Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been attracting attention for cardiovascular as well as antidiabetic effects since the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME Trial) were reported. The hematocrit increases during treatment with SGLT2 inhibitors, which have a diuretic effect but do not cause sufficient hemoconcentration to increase the risk of cerebral infarction. Elevation of the hematocrit during SGLT2 inhibitor therapy is presumed to involve enhancement of erythropoiesis in addition to hemoconcentration. In patients with diabetes, the erythropoietin level increases after initiation of treatment with the SGLT2 inhibitor dapagliflozin and reaches a plateau in 2 -4 weeks. The reticulocyte count increases simultaneously, followed by elevation of hemoglobin and hematocrit. In patients with diabetes, the proximal tubules are overtaxed by excessive glucose reabsorption and the increased oxygen requirement causes tubulointerstitial hypoxia. Consequently, erythropoietin production is impaired because "neural crest-derived" fibroblasts surrounding the damaged renal tubules undergo transformation into dysfunctional fibroblasts. SGLT2 inhibitors reduce the workload of the proximal tubules and improve tubulointerstitial hypoxia, allowing fibroblasts to resume normal erythropoietin production. These drugs represent a new class of diuretics that have a renoprotective effect by improving tubulointerstitial hypoxia, which is the final common pathway to end-stage renal disease. In patients with diabetes, elevation of hematocrit may be a surrogate marker for recovery from reversible tubulointerstitial injury.

BackgroundAcute heart failure (AHF) is a heterogeneous condition, and its characteristics and management patterns differ by region. Furthermore, limited evidence is available on AHF outside of Western countries. A project by the National Consortium of Acute Heart Failure Registries was designed to evaluate the trends over time in patient backgrounds, in‐hospital management patterns, and long‐term outcomes of patients with AHF over 9 years in Japan.Methods and ResultsBetween 2007 and 2015, registry data for patients with AHF were collected from 3 large‐scale quality AHF registries (ATTEND/WET‐HF/REALITY‐AHF). Predefined end points were trends over time in age, sex, and clinical outcomes, including short‐ and long‐term mortality and readmission for heart failure. The final data set consisted of 9075 patients with AHF. No significant differences in patient backgrounds and laboratory findings (eg, anemia or renal function) were observed, with the exception of patient age; mean age became substantially higher over 9 years (71.6–77.0 years; P for trend, <0.001). On the contrary, length of hospital stay became shorter (mean, 26–16 days). These changes were not associated with in‐hospital mortality (4.7–7.5%) or 30‐day heart failure readmission rate (4.8–5.4%), as well as 1‐year mortality and heart failure readmission rate (20.1–23.3% and 23.6–26.2%, respectively).ConclusionsLength of hospital stay in patients with AHF shortened over the 9‐year period despite the increasing age of the patients. However, short‐ and long‐term outcomes do not seem to be affected; continuous efforts to monitor clinical outcomes in patients with AHF are needed.

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BackgroundIt has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real‐time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT).Methods and ResultsThirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO 2 at the HRVT (HRVT‐VO 2) was substantially correlated with the VO 2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P>0.05). Furthermore, the HRVT‐VO 2 was also correlated with the VT‐VO 2 in these myocardial infarction patients (r=0.867), and the mean difference was −0.72 mL/kg per minute and was nonsignificant (P>0.05).ConclusionsA HRV analysis with our method enabled real‐time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

The first clinical study has shown that HI during PCI is feasible and safe and may also promote LV reverse remodeling at 6 months after STEMI. The study was not powered to test efficacy and a further large-scale trial is warranted. (Clinical trials registration: UMIN00006825).