Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

The mid-term effect of intravascular ultrasound on endovascular interventions for lower extremity peripheral arterial disease: A systematic review and meta-analysis.

OBJECTIVE: Intravascular ultrasound (IVUS) is an important adjunctive tool for patients with lower extremity peripheral arterial disease (PAD) undergoing endovascular therapy (EVT). The evidence regarding the advantages of IVUS use is evolving, and recent studies have reported conflicting results. We aimed to perform a meta-analysis to evaluate the efficacy of IVUS during angiography-guided EVT for patients with PAD. METHODS: MEDLINE and EMBASE were searched through April 2023 to identify studies that investigated the outcomes of IVUS with angiography-guided EVT vs angiography-alone-guided EVT. The primary outcome was restenosis/occlusion rate; secondary outcomes were target lesion revascularization, major amputation, and mortality. RESULTS: One randomized controlled trial and 14 observational studies, largely of moderate quality, were included, yielding a total of 708,808 patients with 709,189 lesions that were treated with IVUS-guided EVT (n = 101,405) vs angiography-alone (n = 607,784). Compared with angiography alone, IVUS-guided EVT was associated with a non-significant trend towards decreased restenosis/occlusion (relative risk [RR], 0.74; 95% confidence interval [CI], 0.54-1.00; I2 = 60%). Although the risk of target lesion revascularization and mortality were comparable (RR, 0.85; 95% CI, 0.65-1.10; I2 = 70%; RR, 1.01; 95% CI, 0.79-1.28; I2 = 43%, respectively), the use of IVUS was also associated with significantly lower risk of major amputation (RR, 0.74; 95% CI, 0.67-0.82; I2 = 47%). Subgroup analysis focusing on femoropopliteal disease demonstrated significantly higher patency (RR, 0.72; 95% CI, 0.52-0.98; I2 = 73%). However, superiority with major amputation was not observed. CONCLUSIONS: IVUS-guided EVT for PAD may possibly be associated with a lower major amputation rate compared with angiography alone-guided EVT, although the difference in patency remained an insignificant trend in favor of IVUS-guided EVT. Adjunctive use of IVUS during EVT may be beneficial, and further prospective studies are warranted to delineate this relationship and the applicability of this technology in routine practice.

Prognostic Impact of Reduced Left Ventricular Ejection Fraction After Endovascular Therapy for Lower Extremities.

BACKGROUND: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT).Methods and Results: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52). CONCLUSIONS: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.

Clinical efficacy of tolvaptan in acute decompensated heart failure patients with severe aortic stenosis and atrial fibrillation: a sub-analysis from the LOHAS registry.

BACKGROUND: Severe aortic valve stenosis (AS) and atrial fibrillation (AF) are risk factors of hemodynamic instability in heart failure (HF) management due to low cardiac output, respectively. Therefore, the treatment of HF due to severe AS complicated with AF is anticipated to be difficult. Tolvaptan, a vasopressin V2 receptor inhibitor, is effective in controlling acute decompensated heart failure (ADHF) with hemodynamic stability. However, its clinical efficacy against ADHF caused by AS with AF remains to be determined. METHODS: Clinical information (from September 2014 to December 2017) of 59 patients diagnosed with ADHF due to severe AS (20 patients with AF; 39 patients with sinus rhythm [SR]) was obtained from the LOHAS registry. The registry collected data from seven hospitals and assessed the short-term effects of tolvaptan in patients hospitalized for ADHF with severe AS. We attempted to identify clinical differences from baseline up to 4 days, comparing patients with AF (AF group) versus those with SR (SR group). RESULTS: There were no significant differences between the groups in age (83.7 ± 4.5 vs. 85.8 ± 6.9 years, respectively; p = 0.11) and aortic valve area (0.60 [0.46-0.73] vs. 0.56 [0.37-0.70] cm2, respectively; p = 0.50). However, left atrial volume was larger (104 [85-126] vs. 87 [64-103] mL, respectively; p < 0.01), whereas stroke volume was lower (51.6 ± 14.8 vs. 59.0 ± 18.7 mL, respectively; p = 0.08) in the AF group versus the SR group. Body weight decreased daily from baseline up to day 4 in both groups (from 55.4 to 53.2 kg [p < 0.01] and from 53.5 to 51.0 kg [p < 0.01], respectively) without change in heart rate. Notably, the systolic blood pressure decreased slightly in the AF group after 2 days of treatment with tolvaptan. CONCLUSIONS: Short-term treatment with tolvaptan improved HF in patients hospitalized for severe AS, regardless of the presence of AF or SR. After achieving sufficient diuresis, a slight decrease in blood pressure was observed in the AF group, suggesting an appropriate timeframe for safe and effective use of tolvaptan.

Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Comparison of the incidence of depression before and after endovascular treatment in patients with lower limb peripheral artery disease.

Depression is a chronic illness that affects mood, physical health, and overall vitality and quality of life. Depression has been associated with an increased risk of all-cause and cardiovascular mortality among patients with peripheral arterial disease (PAD). Therefore, this study aimed to compare the incidence of depression before and after endovascular treatment in patients with lower limb PAD. This is an important clinical issue considering the worldwide increase in PAD with the aging population and the known negative impact of depression on recovery. This was a retrospective sub-analysis of data from the Tokyo Peripheral Vascular Intervention Study using the TOMA-CODE registry. The presence and extent of depressive symptoms were evaluated using the patient health questionnaire (PHQ-9), with a depressive tendency score of ≥ 5. The PHQ-9 score was evaluated before endovascular treatment (EVT) and at 4 (± 1) weeks after EVT. The study population consisted of 87 patients who completed the PHQ-9 before EVT, with 76 completing the post-EVT PHQ-9. Of these 76, 19 had a pre-EVT score ≥ 5. Overall, there was no difference in the pre- and post-EVT scores (P = 0.091). There was no significant change in the 19 patients with a pre-EVT score ≥ 5 (mean 9.2 ± 4.4); however, there was a tendency to improve in the pre- to post-EVT score (mean, 6.9 ± 5.2; P = 0.059). Diabetes was a significant negative factor for pre- to post-EVT score improvement (P = 0.023). Overall, symptoms of depression showed the tendency to improve at 30 days post-EVT. However, diabetes was associated with lower improvement in symptoms.

Left Ventricular End-Systolic Diameter May Predict Persistent Heart Failure with Reduced Ejection Fraction.

Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

Sex differences in the prevalence and prognostic impact of physical frailty and sarcopenia among older patients with heart failure.

BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

Sarcopenic obesity is associated with impaired physical function and mortality in older patients with heart failure: insight from FRAGILE-HF.

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

Prognostic Impact of Landiolol in Patients with Acute Heart Failure and Atrial Fibrillation with Rapid Ventricular Rates: A Pilot Observational Study.

INTRODUCTION: Guidelines recommend ventricular rate control to <130 bpm during atrial fibrillation (AF) in patients with acute decompensated heart failure (ADHF) to avoid aggravating deteriorations in cardiac outputs. We aimed to evaluate the prognostic impact of landiolol in patients with ADHF and AF. METHODS: This observational study included 60 patients who were urgently hospitalized with ADHF and presented with AF and a heart rate (HR) ≥130 bpm at admission. The patients were assigned to the landiolol group (n = 37) or the reference group (n = 23) based on their intravenous landiolol use within 24 h after admission. The primary endpoint was death from any cause. RESULTS: The groups' baseline characteristics were similar. A significant HR reduction occurred in the landiolol group at 2 h after admission. Compared with the reference group, the HR was significantly lower (111.6 vs. 97.9 bpm, p = 0.02) and the absolute HR reduction was greater (-32.2 vs. -50.0 bpm, p = 0.006) in the landiolol group at 48 h after admission. The landiolol group's mortality rate was significantly lower than that in the reference group (log-rank test, p = 0.032). landiolol use within 24 h after admission was independently associated with lower all-cause mortality (adjusted hazard ratio: 0.15, 95% confidence interval: 0.02-0.92). CONCLUSION: Patients with ADHF and AF who received landiolol for rate control during the acute phase had better prognoses than those who did not receive landiolol.

Multidomain Frailty as a Therapeutic Target in Elderly Patients with Heart Failure.

Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

[Retrieval of the Ruptured Balloon during Transcatheter Aortic Valve Replacement without Complications:Report of a Case].

A 77-year-old man with a history of coronary artery bypass grafting underwent transcatheter aortic valve replacement(TAVR) via femoral artery for severe aortic stenosis(AS). Preoperative computed tomography(CT) showed there was mild calcification at the sino-tubular junction(STJ). Sapien 3 was implanted successfully, but at the end of full inflation, the balloon ruptured. The ruptured balloon was retrieved without any remnants or vascular injury. A transesophageal echocardiogram showed adequate valve deployment. TAVR with its less invasiveness has become an alternative treatment for high risk patients who cannot endure surgical aortic valve replacement(SAVR). Although there are several complications related to TAVR, they can be predicted in many cases by analysis of preoperative imaging. In this case, the rupture of the balloon was not predicted because there was no significant calcification at the STJ. Caution should be taken even though there seems to be low risk of complications by preoperative imaging modalities.

Differences in Intravascular Ultrasound Measurement Values Between Treatment Modalities for Restenosis in Femoropopliteal Lesions.

BACKGROUND: The risk of restenosis after intervention is higher in femoropopliteal than in aortoiliac lesions. However, the appropriate endovascular therapy (EVT) for preventing restenosis after intervention for femoropopliteal lesions remains unknown. This study aimed to elucidate the relationship between lesion characteristics and patency after EVT using intravascular ultrasound (IVUS) measurement and to determine the predictors of restenosis on IVUS.Methods and Results:This prospective observational study was performed at 18 Japanese centers. We evaluated the lesion characteristics before and after EVT for femoropopliteal lesion using IVUS. Angiographic or duplex ultrasound follow-up was performed at 1 year after EVT. A total of 263 lesions underwent EVT between December 2016 and December 2017. In total, 20 lesions (8 cases of isolated common femoral artery lesion and 12 cases of restenosis lesion) were excluded, and 243 lesions were enrolled in this study. A total of 181 lesions were treated with stent placement, and 62 lesions were treated only with balloon angioplasty. In the case of stent use, a larger distal plaque burden was associated with restenosis, while a lower calcification angle was associated with higher patency in the case of balloon angioplasty alone. CONCLUSIONS: The factors related to patency differed depending on the treating modality. The findings suggest that IVUS is a useful tool for predicting patency because it can provide a more accurate evaluation after EVT for femoropopliteal lesions.

Hemodynamic and Lesion Characteristics Associated with Discordance between the Instantaneous Wave-Free Ratio and Fractional Flow Reserve.

BACKGROUND: The instantaneous wave-free ratio (iFR) is an invasive coronary physiological index that is not inferior to fractional flow reserve- (FFR-) guided revascularization. The indexes of iFR and FFR are similar and closely correlated, but there are a few key differences. Previous studies suggested that patient characteristics and lesion severity could induce discordance between iFR and FFR. This study aimed to clarify the hemodynamics and lesion characteristics that influence discordance between iFR and FFR. METHODS: In this retrospective study, we enrolled 225 patients (304 lesions) who underwent clinically indicated invasive coronary angiography and both iFR and FFR examinations between 2012 and 2017. We included only patients who underwent right heart catheterization and had blood pressure and heart rates recorded immediately prior to iFR and FFR. RESULTS: Discordance (iFR ≤0.89 and FFR >0.8 or iFR >0.89 and FFR ≤0.8) was observed in 80 lesions (26.3%). The heart rate, rate-pressure product, and cardiac index tended to be higher in the iFR ≤0.89 group than in the iFR >0.89 group. These trends were not seen between the FFR ≤0.8 group and FFR >0.8 group. A multivariate analysis showed that independent predictors of iFR ≤0.89 and FFR >0.8 discordance were female sex and higher rate-pressure product. iFR >0.89 and FFR ≤0.8 discordance was rare in hemodialysis patients. CONCLUSION: Even if iFR is functionally significant in intermediate stenosis, additional FFR evaluations should be considered for women, especially those with a high rate-pressure product, to avoid unnecessary percutaneous coronary intervention. If iFR is not functionally significant with intermediate stenosis in hemodialysis patients, then further FFR evaluations are unnecessary.

Safety and Efficacy of Low-Dose Prasugrel as Part of Triple Therapy With Aspirin and Oral Anticoagulants in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention　- From the TWMU-AF PCI Registry.

BACKGROUND: Using the standard maintenance dose of prasugrel (10 mg/day) as part of triple therapy with aspirin and an oral anticoagulant (OAC) is not recommended in the current guidelines because it increases the risk of bleeding compared with clopidogrel. However, the safety and efficacy of low-dose prasugrel (3.75 mg/day) as part of triple therapy has not been reported. Methods and Results: We registered 816 consecutive patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) from January 2011 to June 2016 at 8 hospitals in Japan. We examined the clinical outcomes of patients who received either low-dose prasugrel (n=57) or clopidogrel (n=451) as part of triple therapy after PCI. The incidences of bleeding (TIMI major and minor) and major adverse cerebrocardiovascular events (MACCE; all-cause death, nonfatal myocardial infarction, stent thrombosis, unplanned revascularization, and stroke) were evaluated. The cumulative 1-year incidence of bleeding was not significantly different (prasugrel 5.6% vs. clopidogrel 8.1%, log-rank P=0.55). In addition, the cumulative 1-year incidence of MACCE was also not significantly different (prasugrel 11.5% vs. clopidogrel 12.3%, log-rank P=0.88). CONCLUSIONS: Low-dose prasugrel, as part of triple therapy, did not increase the risk of bleeding compared with clopidogrel. Therefore, it can be an alternative to clopidogrel for patients with AF undergoing PCI.

Variations in the eicosapentaenoic acid-arachidonic acid ratio associated with age in acute myocardial infarction patients undergoing primary percutaneous coronary intervention.

Acute myocardial infarction (AMI) is a life-threatening disease, and its incidence has been increasing even in the young population. Although a low eicosapentaenoic acid (EPA)-arachidonic acid (AA) ratio is associated with an increased risk of coronary artery disease, the effect of age on EPA/AA ratios in AMI patients remains unclear. This study aimed to clarify the independent polyunsaturated fatty acid (PUFA)-related determinants of age in younger and older AMI patients. A total of 153 consecutive patients who underwent primary percutaneous coronary interventions (PCIs) for de novo AMIs were enrolled in this study. Patients' background data, including PUFA and lipid profiles during PCI, were evaluated retrospectively. The EPA/AA ratio correlated positively with age (r = 0.21; P = 0.011) and increased markedly from age 60 years. Patients aged < 60 years (n = 35) had a lower mean EPA/AA ratio (0.25 ± 0.16) than patients aged ≥ 60 years (n = 118) (0.38 ± 0.25) (P < 0.001). The AA level was more dependent on age than on EPA level (r = - 0.34, P < 0.001 vs. r = 0.12, P = 0.16). The multivariate analysis revealed that a 0.1 EPA/AA ratio increase (odds ratio 1.50; 95% confidence interval 1.09-2.06), body mass index, triglyceride level, and aspirin administration were independently associated with the age stratification of AMI patients. The EPA/AA ratio was higher in younger AMI patients who have undergone primary PCIs than in older patients. Younger population at risk for AMI should be managed with multiple interventions including PUFA profiling.

[Transcatheter Aortic Valve Replacement for Aortic Stenosis with Complicated Anatomy;Report of a Case].

An 89-year-old female was admitted with progressive dyspnea. She had history of old myocardial infarction. Echocardiography revealed severe aortic valve stenosis (AS) with bicuspid aortic valve (BAV). Computed tomography (CT) detected an ascending aortic aneurysm and a left ventricular apex aneurysm. CT confirmed the BAV with severe calcification and tight horizontal angulation. We scheduled transfemoral transcatheter aortic valve replacement (TAVR). While careful wire manipulation, the valve was successfully implanted. BAV is frequently associated with dilation of the ascending aorta. The coexistence of an ascending aortic aneurysm would indicate surgery in order to be able to treat both lesions simultaneously and to avoid catastrophic stent-related complications, such as prosthesis dislodgment and aneurysm rupture. In the present case, there was also risk of left ventricular rupture due to wire manipulation. The horizontal aorta also complicates accurate positioning of the prosthesis during TAVR. This case highlights TAVR for AS with complicated anatomy.

Clinical Characteristics and Long-Term Outcomes of Rotational Atherectomy　- J2T Multicenter Registry.

BACKGROUND: Rotational atherectomy (RA) is an adjunct tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the long-term clinical outcomes of RA use remain unclear in this drug-eluting stent era.Methods and Results:This multi-center registry assessed the characteristics and outcomes of patients treated by RA for calcified coronary lesions between 2004 and 2015. Among 1,090 registered patients, mean age was 70±10 years and 815 (75%) were male. Sixty percent of patients had diabetes mellitus and 27.7% were receiving hemodialysis. The procedure was successful in 96.2%. In-hospital death occurred in 33 patients (3.0%), and 14 patients (1.3%) developed definite/probable stent thrombosis. During the median follow-up period of 3.8 years, the incidence of major adverse cardiac events (MACE), defined as all-cause death, acute coronary syndrome, stent thrombosis, target vessel revascularization and stroke, was 46.7%. On multivariable Cox hazard analysis, hemodialysis (HR, 2.08; 95% CI: 1.53-2.86; P<0.0001) and age (HR, 1.03; 95% CI: 1.01-1.04; P<0.0001) were strong independent predictors of MACE. Conversely, statin treatment was associated with lower incidence of MACE (P=0.035). CONCLUSIONS: This study has provided the largest Japanese dataset for long-term follow-up of RA. Although RA in calcified lesions appears feasible with a high rate of procedural success, a high incidence of MACE was observed.

Cardiovascular Outcome and Mortality in Patients Undergoing Endovascular Treatment for Symptomatic Peripheral Artery Disease　- Short-Term Results of the Toma-Code Registry.

BACKGROUND: The present study was performed to clarify whether the preoperative clinical symptoms for endovascular therapy (EVT) can predict post-EVT death and cardiovascular prognosis in Japanese patients with peripheral artery disease (PAD), including acute disease.Methods and Results:The TOkyo taMA peripheral vascular intervention research COmraDE (Toma-Code) Registry is a Japanese prospective cohort of 2,321 consecutive patients with PAD treated with EVT, in 34 hospitals in the Kanto and Koshin'etsu regions, from August 2014 to August 2016. In total, 2,173 symptomatic patients were followed up for a median of 10.4 months, including 1,370 with claudication, 719 with critical limb ischemia (CLI), and 84 with acute limb ischemia (ALI) for EVT. The all-cause death rates per 100 person-years for claudication, CLI and ALI were 3.5, 26.2, and 24.5, respectively. Similarly, major adverse cardiac and cerebrovascular events (MACCE) rates per 100 person-years for claudication, CLI, ALI, and others were 5.2, 31.2, and 29.7, respectively. After adjusting for the predictors of all-cause death and MACCE, namely, age, body mass index <18, diabetes mellitus, dialysis, cerebrovascular disease, and low left ventricular ejection fraction, it was determined that the preoperative indication for EVT was strongly associated with all-cause death and MACCE. CONCLUSIONS: The preoperative clinical symptoms for EVT can predict the prognosis in patients with PAD undergoing EVT.

Good response to tolvaptan shortens hospitalization in patients with congestive heart failure.

Tolvaptan has been gradually spread to use as a potent diuretic for congestive heart failure in the limited country. However, the response to this aquaretic drug still is unpredictable. A total of 92 patients urgently hospitalized due to congestive heart failure and treated with tolvaptan in addition to standard treatment was retrospectively analyzed. Responder of tolvaptan treatment was defined as a patient with peak negative fluid balance greater than 500 mL/day, and clinical profiles were compared between 76 responders and 16 non-responders. Responders started to increase daily urine volume (UV) from Day 1 through Day 3. In contrast, non-responders showed no significant increase in daily UV from the baseline up to Day 5. Time between admission and tolvaptan administration was shorter in responders, even without statistical significance (3.3 vs. 4.6 days, p = 0.053). Multivariate analysis revealed that blood urea nitrogen (BUN) [cutoff: 34 mg/dL, odds ratio (OR) 9.0, 95% confidence interval (CI) 1.42-57.3, p < 0.01] and plasma renin activity (PRA) (cutoff: 4.7 ng/mL/h, OR 6.1, 95% CI 1.01-36.4, p < 0.01) at baseline were independent predictors for tolvaptan responsiveness. It suggests that renal perfusion may affect tolvaptan-induced UV. Finally, durations of stay in intensive care unit and total hospitalization were significantly shorter in responders (median: 6.0 vs. 13.0 days, p = 0.022; 15.0 vs. 25.0 days, p = 0.016, respectively). Responders of tolvaptan have lower BUN and renin activity at baseline, and shorten hospitalization period. Trial Registration The study was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) with the identifier UMIN000023594. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024988.