Jai Raman

Urinary cystatin C as an early biomarker of acute kidney injury following adult cardiothoracic surgery

There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery.

Urinary Biomarkers in the Clinical Prognosis and Early Detection of Acute Kidney Injury

BACKGROUND AND OBJECTIVES 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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. RESULTS 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). CONCLUSION Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.

Real-Time Three-Dimensional Transesophageal Echocardiography in Valve Disease: Comparison With Surgical Findings and Evaluation of Prosthetic Valves

BACKGROUND Recently, a novel real-time 3-dimensional (3D) matrix-array transesophageal echocardiographic (3D-MTEE) probe was found to be highly effective in the evaluation of native mitral valves (MVs) and other intracardiac structures, including the interatrial septum and left atrial appendage. However, the ability to visualize prosthetic valves using this transducer has not been evaluated. Moreover, the diagnostic accuracy of this new technology has never been validated against surgical findings. This study was designed to (1) assess the quality of 3D-MTEE images of prosthetic valves and (2) determine the potential value of 3D-MTEE imaging in the preoperative assessment of valvular pathology by comparing images with surgical findings. METHODS Eighty-seven patients undergoing clinically indicated transesophageal echocardiography were studied. In 40 patients, 3D-MTEE images of prosthetic MVs, aortic valves (AVs), and tricuspid valves (TVs) were scored for the quality of visualization. For both MVs and AVs, mechanical and bioprosthetic valves, the rings and leaflets were scored individually. In 47 additional patients, intraoperative 3D-MTEE diagnoses of MV pathology obtained before initiating cardiopulmonary bypass were compared with surgical findings. RESULTS For the visualization of prosthetic MVs and annuloplasty rings, quality was superior compared with AV and TV prostheses. In addition, 3D-MTEE imaging had 96% agreement with surgical findings. CONCLUSIONS Three-dimensional matrix-array transesophageal echocardiographic imaging provides superb imaging and accurate presurgical evaluation of native MV pathology and prostheses. However, the current technology is less accurate for the clinical assessment of AVs and TVs. Fast acquisition and immediate online display will make this the modality of choice for MV surgical planning and postsurgical follow-up.

Radial artery patency and clinical outcomes: Five-year interim results of a randomized trial

OBJECTIVE This study was undertaken to compare elective angiographic patency and cardiac event-free survival of the radial artery graft with that of the free right internal thoracic artery or saphenous vein during a 10-year period after primary coronary artery bypass surgery. METHODS This prospective, randomized, single-center trial was conducted on two groups of patients undergoing primary coronary artery bypass surgery. In a younger group (group 1, n = 285, <70 years), the radial artery was compared with the free right internal thoracic artery. In an older group (group 2, n = 153, >/=70 years), the radial artery was compared with the saphenous vein. The trial conduit was grafted to the largest available coronary artery other than the left anterior descending coronary artery. Angiography was scheduled at intervals between 0 and 10 years according to a second random assignment. Patients were followed up at yearly intervals to assess clinical outcomes. Clinical outcomes were analyzed on an intent-to-treat basis during the 10-year follow-up with time-related analyses. This interim study reports angiographic and clinical outcome results during the first 5 years. RESULTS Graft patency estimates were as follows: 0.95 (95% confidence interval 0.85-0.99) in 39 radial arteries versus 1.0 in 29 right internal thoracic arteries (P =.4) in group 1, and 0.86 (95% confidence interval 0.67-0.99) in 24 radial arteries versus 0.95 (95% confidence interval 0.83-0.99) in 22 saphenous veins (P =.5) in group 2. Cardiac event-free survival estimates were as follows: 0.91 (95% confidence interval 0.76-0.99) for the radial artery versus 0.82 (95% confidence interval 0.63-0.99) for the right internal thoracic artery (P =.7) in group 1, and 0.84 (95% confidence interval 0.64-0.99) for the radial artery versus 0.89 (95% confidence interval 0.72-0.99) for the saphenous vein (P =.9) in group 2. CONCLUSION The 5-year interim results do not support the hypothesis that the radial artery has superior patency to or is associated with fewer clinical events than free right internal thoracic artery or saphenous vein grafts.

Factors affecting saphenous vein graft patency: clinical and angiographic study in 1402 symptomatic patients operated on between 1977 and 1999

BACKGROUND The purpose of this study was to find the preoperative and intraoperative factors that affect vein graft patency. METHODS A total of 3715 graft angiograms in 1607 patients were studied for recurrence of angina. The preoperative patient characteristics and intraoperative variables were prospectively collected from patients who had primary coronary artery bypass grafting during the period from 1977 to 1999. A total of 1339 (83%) patients were male, with a mean age of 59 years. The mean period from operation to reangiogram was 99 months. The saphenous vein was grafted to the left anterior descending artery in 557 (15%), to the diagonal artery in 669 (18%), to the obtuse marginal artery in 1300 (35%), to the right coronary artery in 409 (11%), and to the posterior descending artery in 780 (21%) cases. Graft failure was defined as >or=80% stenosis. RESULTS During the course of the study, 2266 (61%) grafts were patent, and 1449 (39%) had failed. The patient variables that significantly reduced graft patency were a younger age (P <.001) and an ejection fraction <30% (P =.047). Operative variables associated with reduced graft patency were small coronary artery diameter (P <.001), large conduit diameter (P =.001), and the coronary artery grafted (lowest patency in the right coronary artery and maximum patency in the left anterior descending artery territory; P =.002). The interval from operation to repeat angiogram (P <.001, with 78% patent at 1 year, 78% at 5 years, 60% at 10 years, and 50% at 15 years) and the year in which the operation was performed (more recent operations had better patency; P <.001) significantly affected graft patency. CONCLUSIONS Saphenous vein graft patency improved over the course of the study. The best results were obtained in older patients with good left ventricular function. Large-caliber arteries on the left system, when grafted with a small-diameter vein, were associated with the best outcome.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery

BACKGROUND The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

Passive ventricular constraint amends the course of heart failure: a study in an ovine model of dilated cardiomyopathy

OBJECTIVE Dilated cardiomyopathy (DCM) is associated with a progressive deterioration in cardiac function. We hypothesised that some of the deleterious effects of DCM could be reduced by mechanically limiting the degree of cardiac dilatation. METHODS A Transonic 20A cardiac output (CO) flow-probe was implanted in the pulmonary artery of 12 adult (52 +/- 4 kg) sheep. Early heart failure was created by rapid right ventricular (RV) pacing for 21 days at a rate which resulted in an initial 10% decrease in CO (to a maximum of 190 bpm). A custom polyester jacket (Acorn Cardiovascular, St Paul, MN) was then placed, via a partial lower sternotomy, on the ventricular epicardium of all sheep. Animals were randomised either to jacket retention (wrap) or removal (sham). Pacing was recommenced at a higher rate (that initiated a further 10% decrease in CO) for 28 days. Haemodynamic and echocardiographic parameters were determined at baseline, implant and at termination. RESULTS At termination, the left ventricular fractional shortening was significantly higher (p = 0.03), the degree of mitral valve regurgitation lower (scaled 0-3) (p = 0.03) and the left ventricular long axis area smaller (p = 0.02) in the wrap animals compared with sham. CONCLUSIONS In this model of heart failure, ventricular constraint with a polyester jacket diminished the deterioration in cardiac function associated with progressive dilated cardiomyopathy. These results suggest that maintainance of a more normal cardiac size and shape may be beneficial in patients with dilated cardiomyopathy.

Global surgical experience with the Acorn cardiac support device.

OBJECTIVE Surgical intervention is an option for treating the remodeled and dilated left ventricles of patients with heart failure. Providing end-diastolic support with an innovative mesh-like cardiac support device reduces mechanical stress, improves function, and reverses cardiac remodeling in animal models without safety issues. The objective of this study was to review the global clinical safety and feasibility experience of this device. METHODS The Acorn CorCap cardiac support device (Acorn Cardiovascular, Inc, St Paul, Minn) has been implanted worldwide in more than 130 patients with dilated cardiomyopathy with or without concomitant cardiac surgery. The device is positioned around the ventricles and given a custom fit. A series of 48 patients were implanted with the device in initial safety and feasibility studies, of whom 33 also received concomitant cardiac surgery. RESULTS At implantation, 11 patients were in New York Heart Association class II, 33 were in class III, and 4 were in class IV. The average CorCap implantation time was 27 minutes. The mean intraoperative reduction in left ventricular end-diastolic dimension was 4.6% +/- 1%. There were no device-related intraoperative complications. Eight early and 9 late deaths occurred during follow-up extending to 24 months. Actuarial survival was 73% at 12 months and 68% at 24 months. There were no device-related adverse events or evidence of constrictive disease, and coronary artery flow reserve was maintained. Ventricular chamber dimensions decreased, whereas ejection fraction and New York Heart Association class were improved in patients overall and in those patients implanted with the CorCap device without concomitant operations. CONCLUSIONS The CorCap device appears safe for patients with dilated cardiomyopathy. Randomized clinical trials are underway in Europe, Australia, and North America.

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

S100A12 Mediates Aortic Wall Remodeling and Aortic Aneurysm

Rationale: 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. Objective: 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 22&agr; promoter because S100A12 is not present in mice. Methods and Results: 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 &bgr; 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. Conclusions: S100A12 expression is sufficient to activate pathogenic pathways through the modulation of oxidative stress, inflammation and vascular remodeling in vivo.