Showing papers by "Andrzej Rynkiewicz published in 2014"

Inhibition of delta-protein kinase C by delcasertib as an adjunct to primary percutaneous coronary intervention for acute anterior ST-segment elevation myocardial infarction: results of the PROTECTION AMI Randomized Controlled Trial.

Abstract: Aims Delcasertib is a selective inhibitor of delta-protein kinase C (delta-PKC), which reduced infarct size during ischaemia/reperfusion in animal models and diminished myocardial necrosis and improved reperfusion in a pilot study during primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI). Methods and results A multicentre, double-blind trial was performed in patients presenting within 6 h and undergoing primary PCI for anterior (the primary analysis cohort, n = 1010 patients) or inferior (an exploratory cohort, capped at 166 patients) STEMI. Patients with anterior STEMI were randomized to placebo or one of three doses of delcasertib (50, 150, or 450 mg/h) by intravenous infusion initiated before PCI and continued for ∼2.5 h. There were no differences between treatment groups in the primary efficacy endpoint of infarct size measured by creatine kinase MB fraction area under the curve (AUC) (median 5156, 5043, 4419, and 5253 ng h/mL in the placebo, delcasertib 50, 150, and 450 mg/mL groups, respectively) in the anterior STEMI cohort. No treatment-related differences were seen in secondary endpoints of infarct size, electrocardiographic ST-segment recovery AUC or time to stable ST recovery, or left ventricular ejection fraction at 3 months. No differences in rates of adjudicated clinical endpoints (death, heart failure, or serious ventricular arrhythmias) were observed. Conclusions Selective inhibition of delta-PKC with intravenous infusion of delcasertib during PCI for acute STEMI in a population of patients treated according to contemporary standard of care did not reduce biomarkers of myocardial injury. Clinical trial registration ClinicalTrials.gov Identifier: [NCT00785954][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00785954&atom=%2Fehj%2Fearly%2F2014%2F05%2F05%2Feurheartj.ehu177.atom

Exercise Capacity and Mortality in Patients With Ischemic Left Ventricular Dysfunction Randomized to Coronary Artery Bypass Graft Surgery or Medical Therapy: An Analysis From the STICH Trial (Surgical Treatment for Ischemic Heart Failure)

Abstract: Objectives The objective of this study was to assess the prognostic significance of exercise capacity in patients with ischemic left ventricular (LV) dysfunction eligible for coronary artery bypass graft surgery (CABG). Background Poor exercise capacity is associated with mortality, but it is not known how this influences the benefits and risks of CABG compared with medical therapy. Methods In an exploratory analysis, physical activity was assessed by questionnaire and 6-min walk test in 1,212 patients before randomization to CABG (n = 610) or medical management (n = 602) in the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Mortality (n = 462) was compared by treatment allocation during 56 months (interquartile range: 48 to 68 months) of follow-up for subjects able (n = 682) and unable (n = 530) to walk 300 m in 6 min and with less (Physical Ability Score [PAS] >55, n = 749) and more (PAS ≤55, n = 433) limitation by dyspnea or fatigue. Results Compared with medical therapy, mortality was lower for patients randomized to CABG who walked ≥300 m (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.59 to 0.99; p = 0.038) and those with a PAS >55 (HR: 0.79; 95% CI: 0.62 to 1.01; p = 0.061). Patients unable to walk 300 m or with a PAS ≤55 had higher mortality during the first 60 days with CABG (HR: 3.24; 95% CI: 1.64 to 6.83; p = 0.002) and no significant benefit from CABG during total follow-up (HR: 0.95; 95% CI: 0.75 to 1.19; p = 0.626; interaction p = 0.167). Conclusions These observations suggest that patients with ischemic left ventricular dysfunction and poor exercise capacity have increased early risk and similar 5-year mortality with CABG compared with medical therapy, whereas those with better exercise capacity have improved survival with CABG. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595 )

Noninvasive assessment of endothelial function and vascular parameters in patients with familial and nonfamilial hypercholesterolemia.

Abstract: IntroductIon Endothelial dysfunction is one of the markers of atherosclerosis. oBjectIves The aim of the study was to evaluate endothelial function by assessing flow‑mediated dilation (FMD) and to measure the parameters of brachial arterial stiffness in patients with familial hypercholesterolemia (FH) and those with high low‑density lipoprotein (LDL) cholesterol levels without FH mutations (nonfamilial hypercholesterolemia – non‑FH). PAtIents And methods The study involved 60 patients (mean age, 41.9 ±7.7 y) without documented cardiovascular events and clinical symptoms of cardiovascular diseases: 21 patients with elevated plasma LDL cholesterol levels and genetically confirmed FH, 19 patients with elevated LDL cholesterol levels and without FH mutations, and 20 healthy controls. In each patient, ultrasound imaging was used to assess endothelium‑dependent FMD and nitroglycerin‑induced endothelium‑independent dilation (EID) in the brachial artery. In addition, echo‑tracking and photoplethysmography were used to assess the parameters of arterial stiffness. results FMD was significantly lower in patients with FH (11.0% ±9.9% vs. 21.0% ±14.3%, P <0.01) and non‑FH (14.2% ±10.1% vs. 21.0% ±14.3%, P <0.05) compared with controls. EID and arterial stiff‑ ness parameters were similar between the groups. conclusIons Reduced FMD may suggest endothelial dysfunction. A lack of significant differences in arterial stiffness parameters may indicate that vascular remodeling is not advanced in patients with elevated LDL cholesterol levels. A lack of significant differences in FMD and arterial stiffness between patients with and without FH may indicate that FH mutation itself is not the main determinant of endo‑ thelial dysfunction and vascular remodeling in younger patients with hypercholesterolemia.

Early-generation versus new-generation drug-eluting stents in isolated chronic total occlusion: on the road to extinction?

Abstract: BACKGROUND The performance of second-generation drug-eluting stent (DES) versus first-generation DES implantation in patients with stable angina and single chronic total occlusion (CTO) has not yet been studied. Herein, we sought to investigate whether a successful percutaneous coronary intervention (PCI) for CTO using second-generation versus first-generation polymer-coated DES improved outcomes in a setting of isolated CTO. METHODS Among 7765 patients undergoing elective PCIs between 2006 and 2011, a total of 742 single CTOs were identified. Of these, 496 had a successful PCI and 193 were implanted with DESs. The major adverse cardiovascular event (MACE) records were extracted from the national administrative database and all patients were linked to the 2-year follow-up. RESULTS When compared to first-generation DES implantation, second-generation implantation once significantly reduced risk of MACE, both at 1-year (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.06-0.36; P=.01) and 2-year follow-up (HR, 0.27; 95% CI, 0.13-0.56; P=.01). The symptom-driven target lesion revascularization (TLR) also occurred less frequently in patients with second-generation DES vs first-generation DES within 2 years of follow-up (HR, 0.15; 95% CI, 0.05-0.44; P=.03). The substantial 2-year benefit of second-generation DES over first-generation DES also persisted after incorporating a propensity score analysis for MACE (HR, 0.24; 95% CI, 0.08-0.72; P=.01) and TLR (HR, 0.15; 95% CI, 0.05-0.49; P=.04). CONCLUSIONS Successful PCI for CTO using thin-strut polymer-coated DES vs early-generation DES implantation improves outcomes after recanalization of isolated CTO in a setting of stable angina.