Transforming growth factor β receptor 1 is a new candidate prognostic biomarker after acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Prediction of left ventricular (LV) remodeling after acute myocardial infarction (MI) is clinically important and would benefit from the discovery of new biomarkers.</p> <p>Methods</p> <p>Blood samples were obtained upon admission in patients with acute ST-elevation MI who underwent primary percutaneous coronary intervention. Messenger RNA was extracted from whole blood cells. LV function was evaluated by echocardiography at 4-months.</p> <p>Results</p> <p>In a test cohort of 32 MI patients, integrated analysis of microarrays with a network of protein-protein interactions identified subgroups of genes which predicted LV dysfunction (ejection fraction ≤ 40%) with areas under the receiver operating characteristic curve (AUC) above 0.80. Candidate genes included transforming growth factor beta receptor 1 (TGFBR1). In a validation cohort of 115 MI patients, TGBFR1 was up-regulated in patients with LV dysfunction (P < 0.001) and was associated with LV function at 4-months (P = 0.003). TGFBR1 predicted LV function with an AUC of 0.72, while peak levels of troponin T (TnT) provided an AUC of 0.64. Adding TGFBR1 to the prediction of TnT resulted in a net reclassification index of 8.2%. When added to a mixed clinical model including age, gender and time to reperfusion, TGFBR1 reclassified 17.7% of misclassified patients. TGFB1, the ligand of TGFBR1, was also up-regulated in patients with LV dysfunction (P = 0.004), was associated with LV function (P = 0.006), and provided an AUC of 0.66. In the rat MI model induced by permanent coronary ligation, the TGFB1-TGFBR1 axis was activated in the heart and correlated with the extent of remodeling at 2 months.</p> <p>Conclusions</p> <p>We identified TGFBR1 as a new candidate prognostic biomarker after acute MI.</p

Clinical outcome of patients with malignant ventricular tachyarrhythmias and a multiprogrammable implantable cardioverter-defibrillator implanted with or without thoracotomy: an international multicenter study

Objectives. The long term efficacy and safety of a third-generation implantable cardioverter-defibrillator implanted with thoracotomy and nonthoracotomy lead systems was evaluated in a multicenter international study. Background. The clinical impact of transvenous leads for nonthoracotomy implantation and pacing for bradyarrhythmias and tachyarrhythmias in implantable cardioverter defibrillator systems is not well defined. Methods. The safety of the implantation procedure and clinical outcome of 1,221 patients with symptomatic and life-threatening ventricular tachyarrhythmias who underwent implantation of a third generation cardioverter defibrillator using either a thoracotomy approach with epicardial leads (616 patients) or a nonthoracotomy approach with endocardial leads (605 patients) in a nonrandomized manner was analyzed. The implantable cardioverter defibrillator system permitted pacing, cardioversion, defibrillation, arrhythmia event memory and noninvasive tachycardia induction. Results. Successful implantation of an endocardial lead system was achieved in 605 (88.2%) of 686 patients and an epicardial system in 614 (99.7%) of 616 (p 0.2). Conclusions. Third-generation cardioverter defibrillators with monophasic waveforms can be successfully implanted with epicardial (99.7%) and endocardial (88.2%) lead systems. We conclude that endocardial leads should be the implant technique of first choice. Improved patient management and tolerance for device therapy is achieved with the addition of antitachycardia pacemaker capability in these systems