Prediction of Mortality and Major Cardiac Events by Exercise Echocardiography in Patients With Normal Exercise Electrocardiographic Testing

ObjectivesWe sought to assess the value of exercise echocardiography (EE) for predicting outcome in patients with known or suspected coronary artery disease and normal exercise electrocardiogram (ECG) testing.BackgroundThe prognostic value of EE in patients with normal exercise ECG testing has not been characterized.MethodsWe studied 4,004 consecutive patients (2,358 men, mean age [± SD] 59.6 ± 12.5 years) with interpretable ECG who underwent treadmill EE and did not develop chest pain or ischemic ECG abnormalities during the tests. Wall motion score index (WMSI) was evaluated at rest and with exercise, and the difference (ΔWMSI) was calculated. Ischemia was defined as the development of new or worsening wall motion abnormalities with exercise. End points were all-cause mortality and major cardiac events (MACE).ResultsOverall, 669 patients (16.7%) developed ischemia with exercise. During a mean follow-up of 4.5 ± 3.4 years, 313 patients died, and 183 patients had a MACE before any revascularization procedure. The 5-year mortality and MACE rates were 6.4% and 4.2% in patients without ischemia versus 12.1% and 10.1% in those with ischemia, respectively (p < 0.001). In the multivariate analysis, ΔWMSI remained an independent predictor of mortality (hazard ratio [HR]: 2.73, 95% confidence interval [CI]: 1.40 to 5.32, p = 0.003) and MACE (HR: 3.59, 95% CI: 1.42 to 9.07, p = 0.007). The addition of the EE results to the clinical, resting echocardiographic and exercise hemodynamic data significantly increased the global chi-square of the models for the prediction of mortality (p = 0.005) and MACE (p = 0.009).ConclusionsThe use of EE provides significant prognostic information for predicting mortality and MACE in patients with interpretable ECG and normal exercise ECG testing

Apoptotic Effects of Antilymphocyte Globulins on Human Pro-inflammatory CD4+CD28− T-cells

BACKGROUND: Pro-inflammatory, cytotoxic CD4(+)CD28(-) T-cells with known defects in apoptosis have been investigated as markers of premature immuno-senescence in various immune-mediated diseases. In this study we evaluated the influence of polyclonal antilymphocyte globulins (ATG-Fresenius, ATG-F) on CD4(+)CD28(-) T-cells in vivo and in vitro. PRINCIPAL FINDINGS: Surface and intracellular three colour fluorescence activated cell sorting analyses of peripheral blood mononuclear cells from 16 consecutive transplant recipients and short-term cell lines were performed. In vivo, peripheral levels of CD3(+)CD4(+)CD28(-) T-cells decreased from 3.7 ± 7.1% before to 0 ± 0% six hours after ATG-F application (P = 0.043) in 5 ATG-F treated but not in 11 control patients (2.9 ± 2.9% vs. 3.9 ± 3.0%). In vitro, ATG-F induced apoptosis even in CD4(+)CD28(-) T-cells, which was 4.3-times higher than in CD4(+)CD28(+) T-cells. ATG-F evoked apoptosis was partially reversed by the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk) and prednisolon-21-hydrogensuccinate. ATG-F triggered CD25 expression and production of pro-inflammatory cytokines, and induced down-regulation of the type 1 chemokine receptors CXCR-3, CCR-5, CX3CR-1 and the central memory adhesion molecule CD62L predominately in CD4(+)CD28(-) T-cells. CONCLUSION: In summary, in vivo depletion of peripheral CD3(+)CD4(+)CD28(-) T-cells by ATG-F in transplant recipients was paralleled in vitro by ATG-F induced apoptosis. CD25 expression and chemokine receptor down-regulation in CD4(+)CD28(-) T-cells only partly explain the underlying mechanism

Association of left ventricular mass with all-cause mortality, myocardial infarction and stroke

BACKGROUND: Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1 ± 16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6 ± 3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14-1-27, p<0.001 in women, and HR 1.09, 95% CI 1.04-1-13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31-1.94, p<0.001 in women and HR 1.15, 95% CI 1.02-1.29, p=0.019 in men) and stroke (HR 1.26, 95% CI 1.13-1.40, p<0.001 in women and HR 1.19, 95% CI 1.09-1.30, p<0.001 in men). CONCLUSIONS/SIGNIFICANCE: Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke

Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third international study on syncope of uncertain etiology (ISSUE-3): A randomized trial

BACKGROUND: The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. METHODS AND RESULTS: Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12 ± 10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40-74) with pacemaker OFF and 25% (95% CI, 13-45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4-81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. CONCLUSIONS: Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203

Hazard ratios for all-cause mortality per 100 g increase in left ventricular mass according to sex and stratified by age, hypertension and left ventricular ejection fraction (LVEF).

<p>Hazard ratios for all-cause mortality per 100 g increase in left ventricular mass according to sex and stratified by age, hypertension and left ventricular ejection fraction (LVEF).</p

Kaplan-Meier curves for all-cause mortality, nonfatal myocardial infarction and stroke stratified according to left ventricular mass.

<p>Kaplan-Meier curves for all-cause mortality, nonfatal myocardial infarction and stroke stratified according to left ventricular mass.</p