Severe Aortic Stenosis in Dialysis Patients

Background: Characteristics and prognosis of hemodialysis patients with severe aortic stenosis have not yet been well defined. Methods and Results: The CURRENT AS (contemporary outcomes after surgery and medical treatment in patients with severe aortic stenosis) registry, a Japanese multicenter registry, enrolled 3815 consecutive patients with severe aortic stenosis. There were 405 hemodialysis patients (initial aortic valve replacement [AVR] group: N=135 [33.3%], and conservative group: N=270) and 3410 nonhemodialysis patients (initial AVR group: N=1062 [31.1%], and conservative group: N=2348). The median follow‐up duration after the index echocardiography was 1361 days, with 90% follow‐up rate at 2 years. The cumulative 5‐year incidence of all‐cause death was significantly higher in hemodialysis patients than in nonhemodialysis patients in both the entire cohort (71% versus 40%, P<0.001) and in the initial AVR group (63.2% versus 17.9%, P<0.001). Among hemodialysis patients, the initial AVR group as compared with the conservative group was associated with significantly lower cumulative 5‐year incidences of all‐cause death (60.6% versus 75.5%, P<0.001) and sudden death (10.2% versus 31.7%, P<0.001). Nevertheless, the rate of aortic valve procedure–related death, which predominantly occurred within 6 months of the AVR procedure, was markedly higher in the hemodialysis patients than in the nonhemodialysis patients (21.2% and 2.3%, P<0.001). Conclusions: Among hemodialysis patients with severe aortic stenosis, the initial AVR strategy as compared with the conservative strategy was associated with significantly lower long‐term mortality risk, particularly the risk for sudden death, although the effect size for the survival benefit of the initial AVR strategy was smaller than that in the nonhemodialysis patients

Details on the effect of very short dual antiplatelet therapy after drug-eluting stent implantation in patients with high bleeding risk: insight from the STOPDAPT-2 trial

Previously we briefly reported the effect of 1-month dual antiplatelet therapy (DAPT) for patients with high bleeding risk (HBR) receiving percutaneous coronary intervention (PCI) in the STOPDAPT-2 trial, but full analysis data have not been available. We conducted post hoc subgroup analysis regarding the effect of very short DAPT for HBR patients in STOPDAPT-2 trial. The primary endpoint was a 1-year composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and bleeding (TIMI major/minor bleeding) outcomes. Major secondary endpoints were 1-year cardiovascular composite endpoint and bleeding endpoint. HBR was defined by the academic research consortium (ARC) HBR criteria. Among the 3009 study patients, 1054 (35.0%) were classified as HBR and 1955 (65.0%) were as non-HBR. There were no significant interactions between HBR/non-HBR subgroups and the assigned DAPT group on the primary endpoint (HBR; 3.48% vs. 5.98%, HR 0.57, 95% CI 0.32-1.03, and non-HBR; 1.81% vs. 2.36%, HR 0.78, 95% CI 0.42-1.45; P for interaction = 0.48), the major secondary cardiovascular endpoint (HBR; 3.07% vs. 4.03%, HR 0.77, 95% CI 0.40-1.48, and non-HBR; 1.41% vs. 1.61%, HR 0.89, 95% CI 0.43-1.84; P for interaction = 0.77), and the major secondary bleeding endpoint (HBR; 0.41% vs. 2.71%, HR 0.15, 95% CI 0.03-0.65, and non-HBR; 0.40% vs. 0.85%, HR 0.48, 95% CI 0.14-1.58; P for interaction = 0.22). In conclusion, the effects of 1-month DAPT for the primary and major secondary endpoints were consistent in HBR and non-HBR patients without any significant interactions. The benefit of 1-month DAPT in reducing major bleeding was numerically greater in HBR patients.Clinical trial registration Short and optimal duration of dual antiplatelet therapy after everolimus-eluting cobalt-chromium stent-2 [STOPDAPT-2]; NCT02619760

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year

# ja-Kana

京都大学0048新制・論文博士博士(医学)乙第13207号論医博第2161号新制||医||1031(附属図書館)(主査)教授 福原 俊一, 教授 湊谷 謙司, 教授 小池 薫学位規則第4条第2項該当Doctor of Medical ScienceKyoto UniversityDFA

Excess of Aminopeptidase A in the Brain Elevates Blood Pressure via the Angiotensin II Type 1 and Bradykinin B2 Receptors without Dipsogenic Effect

Aminopeptidase A (APA) cleaves angiotensin (Ang) II, kallidin, and other related peptides. In the brain, it activates the renin angiotensin system and causes hypertension. Limited data are available on the dipsogenic effect of APA and pressor effect of degraded peptides of APA such as bradykinin. Wistar-Kyoto rats received intracerebroventricular (icv) APA in a conscious, unrestrained state after pretreatment with (i) vehicle, (ii) 80 μg of telmisartan, an Ang II type-1 (AT1) receptor blocker, (iii) 800 nmol of amastatin, an aminopeptidase inhibitor, and (iv) 1 nmol of HOE-140, a bradykinin B2 receptor blocker. Icv administration of 400 and 800 ng of APA increased blood pressure by 12.6 ± 3.0 and 19.0 ± 3.1 mmHg, respectively. APA did not evoke drinking behavior. Pressor response to APA was attenuated on pretreatment with telmisartan (vehicle: 22.1 ± 2.2 mmHg versus telmisartan: 10.4 ± 3.2 mmHg). Pressor response to APA was also attenuated with amastatin and HOE-140 (vehicle: 26.5 ± 1.1 mmHg, amastatin: 14.4 ± 4.2 mmHg, HOE-140: 16.4 ± 2.2 mmHg). In conclusion, APA increase in the brain evokes a pressor response via enzymatic activity without dipsogenic effect. AT1 receptors and B2 receptors in the brain may contribute to the APA-induced pressor response

Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Steroid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial

Background/Aims: Angiotensin receptor blockers (ARBs) may be beneficial for clinical remission during conventional therapy with tonsillectomy and steroid pulse (TSP) for active IgA nephropathy. Methods: Seventy-seven patients with active IgA nephropathy were randomly assigned to the control arm with conventional regimen (TSP followed by oral prednisolone) (n = 37) or the ARB arm with conventional regimen plus ARB candesartan for the first 6 months (n = 40). Patients not achieving proteinuria remission at 12 months in either arm were administered candesartan, which was titrated until the 24-month follow-up. The primary endpoints were remission of proteinuria (< 0.3 g/gCr) and hematuria at 12 months. Results: Baseline proteinuria (g/g Cr) were comparable between the control and ARB arm (1.02 vs. 0.97, P = 0.97). Similarly, cumulative remission rates at 6, 12, and 24 months were comparable between the control and ARB arms (37.8% vs. 35% [P = 0.80], 48.7% vs. 38.5% [P = 0.37], 71.4% vs. 51.3% [P = 0.08]). Proteinuria, which was slightly worse in the control arm than in the ARB arm at 6 months, was comparable afterwards (0.20 vs. 0.23 g/g Cr at 12 months; 0.12 vs. 0.13 g/g Cr at 24 months). Significant reductions observed in urinary angiotensinogen were almost comparable between the two treatment arms at both 6 and 12 months. Conclusion: Early candesartan treatment combined with TSP may not benefit clinical remission regardless of the blood pressure. ARB titration later during the treatment might provide benefit for patients with active IgA nephropathy

Responsiveness of α2-adrenoceptor/I1-imidazoline receptor in the rostral ventrolateral medulla to cardiovascular regulation is enhanced in conscious spontaneously hypertensive rat

Stimulation of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla decreases the blood pressure via sympathoinhibition. However, alteration of receptor responses in genetically hypertensive rats remains unclear. We examined cardiovascular responses of α2-adrenoceptor/I1-imidazoline receptor agonist and antagonists microinjected into the rostral ventrolateral medulla of conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Injection of 2-nmol clonidine—an α2-adrenoceptor/I1-imidazoline receptor agonist—unilaterally into the rostral ventrolateral medulla decreased the blood pressure, heart rate, and renal sympathetic nerve activity; the responses were significantly enhanced in spontaneously hypertensive rats than in Wistar Kyoto rats. Co-injection of 2-nmol 2-methoxyidazoxan (a selective α2-adrenoceptor antagonist) or 2-nmol efaroxan (an I1-receptor antagonist) with 2 nmol of clonidine attenuated the hypotensive and bradycardic effects of clonidine-only injection. Injection of 2-methoxyidazoxan alone increased the blood pressure and heart rate in spontaneously hypertensive rats, but not in Wistar Kyoto rats. These results suggest enhanced responsiveness of α2-adrenoceptor/I1-imidazoline receptors in the rostral ventrolateral medulla of spontaneously hypertensive rats