Incremental value of strain rate imaging to wall motion analysis for prediction of outcome in patients undergoing dobutamine stress echocardiography

Background - Wall motion score at dobutamine stress echocardiography is an independent predictor of mortality. We sought to determine whether quantification of DSE by strain rate imaging was incremental to wall motion score for predicting outcome. Methods and Results - In 646 patients undergoing dobutamine stress echocardiography for the evaluation of known or suspected coronary disease, customized software was used to automatically measure peak systolic strain rate (SRs) and end-systolic strain (Se-s) in 18 segments. Results were expressed as the number of abnormal segments and the mean SRs and S-es per patient. All-cause mortality was identified over 7 years of follow-up (mean, 5.2 +/- 1.5 years). Contributions of clinical, wall motion, and SRs and S-es data to outcome were analyzed with Cox models, which also were used to define cut points for SRs and S-es. Ischemia (new or worsening wall motion abnormalities) was detected in 45%, and 39% had a previous myocardial infarction. In patients with no ischemia, annualized mortality without and with previous myocardial infarction were 2% and 3% compared with 5% in patients with ischemia. Peak wall motion score index, mean SRs, segmental S-es, and segmental SRs were all predictors of mortality, but only segmental SRs (hazard ratio, 3.6; 95% CI, 1.7 to 7.2) was independently predictive. In sequential Cox models, the model based on clinical data (overall chi(2), 12.7) was improved by peak wall motion score index (18.4, P = 0.002) and further increased by either segmental SRs (31.8, P < 0.001) or mean SRs (25.7, P = 0.009). Conclusions - Segmental analysis by SRs, derived from automated strain rate imaging analysis of dobutamine stress echocardiography response, offers prognostic information that is independent and incremental to standard wall motion score index

Glycosylation of immunoglobulins determine bone loss in multiple myeloma

Proteomic

Monoclonal immunoglobulins promote bone loss in multiple myeloma

Most patients with multiple myeloma develop a severe osteolytic bone disease. The myeloma cells secrete immunoglobulins, and the presence of monoclonal immunoglobulins in the patient's sera is an important diagnostic criterion. Here, we show that immunoglobulins isolated from myeloma patients with bone disease promote osteoclast differentiation when added to human preosteoclasts in vitro, whereas immunoglobulins from patients without bone disease do not. This effect was primarily mediated by immune complexes or aggregates. The function and aggregation behavior of immunoglobulins are partly determined by differential glycosylation of the immunoglobulin-Fc part. Glycosylation analyses revealed that patients with bone disease had significantly less galactose on immunoglobulin G (IgG) compared with patients without bone disease and also less sialic acid on IgG compared with healthy persons. Importantly, we also observed a significant reduction of IgG sialylation in serum of patients upon onset of bone disease. In the 5TGM1 mouse myeloma model, we found decreased numbers of lesions and decreased CTX-1 levels, a marker for osteoclast activity, in mice treated with a sialic acid precursor, N-acetylmannosamine (ManNAc). ManNAc treatment increased IgG-Fc sialylation in the mice. Our data support that deglycosylated immunoglobulins promote bone loss in multiple myeloma and that altering IgG glycosylation may be a therapeutic strategy to reduce bone loss.Proteomic

Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients - A randomized study

Background - Exercise training reduces the symptoms of chronic heart failure. Which exercise intensity yields maximal beneficial adaptations is controversial. Furthermore, the incidence of chronic heart failure increases with advanced age; it has been reported that 88% and 49% of patients with a first diagnosis of chronic heart failure are &gt; 65 and &gt; 80 years old, respectively. Despite this, most previous studies have excluded patients with an age &gt; 70 years. Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfarction heart failure. Methods and Results - Twenty- seven patients with stable postinfarction heart failure who were undergoing optimal medical treatment, including beta- blockers and angiotensin- converting enzyme inhibitors ( aged 75.5 +/- 11.1 years; left ventricular [ LV] ejection fraction 29%; VO2peak 13 mL . kg(-1) . min(-1)) were randomized to either moderate continuous training ( 70% of highest measured heart rate, ie, peak heart rate) or aerobic interval training ( 95% of peak heart rate) 3 times per week for 12 weeks or to a control group that received standard advice regarding physical activity. V-O2peak increased more with aerobic interval training than moderate continuous training ( 46% versus 14%, P &lt; 0.001) and was associated with reverse LV remodeling. LV end-diastolic and end-systolic volumes declined with aerobic interval training only, by 18% and 25%, respectively; LV ejection fraction increased 35%, and pro- brain natriuretic peptide decreased 40%. Improvement in brachial artery flow- mediated dilation ( endothelial function) was greater with aerobic interval training, and mitochondrial function in lateral vastus muscle increased with aerobic interval training only. The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups. No changes occurred in the control group. Conclusions - Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity, endothelial function, and quality of life in patients with postinfarction heart failure. These findings may have important implications for exercise training in rehabilitation programs and future studies

Aerobic Interval Training Versus Continuous Moderate Exercise as a Treatment for the Metabolic Syndrome: A Pilot Study

Background-- Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome. Methods and Results-- Thirty-two metabolic syndrome patients (age, 52.3{+/-}3.7 years; maximal oxygen uptake [[V]O2max], 34 mL {middle dot} kg-1 {middle dot} min-1) were randomized to equal volumes of either moderate continuous moderate exercise (CME; 70% of highest measured heart rate [Hfmax]) or aerobic interval training (AIT; 90% of Hfmax) 3 times a week for 16 weeks or to a control group. [V]O2max increased more after AIT than CME (35% versus 16%; P&#60;0.01) and was associated with removal of more risk factors that constitute the metabolic syndrome (number of factors: AIT, 5.9 before versus 4.0 after; P&#60;0.01; CME, 5.7 before versus 5.0 after; group difference, P&#60;0.05). AIT was superior to CME in enhancing endothelial function (9% versus 5%; P&#60;0.001), insulin signaling in fat and skeletal muscle, skeletal muscle biogenesis, and excitation-contraction coupling and in reducing blood glucose and lipogenesis in adipose tissue. The 2 exercise programs were equally effective at lowering mean arterial blood pressure and reducing body weight (-2.3 and -3.6 kg in AIT and CME, respectively) and fat. Conclusions-- Exercise intensity was an important factor for improving aerobic capacity and reversing the risk factors of the metabolic syndrome. These findings may have important implications for exercise training in rehabilitation programs and future studie