Intravascular Ultrasound Can Be Used to Locate Nerves, but not Confirm Ablation, During Renal Sympathetic Denervation.

BACKGROUND: No methods exist for confirming nerve ablation in catheter-based renal sympathetic denervation (RDN). METHODS: We investigated the feasibility of using intravascular ultrasound (IVUS) to locate nerves and observe nerve integrity changes during RDN in a pig. To confirm our observations, we used post-RDN histological sections matched anatomically to the IVUS images. RESULTS: IVUS revealed multiple hypoechoic structures along the renal artery, whose locations matched those of nerves in the histological sections. Nerves clustered near the junction between the renal artery and vein. Histology confirmed necrosis of nerve bundles at RDN ablation sites, but no changes in echogenicity were observed using IVUS. CONCLUSIONS: Although IVUS cannot currently be used to confirm ablation during RDN, it clearly reveals some clusters of renal sympathetic nerves. It remains to be demonstrated how IVUS can guide RDN devices and potentially improve ablation success.

Comprehensive Efficacy of the Dipeptidyl Peptidase 4 Inhibitor Alogliptin in Practical Clinical Settings: A Prospective Multi-Center Interventional Observational Study.

BACKGROUND: This study aimed to verify the safety and efficacy, including glycemic control, of the selective dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes. METHODS: This study used a multi-center, open-label, prospective observational design. Type 2 diabetes patients who were undergoing dietary therapy and/or exercise therapy alone without sufficient glycemic control (hemoglobin A1c (HbA1c) ≥ 6.5% and < 10%) were administered alogliptin (25 mg/day). The long-term effects (6 and 12 months) on blood glucose, blood pressure, heart rate, body weight and lipids were assessed. RESULTS: A final 50 patients were included with a high prevalence of hypertension (77%) and dyslipidemia (72%), and a mean duration of diabetes of 4.5 years. Pre-treatment HbA1c was 7.5% and was significantly decreased at 6 and 12 months (6M: 6.4%, 12M: 6.2%; P < 0.02 vs. 0M, respectively). Body weight, blood pressure and low-density lipoprotein cholesterol were significantly decreased by 6 months and maintained at 12 months. Triglycerides showed a significant decrease at 12 months. No significant differences were observed in HbA1c decrease for different grade of age, duration of diabetes, body mass index and renal function. The degree of decrease in HbA1c was most strongly correlated with pre-treatment HbA1c. Adverse events were noted in three patients, with no serious outcomes. CONCLUSION: The blood glucose-lowering effect and safety of alogliptin were demonstrated regardless of baseline HbA1c, although its effect appeared stronger with higher pre-treatment HbA1c values. Additionally, alogliptin appears useful for managing atherosclerotic risk factors such as body weight and blood pressure.

Elevated chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes was observed in the patient of atrial fibrillation.

Chymase is an angiotensin II-forming serine proteinase and elevation of its tissue activity occurs in various cardiovascular diseases. Several authors have suggested that there is an association between the renin-angiotensin system and atrial fibrillation (AF). Chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes (CML chymase dAIIFA) was investigated in patients with AF and patients in sinus rhythm. Consecutive outpatients were recruited at our hospital. CML chymase dAIIFA was measured using a Nma/Dnp-type fluorescence-quenching substrate of modified angiotensin I in the presence or absence of a specific serine proteinase inhibitor. To search the independent contributing factor of existence of AF, the analysis between groups was carried out using multivariate analysis after univariate analysis. The patients were classified into a sinus rhythm (SR) group (n = 459) or an AF group (n = 48). CML chymase dAIIFA was significantly higher in the AF group (622 pmol/min/mg) compared with the SR group (488 pmol/min/mg) (p < 0.001). Logistic regression analysis revealed that high CML chymase dAIIFA was an independent determinant of the existence of AF (p < 0.001). Elevation of CML chymase dAIIFA was associated with AF. Activation of chymase might be linked to atrial structural and electrical remodeling.

Inappropriate direct oral anticoagulant dosing in atrial fibrillation patients is associated with prescriptions for outpatients rather than inpatients: a single-center retrospective cohort study.

BACKGROUND: Inappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF). METHODS: The retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer's labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing). RESULTS: A total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66-81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53-5.62, p < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51, p < 0.001). CONCLUSIONS: Our results demonstrated that the inappropriate dosing of DOACs occurred in approximately 20% of AF patients, and was more frequent in outpatients (vs. inpatients) and in those with a higher risk of bleeding. It is recommended that pharmacists play a greater role in assisting in the prescription process to help physicians make better decisions.

Add-on aliskiren treatment can decrease blood pressure but requires attention to risks of renal impairment and hyperkalemia Chikushi Anti-Hypertension Trial-Rasilez® (CHAT-Ras).

BACKGROUND: Renin is the starting point of the renin angiotensin (RA) system cycle. Aliskiren (AL), which is a direct renin inhibitor, suppressed the entire RA cycle. In the present study, the efficacy of add-on of AL treatment in patients with essential hypertension (HT) was investigated. METHODS: This study was a multi-center, open-label, prospective, observational study. Study subjects were patients with essential HT and poor blood pressure (BP) control, who had received calcium channel blocker monotherapy or angiotensin II receptor blocker monotherapy or had not received any BP lowering drugs. Following add-on of AL for 12 months, BP and additional laboratory findings were analyzed. RESULTS: A total of 150 subjects were enrolled. There were 50 dropout subjects including discontinuation. Dropouts were the highest in the ARB combination therapy group at 9 subjects due to adverse events, and 3 of them were due to hyperkalemia. A significantly higher number of patients with chronic kidney disease (CKD) dropped out compared to patients without CKD (φ = 0.166, p < .05). BP before add-on of AL was 155/88 mmHg. After add-on of AL, BP was significantly improved and this lowering was sustained for 3 months (136/78 mmHg, p < .001), 6 months (136/77 mmHg, p < .001) and 12 months (134/78 mmHg, p < .001). In contrast, add-on of AL increased the potassium level and decreased the estimated glomerular filtration rate. CONCLUSION: While add-on AL treatment achieved a favorable and sustained decrease of BP in this study, caution is necessary with regard to elevation of potassium levels and renal impairment.

A Patient with Bilateral Primary Aldosteronism Refractory to Oral Eplerenone Who Responded to Esaxerenone with Increased Renin Activity.

BACKGROUND When mineralocorticoid receptor antagonist therapy is initiated for primary aldosteronism, the response of plasma renin activity indicates the level of cardiovascular risk. The purpose of this article was to compare the effect of mineralocorticoid receptor blockers on plasma renin activity levels in a patient with primary aldosteronism. CASE REPORT The patient was a 45-year-old male with severe hypertension. Because his aldosterone/renin ratio was high and a saline infusion test was positive, primary aldosteronism was diagnosed. Computed tomography revealed a low-density mass measuring 10 mm in the left adrenal gland. Segmental adrenal vein sampling demonstrated bilateral primary aldosteronism, so pharmacotherapy was started. Before treatment, his plasma renin activity was 0.5 ng/mL/hour. Eplerenone was commenced and the dose was increased to 100 mg/day. However, his plasma renin activity was still 0.8 ng/mL/hour and the maximum dose of eplerenone did not elevate plasma renin activity above 1 ng/mL/hour. Since plasma renin activity remained below 1 ng/mL/hour with mineralocorticoid receptor antagonist therapy, this patient was considered to have a higher cardiovascular risk than patients with essential hypertension. Accordingly, eplerenone was switched to esaxerenone, a new generation mineralocorticoid receptor blocker that became available in May 2019. After switching to esaxerenone (5 mg/day), the patient's plasma renin activity increased to 1.8 ng/mL/hour and subsequently remained at 1 ng/mL/hour or higher. CONCLUSIONS This is the first case report to present interesting changes of plasma renin activity in a primary aldosteronism patient after switching from eplerenone to esaxerenone. Elevation of plasma renin activity by esaxerenone in our primary aldosteronism patient reflected a mineralocorticoid receptor antagonistic effect that may have alleviated excessive mineralocorticoid receptor activation and volume expansion.

Multicenter prospective observational study of teneligliptin, a selective dipeptidyl peptidase-4 inhibitor, in patients with poorly controlled type 2 diabetes: Focus on glycemic control, hypotensive effect, and safety Chikushi Anti-Diabetes Mellitus Trial-Teneligliptin (CHAT-T).

Objective: We purpose to confirm the effect of teneligliptin (Tenelia), a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, on glycemic control and non-glucose risk factors for macroangiopathy, including blood pressure, lipid metabolism, and body weight.Methods: In a prospective, multicenter, open-label, observational study, teneligliptin (20 mg/day) was administered to type 2 diabetic patients with poor glycemic control (HbA1c ≥ 6.5% to <10%) at our hospitals. The safety of teneligliptin and its impact on blood glucose, blood pressure, and the lipid profile were assessed after administration for 3 and 6 months.Results: One hundred and sixty-two patients were enrolled between February 2014 and August 2015. HbA1c was 7.6% at baseline and showed significant reduction to 7.1% after 3 months of treatment and to 6.9% after 6 months (both p < 0.01). Patients with poorly controlled hypertension (systolic blood pressure [SBP] ≥130 mmHg and/or diastolic blood pressure [DBP] ≥80 mmHg) at study initiation were extracted to investigate the effect of teneligliptin on blood pressure. SBP showed a significant decrease from 141.2 ± 9.8 mmHg at baseline to 131.1 ± 14.3 mmHg after 3 months and 133.9 ± 11.5 mmHg after 6 months (both p < 0.001). DBP also decreased significantly from 85.8 ± 5.7 mmHg at baseline to 78.4 ± 10.0 mmHg after 3 months and 79.7 ± 10.1 mmHg after 6 months (both p < 0.001). Adverse events were pruritus in four patients, and cerebral infarction was reported as a cerebrovascular event in one patient.Conclusions: Teneligliptin therapy was safe and improved glycemic control irrespective of baseline HbA1c. Blood pressure was also improved in patients with concomitant hypertension.

Efficacy and safety of a combination antihypertensive drug (olmesartan plus azelnidipine): "Issues with hypertension studies in real-world practice".

Background: This study investigated whether a combination drug containing an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) could provide effective antihypertensive therapy.Methods: A multicenter, prospective, open-label study was conducted at the clinics of Clinical Research Network. The subjects had uncontrolled blood pressure (BP) despite ARB or CCB monotherapy. The effect on both office and home BP was examined after patients switched to a combination drug (REZ: containing 20 mg of olmesartan [OL] and 16 mg of azelnidipine [AZ]).Results: A total of 78 patients were enrolled. After switching to REZ, a significant and sustained reduction of office BP was observed. The proportion of patients who achieved the target for both office and home BP was an increase from 0% to 55%. Switching from amlodipine to REZ resulted in a significant and sustained decrease of office and home BP. There was also a significant decrease of home pulse rate (PR), but office PR was unchanged. To determine the accuracy of the BP and PR values reported by patients, the frequency of each number as the first digit was determined. The frequency of "0" was extremely high for both office and home BP values, and the same was noted for home PR values.Conclusion: The results of this study suggested that switching from a single drug to combination therapy with REZ could achieve a stronger antihypertensive effect. However, concern was raised regarding the methods of BP and PR measurement and recording in this clinical trial involving general practitioners.

Successful Depressor Effect Concomitant with Complete Normalization of High Renin and Aldosterone Profile by Percutaneous Transluminal Renal Angioplasty in a Patient with Acute Exacerbated Heart Failure with Preserved Ejection Fraction.

BACKGROUND Although the effect of percutaneous transluminal renal angioplasty (PTRA) on clinical outcomes has not been established in previous clinical studies, some case reports showed that PTRA drastically improved patient outcomes. The appropriateness of PTRA should be discussed in detail. CASE REPORT A 59-year-old man had been on treatment for hypertension for 5 years, but his blood pressure (BP) had been poorly controlled for the past 5 months. He was hospitalized for pulmonary edema due to heart failure with preserved ejection fraction (HFpEF). During hospitalization, ultrasound and plain computed tomography revealed atrophy of the right kidney, and laboratory investigations indicated secondary aldosteronism with high plasma renin activity (PRA). Unenhanced magnetic resonance imaging (MRI) suggested severe stenosis or occlusion of the right renal artery. PTRA was performed for total occlusion at the origin of the right renal artery, resulting in favorable dilation of the vessel and good blood flow. A differential renal vein renin assay showed a right-left difference of PRA before PTRA, but this disappeared after the procedure. Both PRA and the plasma aldosterone concentration were normalized after PTRA. In addition, the patient's BP decreased, proteinuria was reduced, diuretics could be discontinued, and his calcium channel blocker dosage was decreased. CONCLUSIONS The present case suggests that screening for renal artery stenosis by unenhanced MRI may be useful in patients who have HFpEF because PTRA can be used to achieve marked improvement of hypertension, endocrine abnormalities, and heart failure if stenosis is detected.

Two Years Efficacy of Paclitaxel-Coated Balloon Dilation for In-Stent Renal Artery Restenosis Due to Takayasu Arteritis.

BACKGROUND Endovascular procedures for renal artery stenosis induced by Takayasu arteritis include renal angioplasty (RA); sometimes renal artery bypass surgery may be required. Recently, there have been several reports about the use of drug-coated balloon (DCB) for renal artery stenosis in patients with Takayasu arteritis. CASE REPORT A 19-year-old female was diagnosed with ulcerative colitis in 2012 and was on oral therapy. In 2015, she developed type V Takayasu arteritis, with 90% stenosis of the bilateral common carotid arteries, 90% stenosis of the right renal artery, and 75% stenosis of the infrarenal abdominal aorta. Her abdominal aortic stenosis reduced blood flow to the lower extremities and revascularization was required, so balloon dilatation of the abdominal aorta and renal angioplasty for right renal artery were performed at another hospital in March 2016. However, in-stent restenosis occurred 2 times, we performed renal angioplasty again with DCB. The patient has subsequently shown a stable course without recurrence of hypertension. At 2 years after renal angioplasty with the DCB, her serum renin and aldosterone levels were normal, there was no change of the right renal artery blood flow rate, and the blood pressure was normal. CONCLUSIONS This case suggests that dilation of in-stent restenosis with a DCB is an effective strategy for renal artery stenosis in patients with Takayasu arteritis. It seems desirable to consider expanding the indications for use of DCB to include renal artery stenosis.

High Fib4 index in patients with suspected NASH is associated with elevation of chymase-dependent angiotensin II-forming activity in circulating mononuclear leucocytes.

Fatal hepatic disease is closely related to non-alcoholic fatty liver disease, especially non-alcoholic steatohepatitis (NASH). NASH is associated with cardiovascular events because it develops on the background of lifestyle-related diseases. Chymase-dependent angiotensin II-forming activity (dAIIFA) in circulating mononuclear leucocytes (CML) is a marker of local angiotensin II production and inflammation. This study investigated the association between CML chymase dAIIFA and NASH. Cardiovascular outpatients were recruited and the Fib4 index (F4I) was calculated. Patients with an F4I > 2.67 were classified into the high F4I group and these patients were strongly suspected to have NASH, while patients with an F4I < 1.30 were classified into the low F4I group. Patient background factors were compared between these groups. CML chymase dAIIFA was measured by ELISA using Nma/Dnp-modified angiotensin I. Among 499 patients, 16% were classified into the high F4I group. Compared with the low F4I group, the high F4I group had a significantly higher age, pancytopenia, more frequent diabetes mellitus, lower diastolic blood pressure, lower estimated glomerular filtration rate, higher brain natriuretic peptide, lower plasma aldosterone concentration, higher total AIIFA, higher CML chymase dAIIFA, and higher pulse wave velocity. Contrary to expectations, the body mass index, triglycerides, and low-density lipoprotein cholesterol were relatively low in the high F4I group. Many cardiovascular outpatients have a high F4I and can probably be categorized as NASH. The high F4I patients had few features of metabolic syndrome and were suspected to have elevated tissue chymase dAIIFA contributing to inflammation in the liver as well as in cardiovascular organs.

Investigation of a Dipeptidyl Peptidase-4 Inhibitor/Thiazolidinedione Combination Drug for Patients With Type 2 Diabetes and Poor Glycemic Control: Difficulty With Patient Enrollment.

BACKGROUND: One of the treatment options for type 2 diabetes mellitus (DM) is a combination drug (CD) that contains the dipeptidyl peptidase-4 inhibitor (DPP4I) alogliptin (AG) together with pioglitazone (PG). This CD can improve impaired insulin secretion and insulin resistance, which are the two major pathologic factors for type 2 DM, and is also expected to increase adherence to treatment. We conducted a multicenter open-label prospective study to examine the usefulness of this CD for routine management of type 2 DM. METHODS: In type 2 DM patients with poor glycemic control who had been taking a DPP4I for ≥ 1 month, PG (15 mg/day) was added (first point). When the safety of PG was confirmed after 1 - 3 months, the DPP4I and PG were switched to the CD containing AG (25 mg) and PG (15 mg) (second point). Three months after switching to the CD was defined as the final point. Evaluation of objective findings, laboratory test results, and medication adherence was performed at these three points. RESULTS: Nineteen subjects completed the study, but this was far short of the target (160 subjects). Compared to the first point, white blood cell count (WBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), and fasting blood glucose (FBG) all showed a significant decrease at both the second and final points. No change in medication adherence was observed throughout the study period. The most notable point about this study was the extremely small number of subjects enrolled. As a possible explanation, we considered whether the preferences of the study doctors for antidiabetic drugs differed between specialties. The study doctors were mainly gastroenterologists, followed by endocrinologists/diabetologists and cardiologists in equal numbers. As an additional investigation, we determined the percentages of specialist doctors prescribing DPP4Is, sodium-glucose cotransporter-2 inhibitors (SGLT2Is), PG, or biguanides (BGs) as the main treatment for DM in 1 month at our hospital. We found that a low percentage of endocrinologists/diabetologists prescribing PG compared to other drugs, while cardiologists prescribed PG frequently. CONCLUSIONS: It was confirmed that the combination of DPP4I with PG was effective for the treatment of type 2 DM and improving metabolic function. Our data also showed that prescription of antidiabetic drugs differed between specialties, suggesting differences in their response to the results of various clinical studies and adverse reaction reports.

A Case of Primary Aldosteronism Due to A Primary Adrenal Adenoma Diagnosed by Segmental Adrenal Venous Sampling (S-AVS) Using a Modified Catheter System and Lateral Cine Angiography.

BACKGROUND Before partial adrenalectomy for primary aldosteronism due to a primary adrenal adenoma, the aldosterone-producing tumor can be localized by segmental adrenal vein sampling (S-AVS). Cardiologists, who regularly perform percutaneous coronary intervention (PCI), or coronary angioplasty with stent, may not be familiar with the technique of S-AVS. A case of the use of S-AVS is reported in a patient who presented with primary aldosteronism and a right adrenal adenoma. CASE REPORT A 44-year-old man with a history of hypertension presented with a man in the posterior part of the right adrenal gland. He had hypokalemia, and a high plasma aldosterone concentration/plasma renin activity ratio. A captopril stress test confirmed the diagnosis of primary aldosteronism. Pre-operative S-AVS was performed using a microwire and microcatheter, which were advanced into the segmental adrenal vein using a 6.5 French guiding catheter and a Y-shaped connector, under biplane cine angiography guidance. S-AVS showed a high plasma aldosterone concentration in the right superior tributary adrenal vein draining the adrenal mass. Right partial adrenalectomy was performed. Postoperatively, the patient's blood pressure and plasma aldosterone levels normalized. CONCLUSIONS S-AVS can be performed relatively easily before partial adrenalectomy using a catheter system with biplane cine angiography, which is a technique that is familiar to cardiologists.

Increase of chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes after acute myocardial infarction chymase activity after acute myocardial infarction.

A previous clinical study revealed elevation of chymase- and cathepsin G-dependent angiotensin II-forming activity (AIIFA) in the myocardium after acute myocardial infarction (AMI). This study examined the time course of chymase- and cathepsin G-dependent AIIFA in circulating mononuclear leukocytes (CML) after AMI. Consecutive patients with AMI were recruited. Chymase- and cathepsin G-dependent AIIFA in CML were assayed using a modified angiotensin I substrate with Nma/Dnp fluorescence quenching. The changes of CML AIIFA were monitored over time in the patients. Fifteen consecutive AMI patients admitted to our hospital were recruited. At 1 day after the admission, CML chymase- and cathepsin G-dependent AIIFA were 2.9- and 1.7-fold higher than at discharge, respectively. The ratio of chymase-dependent AIIFA to total AIIFA was significantly increased. AIIFA gradually decreased over time after the admission. The peak value of chymase- and cathepsin G-dependent AIIFA was significantly correlated with the maximum levels of aspartate aminotransferase (r = 0.53, 0.64), lactate dehydrogenase (r = 0.57, 0.62), and creatine kinase (r = 0.60, 0.65). This is the first evidence that chymase- and cathepsin G-dependent AIIFA is elevated in CML after AMI. Our data suggested that chymase-dependent AIIFA is increased in CML as well as in the myocardium after AMI, and that the level of chymase-dependent AIIFA might reflect the severity of infarction.

Renoprotective Benefit of Tolvaptan in Acute Decompensated Heart Failure Patients With Loop Diuretic-Resistant Status.

BACKGROUND: While reduction of accumulated body fluid using loop diuretics is a commonly used therapeutic option for acute heart failure (AHF), some patients, especially those with chronic kidney disease (CKD), show significantly poor treatment response to loop diuretics. Tolvaptan (TLV) has shown effectiveness against AHF in several studies. We have been using TLV for AHF treatment, and it displayed favorable outcome even in patients with CKD. This study aimed to assess the therapeutic effectiveness of TLV in AHF patients. METHODS: Ninety-nine AHF patients who were hospitalized were assessed retrospectively. Patients were divided into two groups: TLV treatment (TLV group, n = 39) and conventional treatment (non-TLV group, n = 60). We retrospectively examined the efficacy of TLV combination therapy for renal insufficiency complications and loop diuretic-resistant AHF patients, and the detail analysis was performed for heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF) in patients. RESULTS: Changes in serum electrolyte levels before and after the treatment were similar in both groups. Although the patients in the TLV group at baseline displayed significantly lower estimated glomerular filtration rate (eGFR) indicating renal insufficiency probably due to higher dose of loop diuretics, the incidence of worsening renal function (WRF) was significantly lower than those in non-TLV group in HFpEF (TLV: 2.5% vs. non-TLV: 15.4%, P = 0.01). We performed logistic regression analysis and found that TLV was an independent contributing factor for reducing WRF (odds ratio: 0.14, 95% CI: 0.02 - 0.98, P = 0.04). CONCLUSIONS: Our results suggest that TLV application in acute stage may be renoprotective for AHF patients with CKD, especially in HFpEF.

Correction to: Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

Unfortunately, the Fig. 1 was published incorrectly in the original publication of the article. The correct figure is as below.

Reduction of Blood Pressure Following After Renal Artery Adventitia Stripping During Total Nephroureterectomy: Potential Effect of Renal Sympathetic Denervation.

BACKGROUND Catheter-based renal sympathetic denervation has been reported to be effective for treatment resistance hypertension in Australia and Europe. However, in the blinded SYMPLICITY HTN-3 trial, renal denervation did not achieve a significant decrease in blood pressure (BP) in comparison to sham controls. There have been various discussions on the factors that influenced this result. CASE REPORT Two men on antihypertensive therapy underwent unilateral radical nephroureterectomy for cancer of the renal pelvis. When the renal artery adventitia was stripped and cauterized just before renal artery ligation, the measured BP of the 2 men increased after stripping adventitia and decreased gradually after cauterization of the renal artery. This was presumably due to removal of renal artery sympathetic nerves, similar to the mechanism of catheter-based renal sympathetic denervation, although anesthesia, fluid infusion, and/or mesenteric traction may have had an influence. CONCLUSIONS A similar strategy involving thoracolumbar sympathectomy was reported about 50 years ago. The clinically significant blood pressure reduction in these patients suggests renal denervation is effective.

Effect of Angiotensin-Converting Enzyme Inhibitor/Calcium Antagonist Combination Therapy on Renal Function in Hypertensive Patients With Chronic Kidney Disease: Chikushi Anti-Hypertension Trial - Benidipine and Perindopril.

BACKGROUND: Appropriate blood pressure control suppresses progression of chronic kidney disease (CKD). If an angiotensin-converting enzyme (ACE) inhibitor is ineffective, adding a calcium antagonist is recommended. We compared the long-term effect of two ACE inhibitor/calcium antagonist combinations on renal function in hypertensive patients with CKD. METHODS: Patients who failed to achieve the target blood pressure (systolic/diastolic: < 130/80 mm Hg) with perindopril monotherapy were randomized to either combined therapy with perindopril and the L-type calcium antagonist amlodipine (group A) or perindopril and the T/L type calcium antagonist benidipine (group B). The primary endpoint was the change of the estimated glomerular filtration rate (eGFR) after 2 years. Eligible patients had a systolic pressure ≥ 130 mm Hg and/or diastolic pressure ≥ 80 mm Hg and CKD (urine protein (+) or higher, eGFR < 60 min/mL/1.73 m2). RESULTS: After excluding 38 patients achieving the target blood pressure with perindopril monotherapy, 121 patients were analyzed (62 in group A and 59 in group B). Blood pressure decreased significantly in both groups, but there was no significant change of the eGFR. However, among patients with diabetes, eGFR unchanged in group B (n = 37, 59.1 ± 15.1 vs. 61.2 ± 27.9, P = 0.273), whereas decreased significantly in group A (n = 31, 57.3 ± 16.0 vs. 53.7 ± 16.7, P = 0.005). CONCLUSIONS: In hypertensive patients with diabetic nephropathy, combined therapy with an ACE inhibitor and T/L type calcium antagonist may prevent deterioration of renal function more effectively than an ACE inhibitor/L type calcium antagonist combination.

Association between discordance of LDL-C and non-HDL-C and clinical outcomes in patients with stent implantation: from the FU-Registry.

It is not yet clear whether the discordance of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) predicts the follow-up clinical outcome (major adverse cardiovascular events: MACEs) in patients with coronary stent implantation. Among 2015 patients with coronary stent implantation (Fukuoka University [FU]-Registry), excluding those with acute coronary syndrome or hemodialysis, we selected 801 patients who had undergone successful stent implantation with a follow-up until 18 months, and classified them into 3 groups according to baseline LDL-C and non-HDL-C levels [percentile(P)non-HDL-C more than (P)LDL-C, (P)non-HDL-C equal to (P)LDL-C, and (P)non-HDL-C less than (P) LDL-C]. We found that the discordance of (P)LDL-C and (P)non-HDL-C was not a significant predictor of MACEs. Higher LDL-C level was consistently and independently associated with higher incidences of MACEs after controlling for conventional risk factors and the type of stent used by multivariate Cox regression analyses. In conclusion, LDL-C levels are more important than non-HDL-C levels and the discordance of LDL-C and non-HDL-C levels as predictors of MACEs in patients with stable angina after stent implantation.