Faculty Bibliography

Left atrial appendage (LAA) contrast filling defects are commonly found in patients undergoing multidetector cardiac computed tomography (CCT) before catheter ablation of atrial fibrillation. Delayed CCT allows quantification of the LAA delayed/initial attenuation ratio and improves accuracy for LAA thrombus detection, which may obviate routine transesophageal echocardiography (TEE) before ablation. CCT with contrast-enhanced scans (initial CCT) and with noncontrast-enhanced scans (delayed CCT) was performed in 176 patients. LAA was evaluated for filling defects. LAA apex, left atrial (LA) body, and ascending aorta (AA) attenuations (Hounsfield units) were measured on initial and delayed cardiac computed tomograms to calculate LAA, LA, LAA/LA, and LAA/AA attenuation ratios. LAA, initial LAA/LA, and initial LAA/AA attenuation ratios differed significantly in patients with versus without filling defects on cardiac computed tomogram, those with atrial fibrillation versus normal sinus rhythm, and those with abnormal left ventricular ejection fraction versus larger LA volumes (p <0.05). In 70 patients (40%) who underwent TEE, 13 LAA filling defects were seen on initial cardiac computed tomogram. Two defects persisted on delayed cardiac computed tomogram and thrombus was confirmed on transesophageal echocardiogram. Sensitivity, specificity, and positive and negative predictive values of initial CCT for LAA thrombi detection were 100%, 84%, 15%, and 100%, respectively. With delayed CCT these values increased to 100%. Intraobserver and interobserver reproducibilities for cardiac computed tomographic measurements were good (intraclass correlation 0.72 to 0.97, kappa coefficients 0.93 to 1.00). In conclusion, delayed CCT provided an increase in diagnostic accuracy of CCT for detection of LAA thrombus in patients with atrial fibrillation before ablation, which may decrease the need for routine TEE before the procedure.

Computer-assisted detection systems are widely used in many areas of radiology. Coronary computed tomography angiography is a growing area of clinical cardiology and computer-assisted detection systems play an integral part in analysis. Truly automated systems are still in clinical-trial stages, but manually assisted programs are in clinical use today for calcium scoring as well as plaque burden, composition, and stenosis analysis. They are being used as a tool for confirmation more than for diagnosis. Accurate plaque-composition analysis would be a critical tool for better understanding the mechanisms and effectiveness of novel therapies for coronary atherosclerosis. A need for a complete quick, safe, noninvasive plaque analysis is the goal of automated coronary stenosis detection systems; however, their potential clinical benefit remains unknown.

Cardiac CT is an accurate and reasonable alternative modality for valvular imaging. It is used primarily for the evaluation of coronary artery disease; however, important information regarding valvular anatomy and function can be derived from CT. Calcification is a common CT finding in various valvular abnormalities and carries important diagnostic and prognostic value. In addition, valvular morphology, stenosis, and regurgitation also are detected on contrast enhanced scans, with good correlation with trans-thoracic echocardiography and other techniques.

Coronary artery disease affects a large population. Recent emphasis on primary and secondary prevention has made an impact on the detection of atherosclerosis, yet the incidence of acute coronary syndromes continues to increase. This has steered the cardiology community toward improving and developing new imaging techniques that are capable of detecting disease at a very early preclinical state. Coronary CT angiography is capable of characterizing plaques and detecting eccentric lesions that would not appear on stress testing or cardiac catheterization. Cardiac MRI provides high-resolution imaging of plaques in addition to tissue characterization without the ionizing radiation associated with other imaging techniques. Positron emission tomography is a rapidly growing imaging tool that detects inflammation associated with coronary atherosclerosis. In the near future, these new noninvasive modalities will play an intricate part in primary prevention and in diagnosis and treatment follow-up.

Direct and specific inhibition of factor Xa is an emerging therapeutic strategy for atherothrombotic disease. Parenteral factor Xa inhibitors promise efficacy comparable to standard therapies, which could be extended to ambulatory patients with oral agents. We evaluated the antithrombotic effect of the oral, direct factor Xa inhibitor DU-176b in a phase-I study. Healthy subjects (n = 12) received a single, 60 mg dose of DU-176b. Antithrombotic effects were assessed by comparing ex-vivo thrombus formation at 1.5, 5, and 12 hours post-dose versus baseline, along with factor Xa activity, thrombin generation and clotting parameters. Under venous flow after 1.5 and 5 hours, the thrombus was 28% and 21% smaller versus baseline, respectively (p < 0.05). Under arterial condition, the reduction was 26% and 17% (p < 0.05). Thrombin generation decreased by 28% at 1.5 hours and 10% at 5 hours. Changes in PT and INR correlated well with plasma drug concentrations (R2 = 0.79 and 0.78). Direct and specific inhibition of factor Xa by DU-176b significantly reduced ex-vivo thrombus formation at both venous and arterial rheologies, up to 5 hours post-dose. The effects mirrored changes in clotting parameters, suggesting their potential usefulness for monitoring in a clinical setting.

Cardiovascular disease is the major cause of mortality in the industrial world today. We are constantly moving towards new and better ways of fighting this epidemic. Advances have been made in various fields such as patient education, imaging techniques, interventional cardiology, and novel therapeutic agents. In particular, antithrombotics are being studied with great interest and hope. Amid this class of agents, factor Xa inhibitors have already begun to show promising results in trials involving patients with acute coronary syndromes. Whereas DX-9065a is in late stage clinical trials, fondaparinux sodium is available for clinical use. Promising results have been obtained with fondaparinux sodium in patients with coronary artery disease in the PENTUA (Pentasaccharide in Unstable Angina) and PENTALYSE (Pentasaccharide as an Adjunct to Fibrinolysis in ST-Elevation Acute Myocardial Infarction) trials. Besides having a direct effect on the coagulation cascade, they have shown properties that indirectly influence the remodeling of plaques in the coronary circulation. Available evidence on factor Xa inhibitors does not ensure a remedy to acute coronary syndromes but it gives hope of improving current treatments and reducing the morbidity and mortality of cardiovascular disease. The efficacy and tolerability of fondaparinux sodium in the prevention and treatment of deep vein thrombosis (with or without pulmonary embolism) has been established in several large trials such as PENTATHLON (Pentasaccharide in Total Hip Replacement Surgery), PENTAMAKS (Pentasaccharide in Major Knee Surgery), EPHESUS (European Pentasaccharide Hip Elective Surgery), PENTHIFRA (Pentasaccharide in Hip-Fracture Surgery), and PENTHIFRA-Plus. Whereas fondaparinux sodium offers benefits over low molecular weight heparins and unfractionated heparin, the incidence of bleeding complications was greater with fondaparinux sodium than with unfractionated heparin. Treatment with factor VIIa can reverse the anticoagulant effect of fondaparinux sodium and this may be particularly important in patients who need to undergo emergency surgical procedures. Fondaparinux sodium has been recently approved for use, in conjunction with warfarin, in patients with symptomatic deep vein thrombosis or acute pulmonary embolism based on the results of two large trials conducted by the Matisse investigators. In conclusion, these observations strongly suggest the clinical potential of this class of agents in preventing arterial and venous thrombosis.