduced mitral regurgitation from Grade 4 to Grade 0, and the effect was sustained through six months despite ongoing pacing. Terminal studies at six months showed no adhesion to the silicone band. All five human subjects were male, NYHA Class III, with LVEF of 20-40%. Epicardial application and adjustment of the BACE Device was performed safely on a beating heart with effective reduction in FMR to grade <1. All five subjects had three bypass grafts. Reduction in MR was sustained for at least six months and there were no unanticipated or device-related adverse events.
Epicardial application and adjustment of the BACE Device can be performed safely without CPB with effective reduction in MR.
[show abstract][hide abstract] ABSTRACT: Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery.
Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), π-glutathione-S-transferase (π-GST), α-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared.
Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best detected early stage 3 AKI. π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC = 0.86; P = 0.002).
Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.
Clinical Journal of the American Society of Nephrology 12/2010; 5(12):2154-65. · 5.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intraaortic balloon pump insertion is traditionally performed through the femoral artery in the groin. However, this restricts the patient to bed rest, and prolonged implantation can be associated with infections in the groin crease. We describe a technique of insertion of a balloon pump through the subclavian artery, which allows the patient to ambulate. This technique can also be performed under local anesthesia in the cardiac catheterization laboratory.
The Annals of thoracic surgery 09/2010; 90(3):1032-4. · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Postoperative mediastinitis is a serious and potentially lethal complication from cardiac surgery. Although postoperative mediastinitis cannot be reliably predicted, a number of preoperative and intraoperative risk factors have been defined by previous work. The authors now present their cumulative experience with primary sternal fixation of high-risk patients as one preventative measure.
A retrospective review from July of 2000 to October of 2006 was performed on 750 patients who had at least three established risk factors for postoperative mediastinitis and received primary titanium plate sternal fixation. Patients were followed for a minimum of 6 weeks and monitored for pain, instability, wound breakdown, and plate migration.
Rigid plate fixation was completed at the end of the primary cardiac surgical procedure in all 750 patients. Sternal dehiscence occurred in 18 patients (2.4 percent), necessitating reexploration. Four of these patients developed postoperative mediastinitis and had other significant comorbidities, such as ongoing inflammatory breast cancer or pneumonia, that were beyond the typical risk factors identified for developing mediastinitis. Successful sternal fixation was therefore accomplished in 732 patients (97.6 percent). Despite changes in instrumentation and technique, this approach was adopted by the cardiac surgical team consistently after an initial mentoring and training period by the plastic surgeons.
Primary sternal fixation is a simple and reliable method for prevention of postoperative mediastinitis development in high-risk patients. This technique, conceptualized by plastic surgeons, is now being implemented by cardiac surgeons in increasing numbers. This demonstrates the ability for plastic surgery to initiate a paradigm shift in other fields of medicine and to decrease the complications that primarily affect our practice.
Plastic and reconstructive surgery 06/2010; 125(6):1720-4. · 2.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Myocardial beta-adrenergic receptor (beta-AR) signaling is severely impaired in chronic heart failure (HF). This study was conducted to determine if left ventricular (LV) beta-AR signaling could be restored after continuous-flow LV assist device (LVAD) support.
Twelve patients received LVADs as a bridge to transplant. Paired LV biopsy specimens were obtained at the time of LVAD implant (HF group) and transplant (LVAD group). The mean duration of LVAD support was 152 +/- 34 days. Myocardial beta-AR signaling was assessed by measuring adenylyl cyclase (AC) activity, total beta-AR density (B(max)), and G protein-coupled receptor kinase-2 (GRK2) expression and activity. LV specimens from 8 non-failing hearts (NF) were used as controls.
Basal and isoproterenol-stimulated AC activity was significantly lower in HF vs NF, indicative of beta-AR uncoupling. Continuous-flow LVAD support restored basal and isoproterenol-stimulated AC activity to levels similar to NF. B(max) was decreased in HF vs NF and increased to nearly normal in the LVAD group. GRK2 expression was increased 2.6-fold in HF vs NF and was similar to NF after LVAD support. GRK2 activity was 3.2-fold greater in HF vs NF and decreased to NF levels in the LVAD group.
Myocardial beta-AR signaling can be restored to nearly normal after continuous-flow LVAD support. This is similar to previous data for volume-displacement pulsatile LVADs. Decreased GRK2 activity is an important mechanism and indicates that normalization of the neurohormonal milieu associated with HF is similar between continuous-flow and pulsatile LVADs. This may have important implications for myocardial recovery.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2010; 29(6):603-9. · 3.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: The ABIOMED BVS 5000 ventricular assist system (ABIOMED Cardiovascular Inc, Danvers, MA) is the most commonly used mechanical circulatory support device for post-cardiotomy and post-myocardial infarction cardiogenic shock after placement of an intra-aortic balloon pump. We describe a simple and reliable technique for left ventricular apical cannulation for this device, which also facilitates decannulation without the use of cardiopulmonary bypass.
The Annals of thoracic surgery 03/2010; 89(3):994-5. · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chronic constrictive pericarditis can result in extrinsic compression of coronary arteries during diastole. We present one such case wherein the coronary compression and the resultant cardiac ischemia developed late after surgical pericardiectomy, and treatment with intracoronary stenting was unsuccessful. Issues pertaining to management of this rare condition are discussed and a case made for surgical treatment for such patients.
The Journal of invasive cardiology 01/2010; 22(1):E13-5. · 1.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Correction of functional mitral regurgitation in ischaemic heart disease, with a better risk:benefit ratio is an unmet need. A new methodology of external approach of correcting the annulus (BACE: basal annuloplasty of the cardia externally) to repair and stabilise the mitral valve without entering the heart was used in this prospective study. This study was conducted to assess the efficacy and safety of the concept BACE device in patients with moderate functional mitral valve regurgitation as a result of symptomatic coronary artery disease and heart failure.
The study involved a group of patients who had complex cardiac surgery between January 2000 and December 2001 at the University of Melbourne Campus Hospitals, Melbourne, Australia. Twelve patients with ischaemic heart disease, congestive heart failure, and moderate functional mitral regurgitation (MR) (minimum 2+) underwent the BACE procedure along with coronary artery bypass grafting and/or left ventricular reconstruction.
No peri-operative complications or deaths related to surgical procedures occurred in the study group. There were no clinically significant problems related to the BACE implantation procedure. Mean MR grade was significantly improved in BACE Group from baseline to post BACE implant (2.8 pre- and 0.3 post-surgery; P<0.05). Mean left ventricular ejection fraction (LVEF) was significantly improved (P<0.05) and maintained at 6, 12, and 18 months post BACE implant compared to pre-operative baseline, with a mean improvement of 20% (24% at baseline to 44% at 18 months post-operatively) (P<0.05). In addition to that the patients also had a significant improvement (P<0.05) in mean New York Heart Association (NYHA) functional status from pre-operative baseline to 6 and 18 months post procedure with BACE.
External stabilisation of the cardiac base with BACE was associated with significant improvement in mitral valve function with no significant intra-operative or post-operative problems in patients with moderate functional MR. These findings support further study of BACE in functional MR.
[show abstract][hide abstract] ABSTRACT: S100A12 is a small calcium binding protein that is a ligand of RAGE (receptor for advanced glycation end products). RAGE has been extensively implicated in inflammatory states such as atherosclerosis, but the role of S100A12 as its ligand is less clear.
To test the role of S100A12 in vascular inflammation, we generated and analyzed mice expressing human S100A12 in vascular smooth muscle under control of the smooth muscle 22alpha promoter because S100A12 is not present in mice.
Transgenic mice displayed pathological vascular remodeling with aberrant thickening of the aortic media, disarray of elastic fibers, and increased collagen deposition, together with increased latent matrix metalloproteinase-2 protein and reduction in smooth muscle stress fibers leading to a progressive dilatation of the aorta. In primary aortic smooth muscle cell cultures, we found that S100A12 mediates increased interleukin-6 production, activation of transforming growth factor beta pathways and increased metabolic activity with enhanced oxidative stress. To correlate our findings to human aortic aneurysmal disease, we examined S100A12 expression in aortic tissue from patients with thoracic aortic aneurysm and found increased S100A12 expression in vascular smooth muscle cells.
S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo.
Circulation Research 10/2009; 106(1):145-54. · 11.86 Impact Factor