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Aim Ubiquitin-Proteasome System (UPS) is of paramount importance regarding the function of the myocardial cell. Consistently, inhibition of this system has been found to affect myocardium in experimental models; yet, the clinical impact of UPS inhibition on cardiac function has not been comprehensively examined. Our aim was to gain insight into the effect of proteasome inhibition on myocardial mechanics in humans. Methods and results We prospectively evaluated 48 patients with multiple myeloma and an indication to receive carfilzomib, an irreversible proteasome inhibitor. All patients were initially evaluated and underwent echocardiography with speckle tracking analysis. Carfilzomib was administered according to Kd treatment protocol. Follow-up echocardiography was performed at the 3rd and 6th month. Proteasome activity (PrA) was measured in peripheral blood mononuclear cells. At 3 months after treatment, we observed early left ventricular (LV) segmental dysfunction and deterioration of left atrial (LA) remodelling, which was sustained and more pronounced than that observed in a cardiotoxicity control group. At 6 months, LV and right ventricular functions were additionally attenuated (P < 0.05 for all). These changes were independent of blood pressure, endothelial function, inflammation, and cardiac injury levels. Changes in PrA were associated with changes in global longitudinal strain (GLS), segmental LV strain, and LA markers (P < 0.05 for all). Finally, baseline GLS < −18% or LA strain rate > 1.71 were associated with null hypertension events. Conclusion Inhibition of the UPS induced global deterioration of cardiac function.

We have previously reported significant benefits of using enoxaparin, compared to tinzaparin, in the 7- and 30-day incidence of the composite triple end point of death, myocardial infarction (MI), or recurrent angina in patients with non-ST-segment elevation acute coronary syndromes (NSTACS). In the present study, we aimed to determine whether the observed benefits of enoxaparin were maintained beyond the early phase and report the results of the 6-m follow-up of patients in the EVET study.We recruited 438 patients with NSTACS. All patients received oral aspirin and were randomized to also receive enoxaparin, 100 IU/kg subcutaneously twice daily (equivalent to 1 mg/kg twice daily; n = 220), or tinzaparin, 175 IU/kg subcutaneously once daily (n = 218), for up to 7 days.At 6 m, the incidence of the composite triple end point of death, MI, or recurrent angina was lower among patients receiving enoxaparin compared to those receiving tinzaparin (25.5% vs 44.0%, P.001). A lower incidence of the secondary composite end point of death or MI was also found in the enoxaparin group compared to tinzaparin group (2.7% vs 6.9%, P = .046). The need for revascularization procedures was also lower in the enoxaparin group compared to tinzaparin group (23.2% vs 37.2%, P = .002).In patients with NSTACS, enoxaparin significantly reduced the rates of recurrent ischemic events and therapeutic procedures in the short term, with sustained benefit at 6 m compared to tinzaparin.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries24 hours after MI with serum creatinine levels ≤2.5 mg/dl. The primary end point was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out using estimated glomerular filtration rate (eGFR) as a continuous variable and by eGFR categories. Long-term follow-up data (maximum 9 years) were used for this analysis. Lower eGFR was associated with development of the primary outcome (6-year life-table rates of 16.9% for eGFR90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR60 ml/min/1.73 m(2); p0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

To investigate the impact of BiodivYsio dexamethazone-eluting stent versus BiodivYsio stent on the 12-month outcomes after revascularisation of patients with single vessel coronary artery disease.From March 2003 to February 2004, 102 patients with non-ST elevation acute coronary syndromes, angina or silent ischemia after recent ST elevation myocardial infarction (1 month) or stable angina pectoris, and single-vessel coronary artery disease were treated solely with dexamethazone-eluting stent implantation in our institution. Patients were followed up prospectively for twelve months. We compared their outcomes to a control group with similar clinical and angiographic characteristics of 160 patients treated solely with BiodivYsio stents in the preceding study enrolment period (January 2002 to March 2003).Approximately 85% of the patients in both groups were treated after an acute coronary syndrome. At 12 months, the major adverse cardiac events rates (death or non-fatal myocardial infarction or target lesion revascularization) were similar in the 2 groups (10.8% in the dexamethazone-eluting and 11.3% in the BiodivYsio group, p=1.00). No difference was found in the individual rates of death, non-fatal myocardial infarction and target lesion revascularization between the 2 groups.We conclude that utilization of dexamethazone-eluting stents has no effect in reducing the incidence of major adverse cardiac events after 12 months, as compared with BiodivYsio stent implantation in the treatment of single vessel coronary artery disease.