Natriuretic peptides for perioperative management of cardiac surgery

AbstractAtrial natriuretic peptide (carperitide) is used to treat heart failure in Japan, while brain natriuretic peptide (nesiritide) is employed in Europe/USA.Patients undergoing cardiac surgery have a complex underlying pathologic state that features increased levels of neurohumoral factors due to activation of the renin–angiotensin–aldosterone system and/or increased sympathetic activity. We considered that perioperative administration of carperitide could be beneficial for cardiac surgery patients, and we have conducted clinical investigations of its use. This article reviews the effects of natriuretic peptides in cardiac surgery patients based on our experience and on previous reports about perioperative management with carperitide or nesiritide

Study of the factors related to atrial fibrillation after coronary artery bypass grafting: A search for a marker to predict the occurrence of atrial fibrillation before surgical intervention

ObjectiveAtrial fibrillation after cardiac surgery is a frequent complication. In this study we studied various factors in addition to trying to identify a marker that would predict the potential for atrial fibrillation before surgical intervention to prevent its occurrence.MethodsWe targeted 234 cases in which isolated coronary artery bypass grafting had been performed. The items for study included age, EuroSCORE, and maximum values of creatine phosphokinase–MB, troponin I, and angiotensin II after surgical intervention and preoperative values of atrial natriuretic peptide, brain natriuretic peptide, and C-reactive protein. As fibrotic markers, we measured levels of the sialylated carbohydrate antigen KL-6 in the blood, hyaluronic acid, and pyridinoline cross-linked carboxyterminal telepeptide of type I collagen C. At the time of surgical intervention, a section of the right atrium was extracted, and atrial natriuretic peptide, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels were measured.ResultsAtrial fibrillation was observed in 73 (31.2%) cases, and preoperative factors that showed statistically significant differences in the occurrence of atrial fibrillation included age, EuroSCORE, and preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood. As for intraoperative and postoperative factors, statistically significant differences were observed in the postoperative maximum of angiotensin II, atrial natriuretic peptide of the right atrium, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels.ConclusionThe fibrosis of tissue associated with age is believed to be closely related to the occurrence of atrial fibrillation after coronary artery bypass grafting. This study suggests that the preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood are useful as a new index for the occurrence of atrial fibrillation after coronary artery bypass grafting

Comparing the Effects of Canagliflozin vs. Glimepiride by Body Mass Index in Patients with Type 2 Diabetes and Chronic Heart Failure : A Subanalysis of the CANDLE Trial

Background: We present results of a 24-week comparative study of the effects of the sodium–glucose cotransporter 2 (SGLT2) inhibitor canagliflozin vs. the sulfonylurea glimepiride, by baseline body mass index (BMI), in patients with type 2 diabetes and chronic heart failure. Methods: We conducted a post hoc analysis of the CANDLE trial. This subanalysis evaluated NT-proBNP, BMI, and other laboratory parameters, according to the subgroups stratified by BMI ≥ 25 kg/m2 vs. BMI < 25 kg/m2. Results: A group ratio of proportional changes in the geometric means of NT-proBNP was 0.99 (p = 0.940) for the subgroup with BMI ≥ 25 kg/m2 and 0.85 (p = 0.075) for the subgroup with BMI < 25 kg/m2, respectively. When baseline BMI was modeled as a continuous variable, results for patients with BMI < 30 kg/m2 showed a slightly smaller increase in NT-proBNP in the canagliflozin group vs. the glimepiride group (p = 0.295); that difference was not seen among patients with BMI ≥30 kg/m2 (p = 0.948). Irrespective of obesity, the canagliflozin group was associated with significant reduction in BMI compared to the glimepiride group. Conclusion: There was no significant difference in the effects of canagliflozin, relative to glimepiride, on NT-proBNP concentrations irrespective of baseline obesity. UMIN clinical trial registration number: UMIN000017669

Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure : a randomized trial (CANDLE)

Aims Little is known about the impact of sodium glucose co‐transporter 2 (SGLT2) inhibitors on cardiac biomarkers, such as natriuretic peptides, in type 2 diabetes (T2D) patients with concomitant chronic heart failure (CHF). We compared the effect of canagliflozin with glimepiride, based on changes in N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), in that patient population. Methods and results Patients with T2D and stable CHF, randomized to receive canagliflozin 100 mg or glimepiride (starting‐dose: 0.5 mg), were examined using the primary endpoint of non‐inferiority of canagliflozin vs. glimepiride, defined as a margin of 1.1 in the upper limit of the two‐sided 95% confidence interval (CI) for the group ratio of percentage change in NT‐proBNP at 24 weeks. Data analysis of 233 patients showed mean left ventricular ejection fraction (LVEF) at randomization was 57.6 ± 14.6%, with 71% of patients having a preserved LVEF (≥50%). Ratio of NT‐proBNP percentage change was 0.48 (95% CI, −0.13 to 1.59, P = 0.226) and therefore did not meet the prespecified non‐inferiority margin. However, NT‐proBNP levels did show a non‐significant trend lower in the canagliflozin group [adjusted group difference; −74.7 pg/mL (95% CI, −159.3 to 10.9), P = 0.087] and also in the subgroup with preserved LVEF [−58.3 (95% CI, −127.6 to 11.0, P = 0.098]). Conclusions This study did not meet the predefined primary endpoint of changes in NT‐proBNP levels, with 24 weeks of treatment with canagliflozin vs. glimepiride. Further research is warranted to determine whether patients with heart failure with preserved ejection fraction, regardless of diabetes status, could potentially benefit from treatment with SGLT2 inhibitors

Febuxostat and carotid atherosclerosis in asymptomatic hyperuricemia

Background An elevated level of serum uric acid (SUA) is associated with an increased risk of cardiovascular disease. Pharmacological intervention with urate-lowering agents, such as the conventional purine analogue xanthine oxidase (XO) inhibitor, allopurinol, has been used widely for a long period of time in clinical practice to reduce SUA levels. Febuxostat, a novel non-purine selective inhibitor of XO, has higher potency for inhibition of XO activity and greater urate-lowering efficacy than conventional allopurinol. However, clinical evidence regarding the effects of febuxostat on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia. Methods and findings The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial undertaken at 48 sites throughout Japan between May 2014 and August 2018. Adults with both asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery (CCA) ≥1.1 mm at screening were allocated equally using a central web system to receive either dose-titrated febuxostat (10–60 mg daily) or as a control-arm, non-pharmacological lifestyle modification for hyperuricemia, such as a healthy diet and exercise therapy. Of the 514 enrolled participants, 31 were excluded from the analysis, with the remaining 483 people (mean age 69.1 years [standard deviation 10.4 years], female 19.7%) included in the primary analysis (febuxostat group, 239; control group, 244), based on a modified intention-to-treat principal. The carotid IMT images were recorded by a single sonographer at each site and read in a treatment-blinded manner by a single analyzer at a central core laboratory. The primary endpoint was the percentage change from baseline to 24 months in mean IMT of the CCA, determined by analysis of covariance using the allocation adjustment factors (age, gender, history of type 2 diabetes, baseline SUA, and baseline maximum IMT of the CCA) as the covariates. Key secondary endpoints included changes in other carotid ultrasonographic parameters and SUA and the incidence of clinical events. The mean values (± standard deviation) of CCA-IMT were 0.825 mm ± 0.173 mm in the febuxostat group and 0.832 mm ± 0.175 mm in the control group (mean between-group difference [febuxostat − control], −0.007 mm [95% confidence interval (CI) −0.039 mm to 0.024 mm; P = 0.65]) at baseline; 0.832 mm ± 0.182 mm in the febuxostat group and 0.848 mm ± 0.176 mm in the control group (mean between-group difference, −0.016 mm [95% CI −0.051 mm to 0.019 mm; P = 0.37]) at 24 months. Compared with the control group, febuxostat had no significant effect on the primary endpoint (mean percentage change 1.2% [95% CI −0.6% to 3.0%] in the febuxostat group (n = 207) versus 1.4% [95% CI −0.5% to 3.3%] in the control group (n = 193); mean between-group difference, −0.2% [95% CI −2.3% to 1.9%; P = 0.83]). Febuxostat also had no effect on the other carotid ultrasonographic parameters. The mean baseline values of SUA were comparable between the two groups (febuxostat, 7.76 mg/dL ± 0.98 mg/dL versus control, 7.73 mg/dL ± 1.04 mg/dL; mean between-group difference, 0.03 mg/dL [95% CI −0.15 mg/dL to 0.21 mg/dL; P = 0.75]). The mean value of SUA at 24 months was significantly lower in the febuxostat group than in the control group (febuxostat, 4.66 mg/dL ± 1.27 mg/dL versus control, 7.28 mg/dL ± 1.27 mg/dL; mean between-group difference, −2.62 mg/dL [95% CI −2.86 mg/dL to −2.38 mg/dL; P < 0.001]). Episodes of gout arthritis occurred only in the control group (4 patients [1.6%]). There were three deaths in the febuxostat group and seven in the control group during follow-up. A limitation of the study was the study design, as it was not a placebo-controlled trial, had a relatively small sample size and a short intervention period, and only enrolled Japanese patients with asymptomatic hyperuricemia. Conclusions In Japanese patients with asymptomatic hyperuricemia, 24 months of febuxostat treatment did not delay carotid atherosclerosis progression, compared with non-pharmacological care. These findings do not support the use of febuxostat for delaying carotid atherosclerosis in this population

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries