The Association of Serum Uric Acid Levels with Outcomes Following Percutaneous Coronary Intervention

Background: Serum uric acid may serve as a marker for the activation of oxidative stress and may therefore be a marker for subsequent cardiovascular events. Our goal was to assess the association of serum uric acid levels and the outcomes of patients who have undergone percutaneous coronary intervention (PCI). Methods: We performed a retrospective cohort study of patients who underwent PCI between 1/1/2000 and 12/31/2007. Data were retrieved from the Cardiac Lab Interventional Clinical Database as well as the medical records. Outcomes of mortality as well as major adverse cardiac events (MACE) that include death, myocardial infarction (MI), and target vessel revascularization were obtained. There were 10,632 unique patients who had a PCI at the Mayo Clinic in Rochester and allowed use of their records for research. During this time, 1,916 had a uric acid measure within 2 years prior to the day of PCI. Results: Of the 1,916 patients in our cohort, 1,353 had normal uric acid levels and 563 had elevated uric acid. After multivariable analysis, there was a strong trend in association with follow‐up mortality in patients with elevated uric acid (HR = 1.25, 95% CI 0.98–1.59, P = 0.07). The association with mortality or MI (HR = 1.15, 95% CI 0.93–1.43, P = 0.20) and the association with MACE (HR = 1.04, CI 0.86– 1.25, P = 0.71) were not significant. Conclusions: In a large single‐center database with complete follow‐up, elevated serum uric acid was associated with increased mortality in PCI patients. These data show a trend for uric acid in the pathophysiology of atherosclerotic coronary artery disease and highlight the need for further research. (J Interven Cardiol 2010;23:277–283)     

Safety and Feasibility of Transcatheter Closure of Large Patent Ductus Arteriosus Measuring ≥4 mm in Patients Weighing ≤6 kg

Objectives: The study aims to find safety of transcatheter closure of large patent ductus arteriosus (PDA) ≥4 mm in patients weighing ≤6 kg.
Background: Large PDA ≥4 mm in patients ≤6 kg challenge the interventionist due to need for large delivery sheath, kink of delivery sheath, and encroachment of aorta or pulmonary artery (PA) by the device. Many institutions refer them for surgery.
Methods: Preterm neonates and ducts with coarctation were excluded. All other patients were taken for catheter closure. Ducts with roomy ampulla were closed with multiple coils aided by bioptome, and others with Amplatzer duct occluders.
Results: Twenty-eight patients aged 2–18 months (median 5.5 months) and weighing 3.8–6 kg (median 4.7 kg) had large PDA (mean diameter 6.3 ± 2 mm) with hyperkinetic pulmonary hypertension. Four patients had bioptome-aided coil closure. Twenty-two other ducts were closed with devices. Two procedures failed due to sheath kink in one patient and device pulling through a duct in the other patient. Four infants needed blood transfusions. The mean procedural time was 42 ± 20 minutes. On a mean follow-up of 25.5 ± 14.8 months, there were no residual flows and no gradients across aorta or pulmonary artery.
Conclusions: Transcatheter closure of large ducts ≥4 mm might be considered safe and effective in infants weighing ≤6 kg also. Decision on coils versus devices depends on ductal morphology. On midterm follow-up with somatic growth, there was no occurrence of aortic or PA gradients.     

Transesophageal Echocardiographic Evaluation for Mural Thrombus Following Radiofrequency Catheter Ablation of Accessory Pathways

Background: Catheter ablation of accessory pathways (APs) provides a definitive therapy for patients with Wolff-Parkinson-White Syndrome. The reported incidence of thrombus formation on ablation-induced injuries with direct current shock varies from 0%-20% in animal studies. The purpose of this study was to determine the prevalence of mural thrombus following catheter ablation with radiofrequency current of accessory pathways in humans. Methods and Results: Radiofrequency current (30–35 warts) was applied through a catheter electrode placed against the mitral or tricuspid annulus guided by catheter recordings of AP potentials. Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 95 of 111 patients, at 18 ± 6 hours following catheter ablation. After ablation. no thrombus was identified at or near the ablation site in any patient. Two out of 95 patients had a mural thrombus at a remote site that was detected by TEE but not by TTE. No new wall motion abnormality was detected in any patient. No significant regurgitant valvular lesion was found in any patient. Conclusion: Intracardiac thrombus was not identified at the site of catheter ablation, possibly owing to the small lesions produced by radiofrequency energy and high blood flow normally present in those areas. However, patients may be at small risk for mural thrombus at a remote site from prolonged placement of catheters.     

Nucleotide receptor signaling in platelets

Upon injury to a vessel wall the exposure of subendothelial collagen results in the activation of platelets. Platelet activation culminates in shape change, aggregation, release of granule contents and generation of lipid mediators. These secreted and generated mediators trigger a positive feedback mechanism potentiating the platelet activation induced by physiological agonists such as collagen and thrombin. Adenine nucleotides, adenosine diphosphate (ADP) and adenosine triphosphate (ATP), released from damaged cells and that are secreted from platelet-dense granules, contribute to the positive feedback mechanism by acting through nucleotide receptors on the platelet surface. ADP acts through two G protein-coupled receptors, the Gq-coupled P2Y1 receptor, and the Gi-coupled P2Y12 receptor. ATP, on the other hand, acts through the ligand-gated channel P2X1. Stimulation of platelets by ADP leads to shape change, aggregation and thromboxane A2 generation. ADP-induced dense granule release depends on generated thromboxane A2. Furthermore, costimulation of both P2Y1 and P2Y12 receptors is required for ADP-induced platelet aggregation. ATP stimulation of P2X1 is involved in platelet shape change and helps to amplify platelet responses mediated by agonists such as collagen. Activation of each of these nucleotide receptors results in unique signal transduction pathways that are important in the regulation of thrombosis and hemostasis.     

Review: Neutrophil gelatinase‐associated lipocalin: A troponin‐like biomarker for human acute kidney injury

Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase‐associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand‐alone troponin‐like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur.     

EFFECTS OF ENFLURANE ON CARDIOVASCULAR FUNCTION IN DOGS WITH INDUCED CHRONIC MITRAL VALUE DISEASE

The effect of enflurane on cardiovascular function was investigatedin normal dogs and in dogs with chronic heart failure becauseof induced mutral valve disease (MVD). No significant changeswere observed in heart rate (HR), right atrial pressure (RAP)and total systemic vascular resistance (TSVR) in normal dogs.However, significant decreases in HR and increases in RAP andTSVR were observed in dogs with MVD. There were no changes inpulmonary arterial pressure and left ventricular end-diastolicpressure in either group. Cardiac output, cardiac index, arterialpressure, left ventricular work index and left ventricular dp/drand dp/rIIP showed a concentration-dependent decrease in bothgroups but the changes were greater in dogs with MVD. ^* Present address: Department of Anaesthesiology, Texas Tech.University, School of Medicine, Lubbock, Texas, U.S.A.