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Changes in the regulatory guidelines by the U.S. Food and Drug Administration and the European Medical Agency requiring large-scale trials that study the cardiovascular safety of new glucose-lowering drugs have improved our understanding of type 2 diabetes mellitus. Unexpectedly, these trials demonstrated that sodium-glucose cotransporter 2 inhibitors reduce adverse cardiovascular outcomes. This second part of this 2-part review summarizes the findings of recent clinical trials and their clinical implications and describes ongoing trials and future areas of research. [ABSTRACT FROM AUTHOR]

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class approved for treatment of diabetes, have been shown to possess a favorable metabolic profile and to significantly reduce atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. Although initially considered to be only glucose-lowering agents, the effects of SGLT2i have expanded far beyond that, and their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes. It is therefore critical for cardiologists, diabetologists, nephrologists, and primary care physicians to be familiar with this drug class. This first part of this 2-part review provides an overview of the current understanding of the mechanisms of the cardio-metabolic-renal benefits of SGLT2i. The second part summarizes the recent clinical trials of SGLT2i. [ABSTRACT FROM AUTHOR]

Abstract Patients with type 2 diabetes mellitus have an increased risk for the development of cardiac and other vascular events, heart failure (HF), and decline in renal function. After several large cardiovascular outcome trials with mostly neutral results, 2 studies of the sodium–glucose co-transporter 2 inhibitors (SGLT2is), empagliflozin and canagliflozin, reported favorable effects on the primary endpoint, a composite of myocardial infarction, stroke, and cardiovascular death. In addition, reductions of hospitalizations for HF were observed; in the case of empagliflozin, reductions in both cardiovascular mortality and total mortality occurred. These findings prompted several analyses to elucidate the mechanisms of action of SGLT2is and have initiated several large clinical trials in patients with HF without type 2 diabetes mellitus. This review summarizes known and possible mechanisms that contribute to these salutary effects of SGLT2is. Also discussed is the interplay between cardiac and renal function, as well as safety issues associated with this class of drugs. Central Illustration [ABSTRACT FROM AUTHOR]

Background Patients with birch pollen allergy often develop allergic reactions to plant foods. Objective To evaluate the prevalence, main symptoms, and triggers of birch pollen–related food allergy and the role of food-specific IgG 4 antibodies in food tolerance. Methods Food-induced symptoms were evaluated in 225 individuals with birch pollen allergy by using a standardized questionnaire. IgE and IgG 4 levels specific for the major birch pollen allergen Bet v 1 and birch profilin Bet v 2 and the Bet v 1 homologs in apple (Mal d 1) and hazelnut (Cor a 1) were quantified by ImmunoCAP. Mock-treated and IgG-depleted sera from patients tolerating hazelnuts in food challenges were compared for their inhibitory activity for binding of Cor a 1–IgE complexes to B cells. Results In total, 73% of the study population experienced food allergy, which was perennial in 86% of the affected individuals. The oral allergy syndrome was the main clinical manifestation. However, more than 58% of the patients also experienced food-induced rhinoconjunctivitis. Apples and hazelnuts were identified as the most frequent triggers. Food allergy correlated with IgE reactivity to Bet v 1 but not to Bet v 2. Mal d 1–specific and Cor a 1–specific IgG 4 /IgE ratios were significantly higher in food-tolerant individuals than individuals with food allergy. Sera from IgG 4 -positive food-tolerant patients possessed IgG-dependent IgE-inhibitory activity. Conclusion Birch pollen–related food allergy is highly prevalent and often perennial. High food allergen–specific IgG 4 /IgE ratios seem associated with food tolerance, potentially because specific IgG 4 blocks IgE binding to food allergens. Thus, the presence of food allergen–specific IgG 4 antibodies is no diagnostic marker for birch pollen–related food allergy. [ABSTRACT FROM AUTHOR]

Background: Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.Objectives: We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.Methods: FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL).Results: When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each).Conclusions: A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633). [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate the ability of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to reduce the risk of complex coronary atherosclerosis requiring revascularization.Background: PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall.Methods: FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was a randomized trial of the PCSK9 inhibitor evolocumab versus placebo in 27,564 patients with stable atherosclerotic cardiovascular disease on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG).Results: In this study, 1,724 patients underwent coronary revascularization, including 1,482 who underwent PCI, 296 who underwent CABG, and 54 who underwent both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (hazard ratio [HR]: 0.78; 95% CI: 0.71 to 0.86; p < 0.001), simple PCI by 22% (HR: 0.78; 95% CI: 0.70 to 0.88; p < 0.001), complex PCI by 33% (HR: 0.67; 95% CI: 0.54 to 0.84; p < 0.001), CABG by 24% (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.019), and complex revascularization by 29% (HR: 0.71; 95% CI: 0.61 to 0.84; p < 0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in the first, second, and beyond second years).Conclusions: Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER); NCT01764633.). [ABSTRACT FROM AUTHOR]

Purpose: Right ventricular longitudinal axis strain (RV-LAS) is a simple measure of RV longitudinal function. The purpose of this study was the evaluation of its diagnostic performance in non-ischemic dilated cardiomyopathy (NIDCM) and the determination of reference values in controls. Methods: 217 NIDCM patients and 200 healthy controls were analysed retrospectively regarding the diagnostic performance of RV-LAS using receiver operating characteristic curves in comparison with RV ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE) and global longitudinal strain (RV-GLS). Hereby, four different approaches were evaluated to assess RV-LAS based on different reference points. RV-LAS LVapex/mid was defined as the change in distance between the LV apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in systole and diastole. The ethical approval was obtained in all participants. Results: NIDCM and controls were 48 years in mean. Controls were equally gender distributed, while the proportion of men with NIDCM was higher with 77%. Among the four approaches RV-LAS LVapex/mid provided the highest diagnostic performance for discrimination between NIDCM and controls (AUC=0.94). Of all RV functional parameters RV-LAS LVapex/mid preformed significantly better than RVEF (delta AUC=0.05; p=0.003), TAPSE (delta AUC=0.23; p<0.0001) and RV-GLS (delta AUC=0.31; p<0.0001). A significant correlation was found between RV-LAS LVapex/mid and RVEF (r=-0.65; p<0.0001). The reference mean values for RV-LAS LVapex/mid were -17.4±3.5 for men and -18.5±3.7 for women. Conclusion: RV-LAS showed better diagnostic accuracy for RV dysfunction than RVEF, TAPSE and RV-GLS. Furthermore, it has a rapid accessibility and low intra- and interobserver variability. [ABSTRACT FROM AUTHOR]