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Background The effects of aspirin‐free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. Methods and Results We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT‐3 (Short and Optimal Duration of Dual Antiplatelet Therapy‐3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46–2.35]; no‐OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73–1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64–3.62]; no‐OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83–1.42]; P for interaction =0.46). Conclusions The no‐aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no‐aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Abstract Background Delirium is common in critically ill patients. Haloperidol has long been used for the treatment of delirium. Dexmedetomidine has recently been used to treat delirium among intubated critically ill patients. However, the efficacy of dexmedetomidine for delirium in non-intubated critically ill patients remains unknown. We hypothesize that dexmedetomidine is superior to haloperidol for sedation of patients with hyperactive delirium, and would reduce the prevalence of delirium among non-intubated patients after administration. We will conduct a randomized controlled trial to compare dexmedetomidine and haloperidol for the treatment of nocturnal hyperactive delirium in non-intubated patients in high dependency units (HDUs). Methods This is an open-label, parallel-group, randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for nocturnal hyperactive delirium in non-intubated patients at two HDUs of a tertiary hospital. We will recruit consecutive non-intubated patients who are admitted to the HDU from the emergency room, and allocate them in a 1:1 ratio to the dexmedetomidine or haloperidol group in advance. The allocated investigational drug will be administered only when participants develop hyperactive delirium (Richmond Agitation-Sedation Scale [RASS] score ≥1 and a positive score on the Confusion Assessment Method for the ICU between 19:00 and 6:00 the next day) during the night at an HDU. Dexmedetomidine is administered continuously, while haloperidol is administered intermittently. The primary outcome is the proportion of participants who achieve the targeted sedation level (RASS score of between -3 and 0) 2h after the administration of the investigational drug. Secondary outcomes include the sedation level and prevalence of delirium on the day following the administration of the investigational drugs, and safety. We plan to enroll 100 participants who develop nocturnal hyperactive delirium and receive one of the two investigational drugs. Discussion This is the first randomized controlled trial to compare the efficacy and safety of dexmedetomidine and haloperidol for sedation of non-intubated critically ill patients with hyperactive delirium in HDUs. The results of this study may confirm whether dexmedetomidine could be another option to sedate patients with hyperactive delirium. Trial registration Japan Registry of Clinical Trials, jRCT1051220015, registered on 21 April 2022.

Abstract Background Primary biliary cholangitis (PBC) is a chronic, progressive liver disease associated with dyslipidemia. There is a consensus that PBC does not accelerate coronary artery disease despite high cholesterol levels, so the screening test for the coronary artery is not routinely performed before liver transplantation (LT). To date, no report has described the potential risk of PBC-related dyslipidemia for developing acute coronary syndrome (ACS) after LT. Case presentation A 40-year-old Asian female with a known history of PBC underwent ABO-incompatible living-donor LT, with her husband as the donor. Although she had high cholesterol and triglyceride levels that were refractory to medications, she passed all routine preoperative examinations, including cardiopulmonary function tests and infection screenings. One week after LT, she developed ACS with 90% stenosis of both the left anterior descending artery and left circumflex artery. Emergent stent implantation was successfully performed followed by dual antiplatelet therapy. The long history of PBC and associated severe dyslipidemia for 10 years would have accelerated the atherosclerosis, causing latent stenosis in the coronary artery. Inapparent stenosis might have become apparent due to unstable hemodynamics during the acute phase after LT. Conclusions PBC-related dyslipidemia potentially brings a risk for developing ACS after LT. This experience suggests that the preoperative evaluation of the coronary artery should be considered for high-risk patients, especially those who have drug-resistant dyslipidemia.

There has been no previous prospective study evaluating 3-month dual antiplatelet therapy (DAPT) after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in patients with acute coronary syndrome (ACS). The STOPDAPT trial is a prospective multi-center single-arm study evaluating 3-month DAPT duration in all-comer population after CoCr-EES implantation. Among 1525 study patients enrolled from 58 Japanese centers, the present study compared the 1-year clinical outcomes between ACS patients (N = 487) and stable coronary artery disease (CAD) patients (N = 1038). In the ACS group, 228 patients (47%) had unstable angina and 259 patients (53%) had myocardial infarction. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis (ST) and TIMI major/minor bleeding. Thienopyridine was discontinued within 4-month in 455 patients (94.0%) in the ACS group and 977 patients (94.3%) in the stable CAD group. Cumulative 1-year incidence of and the adjusted risk for the primary endpoint were not significantly different between the ACS and stable CAD groups (2.3% vs. 3.0%, P = 0.42, and HR 0.94, 95%CI 0.44-1.87, P = 0.87). In the 3-month landmark analysis, cumulative incidence of the primary endpoint was also not significantly different between the ACS and stable CAD groups (1.3% vs. 2.4%, P = 0.16). There was no definite/probable ST through 1-year in both groups. In the propensity matched analysis, the cumulative 1-year incidence of the primary endpoint were similar between the ACS and stable CAD groups (2.3% versus 2.1%, P = 0.82). In conclusion, stopping DAPT at 3 months after CoCr-EES implantation in patients with ACS including 47% of unstable angina was as safe as that in patients with stable CAD.

Background Prior stroke is regarded as risk factor for bleeding after percutaneous coronary intervention (PCI). However, there is a paucity of data on detailed bleeding risk of patients with prior hemorrhagic and ischemic strokes after PCI. Methods and Results In a pooled cohort of 19 475 patients from 3 Japanese PCI studies, we assessed the influence of prior hemorrhagic (n=285) or ischemic stroke (n=1773) relative to no‐prior stroke (n=17 417) on ischemic and bleeding outcomes after PCI. Cumulative 3‐year incidences of the co‐primary bleeding end points of intracranial hemorrhage, non‐intracranial global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) moderate/severe bleeding, and the primary ischemic end point of ischemic stroke/myocardial infarction were higher in the prior hemorrhagic and ischemic stroke groups than in the no‐prior stroke group (6.8%, 2.5%, and 1.3%, P

Background Association of baseline hemoglobin levels with long‐term adverse events after percutaneous coronary interventions has not been yet thoroughly defined. We aimed to assess the clinical impact of baseline hemoglobin on long‐term ischemic and bleeding risk after percutaneous coronary intervention. Methods and Results Using the pooled individual patient‐level data from the 3 percutaneous coronary intervention studies, we categorized 19 288 patients into 4 groups: high‐normal hemoglobin (≥14.0 g/dL; n=7555), low‐normal hemoglobin (13.0–13.9 g/dL in men and 12.0–13.9 g/dL in women; n=5303), mild anemia (11.0–12.9 g/dL in men and 11.0–11.9 g/dL in women; n=4117), and moderate/severe anemia (

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5‐year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5‐year incidence of the primary outcome measure (a composite of aortic valve–related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P

BACKGROUND:Transcatheter aortic valve implantation (TAVI) is criticized by some as an expensive treatment in super-elder patients with limited life expectancy. However, there is a knowledge gap regarding the magnitude of clinical benefit provided by TAVI in comparison with conservative management in patients with severe aortic stenosis (AS) in real clinical practice, which would be important in the decision making for TAVI. METHODS:We combined two independent registries, namely CURRENT AS and K-TAVI registries. CURRENT AS was a multicenter registry enrolling 3815 consecutive patients with severe AS irrespective to treatment modalities between January 2003 and December 2011. K-TAVI was a multicenter, prospective registry including 449 consecutive patients with severe AS, who underwent TAVI with SAPIEN XT balloon-expandable valves between October 2013 and June 2016. In these 2 registries, 449 patients received TAVI and 894 patients were managed with conservative strategy. We conducted propensity score matching and finally obtained a cohort of 556 patients (278 patients for each group) for the analysis. The primary outcome measures were all-cause death and heart failure (HF) hospitalization at 2-year. RESULTS:The cumulative 2-year incidences of all-cause death and HF hospitalization were significantly lower in the TAVI group than in the conservative group (16.8% versus 36.6%, P

BackgroundPrediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention. Methods and ResultsWe developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO‐Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus‐Eluting Versus Everolimus‐Eluting Stent Trial) and NEXT (Nobori Biolimus‐Eluting Versus Xience/Promus Everolimus‐Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ≥75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (≥4, n=682) was associated with higher 3‐year incidence of thrombotic events than a score that was intermediate (2–3, n=1178) or low (0–1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P

Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P

Systemic thromboembolism associated with atrial fibrillation (AF) is usually caused by thrombi in the left atrial appendage and acute onset. We experienced an unusual case of a woman in her 60s who presented to the outpatient district having bilateral intermittent claudication for more than 1month, which turned out to be multiple thromboembolism from asymptomatic AF with tachycardia. She was also complicated with non-ischaemic dilated cardiomyopathy with reduced ejection fraction, consistent with arrhythmia-induced cardiomyopathy (AiCM), along with left atrial and left ventricular thrombi and thromboembolism in multiple organs. Rate control with beta-blockers was not effective. With the administration of amiodarone after adequate anticoagulation therapy, she returned to sinus rhythm, and the ejection fraction was restored. This case is instructive in that AiCM with AF can cause thrombosis in the left ventricle, and the patient may present with worsening intermittent claudication as a result of systemic embolism. [ABSTRACT FROM AUTHOR]

BACKGROUND: We sought to evaluate the impact of patient selection for the STOPDAPT-2 trial (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2) on clinical outcomes in a registry from a single center that participated in the STOPDAPT-2 trial. METHODS: Among 2190 consecutive patients who underwent percutaneous coronary intervention using stent in Kokura Memorial Hospital during the enrollment period of the STOPDAPT-2 trial, 521 patients had exclusion criteria such as inhospital major complications, anticoagulant use, or prior intracranial bleeding (ineligible group). Among 1669 patients who met the eligibility criteria (eligible group), 582 were enrolled (enrolled group) and 1087 were not enrolled (nonenrolled group) in the STOPDAPT-2 trial. The primary outcome measure was defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, stroke, or Thrombolysis in Myocardial Infarction major and minor bleeding. RESULTS: Compared with the enrolled group, patients in the nonenrolled group more often had high bleeding risk according to the Academic Research Consortium for High Bleeding Risk definition (52.6% versus 41.2%; P<0.001) and were frailer according to the Canadian Study of Health and Aging Clinical Frailty Scale (intermediate, 21.4% versus 14.1%; high, 6.4% versus 2.1%; P<0.001). The cumulative 1-year incidences of the primary outcome measure, all-cause death, and major bleeding were significantly higher in the nonenrolled group than in the enrolled group (7.2% versus 4.5%, P=0.03; 4.1% versus 0.9%, P<0.001; and 4.3% versus 2.1%, P=0.03, respectively) and in the ineligible group than in the eligible group (21.2% versus 6.3%, P<0.001; 9.9% versus 3.0%, P<0.001; and 13.5% versus 3.5%, P<0.001, respectively). CONCLUSIONS: Patients who were ineligible, eligible but not enrolled, and enrolled in the STOPDAPT-2 trial had different risk profiles and clinical outcomes, suggesting important implications in applying the trial results in daily clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal cutoff value of fraCTional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) remains unclear. METHODS: The current study population consisted of 93 patients with 139 vessels, who had suspeCTed coronary artery disease by computed tomography angiography and underwent invasive FFR. We evaluated diagnostic performance of FFRCT according to different FFRCT cutoff values and FFRCT ranges with invasive FFR ≤0.80 as the reference standard. RESULTS: In per-vessel analysis, median invasive FFR was 0.85 (interquartile range, 0.75-0.90), and 57 out of 139 vessels (41%) showed hemodynamically significant stenosis (≤0.80). Median FFRCT was 0.77 (interquartile range, 0.66-0.84; mean difference [invasive FFR-FFRCT], 0.06±0.11). Per-vessel accuracy, sensitivity, specificity, positive prediCTive value, and negative prediCTive value were 73%, 95%, 59%, 61%, and 94% for the cutoff value of FFRCT ≤0.80, 81%, 86%, 78%, 73%, and 89% for FFRCT ≤0.75, and 83%, 74%, 89%, 82%, and 83% for FFRCT ≤0.70, respeCTively. Per-vessel accuracy across the different ranges of FFRCT ≤0.60, 0.61 to 0.70, 0.71 to 0.80, 0.81 to 0.90, and >0.90 with the cutoff value of FFRCT ≤0.80 were 95%, 74%, 32%, 93%, and 100%, respeCTively. Setting a gray zone of FFRCT 0.71 to 0.80 provided high positive prediCTive value (82%; n=42/51) in the range of FFRCT ≤0.70 and high negative prediCTive value (94%; n=48/51) in FFRCT >0.80. CONCLUSIONS: This study suggested that referral to invasive coronary angiography should be considered individually in the range of FFRCT 0.71 to 0.80, whereas dichotomous decision could be made in FFRCT ≤0.70 and >0.80. Future prospeCTive studies evaluating clinical outcomes are needed to establish optimal FFRCT-based diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Background: Post-challenge hyperglycemia (PH) is well-established as one of risk factors for coronary artery disease. However, it remains unclear whether PH affects clinical outcomes in patients with stable angina undergoing percutaneous coronary intervention (PCI). Methods: A total of 828 patients with stable angina undergoing PCI were retrospectively analyzed. Of these, 452 patients with previously diagnosed diabetes mellitus (DM) or fasting plasma glucose (PG) ⩾126 mg/dl and HbA1c ⩾6.5% were defined as known DM. The remaining 376 patients were divided into the two groups according to 2-h PG: PH (2-h PG ⩾140 mg/dl, n=236) and normal glucose tolerance (NGT, 2-h PG <140 mg/dl, n=140). We assessed the rate of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, and clinically-driven revascularization. Results: During the median follow-up of 4.3 years, the MACE rate was significantly higher in the DM and PH groups than the NGT group (39.3% vs. 20.7%, P <0.001; 31.4% vs. 20.7%, P=0.044, respectively). Compared with the NGT group, the cumulative incidence of revascularization was significantly higher in the DM group (35.1% vs. 18.5%, P <0.001) and tended to be higher in the PH group (27.1% vs. 18.5%, P=0.067). In the multivariate analysis, known DM (Hazard ratio [HR]: 2.16, 95% confidence interval (CI): 1.49-3.27, P < 0.001), PH (HR: 1.62, 95% CI: 1.07-2.53, P = 0.023), LDL-C >100 mg/ dl (HR: 1.62, 95% CI: 1.26 to 2.10, P < 0.001), and previous stroke (HR: 1.47, 95% CI: 1.03-2.04, P = 0.034) were predictors of MACE. Conclusion: PH is associated with future cardiovascular events in patients with stable angina undergoing PCI. [ABSTRACT FROM AUTHOR]

It has not been adequately addressed yet how long the excess cardiovascular event risk persists after acute myocardial infarction (AMI) compared with stable coronary artery disease. Of 10,470 consecutive patients who underwent percutaneous coronary intervention either with sirolimus-eluting stent (SES) only or with bare-metal stent (BMS) only in the Coronary Revascularization Demonstrating Outcome Study-Kyoto Registry Cohort-2, 3,710 (SES: n = 820 and BMS: n = 2,890) and 6,760 patients (SES: n = 4,258 and BMS: n = 2,502) presented with AMI (AMI group) and without AMI (non-AMI group), respectively. During the median 5-year follow-up, the excess adjusted risk of the AMI group relative to the non-AMI group for the primary outcome measure (cardiac death or myocardial infarction) was significant (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.30 to 1.80, p <0.001). However, the excess event risk was limited to the early period within 3 months. Late adjusted risk beyond 3 months was similar between the AMI and non-AMI groups (HR 1.16, 95% CI 0.95 to 1.41, p = 0.15). The higher risk of the AMI group relative to the non-AMI group for stent thrombosis (ST) was significant within 3 months (HR 3.38, 95% CI 2.04 to 5.60, p <0.001), whereas the risk for ST was not different between the 2 groups beyond 3 months (HR 1.11, 95% CI 0.65 to 1.90, p = 0.70). There were no interactions between the types of stents implanted and the risk of the AMI group relative to the non-AMI groups for all the outcome measures including ST. In conclusion, patients with AMI compared with those without AMI were associated with similar late cardiovascular event risk beyond 3 months after percutaneous coronary intervention despite their higher early risk within 3 months. [ABSTRACT FROM AUTHOR]

Background Although patients with immunoglobulin light chain (AL) cardiac amyloidosis exhibit worse outcomes than those with transthyretin (TTR) cardiac amyloidosis, few data exist regarding the occurrence of cardiac events and the echocardiographic indices in endomyocardial biopsy (EMBx) proven amyloidosis. Methods From November 2007 to October 2012, we identified 33 patients with EMBx-proven amyloidosis. There were 12 patients (8 men; mean age: 66 years) with AL and 21 patients (20 men; mean age: 78 years) with TTR. We performed serial echocardiography and observed the patients during follow-up; defining all-cause mortality as the primary endpoint and hospitalization for heart failure as the secondary endpoint. Results The survival rates at 12 months were 20.8% and 85.7% in AL and TTR, respectively (p < 0.001). The cumulative incidences of the composite of death or readmission for heart failure at 12 months were 91.7% and 51.3% in AL and TTR, respectively (p < 0.001). A multivariate analysis showed that the AL type amyloid was the powerful predictor of mortality (hazard ratio: 8.50, 95% confidence interval: 1.79 to 40.57, p < 0.05). Under these conditions, the E/e' in AL tended to increase from 23 ± 13 to 28 ± 11 (p = 0.06) with marked increases in B-type natriuretic peptide (779 ± 456 pg/ml to 1576 ± 895 pg/ml, p < 0.05), although these remained unchanged in TTR, which exhibited significantly increased left ventricular end-diastolic dimensions from 40 ± 4 mm to 42 ± 4 mm (p < 0.05). Conclusions The survival rate was generally worse in AL cardiac amyloidosis, although the readmission for heart failure remains high in TTR cardiac amyloidosis with the occurrence of left ventricular dilatation. [ABSTRACT FROM AUTHOR]