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1.
J Clin Med ; 13(5)2024 Mar 04.
Article En | MEDLINE | ID: mdl-38592314

Background: We conducted a systematic review and meta-analysis to examine the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo lesions in patients with acute coronary syndrome (ACS) by comparing with drug-eluting stent (DES) placement. Methods: By a systematic literature search, nine (five randomized controlled, two retrospective propensity-score matched, and two retrospective baseline-balanced) studies comparing the midterm clinical and angiographic outcomes after PCB angioplasty and DES placement were included, yielding 974 and 1130 ACS cases in PCB and DES groups, respectively. Major adverse cardiac event (MACE) was defined as a composite of cardiac mortality (CM), all-cause mortality (ACM), myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR). Late luminal loss (LLL) and bleeding events (BLD) were also estimated. Results: The frequencies of MACE in PCB and DES groups were 8.42% and 10.62%, respectively. PCB angioplasty had no significant impacts on all of MACE (risk ratio: 0.90, 95%CI: 0.68-1.18, p = 0.44), CM, ACM, MI, TVR, TLR, BLD, and LLL, compared to DES placement in random-effects model. Conclusions: The present systematic review and meta-analysis showed the feasibility of PCB angioplasty for the de novo lesions in patients with ACS in comparison with DES placement by the emergent procedures.

2.
Circulation ; 149(8): 585-600, 2024 02 20.
Article En | MEDLINE | ID: mdl-37994553

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.


Acute Coronary Syndrome , Aspirin/analogs & derivatives , Nitrates , Percutaneous Coronary Intervention , Thrombosis , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Platelet Aggregation Inhibitors/adverse effects , Prasugrel Hydrochloride/adverse effects , Acute Coronary Syndrome/drug therapy , Percutaneous Coronary Intervention/adverse effects , Drug Therapy, Combination , Aspirin/adverse effects , Hemorrhage/etiology , Stents , Thrombosis/epidemiology , Thrombosis/etiology , Thrombosis/prevention & control , Treatment Outcome
3.
Eur J Med Res ; 28(1): 238, 2023 Jul 17.
Article En | MEDLINE | ID: mdl-37461063

INTRODUCTION: Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. METHODS: This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. RESULTS: Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was - 35.8% (95% confidence interval [CI] - 39.7% to - 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. CONCLUSION: In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad. Trial registration jRCTs021210013, registration date June 24, 2021.


Hypertension , Hyperuricemia , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Female , Hyperuricemia/drug therapy , Uric Acid , Prospective Studies , Uricosuric Agents/therapeutic use , Hypertension/drug therapy
4.
Int Heart J ; 64(2): 145-153, 2023.
Article En | MEDLINE | ID: mdl-37005310

We retrospectively examined the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo stenosis in large coronary vessels (LV; pre- or postprocedural reference vessel diameter ≥ 2.75 mm) in comparison with placement of drug-eluting stents (DESs).Consecutive de novo stenotic lesions in the LV electively and successfully treated with either PCB (n = 73) or DESs (n = 81) from January 2016 to December 2018 at our center were included. The primary endpoint was the incidence of target lesion failure (TLF), including cardiac death, nonfatal myocardial infarction, and target vessel revascularization. The impact of PCB on TLF was examined using Cox proportional hazards models by including 39 variables. The secondary endpoint, angiographic restenosis, defined as a follow-up percent diameter stenosis > 50, was examined in angiographic follow-up lesions after PCB angioplasty (n = 56) and DES placement (n = 53). This retrospective investigation was conducted in July 2022.The mean PCB size and length were 3.23 ± 0.42 and 18.4 ± 4.3 mm, respectively. The TLF frequency in the PCB group (6.8% during the mean observational interval of 1536 ± 538 days) was not significantly different from that in the DES group (14.6%, 1344 ± 606 days, P = 0.097). PCB was not a significant predictor of TLF in the univariate analysis (hazard ratio: 0.424; 95%CI: 0.15-1.21; P = 0.108). There was no angiographic restenosis after PCB angioplasty.The present observational single-center study showed that PCB for de novo stenosis in the LV had no significant adverse impact on TLF and had favorable angiographic outcomes.


Angioplasty, Balloon, Coronary , Coronary Artery Disease , Coronary Restenosis , Drug-Eluting Stents , Humans , Coronary Artery Disease/complications , Paclitaxel/pharmacology , Drug-Eluting Stents/adverse effects , Retrospective Studies , Constriction, Pathologic , Coronary Angiography/adverse effects , Treatment Outcome , Angioplasty, Balloon, Coronary/adverse effects , Coronary Restenosis/epidemiology , Coronary Restenosis/etiology , Stents/adverse effects
6.
Circ Rep ; 5(4): 123-132, 2023 Apr 10.
Article En | MEDLINE | ID: mdl-37025938

Background: The prognostic impact of CHADS2, CHA2DS2-VASc, and CHA2DS2-VASc-HS scores on clinical outcomes after drug-eluting stent (DES) placement has not been fully elucidated. Methods and Results: The present study was a retrospective, non-randomized, single-center, and lesion-based study. Target lesion failure (TLF), comprising cardiac death, non-fatal myocardial infarction, and target vessel revascularization, occurred in 7.1% of 872 consecutive de novo coronary lesions in 586 patients. These patients were electively and exclusively treated by DESs from January 2016 to January 2022 until July 2022 with a mean (±SD) observational interval of 411±438 days. Multivariate Cox proportional hazard analysis revealed that CHA2DS2-VASc-HS scores ≥7 (hazard ratio [HR] 1.800; 95% CI 1.06-3.05; P=0.029) was a significant predictor of cumulative TLF among 24 variables evaluated. CHADS2 scores ≥2 (HR 3.213; 95% CI 1.32-7.80; P=0.010) and CHA2DS2-VASc scores ≥5 (HR 1.980; 95% CI 1.10-3.55; P=0.022) were also significant in the multivariate analysis. Pairwise comparisons of receiver operating characteristic curves for CHADS2 score ≥2, CHA2DS2-VASc score ≥5, and CHA2DS2-VASc-HS score ≥7 showed they were equivalent in terms of predicting the incidence of TLF, with areas under the curve of 0.568, 0.575, and 0.573, respectively. Conclusions: All 3 cardiocerebrovascular thromboembolism risk scores were strong predictors of the incidence of cumulative mid-term TLF after elective DES placement, with cut-off values of 2, 5, and 7, respectively, and equivalent prognostic impacts.

7.
Heart Vessels ; 38(5): 711-720, 2023 May.
Article En | MEDLINE | ID: mdl-36446927

Preventing phrenic nerve injury (PNI) during balloon-based ablation is essential. The superior vena cava-right atrial (SVC-RA) junction is located just opposite the balloon position during right superior pulmonary vein (RSPV) ablation, and the phrenic nerve runs nearby on the lateral side. We compared the occurrence of PNI between the two balloon-based ablation systems and also the lesions created at the SVC-RA junction, which were expected to represent the effect on extra-PV structures. Cryoballoon ablation (CBA, n = 110) and hot-balloon ablation (HBA, n = 90) were performed in atrial fibrillation patients. High-density maps of the SVC-RA junction were created in 93 patients (CBA = 53, HBA = 40), and the damaged area (< 1.0 mV) was determined as an "SVC lesion". CBA had a higher occurrence of transient PNI (7.3% vs 1.1%, p = 0.035), but all recovered during the 6-month follow-up. An apparent SVC lesion was documented in 43% of the patients (40/93), and all patients with PNI had this lesion. CBA created a frequent (CBA vs HBA = 55% vs 28%, p = 0.008) and wider (0.8[0.4-1.7] cm2 vs 0.5[0.3-0.7] cm2, p = 0.005) SVC lesion than HBA. A multivariate analysis revealed that the use of a CBA system was a predictive factor of the occurrence of SVC lesions. CBA had a higher occurrence of transient PNI but not a permanent form. Every patient with PNI had lesions on the SVC-RA junction, and CBA revealed more substantial ablation effects at the SVC-RA junction than HBA. This may be caused by the different characteristics of the two balloon-based ablation systems and their balloon positions.


Atrial Fibrillation , Catheter Ablation , Cryosurgery , Pulmonary Veins , Humans , Vena Cava, Superior/surgery , Phrenic Nerve/injuries , Cryosurgery/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Pulmonary Veins/surgery , Biomarkers , Catheter Ablation/adverse effects , Treatment Outcome
8.
J Interv Card Electrophysiol ; 66(3): 701-710, 2023 Apr.
Article En | MEDLINE | ID: mdl-36251130

BACKGROUND: Despite reports of remote pulmonary vein (PV) stenosis after visually guided laser balloon (VGLB) ablation, circumferential (360°) lesion sets are routinely performed. This study aimed to determine whether fully circumferential lesion creations are required for all PVs to achieve PV isolations (PVIs) and to determine PV's vulnerability to chronic-phase stenosis. METHODS: Fifty-one patients with paroxysmal atrial fibrillation underwent mapping-guided PVIs using circular mapping catheters. VGLB ablation was performed circumferentially beginning at the 12 o'clock position and continued clockwise or counterclockwise. PVIs obtained within the bounds of the first half of the circumferential lesion (≤ 180°) were defined as "early PVIs." RESULTS: "Early PVIs" were documented in real time for 39% (80/204) of the PVs and at a significantly greater frequency among lower PVs than upper PVs (60.1% vs. 17.6%; p < 0.0001). The PV sleeve length, PV diameter, and isolation of ipsilateral PVs within a semicircular lesion set were identified as predictors of an "early PVI" phenomenon. The amount of energy delivered to the lower PVs was significantly less than that to the upper PVs (5553 [5089-6188] vs. 3559 [2793-4380] J; p < 0.0001), but the incidence of narrowing of the lower PVs at 6 months was comparable to that of the upper PVs (p = 0.73). CONCLUSION: Our study revealed electrical isolations of more than 60% of the lower PVs while creating the first half of the circumferential lesions. Crosstalk via the carina region was presumably involved due to the preceding upper PVI. Further study is needed to determine whether energy delivery adjustments are needed for lower PVs to avoid chronic narrowing.


Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Stenosis, Pulmonary Vein , Humans , Pulmonary Veins/surgery , Constriction, Pathologic , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Stenosis, Pulmonary Vein/surgery , Lasers , Treatment Outcome
9.
Hypertens Res ; 46(2): 495-506, 2023 02.
Article En | MEDLINE | ID: mdl-36380202

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of heart failure progression and mortality rates. Moreover, osmotic diuresis induced by SGLT2 inhibition may result in an improved heart failure prognosis. Independent of conventional diuretics in patients with type 2 diabetes (T2D) and chronic heart failure, especially in patients with heart failure with preserved ejection fraction (HFpEF), it is unclear whether SGLT2i chronically reduces estimated plasma volume (ePV). As a subanalysis of the CANDLE trial, which assessed the effect of canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP), we examined the change (%) in ePV over 24 weeks of treatment based on the baseline level associated with diuretic usage. In the CANDLE trial, nearly all patients were clinically stable (NYHA class I-II), with approximately 70% of participants presenting a baseline phenotype of HFpEF. A total of 99 (42.5%) patients were taking diuretics (mostly furosemide) at baseline, while 134 (57.5%) were not. Relative to glimepiride, canagliflozin significantly reduced ePV without worsening renal function in patients in both groups: -4.00% vs. 1.46% (p = 0.020) for the diuretic group and -6.14% vs. 1.28% (p < 0.001) for the nondiuretic group. Furthermore, canagliflozin significantly reduced serum uric acid without causing major electrolyte abnormalities in patients in both subgroups. The long-term beneficial effect of SGLT2i on intravascular congestion could be independent of conventional diuretic therapy without worsening renal function in patients with T2D and HF (HFpEF predominantly). In addition, the beneficial effects of canagliflozin are accompanied by improved hyperuricemia without causing major electrolyte abnormalities.


Diabetes Mellitus, Type 2 , Heart Failure , Humans , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/complications , Heart Failure/drug therapy , Diuretics/therapeutic use , Plasma Volume , Uric Acid , Stroke Volume/physiology , Chronic Disease , Electrolytes
10.
J Cardiol ; 81(6): 537-543, 2023 06.
Article En | MEDLINE | ID: mdl-36481299

BACKGROUND: The safety and efficacy of elective drug-coated balloon (DCB) angioplasty for unrestrictive de novo coronary stenosis in daily practice is not fully understood, especially in comparison to those of drug-eluting stents (DESs). METHODS: A total of 588 consecutive de novo coronary stenotic lesions electively and successfully treated with either DCB (n = 275) or DESs (n = 313) between January 2016 and December 2019 at our medical center were included. The primary safety endpoint was the incidence of target lesion failure (TLF), comprising cardiac death, non-fatal myocardial infarction, and target vessel revascularization. The secondary angiographic efficacy endpoint was angiographic restenosis frequency, defined as a follow-up percent diameter stenosis of >50. The endpoints were compared after baseline adjustment using propensity score matching. In addition, the frequency and predictors of late lumen enlargement (LLE), defined as minus late luminal loss, were examined in 201 crude angiographic follow-up lesions after DCB angioplasty. RESULTS: A total of 31 baseline parameters were adjusted to analyze 177 lesions in each group. The TLF frequencies (DCB group: 9.6 % during a mean observational interval of 789 ±â€¯488 days vs. DES group: 10.2 %, 846 ±â€¯484 days, p = 0.202) and cumulative TLF-free ratios of both groups were not significantly different (p = 0.892, log-rank test). The angiographic restenosis frequency in the DCB group (6.3 %, n = 128) was not significantly different from that of the DES group (10.1 %, n = 100, p = 0.593). LLE was observed in 45.3 % of entire lesions, and a type-A dissection was a significant predictor of LLE among 23 variables (odds ratio: 3.02, 95 % CI: 1.31-6.95, p = 0.010). CONCLUSIONS: The present single-center retrospective study revealed statistically equivalent midterm clinical safety and angiographic efficacy among both elective DCB angioplasty and DESs placements in the treatment of unrestrictive de novo coronary lesions. In our daily practice environment, LLE was achieved in approximately half after DCB angioplasty.


Angioplasty, Balloon, Coronary , Coronary Artery Disease , Coronary Restenosis , Drug-Eluting Stents , Myocardial Infarction , Humans , Drug-Eluting Stents/adverse effects , Retrospective Studies , Angioplasty, Balloon, Coronary/adverse effects , Myocardial Infarction/etiology , Treatment Outcome , Coronary Restenosis/etiology , Coronary Restenosis/therapy , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/complications , Coronary Angiography/adverse effects
11.
Int Heart J ; 63(2): 217-225, 2022 Mar 30.
Article En | MEDLINE | ID: mdl-35185090

We conducted a single-center, retrospective, lesion-based study to examine the safety and efficacy of drug-coated balloons (DCBs) for de novo coronary stenosis in patients with acute coronary syndrome (ACS) by comparing them with those of drug-eluting stents (DESs).A total of 309 consecutive lesions in patients with ACS who were successfully treated by emergent procedures using either a DCB (n = 107) or a DES between January 2016 and December 2019 were included in the study. The primary endpoint was the incidence of target lesion failure (TLF), defined as cardiac death without mortality due to ACS, non-fatal myocardial infarction, and any target lesion revascularization, including acute occlusion, after DCB use and definite stent thrombosis after DES placement. A propensity score-matched analysis was used to adjust the 36 baseline variables. Retrospective investigations were conducted in January 2021.Baseline adjustment yielded 91 lesions in each group, with a mean balloon size of 3.02 ± 0.22 mm and a mean length of 20.9 ± 6.2 mm in the DCB group. The frequency of TLF in the DCB group (9.9% during the mean observational interval of 671 ± 508 days) was not significantly different from that in the DES group (13.2% during a period of 626 ± 543 days, P = 0.467). The cumulative TLF-free ratio in the DCB group was not significantly different from that in the DES group (P = 0.475, log-rank test).The present propensity score-matched comparison showed statistically equivalent midterm clinical outcomes after DCB use to those of DES placement for de novo lesions in patients with ACS treated by emergent procedures.


Acute Coronary Syndrome , Coronary Artery Disease , Coronary Restenosis , Drug-Eluting Stents , Myocardial Infarction , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/surgery , Coated Materials, Biocompatible , Coronary Artery Disease/complications , Coronary Restenosis/etiology , Drug-Eluting Stents/adverse effects , Humans , Myocardial Infarction/complications , Propensity Score , Retrospective Studies , Treatment Outcome
12.
J Atheroscler Thromb ; 28(7): 696-702, 2021 Jul 01.
Article En | MEDLINE | ID: mdl-32908115

AIM: We examined the impact of baseline high-density lipoprotein cholesterol efflux capacity (CEC) on major cardiac adverse events (MACE) in patients with coronary artery disease (CAD) during a long-term secondary prevention. METHOD: CEC was measured using a cell-based efflux system in (3)[H]-cholesterol-labeled J774 macrophages in apolipoprotein B-depleted plasma between January 2011 and January 2013. Patients with CAD were divided into 2 groups as a boundary CEC value of 1: 0.19 ≤ CEC <1 (impaired CEC group, mean CEC of 0.76±0.16, n=136), and 1 ≤ CEC ≤ 2.08 (enhanced CEC group, 1.20±0.19, n=44). MACE, comprised the incidence of cardiac death, non-fatal myocardial infarction, and any revascularizations (RV) without restenosis approximately 1 year after vascularization, was retrospectively investigated at September 2019. Impact of enhanced CEC on MACE among 22 variables was examined by applying a Cox proportional hazard model. RESULT: The frequency of MACE in impaired CEC group (16.9%, mean observational interval of 2111±888 days) was significantly higher than that in enhanced CEC group (2.3%, 2,252±685, p=0.013), largely driven by the significantly higher RV incidence (14.0 % versus 2.3 %, p=0.032). Enhancement of CEC was the significant predictor of MACE (hazard ratio: 0.11; 95% CI: 0.013-0.879; p=0.038). CONCLUSION: A baseline CEC level of more than 1 in patients with CAD brought favorable long-term clinical outcomes, suggesting that CEC is a useful prognostic and therapeutic surrogate for secondary prevention of CAD.


Cholesterol, HDL , Coronary Artery Disease , Coronary Restenosis/prevention & control , Macrophages , Myocardial Revascularization , Secondary Prevention , Aged , Biomarkers/analysis , Cardiometabolic Risk Factors , Cholesterol, HDL/blood , Cholesterol, HDL/metabolism , Coronary Angiography/statistics & numerical data , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Artery Disease/surgery , Female , Humans , Japan/epidemiology , Macrophages/metabolism , Macrophages/pathology , Male , Myocardial Revascularization/adverse effects , Myocardial Revascularization/statistics & numerical data , Predictive Value of Tests , Prognosis , Secondary Prevention/methods , Secondary Prevention/statistics & numerical data , Transcytosis
13.
J Diabetes Investig ; 11(6): 1551-1563, 2020 Nov.
Article En | MEDLINE | ID: mdl-32537887

AIMS/INTRODUCTION: Recent clinical trials on sodium-glucose cotransporter 2 inhibitors showed improved outcomes in patients with type 2 diabetes at a high risk of cardiovascular events. However, the underlying effects on endothelial function remain unclear. MATERIALS AND METHODS: The effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi-center placebo-controlled double-blind randomized (EMBLEM) trial in patients with type 2 diabetes and cardiovascular disease showed empagliflozin treatment for 24 weeks had no effect on peripheral endothelial function measured by reactive hyperemia peripheral arterial tonometry. This post-hoc analysis of the EMBLEM trial included a detailed evaluation of the effects of empagliflozin on peripheral endothelial function in order to elucidate the clinical characteristics of responders or non-responders to treatment. RESULTS: Of the 47 patients randomized into the empagliflozin group, 21 (44.7%) showed an increase in the reactive hyperemia index (RHI) after 24 weeks of intervention, with no apparent difference in the clinical characteristics between patients whose RHI either increased (at least >0) or did not increase. There was also no obvious difference between the treatment groups in the proportion of patients who had a clinically meaningful change (≥15%) in log-transformed RHI. No correlation was found between changes in RHI and clinical variables, such as vital signs and laboratory parameters. CONCLUSIONS: Treatment with empagliflozin for 24 weeks in patients with type 2 diabetes and cardiovascular disease did not affect peripheral endothelial function, and was not related to changes in clinical variables, including glycemic parameters. These findings suggest that the actions of sodium-glucose cotransporter 2 inhibitors other than direct improvement in peripheral endothelial function were responsible, at least in the early phase, for the clinical benefits found in recent cardiovascular outcome trials.


Benzhydryl Compounds/therapeutic use , Biomarkers/analysis , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Endothelium, Vascular/drug effects , Glucosides/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Aged , Blood Glucose/analysis , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Double-Blind Method , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Prognosis , Prospective Studies
14.
ESC Heart Fail ; 7(4): 1585-1594, 2020 08.
Article En | MEDLINE | ID: mdl-32349193

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.


Diabetes Mellitus, Type 2 , Heart Failure , Canagliflozin , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/drug therapy , Humans , Natriuretic Peptide, Brain , Stroke Volume , Ventricular Function, Left
16.
Int Heart J ; 58(6): 1020-1023, 2017 Dec 12.
Article En | MEDLINE | ID: mdl-29162777

Here, we report on a healthy 30-year-old man with no significant medical history, who tested negative for human immunodeficiency virus antigenemia but developed Aspergillus pancarditis. A case of this kind is extremely rare, and to the best of our knowledge, this is the first report of a patient with Aspergillus pancarditis, which generally leads to a very poor outcome, who had a long-term favorable clinical course. A biopsy from the right atrium of hypertrophied atrial septum was essential for obtaining the definitive diagnosis. Long-term administration of an effective antifungal oral agent might account for the patient's favorable outcome.


Antifungal Agents/administration & dosage , Aspergillosis/drug therapy , Heart Diseases/microbiology , Voriconazole/administration & dosage , Adult , Heart Diseases/drug therapy , Humans , Male
17.
Circ J ; 80(3): 657-62, 2016.
Article En | MEDLINE | ID: mdl-26821581

BACKGROUND: Percutaneous coronary intervention (PCI) is an effective treatment for patients with ischemic heart disease. In particular, restenosis is suppressed after drug-eluting stent (DES) implantation. However, several problems remain. Previously, we reported neointimal proliferation after DES implantation, which was associated with insulin resistance (IR). The aim of the present study was to clarify whether IR is associated with mortality and major adverse cardiac and cerebrovascular events (MACCE) after 1st-generation DES implantation. METHODS AND RESULTS: We researched the clinical records of 109 patients who had undergone elective PCI and DES implantation between May 2007 and December 2010. We segregated these patients according to the value of the homeostasis model assessment of IR (HOMA-IR) into Group P (n=63; HOMA-IR ≥2.5, positive) and Group N (n=46; HOMA-IR <2.5, negative), and examined the relationship between HOMA-IR and MACCE. The observation period was 7.4±1.6 years. There were no differences between the 2 groups in the occurrence of all-cause death, cardiac death, restenosis, myocardial infarction, stroke, heart failure, or stent thrombosis. However, the late catch-up phenomenon was significantly more common in Group P than in Group N (12.7% vs. 2.2% P=0.048). CONCLUSIONS: IR is a useful predictor of the late catch-up phenomenon after DES implantation, and improvement of IR may help to prevent the phenomenon. (Circ J 2016; 80: 657-662).


Drug-Eluting Stents , Graft Occlusion, Vascular , Insulin Resistance , Myocardial Ischemia/surgery , Neointima , Aged , Female , Follow-Up Studies , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/pathology , Humans , Male , Middle Aged , Myocardial Ischemia/pathology , Neointima/etiology , Neointima/pathology , Predictive Value of Tests
18.
Hypertens Res ; 38(11): 765-9, 2015 Nov.
Article En | MEDLINE | ID: mdl-26178150

Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients' prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6 mg ml(-1), P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65 U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress.


Antihypertensive Agents/therapeutic use , Biphenyl Compounds/therapeutic use , Hypertension/drug therapy , Oxidative Stress/drug effects , Tetrazoles/therapeutic use , Uric Acid/blood , Aged , Aged, 80 and over , Antihypertensive Agents/pharmacology , Biphenyl Compounds/pharmacology , Female , Humans , Hypertension/blood , Irbesartan , Male , Middle Aged , Tetrazoles/pharmacology
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