Identification of epicardial connections can improve the success rate of first-pass right pulmonary vein isolation.

Background: Epicardial connections between the right pulmonary vein (PV) and the right atrium have been reported. Objective: The purpose of this study was to evaluate the usefulness of our new pulmonary vein isolation (PVI) strategy with identification of these epicardial connections. Methods: Overall, 235 patients with atrial fibrillation were included. High-density mapping of the left atrium was performed to identify the earliest activation sites (EASs) before PVI in all patients. With our new strategy, if EASs around the right PV carina were identified, we ablated these sites and performed usual first-pass circumferential PVI. The patients were divided into 2 groups according to the ablation strategy. One hundred fifteen patients underwent first-pass PVI without information on EASs (nonanalyzed group), and 78 patients underwent ablation at EASs around the right PV carina in addition to PVI (analyzed group). After first-pass ablation around the PV antrum, remapping was performed. Results: High-density mapping before PVI showed that the prevalence of EASs around the right PV carina was 10.9% in all patients (9.6% in the nonanalyzed group, 12.8% in the analyzed group; P = .74. The first-pass right PVI success rate was higher in the analyzed group than in the nonanalyzed group (93.6% vs 82.6%; P = .04). The radiofrequency application time for PVI was significantly shorter in the analyzed group than in the nonanalyzed group (45.6 ± 1.0 minutes vs 51.2 ± 0.9 minutes; P <.05). Conclusion: Identification of epicardial connections before ablation could improve the success rate of first-pass right PVI.

Treatment Burden on Once-Weekly Omarigliptin Versus Daily Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes: Randomized Controlled Trial (ONWARD-DPP4 Study).

INTRODUCTION: Preference for quality of life is important in deciding the treatment strategy for patients with type 2 diabetes mellitus. This study aimed to assess the effect of omarigliptin on patients' psychological attitudes and responses compared with daily dipeptidyl peptidase-4 inhibitors (DPP4is) by measuring the burden of pharmacotherapy using the Diabetic Treatment Burden Questionnaire (DTBQ). METHODS: Patients with type 2 diabetes mellitus who were taking daily DPP-4is were enrolled and randomized to a group that switched to omarigliptin or a group that continued daily DPP4is and were monitored for 12 weeks. The primary endpoint was the change in the DTBQ score from baseline to week 12. The secondary endpoints included changes in blood test results, medication preferences and medication adherence. RESULTS: The DTBQ total score significantly decreased from baseline to week 12 in both groups; however, no significant intergroup differences were observed. The DTBQ subscale, implementation and flexibility burden scores significantly decreased in the group that switched to omarigliptin, although no significant intergroup difference in the change was observed. DTBQ scores and medication preferences were associated with improvements in the DTBQ scores. CONCLUSION: Although this study failed to demonstrate the improvement of DTBQ total score by switching from daily DPP4is to omarigliptin compared with continuing the daily DPP4is, the DTBQ subscale score implementation and flexibility burden score were significantly improved only in the group that switched to omarigliptin, suggesting the possibility of switching from daily DPP4is to omarigliptin to decrease the patients' medication burden. TRIAL REGISTRATION: jRCTs031200437.

Marked Increase in Urinary C-peptide Levels after Treatment with Sacubitril/Valsartan in Patients with Type 2 Diabetes Mellitus and Hypertension.

Sacubitril/valsartan, a novel therapy in chronic heart failure (CHF), inhibits the breakdown of various peptides. However, whether or not sacubitril/valsartan administration affects urinary C-peptide levels is unclear. We herein report a 70-year-old man with type 2 diabetes mellitus (T2DM) and hypertension coexisting with CHF and nephrotic syndrome. The patient's urinary C-peptide levels dramatically increased after sacubitril/valsartan administration and decreased after discontinuation of the drug. Furthermore, sacubitril/valsartan administration to five other patients with hypertension and T2DM markedly increased urinary C-peptide levels. Thus, the insulin secretory capacity of patients with T2DM receiving sacubitril/valsartan may be overestimated when their urinary C-peptide level is measured.

Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study.

AIM: To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria. METHODS: The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope. RESULTS: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g. CONCLUSIONS: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria.

Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation.

Rapidly progressive in-stent restenosis (ISR) after stent deployment from the left main trunk (LMT) to the left anterior descending artery (LAD) without plaque at the LMT ostium has not been reported. A 60-year-old Japanese man with a history of scleroderma, pulmonary fibrosis, and type 2 diabetes developed acute myocardial infarction of the right coronary artery (RCA) and was treated by emergency percutaneous coronary intervention (PCI) for RCA. Nine days later he underwent PCI from the LMT to the LAD. Follow-up coronary angiography (CAG) at 9 and 21 months post-PCI did not reveal ISR in any lesion, but the patient experienced cardiac arrest at 25 months post-PCI. Emergency CAG after resuscitation revealed ISR of the LMT ostium; emergency PCI was conducted. The development of ISR at the ostium of the LMT although the patient was free of plaque 4 months before is extremely unusual. This rare ISR of the LMT ostium progressed rapidly after follow-up CAG revealed no ISR at 21 months post-stent implantation.

Impact of COVID-19 pandemic on glycemic control among outpatients with type 2 diabetes in Japan: A hospital-based survey from a country without lockdown.

AIMS: Some studies have reported changes in glycemic control of patients with diabetes mellitus under lockdown. However, no previous study examined the impact of the pandemic on glycemic control in patients with diabetes in countries that did not introduce a lockdown such as Japan. This study aimed to assess changes in glycemic control during the pandemic in patients with type 2 diabetes treated at a Japanese clinic. METHODS: We conducted a historical cohort study, using electronic medical records of patients with type 2 diabetes who visited our clinic between January 2019 and August 2020. Differences in HbA1c values before and after the outbreak of COVID-19 were the primary outcome, examined using the linear mixed model. RESULTS: HbA1c values significantly increased from 7.45% to 7.53% after the state of emergency was introduced (n = 1,009). Furthermore, a deterioration in HbA1c values was observed in particular among women, patients aged ≥ 65 years, those with body mass index of ≥ 25 kg/m2, and those that were not using insulin. CONCLUSIONS: Glycemic control deteriorated in patients with type 2 diabetes during the pandemic even in a country without a national lockdown.

Fibrosis-4 index reflects right ventricular function and prognosis in heart failure with preserved ejection fraction.

AIMS: Fibrosis-4 index (FIB-4 index), calculated by age, aspartate aminotransferase, alanine aminotransferase, and platelet count, is a simple marker to evaluate liver fibrosis and is associated with right-sided heart failure. However, the clinical relevance of FIB-4 in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear. We investigated the prognostic implication of the FIB-4 index regarding right ventricular dysfunction in patients with HFpEF. METHODS AND RESULTS: This prospective study included 116 consecutive HFpEF patients (mean age 79 years, 43% male) hospitalized with acute decompensated heart failure. We evaluated the association of the FIB-4 index with right ventricular function determined by tricuspid annular plane systolic excursion (TAPSE) and tricuspid lateral annular systolic velocity (S') before discharge. Cox regression analysis was performed to evaluate the association between the FIB-4 index and major adverse cardiovascular events (MACE) defined as the composite of cardiovascular death, readmission for heart failure, nonfatal myocardial infarction, and nonfatal stroke. FIB-4 index before discharge was significantly lower than that at admission (2.62 [1.92-3.46] and 3.03 [2.05-4.67], median [interquartile range], P < 0.001). Left ventricular ejection fraction, TAPSE, and S' before discharge were 62.7 (55.9-68.6) %, 17.5 ± 4.6 mm (mean ± standard deviation), and 10.0 (8.0-12.0) cm/s, respectively. In multiple linear regression analysis, the FIB-4 index before discharge was inversely correlated with TAPSE (ß minus;0.244, P = 0.014) and S' (ß -0.266, P = 0.009). During a median follow-up of 736 days, 37 MACE occurred. Multivariate Cox regression analysis revealed that a high FIB-4 index before discharge (per 1 point) was a significant predictor of MACE (hazard ratio 1.270, 95% confidence interval 1.052-1.532) after adjustment for male, serum creatinine, and haemoglobin. Receiver operating characteristic analysis indicated that the optimal cut-off value of FIB-4 index before discharge to predict MACE was 3.11. Kaplan-Meier survival analysis showed that patients with a FIB-4 index before discharge ≥3.11 had a significantly poorer prognosis than patients with FIB-4 index before discharge <3.11 (P = 0.029). Patients with an FIB-4 index ≥3.11 had a 2.202-fold (95% confidence interval 1.110-4.368) increased risk of MACE compared with those with an FIB-4 index <3.11 after adjustment for male, serum creatinine, and haemoglobin. CONCLUSIONS: An increase in the FIB-4 index was associated with right ventricular dysfunction and a higher risk of future MACE in patients with HFpEF.

Randomized trial of an intensified, multifactorial intervention in patients with advanced-stage diabetic kidney disease: Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan).

AIMS/INTRODUCTION: We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced-stage diabetic kidney disease (DKD). MATERIALS AND METHODS: The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan) is a multicenter, open-label, randomized controlled trial with a 5-year follow-up period. We randomly assigned 164 patients with advanced-stage diabetic kidney disease (urinary albumin-to-creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2-2.5 mg/dL in men and 1.0-2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end-stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention-to-treat population. RESULTS: The IT tended to reduce the risk of primary end-points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43-1.11; P = 0.13). Meanwhile, the decrease in serum low-density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05-1.23, P < 0.001 and hazard ratio 0.53, 95% confidence interval 0.28-0.998, P < 0.05, respectively). The incidence of adverse events was not different between treatment groups. CONCLUSIONS: The risk of kidney events tended to decrease by IT, although it was not statistically significant. Lipid control using statin was associated with a lower risk of adverse kidney events. Further follow-up study might show the effect of IT in patients with advanced diabetic kidney disease.