Search

Abstract: There were few clinical studies on the relationship between sodium glucose cotransporter 2 inhibitors (SGLT2i) and hematopoiesis in patients with diabetes (DM) and heart failure (HF) with consideration of systemic volume status. A total of 226 DM patients with HF enrolled in the CANDLE trial, a multicenter, prospective, randomized open-label blinded-endpoint trial, were studied. Estimated plasma volume status (ePVS) was calculated based on a weight- and hematocrit-based formula. At baseline, there was no significant difference in hematocrit and hemoglobin between the canagliflozin (n = 109) and glimepiride (n = 116) groups. Hematocrit and hemoglobin at 24 weeks, changes in hematocrit and hemoglobin difference (24 weeks-baseline), and hematocrit and hemoglobin ratio (24 weeks/baseline) were significantly higher in the canagliflozin than in the glimepiride group, respectively. There was no significant difference in ePVS at baseline and 24 weeks between the 2 groups. After adjustment for baseline parameters, canagliflozin correlated positively with changes in hematocrit and hemoglobin difference, and hematocrit and hemoglobin ratio by multivariate linear regression analyses. The difference in hematocrit and hemoglobin between the 2 groups became statistically significant at 3 and 6 months after randomization. There was no heterogeneity between canagliflozin and the characteristics of the patients for hematocrit and hemoglobin difference and ratio. A correlation of the changes in hematocrit and hemoglobin with cardiac and renal improvement was not observed. In conclusion, canagliflozin was associated with an increased hematocrit and hemoglobin in patients with diabetes and HF regardless of their volume status and characteristics., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Recent accumulating evidence reveals that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcome in patients with heart failure (HF), RV dysfunction, and pulmonary hypertension. However, the prognostic utility of RV-PA uncoupling in HF with preserved ejection fraction (HFpEF) remains elusive. In this study, we aim to investigate the associations of RV-PA uncoupling with outcomes of HFpEF inpatients., Methods: We prospectively studied 655 patients, registered in PURSUIT-HFpEF (The Prospective Multicenter Obervational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter observational study of Japanese HFpEF inpatients. We assigned registered patients based on the determined value of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio that can predict primary outcome as an indicator of RV-PA uncoupling., Results: Univariable Cox regression testing revealed that RV-PA uncoupling was associated with the primary endpoint of all-cause death, HF rehospitalization, and cerebrovascular events (hazard ratio [HR] 1.77 [95% CI, 1.34-2.32], P <0.0001) and the secondary endpoints of all-cause death and HF rehospitalization (HR 2.75 [95% CI, 1.77-4.33], P <0.0001, HR 1.63 [95% CI, 1.18-2.26], P =0.0036, respectively). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with primary endpoint and all-cause death independent of age, sex, atrial fibrillation, renal dysfunction, elevated E/e', and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) (HR 1.38 [95% CI, 1.01-1.88], P =0.0413, HR 1.85 [95% CI, 1.14-3.01], P =0.0129, respectively)., Conclusions: Prospective study of a hospitalized cohort revealed that RV-PA uncoupling was independently associated with adverse outcomes in acute decompensated patients with HFpEF. Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Rationale: Despite a recent decline of in-hospital mortality attributable to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Although various microRNAs have been proposed as diagnostic indicators for AMI, no microRNAs have been established as predictors of ischemic HF that develops after AMI., Objective: We attempted to identify circulating microRNAs that can serve as reliable predictors of ischemic HF in post-AMI patients., Methods and Results: Using sera collected a median of 18 days after AMI onset, we screened microRNAs in 21 patients who experienced development of HF within 1 year after AMI and in 65 matched controls without subsequent cardiovascular events after discharge. Among the 377 examined microRNAs, the serum level of only miR-192 was significantly upregulated in AMI patients with development of ischemic HF. Because miR-192 is reported to be p53-responsive, the serum levels of 2 other p53-responsive microRNAs, miR-194 and miR-34a, also were investigated. Interestingly, both microRNAs were coordinately increased with miR-192, particularly in exosomes, suggesting that these microRNAs function as circulating regulators of HF development via the p53 pathway. Furthermore, miR-194 and miR-34a expression levels were significantly correlated with left ventricular end-diastolic dimension 1 year after AMI., Conclusions: In the sera of post-AMI patients who experienced development of de-novo HF within 1 year of AMI onset, the levels of 3 p53-responsive microRNAs had been elevated by the early convalescent stage of AMI. Further investigations are warranted to confirm the usefulness of these circulating microRNAs for predicting the risk of development of ischemic HF after AMI.

Background: Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated., Methods and Results: We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type., Conclusions: DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

Objectives: Oestrogen has been shown to increase nitric oxide-mediated vasodilatation and modulate sympathetic tone in postmenopausal women. We investigated the acute effects of oestrogen on the coronary microcirculation in men., Methods: Myocardial blood flow was quantified using N-ammonia positron emission tomography before and 20 min after an intravenous administration of conjugated oestrogen (10 mg) in nine healthy men., Results: There were no significant changes in either systemic blood pressure or heart rate before and after oestrogen infusion. However, myocardial blood flow was increased by oestrogen from 0.88 +/-0.06 to 1.05+/-0.09 ml x g x min (P<0.05). Although serum levels of nitrite/nitrate (end products of nitric oxide) were not increased, circulating norepinephrine (noradrenaline) levels were decreased after the administration of oestrogen from 401+/-114 to 346+/-112 pg x ml (P<0.01). A significant negative correlation was found between myocardial blood flow and plasma norepinephrine levels (r=-0.67, P<0.05)., Conclusions: A single administration of oestrogen enhanced myocardial circulation in healthy men. The oestrogen-induced increase in myocardial blood flow may be due to direct effects on the coronary circulation or through the modulation of norepinephrine levels, rather than the production of nitric oxide.

Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged < or =50 years (n=10), and older men aged >50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; P<0.05 each). Although the age dependent impairment is thought to cause this depression, neither the per cent increase in EF nor the per cent decrease in VR in the older men was significantly different from that in the younger men. Post-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

Background: Several studies have associated depressive symptoms with an increased risk for cardiac events after the onset of acute myocardial infarction (AMI). The aim of the present study is to investigate the impact of the depressive symptoms on prognosis of the elderly patients with AMI., Method: Depression was assessed in consecutive patients with AMI (n = 1042; mean age 63 +/- 11 years) using the Zung Self-Rating Depression Scale (SDS). Patient with a score > or = 40 was classified as having depressive symptoms. Cardiac events (cardiac death, nonfatal re-MI, coronary angioplasty or bypass surgery, readmission for heart failure, unstable angina, or uncontrolled arrhythmia) were examined during 12 months follow-up period., Results: Depressive symptoms were observed in 438 patients (42.0%). Prevalence of depression was not dependent of age (P = 0.60) and gender (P = 0.91). The rate of cardiac events was 31.2% per year in patients with depressive symptoms whereas 23.9% per year in patients without depressive symptoms. Multiple logistic regression analyses showed that depression was significantly associated with 1-year cardiac events (odds ratio 1.41, 95% CI 1.03 to 1.92, P = 0.03) after controlling for age, gender, severity of myocardial infarction, coronary risk factors, e.g. hypertension, diabetes mellitus and smoking habits. Depression was a significant risk factor for the cardiac events (log rank, P = 0.02) in the elderly patients (> or = 65 years old, 501 patients). However, the association of depression with cardiac events in the young patients (< 65 years old, 541 patients) was not statistically significant (P = 0.11)., Conclusion: Depression after AMI is a significant predictor of 1-year cardiac events for Japanese population, and its presence augments the risk especially in the elderly patients.