Tamas Seres

A Framework for Systematic Characterization of the Mitral Valve by Real-Time Three-Dimensional Transesophageal Echocardiography

Because of the complex anatomy of the mitral valve, detailed imaging is a challenge. Transesophageal echocardiography (TEE) using two-dimensional echocardiography provides the backbone for the structural evaluation of the mitral valve. Interventional and surgical procedures on the mitral valve demand precise and sophisticated imaging for guidance and support. Three-dimensional (3D) transthoracic echocardiography and 3D transesophageal echocardiography (TEE) are now being used with increasing frequency to provide more comprehensive evaluations of the structure and function of the mitral valve complex. In this review, the authors present a framework for the application of 3D TEE in the evaluation of patients with structural or functional mitral valve disease, outline an examination protocol, and address the advantages and limitations of the current platform for 3D TEE. Real-time 3D TEE has the real potential to become the main imaging tool for the guidance of surgical and interventional procedures on the mitral valve. Although 3D TEE provides impressive images of the mitral valve, it now must be demonstrated, through scientific studies, that these beautiful images add clinical value to the management of patients with mitral valve disease.

Association of DJ-1/PTEN/AKT- and ASK1/p38-mediated cell signalling with ischaemic cardiomyopathy

AIMSnDilated cardiomyopathies from chronic ischaemia (ISCM) or idiopathic (IDCM) pathological mechanisms are accompanied by similar clinical symptoms but may differ in protein expression, cell metabolism, and signalling processes at the cellular level. Using a combination of proteomic and metabolomic profiling, we sought to decipher the relationships between the metabolism and cellular signalling pathways in human heart tissues collected from patients with ISCM, IDCM, and those without heart disease and dilation.nnnMETHODS AND RESULTSnThe comparative analysis suggested a decrease in glycolysis, Krebs cycle, and malate-aspartate shuttle activities in both types of cardiomyopathies and an increase in ketone body oxidation only in ISCM. Chronic ischaemic injury was associated with increased DJ-1 and decreased phosphatase and tensin homolog (PTEN) protein expression. The reduced PTEN expression was accompanied by increased phosphorylation of cell-protective AKT. Phosphorylation at T845 of apoptosis signal-regulating kinase 1 and p38 mitogen-activated protein kinase proteins, with no change in the phosphorylation of extracellular signal-regulated kinases, was also observed. The downregulation of peptidyl-prolyl cis/trans isomerase and NF-κB essential modulator potentially inhibits NF-κB-initiated processes.nnnCONCLUSIONnThe present study characterized differences in the molecular mechanisms, metabolism, and pathological cell signalling associated with ISCM and IDCM, which may provide novel targets for intervention at the cellular level.

Early effect of tidal volume on lung injury biomarkers in surgical patients with healthy lungs.

Background:The early biological impact of short-term mechanical ventilation on healthy lungs is unknown. The authors aimed to characterize the immediate tidal volume (VT)-related changes on lung injury biomarkers in patients with healthy lungs and low risk of pulmonary complications. Methods:Twenty-eight healthy patients for knee replacement surgery were prospectively randomized to volume-controlled ventilation with VT 6 (VT6) or 10 (VT10) ml/kg predicted body weight. General anesthesia and other ventilatory parameters (positive end-expiratory pressure, 5 cm H2O, FIO2, 0.5, respiratory rate titrated for normocapnia) were managed similarly in the two groups. Exhaled breath condensate and blood samples were collected for nitrite, nitrate, tumor necrosis factor-&agr;, interleukins-1&bgr;, -6, -8, -10, -11, neutrophil elastase, and Clara Cell protein 16 measurements, at the onset of ventilation and 60 min later. Results:No significant differences in biomarkers were detected between the VT groups at any time. The coefficient of variation of exhaled breath condensate nitrite and nitrate decreased in the VT6 but increased in the VT10 group after 60-min ventilation. Sixty-minute ventilation significantly increased plasma neutrophil elastase levels in the VT6 (35.2 ± 30.4 vs. 56.4 ± 51.7 ng/ml, P = 0.008) and Clara Cell protein 16 levels in the VT10 group (16.4 ± 8.8 vs. 18.7 ± 9.5 ng/ml, P = 0.015). Exhaled breath condensate nitrite correlated with plateau pressure (r = 0.27, P = 0.042) and plasma neutrophil elastase (r = 0.44, P = 0.001). Plasma Clara Cell protein 16 correlated with compliance (r = 0.34, P = 0.014). Conclusions:No tidal volume-related changes were observed in the selected lung injury biomarkers of patients with healthy lungs after 60-min ventilation. Plasma neutrophil elastase and plasma Clara Cell protein 16 might indicate atelectrauma and lung distention, respectively.

Detection of Left Ventricular Apical Thrombus With Three-Dimensional Transesophageal Echocardiography:

Objective. Left ventricular (LV) thrombosis persists as a clinical challenge in echocardiographic diagnosis and is an important risk factor for perioperative embolic events in cardiac surgery. Appropriate detection and monitoring when thrombus is suspected is critical in surgical planning and in avoiding catastrophic patient outcomes. Case Presentation. The authors present a case of a laminated LV apical thrombus, which was discovered intraoperatively by real-time 3-dimensional (3D) transesophageal echocardiography. Clinical Challenges. The clinical challenges were (a) LV thrombosis impact on surgical management, (b) key echocardiographic challenges in diagnosing LV thrombosis, and (c) role of 3D echocardiography in the diagnostic algorithm. Conclusion. Because of the lack of a gold standard, 2D transthoracic echocardiography remains the imaging modality of choice in assessment; however, there is increasing evidence that 3D technology can be more accurate in intracardiac mass detection and should be considered in the diagnostic algorithm.

Postreperfusion Syndrome During Liver Transplantation

Each Roundtable Discussion involves discussion of a clinical case scenario with various experts in the field. This issue will be a discussion regarding postreperfusion syndrome and involves 3 anesthesiologists and a liver transplant surgeon as our discussants. Matthew Fiegel, MD, is an Associate Professor of anesthesiology at University of Colorado Denver. He is a liver transplant specialist as well as the head of the Acute Pain Service. Sara Cheng MD, PhD, is an Assistant Professor of anesthesiology at the University of Colorado Denver. She is an active research scientist with interest in liver transplant and coagulation studies, as well as a specialist in liver transplantation. Micheal Zimmerman, MD, is an Associate Professor of surgery in the Transplant Surgery Division of the University of Colorado Denver. He is an active research scientist, with a clinical and research interest in liver transplant. Tamas Seres MD, PhD, is an Associate Professor of anesthesiology and the Chief of the Cardiothoracic Anesthesiology Service at the University of Colorado Denver. He has an active interest in transesophageal echocardiography applications in both cardiac surgery and transplant.

Exhaled Breath Condensate Nitrate Levels are Inversely Associated withthe Body Mass Index of Patients without Respiratory Disease

Background: Repeated observations suggest that the incidence and/or severity of the Acute Respiratory Distress Syndrome (ARDS) is lower in mildly obese humans compared to lean subjects, phenomenon called the Obesity-ARDS Paradox. A reduced lung nitrosative stress could contribute to this unexplained protection. We measured levels of nitrate, the most oxidized nitric oxide (NO) metabolite, and other related metabolites in the exhaled breath condensate (EBC) of obese (composed of both overweight or mildly obese) and normal weight patients. nMethods: We studied patients without respiratory disease immediately after starting mechanical ventilation for elective surgery. We performed targeted metabolomics analyses of EBC and blood samples. We measured concentrations of arginine, asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), nitrite, and nitrate and then analyzed their relationship to body mass index (BMI). We compared patients classified as BMI<25 (normal) or 25-34.9 (obese). nResults: 21 patients were included in the analysis: 5 with a BMI<25 and 16 with a BMI 25-34.9. Concentrations of nitrate in EBC, but not in plasma, inversely correlated with BMI. EBC nitrate levels positively correlated with EBC nitrite but not with plasma nitrate levels. EBC nitrite levels inversely correlated with plasma nitrite levels. Patients with a BMI 25-34.9 had significantly lower EBC nitrate levels than patients with a BMI<25. nConclusion: Our results suggest a lower nitrosative stress in the lungs of overweight and mildly obese patients compared to normal weight patients. This observation deserves further evaluation as a possible contributing factor to the Obesity ARDS Paradox.

A Review of Intraoperative Goal-Directed Therapy Using Arterial Waveform Analysis for Assessment of Cardiac Output

Increasing evidence shows that goal-directed hemodynamic management can improve outcomes in surgical and intensive care settings. Arterial waveform analysis is one of the different techniques used for guiding goal-directed therapy. Multiple proprietary systems have developed algorithms for obtaining cardiac output from an arterial waveform, including the FloTrac, LiDCO, and PiCCO systems. These systems vary in terms of how they analyze the arterial pressure waveform as well as their requirements for invasive line placement and calibration. Although small-scale clinical trials using these monitors show promising data, large-scale multicenter trials are still needed to better determine how intraoperative goal-directed therapy with arterial waveform analysis can improve patient outcomes. This review provides a comparative analysis of the different arterial waveform monitors for intraoperative goal-directed therapy.

Total Ischemia Time Alters the Longitudinal and Circumferential Shortening of the Right Ventricle in Transplanted Hearts

Objectives. Ischemia time is a risk factor for mortality and right ventricular (RV) failure after heart transplantation. The purpose of this study was to determine the effect of ischemia time on known transesophageal echocardiography (TEE) parameters of RV function and on a novel quantitative measurement of RV circumferential shortening. Methods. Right and left ventricular (LV) function was evaluated retrospectively in 20 consecutive patients after heart transplant using known TEE parameters as well as a quantitative measurement of circumferential contraction. The control group consisted of 20 patients undergoing coronary artery bypass grafting (CABG) with no documented RV dysfunction. Results. Posttransplant TEE parameters of RV function were depressed compared with post–cardiopulmonary bypass CABG patients. Significant correlation was observed between tricuspid annular planar systolic excursion, basal, mid, and global circumferential shortening and total ischemia time. Conclusion. Total ischemia time of the transplanted heart may play a role in deterioration of longitudinal and circumferential shortening of the RV.

Ablation of Cyclophilin D Results in an Activation of FAK, Akt and ERK Pathways in the Mouse Heart.

Cyclophilin D (CypD) is a mitochondrial chaperone that regulates the mitochondrial permeability transition pore. Metabolically, deletion of Ppif (the gene encoding CypD) in mice is associated with elevated levels of mitochondrial matrix Ca2+ that leads to increased glucose as relative to fatty acid oxidation. Here, we characterized the adaptive mechanisms involved in the regulation of glucose metabolism including the regulation of Akt and ERK kinases that we evaluated by Western blot analysis of Ppif−/− in comparison to wild type (WT) mouse hearts. CypD loss led to adaptive mechanisms in the heart resulting in an upregulation of focal adhesion kinase (phosphorylated at Tyr925) and increased phosphorylation of Akt at S473. The increased activity of this pathway (pAktS473 increased to 170% and 145% in Ppif−/− versus WT males and females, respectively) could be responsible for the observed metabolic switch towards glycolysis. Furthermore, the phosphorylation of ERK1/2 proteins was elevated following CypD ablation. In addition, we observed differences in protein expression and activity in male versus female hearts that were independent of CypD expression. This included an upregulation of pAktS473 (to 273% and 269% in Ppif−/− and WT females as compared to their corresponding males, respectively). Furthermore, decreased levels of endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine were accompanied by an upregulation of eNOS in female mice. The higher extent of kinases phosphorylation may be responsible for the reported lowered tolerance of CypD animals to stress. Moreover, the higher nitric oxide production could be responsible for the cardioprotective properties observed only in female hearts. J. Cell. Biochem. 118: 2933–2940, 2017.

Percutaneous repair of right ventricular perforation with Amplatzer septal defect occlusion device

A 65-year-old man with non-ischaemic cardiomyopathy and electrical storm was referred for catheter ablation of refractory ventricular tachycardia (VT). The patient had a remote history of prior endo- and epicardial VT ablation. Electrocardiogram characteristics of the presenting VT were consistent with an epicardial exit. Epicardial access was obtained without complication, although …