Takahiro Fujii

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

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.

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

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.

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

ABSTRACT 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 (123I-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.

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

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 123I-metaiodobenzylguanidine cardiac-scintigraphy (123I-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.

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

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.

Prognostic Utility of Indoxyl Sulfate for Patients with Acute Coronary Syndrome

Aim: We investigated whether indoxyl sulfate (IS), a protein-bound uremic toxin, predicts prognosis after acute coronary syndrome (ACS). Methods: Serum IS level was determined prospectively in 98 patients who underwent successful primary percutaneous coronary intervention for ACS. Patients on hemodialysis were excluded. The endpoint of this study was six-month composite events including death, nonfatal myocardial infarction, heart failure requiring hospitalization, and adverse bleeding events. Results: During the mean follow-up period of 168 days, composite events occurred in 13.3% of cases. Serum IS level was significantly higher in subjects who developed composite events than in those without events (0.14 ± 0.11 mg/dl vs. 0.06 ± 0.04 mg/dl; p < 0.001). After adjusting for confounding factors, a Cox proportional hazard analysis revealed that the IS level (hazard ratio (HR): 10.6; 95% confidence interval (CI): 1.63–69.3, p = 0.01), hemoglobin level (HR: 0.61; 95% CI: 0.43–0.87; p < 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.95; 95% CI: 0.91–0.99; p = 0.03) were independent predictive factors of composite events. Furthermore, IS level significantly conferred additional value to the combined established risks of LVEF and hemoglobin level for predicting the incidence of composite events (area under the curve: 0.82 vs. 0.88, p = 0.01; net reclassification improvement: 0.67, p = 0.01; and integrated discrimination improvement: 0.15, p < 0.01). Conclusions: The assessment of serum IS level has prognostic utility for the management of ACS.

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

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 123I-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.

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

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.

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

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.