Experience with pre-diluted plasma exchange therapy for hyperviscosity syndrome.

INTRODUCTION: Plasma exchange therapy (PE) is useful for patients with primary macroglobulinemia and multiple myeloma who present with hyperviscosity syndrome. However, hyperviscous blood may coagulate in the circuit during treatment, and in that case necessitate discontinuation of the treatment. This time, we report that we were able to prevent coagulation in the circuit by adding some ideas during the membrane separation method. METHODS: Physiological saline is injected in front of the plasma separation membrane to pre-dilute the blood, followed by filtration through the plasma separation membrane. RESULTS: As a result of pre-diluting with physiological saline to reduce the viscosity entering the separation membrane, it was possible to process the planned target amount. CONCLUSION: In patients with hyperviscosity syndrome who showed intracircuit coagulation during plasma exchange therapy, devising a predilution method should be considered as one of the ways to continue treatment.

Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure.

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction.

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus.

Background Effects of sodium-glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open-label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B-type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, -9.0% versus -1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78-1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000018395.

Changes in left ventricular relaxation after azelnidipine treatment in hypertensive patients with diabetes: subanalysis of a prospective single-arm multicentre study.

OBJECTIVES: We previously demonstrated that a calcium channel blocker, azelnidipine, improves left ventricular relaxation in patients with hypertension and diastolic dysfunction in a multicentre, Clinical impact of Azelnidipine on Left VentricuLar diastolic function and OutComes in patients with hypertension (CALVLOC) trial. The objectives of the present subanalysis were to investigate the differences in diastolic function in hypertensive patients with and without diabetes, and the efficacy of azelnidipine on diastolic function among them. DESIGN: Subanalysis of a prospective single-arm multicentre study. PARTICIPANTS: 228 hypertensive patients with normal ejection fraction and impaired left ventricular relaxation (septal e' velocity<8 cm/s on echocardiography) enrolled for CALVLOC trial. They were divided into two groups based on presence or absence of diabetes. INTERVENTIONS: Administration of 16 mg of azelnidipine for 8 months (range 6-10 months). MAIN OUTCOME MEASURES: Septal e' velocity before and at the end of the study. RESULTS: Whereas patients with diabetes (n=53, 23.2%) had lower systolic blood pressure (BP) than patients without diabetes (155±17 vs 161±16 mm Hg, p=0.03), they had lower e' velocity (5.7±1.5 vs 6.1±1.4 cm/s, p=0.04) at baseline. Azelnidipine decreased BP and heart rate, and increased e' velocity similarly in patients with diabetes (5.7±1.5 to 6.3±1.5 cm/s, p=0.0003) and without diabetes (6.1±1.4 to 6.9±1.4 cm/s, p<0.0001). Increase in e' velocity was not influenced by presence of diabetes, and patients with diabetes still had lower e' velocity after treatment (p=0.006). There was a significant correlation between increase in e' velocity and decrease in systolic BP (R=0.25, p=0.0001), which was not influenced by diabetes. CONCLUSIONS: Comorbid diabetes could impair left ventricular relaxation independently in patients with hypertension, which might not be improved solely by BP lowering.

Impact of azelnidipine treatment on left ventricular diastolic performance in patients with hypertension and mild diastolic dysfunction: multi-center study with echocardiography.

We investigated the impact of lowering blood pressure (BP) with azelnidipine, a newly developed calcium channel blocker, generation on the left ventricular (LV) diastolic function and LV filling pressure by assessing non-invasive indices derived from echo Doppler study. This study evaluated 232 hypertensive patients with diastolic dysfunction. This study had two groups: (1) in which azelnidipine was administered to patients as a first-line therapy, and (2) in which amlodipine was converted to azelnidipine. Early diastolic mitral annulus velocity (e', cm s(-1)), the ratio of peak E velocity to e' velocity (E/e' ratio) and level of brain natriuretic peptide (BNP) were measured before and, an average of, 8 months after azelnidipine treatment. In the first-line azelnidipine group, the systolic and diastolic BP reduced by 26 and 11 mm Hg, respectively. The e' increased, and E/e' ratio and BNP level decreased significantly. In the converted-from-amlodipine group, the systolic and diastolic BP decreased by 14 and 6 mmHg, respectively. The e' velocity increased, but the E/e' ratio and BNP level did not change. In both groups, azelnidipine lowered BP and improved LV diastolic function (an increase in the e' velocity). Possible reduction in LV filling pressure (a decrease in the E/e' ratio and BNP level) is observed only in the first-line azelnidipine group.

Renoprotective effect of the addition of losartan to ongoing treatment with an angiotensin converting enzyme inhibitor in type-2 diabetic patients with nephropathy.

Angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects. To many patients who are nonresponsive to monotherapy with these agents, combination therapy appears to be a good treatment option. In the present study, we examined the effects of the addition of an ARB (losartan) followed by titration upon addition and at 3 and 6 months (n=14) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months (n=20) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure (BP) of 130/80 mmHg and to reduce urinary albumin to <30 mg/day. During the 12-month treatment, addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure (SBP) by 10% and 12%, diastolic blood pressure (DBP) by 7% and 4%, and urinary albumin excretion by 38% and 20% of the baseline value, respectively. However, the effects on both BP and urinary albumin were not significantly different between the two therapies. In conclusion, addition of losartan or an ACE-I to an ongoing treatment with an ACE-I, or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP, and provided renal protection in patients with type-2 diabetic nephropathy.

Clinical features of emergency electrocardiography in patients with acute myocardial infarction caused by left main trunk obstruction.

BACKGROUND: To diagnose left main trunk (LMT) infarction by 12-lead standard electrocardiogram (ECG) is an important emergency technique, but the features in LMT infarctions have not been clarified. METHODS AND RESULTS: The study enrolled 140 subjects who were divided into 4 groups according to the location of the culprit artery: 35 with LMT, 35 with left anterior descending artery (LAD), 35 with right coronary artery and 35 with left circumflex artery. Various parameters obtained from the ECGs were analyzed. Average QTc interval (0.51 +/- 0.06 s) in LMT group was markedly longer than that in the 3 other groups. Average QRS axis (-10 +/- 77 degrees) in LMT infarction showed a remarkable left deviation. ST-segment elevation in lead aVR occurred in 28 patients (80.0%) in the LMT group. The ECG features of the LMT group could be classified into 2 main groups: right bundle branch block (RBBB) with a marked left axis deviation (RBBB + LADEV type) and ST-segment elevation in leads V2-5, I and aVL without abnormal axis deviation (LAD type). CONCLUSION: Either ST-segment elevation in lead aVR and marked prolongation of both the QRS width and QTc interval with a prominent abnormal axis deviation or ST-segment elevation in the broad anterior precordial lead with a normal QRS axis strongly suggests LMT infarction.