Subanalyses of secondary prevention implantable cardioverter-defibrillator trials: antiarrhythmics versus implantable defibrillators (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH)

PURPOSE OF REVIEW: Controlled trials for secondary prevention of sudden death--Antiarrhythmics Versus Implantable Defibrillators (AVID), Canadian Implantable Defibrillator Study (CIDS), and Cardiac Arrest Study Hamburg (CASH)--have been published and subanalyses of them provide useful clinical information on the outcome during the follow-up of this population. RECENT FINDINGS: Results from a meta-analysis showed a significant risk reduction (RR) of 25 to 27% of total mortality (P < 0.001) and 50 to 52% of arrhythmic death (P < 0.001). Compared with amiodarone, patients treated with an implantable cardioverter-defibrillator (ICD) in AVID had a maximal benefit in survival when the ejection fraction (EF) was between 20 and 34%. In CIDS, the group of higher risk (older than 70 years, EF less than 3.5%, and New York Heart Association class III-IV) presented a 50% RR of mortality. It has been demonstrated that the imbalance in beta-blocker use cannot explain the better survival in the ICD patients. After 3 years the recurrence of arrhythmia was 64% in the ICD group of the AVID trial. Patients enrolled after an episode of ventricular tachycardia were more likely to have appropriate therapy during follow-up. Older age, lower blood pressure, history of atrial fibrillation, diabetes, congestive heart failure, and prior pacemaker were parameters used for high-risk stratification. Conversely, inducibility of ventricular tachyarrhythmias on electrophysiology did not predict death. SUMMARY: Patients with ICD after ventricular tachyarrhythmias have a 28% RR in total mortality. Individuals with EF between 20 to 34% received the highest benefit with ICD therapy.     

Multifunctional cells in human pituitary adenomas: implications for paradoxical secretion and tumorigenesis

Pituitary adenomas are very common in humans. They are of monoclonal origin, very heterogeneous, and produce frequently paradoxical secretion. The normal anterior pituitary (AP) contains some unorthodox multifunctional cells able to store more than one AP hormone (polyhormonal) and/or to express multiple hypothalamic-releasing hormone receptors (multiresponsive). Multifunctional AP cells seem to be involved in plasticity processes such as transdifferentiation or paradoxical secretion. Here, we have characterized the single-cell phenotypes of 15 human pituitary tumors, including prolactinomas, nonfunctioning adenomas, and adenomas from multiple endocrine neoplasia type I (MEN-I) and pituitary Cushing's disease patients. Individual tumor cells were typed according to expression of AP hormones and hypothalamic-releasing hormone receptors by combination of calcium imaging and multiple sequential immunocytochemistry in the same cells. We found a large heterogeneity among the different tumors. In eight of the 15 tumors studied, more than 80% of the cells presented a multifunctional phenotype. This may explain the occurrence of paradoxical secretion. In addition, our results suggest that human pituitary adenomas might derive from multifunctional cells. This is consistent with the existence of a link between pituitary plasticity and tumorigenesis.     

Late recovery of coronary flow reserve in patients successfully treated with a percutaneous procedure

INTRODUCTION AND OBJECTIVES: Coronary angiograms are of limited value for the assessment of the results of percutaneous interventions. Intracoronary Doppler studies have been used to overcome these difficulties. The achievement of a coronary flow reserve (CFR) > 2-2.5 after the procedure is considered a good result and further optimization is generally not required. However, coronary flow reserve may not recover immediately, despite optimal procedural results. The aim of this study is to assess the temporal course of the recovery of coronary flow reserve after successful revascularization. PATIENTS AND METHOD: We studied 34 patients with coronary heart disease who were successfully treated by balloon angioplasty (n = 8) or stent implantation (n = 26). In all patients, serial observations were made by quantitative angiography and intracoronary Doppler (0.014 = flow-wire). Patients were studied: a) before treatment; b) immediately after, and c) 8 3 months later. RESULTS: The baseline coronary flow reserve was 1.3 0.4 and increased to 2.4 0.8 after the procedure (p < 0.01). At 8 months follow-up there was a significant increase (3 0.8; p < 0.01). This late improvement in coronary flow reserve was associated with a decline in average peak velocity at follow-up. Patients with impaired CFR immediately after treatment had a greater increase in CFR during followup than those with CFR > 2 after treatment (1.4 0.9 vs 0.4 0.6; p < 0.01). CONCLUSIONS: After a successful coronary intervention, CFR increases immediately, but some patients may experience additional improvement during follow-up. This increase was greater in patients who showed less improvement in coronary flow reserve immediately after treatment. Our findings suggest that the use of Doppler parameters in the immediate assessment of percutaneous coronary intervention results have limitations.     

Digoxin use is associated with increased platelet and endothelial cell activation in patients with nonvalvular atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine whether digoxin use is associated with increased flow cytometric markers of endothelial cell and platelet activation in patients with nonvalvular atrial fibrillation (AF). BACKGROUND: Increased intracellular calcium is a key event in platelet activation, and several studies have demonstrated that digitalis activates platelets in vitro. Intracellular calcium also is a key regulator of endothelial cell function, and endogenous digitalis-like substances have been shown to affect biologic processes in endothelial cells. METHODS: We studied 30 patients with nonvalvular AF. We measured the levels of (1) platelet expression of P-selectin (CD62P), (2) platelet microparticles (PMP); and (3) endothelial microparticles (EMP) identified by anti-CD31 (EMP31) and by anti-E-selectin antibodies (EMP62E). RESULTS: Patients who were taking digoxin (n = 16; mean digoxin level = 0.93 ng/dL) did not demonstrate any significant differences in clinical or echocardiographic characteristics compared with patients not taking digoxin (n = 14). Patients taking digoxin had significantly increased levels of CD62P expression in platelets and platelet-leukocyte conjugates and markedly increased markers of endothelial activation: EMP62E and EMP31. After adjusting for potential confounders (including age, congestive heart failure, coronary artery disease, ejection fraction, antiplatelet, beta-blocker, and calcium channel blocker use), the differences persisted. CONCLUSIONS: Digoxin use in patients with AF is associated with increased levels of endothelial and platelet activation. If digitalis activates endothelial cells and platelets at pharmacologic doses, use of digitalis in conditions such as AF could predispose to thrombosis and vascular events.     

Neoatherosclerosis in Patients With Coronary Stent Thrombosis: Findings From Optical Coherence Tomography Imaging (A Report of the PRESTIGE Consortium)

Objectives

The purpose of this study was to assess neoatherosclerosis in a registry of prospectively enrolled patients presenting with stent thrombosis using optical coherence tomography.

Young adult survivors of sudden cardiac arrest: analysis of invasive evaluation of 22 subjects

Twenty-two young adult (mean age 27.8 +/- 5.3 years) survivors of sudden cardiac arrest underwent invasive cardiac assessment. Initial evaluation by cardiac catheterization, coronary angiography, and hemodynamic studies identified two groups of young survivors. The first consisted of 13 (60%) subjects who had definable structural cardiac or lung disease accountable for a cardiac arrest event. Dilated cardiomyopathy dominated this group. Mitral valve prolapse, hypertrophic cardiomyopathy, left ventricular hypertrophy, anomalous origin of the right coronary artery, and tetralogy of Fallot were also encountered. The second group included nine subjects (40%) with normal cardiac structure and normal hemodynamic parameters. Electrophysiologic testing demonstrated in three of these patients the presence of Wolff-Parkinson-White syndrome. The electrophysiologic studies had a higher yield in reproduction of life-threatening arrhythmias among the subjects in the second group as opposed to the first group. The observation that 10 subjects (45%) from both groups had preceding symptoms varying from palpitations and chest pain to syncope and recurrent cardiac arrest events, is in contradiction to previous findings in the literature and raises a question of appropriate evaluation of young adults with cardiac symptoms.     

Left ventricular diastolic function in trained male weight lifters at rest and during isometric exercise

Individuals involved in intense resistance training present with increased absolute left ventricular (LV) wall thickness and mass and show good systolic responses to isometric exercise. There is no consensus regarding diastolic features and no available information regarding diastolic function in athletes during isometric exertion itself. Therefore, the main aim of this study was to assess diastolic LV function at baseline and during exercise in athletes. The population consisted of 96 men (mean age 29 +/- 7 years): 48 weight lifters who trained for 15 to 20 hours/week and 48 sedentary men. All weight lifters had been active for >6 years, including the 6 months before the study. Ultrasound was performed using a commercially available Doppler echocardiographic system. Isometric exercise was performed in the supine position using a standard 2-hand bar dynamometer. The man end-diastolic volumes at rest were 97 +/- 6 ml in sedentary subjects and 101 +/- 5 ml in weight lifters, increasing to 100 +/- 6 and 118 +/- 11 ml during exercise (p = 0.06 and p <0.01, respectively). End-systolic volumes at rest were similar in the 2 groups, showing significantly greater reductions during exercise in the weight lifters. The mean absolute LV mass was 167 +/- 30 g in sedentary subjects and 202 +/- 32 g in weight lifters (p <0.0001). The mean stroke volume increased from 65 +/- 7 to 86 +/- 7 ml in sedentary subjects and from 70 +/- 6 to 107 +/- 11 ml in weight lifters (intergroup significance p = 0.05 and p <0.01, respectively). A similar pattern of response was documented for the ejection fraction (i.e., significantly greater increases during exercise in weight lifters). Regarding diastolic indexes, in the weight lifters, the mean peak early velocity at rest was 68 +/- 7 cm/s, the mean acceleration rate was 1,242 +/- 176 cm/s/s, and the mean deceleration rate was 414 +/- 44 cm/s/s. All these values were significantly higher than in sedentary subjects, with further increases during exercise (p <0.0001). In weight lifters, the mean peak atrial velocity at rest was 37 +/- 6 cm/s, the mean acceleration time was 55 +/- 4 ms, the mean isovolumic relaxation time was 63 +/- 3 ms, and the mean deceleration time was 164 +/- 4 ms; these values were lower than in sedentary subjects (p <0.0001 for all). In conclusion, intense resistance training leads to enhanced LV diastolic function at rest and during isometric exercise despite the markedly increased LV mass.