Publications by authors named "Shintaro Dobashi"

18 Publications

  • Page 1 of 1

Efficacy and Safety of Ivabradine in an Elderly Patient with Heart Failure with Reduced Ejection Fraction.

Clin Drug Investig 2021 Feb 27;41(2):193-196. Epub 2021 Jan 27.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

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http://dx.doi.org/10.1007/s40261-021-01004-xDOI Listing
February 2021

The serum angiotensin-converting enzyme 2 and angiotensin-(1-7) concentrations after optimal therapy for acute decompensated heart failure with reduced ejection fraction.

Biosci Rep 2020 06;40(6)

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

Objective: Elucidation of the role of angiotensin-converting enzyme (ACE) 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor axis in heart failure is necessary. No previous study has reported serial changes in ACE2 and Ang-(1-7) concentrations after optimal therapy (OT) in acute heart failure (AHF) patients. We aimed to investigate serial changes in serum ACE2 and Ang-(1-7) concentrations after OT in AHF patients with reduced ejection fraction (EF).

Methods: ACE2 and Ang-(1-7) concentrations were measured in 68 AHF patients with reduced EF immediately after admission and 1 and 3 months after OT. These parameters were compared with the healthy individuals at three time points.

Results: In the acute phase, Ang-(1-7) and ACE2 concentrations was statistically significantly lower and higher in AHF patients than the healthy individuals (2.40 ± 1.11 vs. 3.1 ± 1.1 ng/ml, P<0.005 and 7.45 ± 3.13 vs. 4.84 ± 2.25 ng/ml, P<0.005), respectively. At 1 month after OT, Ang-(1-7) concentration remained lower in AHF patients than the healthy individuals (2.37 ± 1.63 vs. 3.1 ± 1.1 ng/ml, P<0.05); however, there was no statistically significant difference in ACE2 concentration between AHF patients and the healthy individuals. At 3 months after OT, there were no statistically significant differences in Ang-(1-7) and ACE2 concentrations between AHF patients and the healthy individuals.

Conclusion: ACE2 concentration was equivalent between AHF patients and the healthy individuals at 1 and 3 months after OT, and Ang-(1-7) concentration was equivalent at 3 months after OT.
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http://dx.doi.org/10.1042/BSR20192701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295637PMC
June 2020

Cardio-ankle vascular index predicts the 1-year prognosis of heart failure patients categorized in clinical scenario 1.

Heart Vessels 2020 Nov 26;35(11):1537-1544. Epub 2020 May 26.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

The sudden increase in blood pressure by vascular dysfunction is associated with the development of acute decompensated heart failure (ADHF) categorized in clinical scenario (CS) 1. However, the relationship between vascular function and prognosis in ADHF patients with CS1 is unclear. 3239 consecutive ADHF patients between January 2012 and June 2018 were enrolled. ADHF patients with CS1 undergoing ankle brachial index/cardio-ankle vascular index (CAVI) were included and patients with peripheral artery disease were excluded. Finally, 113 patients were analyzed. The primary endpoint of the present study was composite endpoint at 1 year (the cardiac death or re-hospitalization by ADHF). Cox proportional hazard analysis was conducted to identify independent predictors of composite endpoint. 25 patients (22.1%) were developed composite endpoint. CAVI in patients who have composite endpoint were significantly higher than without non-composite endpoint (composite endpoint group: 9.9 ± 1.3 non-composite endpoint group 8.7 ± 1.7, P = 0.001). The composite endpoint group was elderly and had higher ejection fraction, lower hemoglobin, and less used beta blockers, and renin angiotensin aldosterone system inhibitors. After adjustment by these confounding factors, CAVI was independently associated with the occurrence of composite endpoint (hazard ratio 1.69, 95% CI 1.05-2.73, P = 0.032). A cut-off value of CAVI for predicting composite endpoint was 8.65 (sensitivity 0.444, specificity 0.920, area under the curve 0.724, 95% CI 0.614-0.834). High CAVI was associated with the occurrence of composite endpoint after CS1 ADHF.
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http://dx.doi.org/10.1007/s00380-020-01633-wDOI Listing
November 2020

Bisoprolol transdermal patch improves orthostatic hypotension in patients with chronic heart failure and hypertension.

Clin Exp Hypertens 2020 Aug 2;42(6):539-544. Epub 2020 Feb 2.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine , Tokyo, Japan.

β blockers (BBs) play an important role in heart failure (HF) treatment. However, orthostatic hypotension (OH) is sometimes caused by BBs. The bisoprolol transdermal patch works more slowly and is long acting compared with the bisoprolol fumarate tablet. The risk of OH may be reduced by using the bisoprolol transdermal patch. We evaluated 57 consecutive patients who were taking the bisoprolol fumarate tablet for chronic HF with hypertension from November 2016 to September 2017. We switched the patients to the bisoprolol transdermal patch. Because 12 of 57 subjects could not continue using the bisoprolol transdermal patch, we analyzed the remaining 45 patients. We investigated BP, blood tests, and changes in BP from supine to standing positions before and after 6 months of switching from tablet to patch. OH was diagnosed by observing a systolic/diastolic BP drop of at least 20/10 mmHg or an absolute systolic BP (sBP) of <90 mmHg from the standing position. No significant changes were observed in the BP and BPs from supine to standing positions, whereas log brain natriuretic peptide was significantly reduced after switching from patch to tablet (2.102 to 2.070pg/dl, = .039). OH, which occurred in originally 17 patients, showed improvement and eventually appeared in 4 patients. In these patients, changes in BP from supine to standing positions were also significantly improved (changes in sBP, -11 to -6mmHg, = .016). This study demonstrated that switching from the bisoprolol fumarate tablet to transdermal patch reduced the morbidity of OH in HF patients.
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http://dx.doi.org/10.1080/10641963.2020.1723616DOI Listing
August 2020

Comparing the effects of milrinone and olprinone in patients with congestive heart failure.

Heart Vessels 2020 Jun 21;35(6):776-785. Epub 2019 Dec 21.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.

Phosphodiesterase-3 (PDE3) inhibitors are widely used among patients with congestive heart failure (CHF). However, no studies have compared the cardiovascular outcomes between different PDE3 inhibitors in CHF management. In this report, we retrospectively compared the clinical benefits of two PDE3 inhibitors, milrinone and olprinone, to determine which better controls the progression of CHF. A total of 288 hospitalized patients who received PDE3 inhibitors [(milrinone; n = 77 and olprinone; n = 211, respectively)] for CHF were retrospectively enrolled. The primary endpoint was defined as having a major adverse cardiovascular and cerebrovascular event (MACCE) or cardiac death by day 60. Kaplan-Meier curves and multivariate Cox proportional models were used to compare the outcomes for patients treated with milrinone and olprinone. We found no significant differences in the baseline characteristics between the two groups. In patients treated with milrinone, a greater incidence of a MACCE or cardiac death was observed (log rank; P = 0.005 and P = 0.01, respectively). Milrinone-treated patients with ischemic heart disease and chronic kidney disease (CKD) at stage ≥ 4 presented with greater incidence of MACCE (log rank; P < 0.001 and P = 0.006, respectively). Similarly, these patients were significantly more likely to succumb to cardiac death (log rank; P < 0.001 and P = 0.02). Multivariate Cox proportional hazard models demonstrated that milrinone treatment was an independent predictor of MACCE [hazard ratio (HR) 3.17; 95% CI 1.64-6.10] and cardiac death (HR 2.64; 95% CI 1.42-4.91). Oral administration of a β-blocker at discharge occurred more often in the olprinone-treated patients than in the milrinone-treated patients (63% vs. 29%, P = 0.004). We compared the outcomes of milrinone and olprinone treatment in patients with CHF. Those treated with milrinone were more likely to succumb to a MACCE or cardiac death within 60 days of treatment, which was especially true for patients with ischemic heart disease or CKD.
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http://dx.doi.org/10.1007/s00380-019-01543-6DOI Listing
June 2020

Comparable effect of tolvaptan in heart failure patients with preserved or reduced ejection fraction.

Clin Exp Hypertens 2020 22;42(2):110-117. Epub 2019 Feb 22.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

: It is unclear that the difference in efficacy of tolvaptan (TLV) on the length of hospital stay for both heart failure (HF) preserved ejection fraction (EF) (HFpEF) and reduced EF (HFrEF) patients.: We investigated 369 patients who were hospitalized with HF from February 2011 to June 2016 and initiated TLV. Patients who died in hospital, transferred hospital or clinical scenario 4 or 5 were excluded. Finally, we analyzed 108 patients with HFpEF and 96 patients with HFrEF. We evaluated the relationship between the length of hospital stay and the date of TLV initiation. Moreover, we compared the early use (within the median) and delayed use (the median or later) of TLV.: The date of TLV initiation was statistically associated with the length of hospital stay in both HFpEF and HFrEF (HFpEF: r = 0.625, P < 0.001, HFrEF: r = 0.618, P < 0.001). In HFpEF, the length of hospital stay in delayed use group was significantly longer than the early use group (22.2 ± 10.7 days and 38.1 ± 22.6 days, P < 0.001). The result was similar in HFrEF (22.0 ± 15.0 days and 32.1 ± 22.0 days, P = 0.008). On the other hand, there were no statistically significant differences in the length of hospital stay after initiation of TLV in both HFpEF and HFrEF. Other findings (including the severity of HF) were similar between the early use group and the delayed group in HFpEF and HFrEF.: The time until TLV initiation after hospitalization was related to the length of hospital stay in HFpEF and HFrEF patients.
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http://dx.doi.org/10.1080/10641963.2019.1583244DOI Listing
March 2020

Long-term use of ipragliflozin improved cardiac sympathetic nerve activity in a patient with heart failure: A case report.

Drug Discov Ther 2018 Mar 25;12(1):51-54. Epub 2018 Feb 25.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine.

Ipragliflozin is the first SGLT2 inhibitor approved in Japan. Reported here is a case where long-term administration of ipragliflozin decreased the rate of re-hospitalization due to heart failure (HF). An 83-year-old man with chronic HF and diabetes mellitus (DM) was hospitalized four times in the last five years. He was discharged six months after his last hospitalization, but he continued to have class III HF according to the New York Heart Association classification (NYHA), and his DM was also not properly managed. Therefore, he received ipragliflozin. One year after initiation of ipragliflozin, he lost weight (body weight (BW): 79.0 to 76.2 kg), his levels of brain natriuretic peptide (BNP) decreased (191.4 to 122.5 mg/dL), and the class of his HF improved (class III to class II). The management of DM also improved (fasting blood glucose: 100 to 110 mg/dL; hemoglobin A1C: 6.8 to 6.6%). In addition, cardiac sympathetic nerve function evaluated with I-metaiodobenzylguanidine cardiac-scintigraphy (I-MIBG) also improved (the average of the heart-to-mediastinum ratio in early and delayed phases; 1.44 to 2.17 in the early phase, 1.41 to 1.92 in the delayed phase, washout rate; 43.3 to 35.6). The patient was not re-hospitalized due to HF two years after administration of ipragliflozin started. A reduction in cardiac sympathetic nerve hyperactivity by an SGLT2 inhibitor might be one of the mechanisms of its cardio-protective effect, but clinical studies need to be conducted to verify this finding.
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http://dx.doi.org/10.5582/ddt.2017.01069DOI Listing
March 2018

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

Int Heart J 2018 Jan 20;59(1):120-125. Epub 2017 Dec 20.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine.

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.
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http://dx.doi.org/10.1536/ihj.17-024DOI Listing
January 2018

The relationship between the time until commencement of tolvaptan and the length of hospital stay in heart failure patients.

Heart Vessels 2018 Apr 11;33(4):367-373. Epub 2017 Nov 11.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, 6-11-1 Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan.

The effect of early use of tolvaptan (TLV) for acute decompensated heart failure (ADHF) is unclear. We investigated the relationship between early use of TLV and the length of hospital stay. 369 consecutive ADHF patients who received TLV during hospitalization between February 2011 and June 2016 were initially enrolled. Patients who died in hospital, transferred hospital or clinical scenario 4 or 5 were excluded. We analyzed 247 ADHF patients. We evaluated the relationship between the length of hospital stay and the following findings: blood pressures, heart rate, New York Heart Association classification, and blood tests on admission. Moreover, we also evaluated treated agents and TLV initiated days from admission. TLV initiated days was statistically associated with the length of hospital stay (r = 0.625, P < 0.001). We compared the early use (within 4 days) vs delayed use of TLV (5 days or later), because the median of time until commencement of TLV from hospitalization was 4 days. The length of hospital stay in the delayed use group was significantly longer than early use group (31.9 ± 20.4 and 21.0 ± 12.9 days, P < 0.001). However, there was no difference in the length of hospital stay after initiation of TLV in both groups. Moreover, we investigated the factors related to the long-term hospitalization (hospital stay of median length or more). Multivariate analysis showed that TLV initiated days was independently related to the long-term hospitalization (odds ratio 1.32, 95% confidence interval 1.13-1.53, P < 0.001). Early use of TLV was related to the length of hospital stay for ADHF patients.
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http://dx.doi.org/10.1007/s00380-017-1067-3DOI Listing
April 2018

Experience with long-term administration of tolvaptan to patients with acute decompensated heart failure.

Drug Discov Ther 2017 Jul 19;11(3):133-139. Epub 2017 Jul 19.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine.

Tolvaptan (TLV) is an oral selective vasopressin type 2 receptor antagonist. Long-term use of TLV is not recommended in patients with heart failure (HF) if fluid retention disappears and/or body weight is within the target range. However, some patients require long-term use of TLV. The current study investigated the efficacy and safety of long-term use of TLV. Subjects were 258 consecutive patients with HF who received TLV during hospitalization from January 2011 to March 2015. The rate of continuing administration of TLV was evaluated. Moreover, the one-year mortality rate and rate of re-hospitalization either with or without TLV were investigated. Results at discharge and one year later were compared for patients who continued to receive TLV one year after discharge. Oral concomitant medications, blood pressures, heart rate, blood tests, chest X-ray and transthoracic echocardiography were investigated. In-hospital and one-year mortality rates were 15.9% and 27.8%, respectively. Moreover, the mortality rate and/or rate of re-hospitalization within one year was 54.4%. The rate of re-hospitalization for HF was significantly higher in patients who continued to receive TLV after discharge compared to patients who ceased receiving TLV after discharge (p < 0.001). However, the subjects who continued to receive TLV for up to one year after discharge tended to have a longer duration until re-hospitalization for HF and significantly decreased brain natriuretic peptide levels (577.6 ± 528.5 pg/mL to 397.3 ± 365.8 pg/mL, p = 0.015). Long-term use of TLV might delay re-hospitalization for HF in patients with severe HF. Large-scale clinical studies are necessary to verify these results.
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http://dx.doi.org/10.5582/ddt.2017.01018DOI Listing
July 2017

Azelnidipine is a useful medication for the treatment of heart failure preserved ejection fraction.

Clin Exp Hypertens 2017 17;39(4):350-354. Epub 2017 May 17.

a Department of Cardiovascular Medicine , Toho University Faculty of Medicine , Tokyo , Japan.

Background: The optimal therapy in patients with heart failure preserved ejection fraction (HFpEF) and hypertension (HT) has not been revealed. The beta blocker (BB) and the renin angiotensin aldosterone system inhibitor (RAAS-I) are recommend as class IIa in patients with HFpEF. The calcium channel blocker (CCB), a major anti-hypertensive drugs in Japan, is also recommend as class IIa in patients with HFpEF. However, the difference between azelnidipine, an L type CCB, and cilnidipine, an N type CCB, is unclear. We investigated the difference between azelnidipine and cilnidipine in patients with HFpEF and HT.

Methods: Twenty-five consecutive HFpEF patients treated with BB and RAAS-I from April 2013 to March 2015 were enrolled. Initially, cilnidipine was used, and then switched to azelnidipine. Age, gender, blood pressure (BP), heart rate (HR), blood tests, echocardiography, and cardiac-scintigraphy (I-metaiodobenzylguanidine: MIBG) were measured before and after six months from azelnidipine administration.

Results: There was no statistically significant difference in BP. B type natriuretic peptides were significantly reduced (pre-state: 195.4 ± 209.7 pg/ml and post-state: 140.7 ± 136.4 pg/ml, p = 0.050). In echocardiography, the TEI index tended to be decreased (pre-state: 0.47 ± 0.15 and post-state: 0.42 ± 0.08, p = 0.057). As for MIBG, there was no significant change in the heart/mediastinum ratio. However, the washout rate was significantly reduced (pre-state: 44.7 ± 12.2 and post-state: 40.7 ± 12.1, p = 0.011). In addition, there was no statistically significant change, although HR tended to decrease by switching to azelnidipine (pre-state: 62.7 ± 11.6 and post-state: 61.8 ± 16.5, p = 0.373).

Conclusions: In patients with HT and HFpEF, azelnidipine improved the severity of HF and cardiac sympathetic nerve activity compared with cilnidipine.
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http://dx.doi.org/10.1080/10641963.2016.1267198DOI Listing
February 2018

Cardio-Ankle Vascular Index and C-Reactive Protein Are Useful Parameters for Identification of Ischemic Heart Disease in Acute Heart Failure Patients.

J Clin Med Res 2017 May 1;9(5):439-445. Epub 2017 Apr 1.

Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.

Background: The most common cause of heart failure (HF) is ischemic heart disease (IHD). Evaluation of IHD with non-invasive examinations is useful for the treatment of HF, and cardio-ankle vascular index (CAVI) is a good parameter for detecting systemic arteriosclerosis. However, the relationship between IHD and CAVI in acute HF (AHF) patients is still unclear. Therefore, we investigated the effect of non-invasive examinations, including CAVI to detect IHD.

Methods: We studied 53 consecutive patients (average age of 66.5 ± 10.9 years old, 36 males) with AHF from January 2009 to December 2012. These patients were classified into the IHD group (n = 19) and non-IHD group (n = 34) according to the coronary artery angiography results. We evaluated the vital signs, laboratory findings and CAVI.

Results: According to the laboratory findings, the C-reactive protein (CRP) in IHD group was significantly higher than non-IHD group (1.5 ± 2.1 mg/dL vs. 0.4 ± 0.4 mg/dL, P = 0.002). CAVI in IHD group was significantly higher than non-IHD group (9.58 ± 1.73 vs. 7.83 ± 1.86, P < 0.001). In the receiver operating characteristic (ROC) curve for discriminating the probability of IHD, the cut-off point of the CRP plus CAVI was 9.00. At that cut-off point, the sensitivity and the specificity were 69.7% and 89.5%, respectively. The mean area under the ROC curve (AUC) defined by the CRP plus CAVI was the greatest at all parameters.

Conclusion: The CRP and CAVI were useful parameters for the identification of IHD in patients with AHF.
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http://dx.doi.org/10.14740/jocmr2994wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380178PMC
May 2017

Efficacy of Intravenous Administration of Landiolol in Patients With Acute Heart Failure and Supraventricular Tachyarrhythmia.

J Clin Med Res 2017 May 1;9(5):426-432. Epub 2017 Apr 1.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan.

Background: Patients with acute heart failure (HF) complicated by supraventricular tachyarrhythmia (SVT) often receive continuous intravenous infusion of landiolol or diltiazem for rate control. It is unclear whether the interval from initiation of infusion to commencement of oral beta-blocker (BB) therapy differs for these two drugs.

Methods: From January 2013 to July 2015, 94 consecutive patients were hospitalized for acute HF complicated by SVT. After 35 patients were excluded, the remaining 59 were divided into groups treated with diltiazem or landiolol. We investigated the blood pressure, heart rate, New York Heart Association classification, brain natriuretic peptide, chest X-ray film, echocardiographic findings (ejection fraction (EF)), time until commencement of oral BB therapy, and hospital stay.

Results: There were no significant between-group differences of heart rate, blood pressure, or the severity of HF. The time until commencing oral BB therapy was significantly shorter in the landiolol group compared with the diltiazem group (median: 2 vs. 4 days, P = 0.002), but there was no significant difference in hospital stay. This interval was significantly shorter in patients with a reduced EF in the landiolol group (median: 2 days) compared with those with a reduced EF in the diltiazem group (median: 5 days, P = 0.008), and patients with a preserved EF in the landiolol group tended to have a shorter interval (median: 2 days) than those with a preserved EF in the diltiazem group (median: 4 days, P = 0.092).

Conclusions: Switching to oral BBs was accomplished earlier with landiolol than with diltiazem.
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http://dx.doi.org/10.14740/jocmr2954wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380176PMC
May 2017

Short-Term Subcutaneous Fondaparinux and Oral Edoxaban for Acute Venous Thromboembolism.

Circ J 2017 May 25;81(6):855-861. Epub 2017 Feb 25.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine.

Background: No studies have compared treatment efficacy between subcutaneous (SC) fondaparinux and oral edoxaban, which are categorized as factor Xa inhibitors, for venous thromboembolism (VTE) in the acute phase, and only a limited number of imaging-based quantitative studies have evaluated treatment.Methods and Results:In this open-label, randomized study, 50 patients with acute non-massive pulmonary embolism (PE) and/or deep-vein thrombosis (DVT) were assigned to fondaparinux or edoxaban groups. Lower-limb venous ultrasonography (US), and chest computed tomography (CT) were compared before and 7 days after treatment. Thrombus volume in DVT was calculated using quantitative ultrasound thrombosis (QUT) score on US. For evaluation of PE thrombus volume, lung perfused blood volume (PBV) on CT was calculated. The measurements before and after treatment, respectively, were as follows: QUT score: fondaparinux, 8.1±7.3 to 4.1±4.5; edoxaban, 7.7±6.3 to 4.4±4.3, both significant decreases (P=0.001, P<0.001, respectively); lung PBV: fondaparinux, 32.0±7.8 to 32.1±8.2 HU; edoxaban, 34.2±8.6 to 38.5±11.8 HU (P=0.732, P=0.426, respectively). On subjective CT-based evaluation, all pulmonary artery-related filling defects decreased/disappeared after treatment in both groups (P=NS).

Conclusions: Both SC fondaparinux and oral edoxaban are effective in acute VTE. Effects on thrombus regression on imaging-based quantitative measurement did not differ between the 2 drugs.
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http://dx.doi.org/10.1253/circj.CJ-16-1012DOI Listing
May 2017

Pulse Pressure and Upstroke Time Are Useful Parameters for the Diagnosis of Peripheral Artery Disease in Patients With Normal Ankle Brachial Index.

Cardiol Res 2016 Oct 3;7(5):161-166. Epub 2016 Nov 3.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan.

Background: Some peripheral artery disease (PAD) patients have normal ankle brachial index (ABI) (0.9 - 1.4), although ABI is a useful parameter for the diagnosis of PAD. We investigated whether other parameters of ABI report sheet are useful to detect these patients.

Methods: We initially enrolled 3,912 patients (7,824 limbs) who underwent ABI for the first time. Subjects who have normal ABI were divided into the PAD group (n = 136) and the non-PAD group (n = 240) by lower extremity ultrasonography. We investigated blood pressures (BP) (systolic (SBP), diastolic (DBP), mean (mBP) and pulse pressure (PP)), heart rate, upstroke time (UT), and %mean arterial pressure (%MAP).

Results: SBP, mBP, PP, UT, and %MAP in the PAD group were significantly higher. A multivariate analysis showed that mBP, DBP, PP, UT and %MAP were independently associated with the presence of PAD (mBP: odds ratio (OR) 2.30, 95% confidence interval (CI) 1.22 - 4.37, P = 0.010; DBP: OR 0.52, 95% CI 0.28 - 0.97, P = 0.039; PP: OR 1.30, 95% CI 0.69 - 2.46, P = 0.041; UT: OR 3.40, 95% CI 2.03 - 5.83, P < 0.001; %MAP: OR 1.77, 95% CI 1.05 - 2.98, P = 0.031). Maximal area under the curve (AUC) of BPs for associating PAD was PP. The cut-off value of PP was 53.0 mm Hg (sensitivity 0.500, specificity 0.721, AUC 0.628, 95% CI 0.569 - 0.687).

Conclusions: The present study demonstrated that BPs are associated with PAD in patients with normal ABI. The measurement of BPs could provide additional information for the diagnosis of PAD.
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http://dx.doi.org/10.14740/cr508eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295562PMC
October 2016

A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute venous thromboembolism.

J Cardiol 2017 Aug 12;70(2):163-168. Epub 2016 Dec 12.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan.

Background: The factor Xa inhibitors have been widely used for the treatment and prevention of venous thromboembolism (VTE). However, the efficacy of factor Xa inhibitors in Japanese patients with VTE has not been well examined. In this study, we investigated the effect of the sequential use of two factor Xa inhibitors in patients with acute VTE.

Methods: We conducted an observational study of 87 consecutive patients diagnosed with VTE. As an initial treatment, we administered subcutaneous fondaparinux to the patients for 7-10 days, and then switched to oral rivaroxaban. The symptoms and findings were assessed after the initial treatment and after using rivaroxaban for 7-14 days. We evaluated the deep vein thrombosis (DVT) in the legs using our own scoring system [quantitative ultrasound thrombosis (QUT) score].

Results: Of the 87 patients, 33% had symptoms, half had pulmonary embolism (PE), and 95% had DVT of the legs. Out of the 87 patients, VTE worsened during the administration of fondaparinux in 4 patients. All of them had experienced malignancy, and died within 6 months. Of two patients developing bleeding, one patient required a transfusion. Eventually, this strategy was effective in 80 patients and had no change in one. The D-dimer level was significantly reduced by fondaparinux (17.8μg/ml±16.0μg/ml vs. 8.3μg/ml±7.2μg/ml, p<0.0001), followed by rivaroxaban (8.3μg/ml±7.2μg/ml vs. 5.5μg/ml±4.9μg/ml, p<0.0001). Similarly, the QUT score was improved by fondaparinux (4.7±2.6 vs. 2.5±2.5, p<0.0001), and further reduced by rivaroxaban (2.5±2.5 vs. 1.9±1.8, p<0.0001).

Conclusions: A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute VTE in Japanese patients.
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http://dx.doi.org/10.1016/j.jjcc.2016.10.013DOI Listing
August 2017

Serum angiotensin-converting enzyme 2 concentration and angiotensin-(1-7) concentration in patients with acute heart failure patients requiring emergency hospitalization.

Heart Vessels 2017 Mar 15;32(3):303-308. Epub 2016 Jul 15.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, 6-11-1 Omorinishi, Ota-ku, Tokyo, 143-8541, Japan.

The existence of a new cascade, angiotensin-converting enzyme (ACE) 2/angiotensin (Ang)-(1-7)/Mas receptor axis, has been recently established in the renin-angiotensin system. However, the dynamics of this cascade under various pathological conditions in clinical settings is still unclear. Forty-nine patients who underwent emergency hospitalization because of acute heart failure (AHF) consented to participate in this study. Thirty-eight healthy volunteers served as controls. Serum ACE activity, ACE2, Ang-(1-7) concentration, plasma Ang II, aldosterone concentration, and plasma renin activity (PRA) were measured at the acute stage. We conducted a comparative study between patients with AHF and healthy volunteers. Patients with AHF showed lower serum ACE activity and plasma aldosterone concentration than healthy volunteers (12.3 vs. 15.1 IU/L, respectively; P = 0.01, 75.6 vs. 125.3 pg/mL, respectively; P = 0.000); there were no differences between the two groups in PRA and plasma Ang II concentration. Patients with AHF had a higher serum ACE2 concentration than healthy volunteers (7.9 vs. 4.8 ng/mL, respectively; P = 0.002), but their serum Ang-(1-7) concentration was significantly lower (2.4 vs 3.1 ng/mL, respectively; P = 0.005). Patients with AHF had a higher serum ACE2 concentration, lower serum Ang-(1-7) concentration, and lower serum ACE activity and plasma aldosterone concentrations than healthy volunteers, whereas PRA and plasma Ang II concentration were the same.
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http://dx.doi.org/10.1007/s00380-016-0877-zDOI Listing
March 2017

Use of apixaban for an elderly patient with left atrial thrombus.

BMJ Case Rep 2014 Jun 24;2014. Epub 2014 Jun 24.

Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan.

An 86-year-old man had long-standing persistent atrial fibrillation, but had not received any anticoagulants. Transthoracic echocardiography revealed a large thrombus formation in the left atrium. We hesitated to use the conventional anticoagulant, warfarin, because he was very old and had dementia. We decided to resolve the thrombus at our outpatient clinic. He was started on the novel oral anticoagulant, apixaban, 2.5 mg twice daily, which is a direct factor Xa (FXa) inhibitor. After 11 weeks on that therapy, the thrombus formation had almost resolved. During oral anticoagulant therapy, no serious bleeding complications, systemic embolisms or strokes were noted. To the best of our knowledge, we are the first to report that apixaban (5 mg/day) can possibly resolve a thrombus formation in the left atrium.
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http://dx.doi.org/10.1136/bcr-2014-203870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069635PMC
June 2014
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