The –429 T/C and –374 T/A Gene Polymorphisms of the Receptor of Advanced Glycation End Products Gene (RAGE) are not Risk Factors for Coronary Artery Disease in Slovene Population With Type 2 Diabetes

Receptor for advanced glycation end products (RAGE) plays a role in atherosclerosis in diabetics. There are two functional polymorphisms in the promoter of the RAGE gene (–429T/C and –374T/A). The aim of this study was to look for a relationship between the –429T/C and the –374T/A gene polymorphisms of the RAGE gene and the development of coronary artery disease (CAD) in the Slovene population with type 2 diabetes of duration longer than 10 years. One hundred and sixty-eight subjects with diabetes and CAD were compared to 241 diabetic subjects without CAD. The –429T/C and the –374T/A RAGE genotype distributions in patients with CAD (–429T/C: CC: 3%, TC: 31%, TT: 66.0%; 374T/A: AA: 7.7%, TA: 48.2%, TT: 44.1%) were not significantly different from those in patients without CAD (–429 T/C: CC: 1.7%, TC: 26.1%, TT: 72.2%; –374T/A: AA: 11.2%, TA: 43.2%, TT: 45.6%). Our study failed to demonstrate an association between either the –429T/C or the –374T/A gene polymorphism of the RAGE gene and CAD in the Slovene population with type 2 diabetes of duration longer than 10 years

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest

Background: Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitantdual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI.Methods: In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose.Results: In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0–12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6–24] vs. 4 [2–12] h, p = 0.01).Conclusions: Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. Trial registration: ClinicalTrials.gov Identifier: NCT0261193

Technical Aspects and Development of Transcatheter Aortic Valve Implantation

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist—balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues

Percutaneous mechanical thrombectomy in patients with high-risk pulmonary embolism and contraindications for thrombolytic therapy

High-risk pulmonary embolism is associated with a high early mortality rate. We report our experience with percutaneous mechanical thrombectomy in patients with high-risk pulmonary embolism and contraindications for thrombolytic therapy

The –429 T/C and –374 T/A Gene Polymorphisms of the Receptor of Advanced Glycation End Products Gene (RAGE) are not Risk Factors for Coronary Artery Disease in Slovene Population With Type 2 Diabetes

Receptor for advanced glycation end products (RAGE) plays a role in atherosclerosis in diabetics. There are two functional polymorphisms in the promoter of the RAGE gene (–429T/C and –374T/A). The aim of this study was to look for a relationship between the –429T/C and the –374T/A gene polymorphisms of the RAGE gene and the development of coronary artery disease (CAD) in the Slovene population with type 2 diabetes of duration longer than 10 years. One hundred and sixty-eight subjects with diabetes and CAD were compared to 241 diabetic subjects without CAD. The –429T/C and the –374T/A RAGE genotype distributions in patients with CAD (–429T/C: CC: 3%, TC: 31%, TT: 66.0%; 374T/A: AA: 7.7%, TA: 48.2%, TT: 44.1%) were not significantly different from those in patients without CAD (–429 T/C: CC: 1.7%, TC: 26.1%, TT: 72.2%; –374T/A: AA: 11.2%, TA: 43.2%, TT: 45.6%). Our study failed to demonstrate an association between either the –429T/C or the –374T/A gene polymorphism of the RAGE gene and CAD in the Slovene population with type 2 diabetes of duration longer than 10 years

Enhanced detection of cardiac surgery-associated acute kidney injury by composite biomarker panel in patients with normal preoperative kidney function

We have shown recently that minor subclinical creatinine dynamic changes enable excellent de-tection of acute kidney injury (AKI) within 6-12 hours after cardiac surgery. The aim of the pre-sent study was to examine combination of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and creatinine for enhanced AKI detection early after cardiac surgery. Elective patients with normal renal function undergoing cardiac surgery using cardiopulmonary bypass were enrolled. Concentrations of plasma NGAL, serum CysC and serum creatinine concentra-tions were determined after induction of general anaesthesia, at termination of cardiopulmo-nary bypass and 2 hours thereafter. Out of 119 enrolled patients 51 (43%) developed AKI. A model utilizing NGAL, CysC and creatinine triple biomarker panel including sequential rela-tive changes provides better prediction of cardiac surgery-associated acute kidney injury then any biomarker alone already 2 hours after the termination of cardiopulmonary bypass. The area under receiver-operator curve was 0.77, sensitivity 77% and specificity 68%

The impact of mild therapeutic hypothermia on platelet reactivity in comatose survivors of cardiac arrest with acute myocardial infarction treated with ticagrelor

Background: The aim of the study was to assess the antiplatelet effect of ticagrelor in patients with myocardial infarction (MI) after out-of-hospital cardiac arrest (OHCA) treated with percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) vs. MI patients without OHCA treated with PCI. Methods: The study was designed and performed as a phase IV, single-center, investigator-initiated, prospective, observational study assessing the early pharmacodynamic effect (within first 24 h) of a ticagrelor loading dose (180 mg) in both groups of patients (MTH group vs. MI group). For assessment of ticagrelor pharmacodynamics Multiple Electrode Aggregometry (MEA) was applied. Results: Compared with the MTH group, platelet inhibition was persistently stronger in the MI group over the entire observation period (up to 24 h), with the highest difference at 4 hours after loading with ticagrelor (25.8 ± 26.4 vs. 75.8 ± 40.9 U, p = 0.002). As a consequence, there was a higher prevalence of high platelet reactivity in the MTH group, with the most explicit difference at 6 hours after the loading dose of ticagrelor (78% vs. 7%, p < 0.001). Conclusions: In comparison with patients treated with primary PCI for uncomplicated MI, the antiplatelet effect of ticagrelor in patients with MI complicated with OHCA, undergoing MTH and primary PCI, is attenuated and delayed

Clinical outcomes of transcatheter aortic valve implantation in patients younger than 70 years rejected for surgery: the AMTRAC registry

Background: The mean age of transcatheter aortic valve implantation (TAVI) patients is steadily decreasing. Aims: The aim of the study was to describe the characteristics, the indications for and the outcomes of TAVI in patients 4% in 20.4%. Five-year mortality was similar (29.4 vs 29.8%, HR 0.95, p=0.432) in the 70 groups. In the <70 group, mortality was higher for those referred for TAVI due to an increased surgical risk compared to those referred for other reasons (31.6 vs 24.5%, HR 1.23, p=0.021). Mortality was similar regardless of the STS stratum in patients judged by the Heart Team to be at increased surgical risk (32.6 vs 30.4%, HR 0.98, p=0.715). Conclusions: Use of TAVI in patients <70 is becoming more frequent. The main reason for choosing TAVI is due to an increased surgical risk not adequately represented by the STS score. The outcomes for these patients are similar to those for older TAVI patients. Dedicated trials of TAVI/SAVR in younger patients are needed to guide decisions concerning expansion of TAVI indications. (NCT04031274)

Center Valve Preference and Outcomes of Transcatheter Aortic Valve Replacement: Insights From the AMTRAC Registry

Background: Data on outcomes of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves (BEVs) or self-expandable valves (SEVs) as well as the impact of center valve preference on these outcomes are limited. Objectives: The aim of this study was to compare outcomes of TAVR procedures using third-generation BEVs and SEVs stratified by center valve preference. Methods: In a multicenter registry (n = 17), 13 centers exhibited valve preference (66.6%-90% of volume) and were included. Outcomes were compared between BEVs and SEVs stratified by center valve preference. Results: In total, 7,528 TAVR procedures (3,854 with SEVs and 3,674 with BEVs) were included. The mean age was 81 years, and the mean Society of Thoracic Surgeons score was 5.2. Baseline characteristics were similar between BEVs and SEVs. Need for pacemaker implantation was higher with SEVs at BEV- and SEV-dominant centers (17.8% vs 9.3% [P < 0.001] and 12.7% vs 10.0% [P = 0.036], respectively; HR: 1.51; P for interaction = 0.021), risk for cerebrovascular accident was higher with SEVs at BEV-dominant but not SEV-dominant centers (3.6% vs 1.1% [P < 0.001] and 2.2% vs 1.4% [P = 0.162]; HR: 2.08; P for interaction < 0.01). Aortic regurgitation greater than mild was more frequent with SEVs at BEV-dominant centers and similar with BEVs regardless of center dominance (5.2% vs 2.8% [P < 0.001] and 3.4% vs 3.7% [P = 0.504], respectively). Two-year mortality was higher with SEVs at BEV-dominant centers but not at SEV-dominant centers (21.9% vs 16.9% [P = 0.021] and 16.8% vs 16.5% [P = 0.642], respectively; HR: 1.20; P for interaction = 0.032). Conclusions: Periprocedural outcomes, aortic regurgitation greater than mild, and 2-year mortality are worse when TAVR is performed using SEVs at BEV-dominant centers. Outcomes are similar regardless of valve type at SEV-dominant centers. The present results stress the need to account for this factor when comparing BEV and SEV outcomes. (The Aortic+Mitral Transcatheter [AMTRAC] Valve Registry; NCT04031274

Effect of Transcatheter Aortic Valve Replacement on Concomitant Mitral Regurgitation and Its Impact on Mortality

OBJECTIVES The purpose of this study was to examine the impact of residual mitral regurgitation (MR) on mortality in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND MR is common in patients undergoing TAVR. Data on optimal management of patients with significant MR after TAVR are limited. METHODS The registry consisted of 16 TAVR centers (n = 7,303). Outcomes of patients with $moderate versus lesser grade MR after TAVR were compared. RESULTS In 1,983 (27.2$ moderate. MR regressed in 874 (44.1%) patients and persisted in 1,109 (55.9%) after TAVR. Four-year mortality was higher for those with MR persistence, but not for those with MR regression after TAVR, compared with nonsignificant baseline MR (43.8% vs. 35.1% vs. 32.4%; hazard ratio [HR]: 1.38; p = 0.008; HR: 1.02; p = 0.383, respectively). New York Heart Association functional class III to IV after TAVR was more common in those with MR persistence vs. regression (14.4% vs. 3.9%; p < 0.001). In a propensity score-matched cohort (91 patients' pairs), with significant residual MR after TAVR who did or did not undergo staged mitral intervention, staged intervention was associated with a better functional class through 1 year of follow-up (82.4% vs. 33.3% New York Heart Association functional class I or II; p < 0.001), and a numerically lower 4-year mortality, which was not statistically significant (64.6% vs. 37.5%; HR: 1.66; p = 0.097). CONCLUSIONS Risk stratification based on improvement in MR and symptoms after TAVR can identify patients at increased mortality risk after TAVR. These patients may benefit from a staged transcatheter mitral intervention, but this requires further proof from future studies. (C) 2021 by the American College of Cardiology Foundation