Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Appropriate Selection of Substrate Ablation for Persistent Atrial Fibrillation Using Intraprocedural Assessment.

BACKGROUND: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers.Methods and Results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70). CONCLUSIONS: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Postdischarge functional outcomes in older patients with acute heart failure in Japan: the Longevity Improvement & Fair Evidence study.

BACKGROUND: The association between care needs level (CNL) at hospitalisation and postdischarge outcomes in older patients with acute heart failure (aHF) has been insufficiently investigated. METHODS: This population-based cohort study was conducted using health insurance claims and CNL data of the Longevity Improvement & Fair Evidence study. Patients aged ≥65 years, discharged after hospitalisation for aHF between April 2014 and March 2022, were identified. CNLs at hospitalisation were classified as no care needs (NCN), support level (SL) and CNL1, CNL2-3 and CNL4-5 based on total estimated daily care time as defined by national standard criteria, and varied on an ordinal scale between SL&CNL1 (low level) to CNL4-5 (fully dependent). The primary outcomes were changes in CNL and death 1 year after discharge, assessed by CNL at hospitalisation using Cox proportional hazard models. RESULTS: Of the 17 724 patients included, 7540 (42.5%), 4818 (27.2%), 3267 (18.4%) and 2099 (11.8%) had NCN, SL&CNL1, CNL2-3 and CNL4-5, respectively, at hospitalisation. One year after discharge, 4808 (27.1%), 3243 (18.3%), 2968 (16.7%), 2505 (14.1%) and 4200 (23.7%) patients had NCN, SL&CNL1, CNL2-3, CNL4-5 and death, respectively. Almost all patients' CNLs worsened after discharge. Compared to patients with NCN at hospitalisation, patients with SL&CNL1, CNL2-3 and CNL4-5 had an increased risk of all-cause death 1 year after discharge (hazard ratio [95% confidence interval]: 1.19 [1.09-1.31], 1.88 [1.71-2.06] and 2.56 [2.31-2.84], respectively). CONCLUSIONS: Older patients with aHF and high CNL at hospitalisation had a high risk of all-cause mortality in the year following discharge.

Angioscopic Comparison of Early- and Mid-Term Vascular Responses Following Treatment of ST-Elevation Acute Myocardial Infarction With Biodegradable vs. Durable Polymer Everolimus-Eluting Stents　- A Prespecified Subanalysis of the MECHANISM AMI RCT.

BACKGROUND: The vessel healing process after implantation of biodegradable polymer (BP) and durable polymer (DP) everolimus-eluting stent (EES) in ST-elevation myocardial infarction (STEMI) lesions remains unclear.Methods and Results: We conducted a multicenter prospective randomized controlled trial to compare early (2 weeks) and mid-term (12 months) vascular responses after implantation of BP-EES vs. DP-EES in STEMI patients. In this prespecified subanalysis, serial coronary angioscopy (CAS) analysis was performed in 15 stents in the BP-EES arm (n=10 patients) and 14 stents in the DP-EES arm (n=10 patients). At the 2-week follow-up, there was no significant difference in the estimated marginal means of the neointimal coverage grade (primary endpoint) between the 2 arms (mean [±SE] 0.00±0.00 in both arms; P>0.999). There were no significant differences between the BP-EES and DP-EES groups in the yellow color grade (1.046±0.106 vs. 0.844±0.114, respectively; P=0.201) or the presence of thrombus (77.8% vs. 88.8%, respectively; P=0.205). At 12 months, competent strut coverage, defined as yellow color grade ≤1, no thrombus, and a neointimal coverage grade ≥1 was achieved more frequently in the BP-EES than DP-EES arm (85.2% vs. 53.1%; adjusted odds ratio 2.11 [95% confidence interval 1.26-3.53]; P=0.023). CONCLUSIONS: Neointimal coverage 2 weeks after implantation of BP-EES and DP-EES in STEMI lesions was comparable on CAS evaluation. However, at 1 year, BP-EES was independently associated with competent strut coverage.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

Impact of Structural Abnormalities in Left Ventricle and Left Atrium on Clinical Outcomes in Heart Failure with Preserved Ejection Fraction.

Two key echocardiographic parameters, left ventricular mass index (LVMI) and left atrial volume index (LAVI), are important in assessing structural myocardial changes in heart failure (HF) with preserved ejection fraction (HFpEF). However, the differences in clinical characteristics and outcomes among groups classified by LVMI and LAVI values are unclear.We examined the data of 960 patients with HFpEF hospitalized due to acute decompensated HF from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. Four groups were classified according to the cut-off values of LVMI and LAVI [LVMI = 95 g/m2 (female), 115 g/m2 (male) and LAVI = 34 mL/m2]. Clinical endpoints were the composite of HF readmission and all-cause death. Study endpoints among the 4 groups were evaluated. The composite endpoint occurred in 364 patients (37.9%). Median follow-up duration was 445 days. Kaplan-Meier analysis revealed significant differences in the composite endpoint among the 4 groups (P < 0.001). Cox proportional hazards analysis demonstrated that patients with increased LAVI alone were at significantly higher risk of HF readmission and the composite endpoints than those with increased LVMI alone (P = 0.030 and P = 0.024, respectively). Age, male gender, systolic blood pressure at discharge, atrial fibrillation (AF) hemoglobin, renal function, and LAVI were significant determinants of LVMI and female gender, AF, hemoglobin, and LVMI were significant determinants of LAVI.In HFpEF patients, increased LAVI alone was more strongly associated with HF readmission and the composite of HF readmission and all-cause death than those with increased LVMI alone.

Abdominal obesity, and not general obesity, is associated with a lower 123I MIBG heart-to-mediastinum ratio in heart failure patients with preserved ejection fraction.

BACKGROUND: The relationship between general obesity or abdominal obesity (abdominal circumference of ≥85 cm in men and ≥ 90 cm in women) and the heart-to-mediastinum ratio (HMR), a measure of cardiac sympathetic innervation, on cardiac iodine-123-metaiodobenzylguanidine scintigraphy (MIBG) in patients with heart failure with preserved ejection fraction (HFpEF) has not been clarified. METHODS: A total of 239 HFpEF patients with both MIBG and abdominal circumference data were examined. We divided these patients into those with abdominal obesity and those without it. In the cardiac MIBG study, early phase image was acquired 15-20 min after injection, and late phase image was acquired 3 h after the early phase. A HMR obtained from a low-energy type collimator was converted to that obtained by a medium-energy type collimator. RESULTS: Early and late HMRs were significantly lower in those with abdominal obesity, although washout rates were not significantly different. The incidence of patients with early and late HMRs <2.2 was significantly higher in those with abdominal obesity. Multivariate linear regression analysis revealed that abdominal obesity was independently associated with early HMR (standardized ß = -0.253, P = 0.003) and late HMR (standardized ß = -0.222, P = 0.010). Multivariate logistic regression analysis revealed that abdominal obesity was independently associated with early (odds ratio [OR] [95% confidence interval {CI}] = 4.25 [2.13, 8.47], P < 0.001) and late HMR < 2.2 (OR [95% CI] = 2.06 [1.11, 3.83], P = 0.022). Elevated BMI was not significantly associated with low early and late HMR. The presence of abdominal obesity was significantly associated with low early and late HMR even in patients without elevated BMI values. CONCLUSION: Abdominal obesity, but not general obesity, in HFpEF patients was independently associated with low HMR, suggesting that visceral fat may contribute to decreased cardiac sympathetic activity in patients with HFpEF. TRIAL REGISTRATION: UMIN000021831.

Factors Associated With Prehospital Delay Among Patients With Acute Myocardial Infarction in the Era of Percutaneous Coronary Intervention　- Insights From the OACIS Registry.

BACKGROUND: The Japan Circulation Society launched the STOP-MI campaign in 2014, focusing on immediate hospital arrival for acute myocardial infarction (AMI) treatment. This study aimed to determine the factors influencing longer prehospital time among patients with AMI in Japan.Methods and Results:This study analyzed a total of 4,625 AMI patients enrolled in the Osaka Acute Coronary Insufficiency Study registry from 1998 to 2014. The prehospital time delay was defined as the time interval from the onset of initial symptoms to hospital arrival time ≥2 h. Among eligible patients, 2,927 (63.3%) had a prehospital time ≥2 h. In multivariable analyses, age 65-79 years (adjusted odds ratio [AOR] 1.19, 95% confidence interval [CI] 1.02-1.39), age ≥80 years (AOR 1.42, 95% CI 1.13-1.79), diabetes mellitus (AOR 1.33, 95% CI 1.16-1.52), and onset time of 0:00-5:59 h (AOR 1.63, 95% CI 1.37-1.95) were positively associated with prehospital time ≥2 h, whereas smoking (AOR 0.78, 95% CI 0.68-0.90) and ambulance use (AOR 0.37, 95% CI 0.32-0.43) were negatively associated with prehospital time ≥2 h. CONCLUSIONS: Older age, diabetes mellitus, and nighttime onset were associated with prehospital time delay for AMI patients, whereas smoking and ambulance use were associated with no prehospital time delay. Healthcare providers and patients could help reduce the time to get to a medical facility by being aware of these findings.

Sex Differences in the Efficacy of Pulmonary Vein Isolation Alone vs. Extensive Catheter Ablation in Patients With Persistent Atrial Fibrillation.

BACKGROUND: Women experience more severe arrhythmogenic substrates. This study hypothesized that an extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might be effective for women, whereas the PVI alone strategy (PVI-alone) might be sufficient for men to maintain sinus rhythm. The aim of this study was to test this hypothesis.Methods and Results: This study is a post-hoc subanalysis of the EARNEST-PVI trial focusing on sex differences in the efficacies of different ablation strategies. The EARNEST-PVI trial was a prospective, multicenter, randomized, and open-label non-inferiority trial in patients with persistent AF. The primary endpoint was recurrence of AF, atrial flutter, or atrial tachycardia. The EARNEST-PVI trial randomized 376 (76%) men (PVI-alone 186, PVI-plus 190) and 121 (24%) women (PVI-alone 63, PVI-plus 58). The event rate was significantly lower for men and numerically lower for women in the PVI-plus than the PVI-alone group, and there was no interaction between men and women (hazard ratio, 0.641; 95% confidence interval, 0.417-0.985; P value, 0.043 for men vs. hazard ratio, 0.661; 95% confidence interval, 0.352-1.240; P value, 0.197 for women; P value for interaction, 0.989). CONCLUSIONS: The superiority of the extensive ablation strategy vs. the PVI-alone strategy for persistent AF was consistent across both sexes.

Sex-related difference in bleeding and thromboembolic risks in patients with atrial fibrillation treated with direct oral anticoagulants.

BACKGROUND: Sex-related difference in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) is still to be investigated. We aimed to investigate sex difference in patient characteristics and clinical outcomes of the NVAF patients treated with DOAC in the real-world Japanese clinical practice. METHODS AND RESULTS: We conducted a single-center prospective observational registry of NVAF patients treated with DOACs: the DIRECT registry (women, N = 806; men, N = 1410; follow-up duration, 407 ± 388 days). In the present study, all patients were stratified by sex. Women had significantly higher age, lower body weight, lower hemoglobin, lower creatinine clearance, and a higher bleeding risk estimate (ORBIT score) and higher thromboembolic risk estimates (CHADS2 score and CHA2DS2VAS score) than men. Albeit the different bleeding risk estimates by the ORBIT score between both sexes, the Kaplan-Meier estimates of bleeding events were similar between both sexes (Log-rank test P = 0.152 for clinically significant bleeding, and P = 0.122 for major bleeding). The Kaplan-Meier estimated 2 year rate of stroke/systemic embolism was higher in women than in men (4.9 ± 1.3% vs. 2.3 ± 0.6%, Log-rank test P = 0.048). CONCLUSIONS: Our real-world study of patients treated with DOAC showed that Japanese women experienced comparable bleeding events as compared to men despite the higher bleeding risk estimates. The higher thromboembolic risk estimates in women than in men translated into the higher thromboembolic event rates.Clinical trials identifier: UMIN000033283.

Efficacy of Extensive Ablation for Persistent Atrial Fibrillation With Trigger-Based vs. Substrate-Based Mechanisms　- A Prespecified Subanalysis of the EARNEST-PVI Trial.

BACKGROUND: Extensive ablation in addition to pulmonary vein isolation (PVI) would be effective for modification of non-pulmonary vein (non-PV) substrates, whereas PVI might be sufficient for elimination of PV triggers. This study aimed to test the hypothesis that in patients with reproducible atrial fibrillation (AF) triggered by premature atrial contractions originating only from PVs, PVI alone can be sufficient to maintain sinus rhythm.Methods and Results:This study is a prespecified subanalysis of the EARNEST-PVI randomized controlled trial. This study investigated the efficacy of the PVI-alone strategy (PVI-alone) in comparison with the extensive strategy (PVI-plus) for persistent AF with a trigger-based mechanism vs. a substrate-based mechanism. Patients were stratified into 3 groups based on AF mechanisms: (1) Substrate group (N=236); (2) PV trigger group (N=236); and (3) non-PV trigger group (N=24). The hazard ratios for AF recurrence of the PVI-alone strategy with reference to the PVI-plus strategy were 1.456 (95% confidence interval [CI] [0.864-2.452]) in the substrate group, 1.648 (95% CI 0.969-2.801) in the PV trigger group, and 0.937 (95% CI 0.252-3.488) in the non-PV trigger group. No significant interaction between ablation strategy and AF mechanism was observed (P for interaction=0.748). CONCLUSIONS: This study indicated that the efficacies of the PVI-alone strategy compared with the PVI-plus strategy were consistent across persistent AF with trigger-based and substrate-based mechanisms.

Prognostic Impact of Echocardiographic Diastolic Dysfunction on Outcomes in Patients With Heart Failure With Preserved Ejection Fraction　- Insights From the PURSUIT-HFpEF Registry.

BACKGROUND: Although diastolic dysfunction is important pathophysiology in heart failure with preserved ejection fraction (HFpEF), its prognostic impact in HFpEF patients, including those with atrial fibrillation (AF), remains to be elucidated.Methods and Results:We included the data for 863 patients (321 patients with AF) registered in a prospective multicenter observational study of patients with HFpEF. Patients were divided into 3 groups according to the 2016 ASE/EACVI recommendations. The primary endpoint was a composite of all-cause death or HF rehospitalization. Median age was 83 years, and 55.5% were female. 196 (22.7%) were classified with normal diastolic function (ND), 253 (29.3%) with indeterminate (ID) and 414 (48.0%) with diastolic dysfunction (DD). The primary endpoint occurred more frequently in patients with DD than in those with ND or ID (log-rank P<0.001 for DD vs. ND, and log-rank P=0.007 for DD vs. ID, respectively). Taking ND as the reference, multivariable Cox regression analysis revealed that DD (hazard ratio (HR): 1.57, 95% confidence interval (CI):1.06-2.32, P=0.024) was independently associated with the composite endpoint, whereas ID (HR: 1.28, 95% CI: 0.84-1.95, P=0.255) was not. DD was associated with the composite endpoint in both patients with and without AF. CONCLUSIONS: HFpEF patients classified with DD using the 2016 ASE/EACVI recommendations had worse clinical outcomes than those with ND or ID. DD may be considered a prognostic marker in patients with HFpEF regardless of AF.

Prevalence of the Japanese high bleeding risk criteria and its prognostic significance for fatal bleeding in patients with acute myocardial infarction.

BACKGROUND: The Japanese high-bleeding-risk criteria (Japanese-HBR), modified criteria of the Academic Research Consortium (ARC) HBR, has been recently proposed. We aimed to investigate the prevalence of the ARC-HBR and the Japanese-HBR, and to assess their prognostic significance in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We applied the ARC-HBR and the Japanese-HBR criteria to the OACIS prospective multicenter acute myocardial infarction registry (12,093 patients, 66 ± 12 years, 9,096 males). The primary endpoint was fatal bleeding (BARC-5). Median follow-up duration was 4.84 [inter-quartile range 1.35, 5.01] years. Prevalence of the ARC-HBR was 43.8%, while that of the Japanese-HBR was 61.8%. Cumulative incidence of fatal bleeding was higher in the ARC-HBR group than in the no ARC-HBR group at 1 year (1.3 vs. 0.6%) and at 5 years (2.0 vs. 0.7%). The Kaplan-Meier curves stratified by the Japanese-HBR criteria more prominently diverged (1.3 vs. 0.2% at 1 year; and 1.9 vs. 0.3% at 5 years). The Japanese-HBR criteria showed superior discriminative performance over the ARC-HBR criteria (C-statistics: 0.677 vs. 0.598, P < 0.001). CONCLUSIONS: In the real-world Japanese AMI registry, nearly half of the patients fulfilled the criteria of ARC-HBR, and two-thirds met the Japanese-HBR. Our findings support the validity of both ARC- and Japanese-HBR criteria in AMI patients but encourage the future application of the Japanese-HBR criteria to the Japanese AMI cohort. TRIAL REGISTRATION NUMBER: UMIN000004575.

Underweight Is Associated with Poor Prognosis in Heart Failure with Preserved Ejection Fraction.

The obesity paradox states higher body mass index (BMI) is associated with better outcomes than normal weight in patients with heart failure with preserved ejection fraction (HFpEF). However, underweight was defined by BMI < 18.5 kg/m2, and results have been inconclusive, in part due to small number of participants. The number of underweight patients with HFpEF is higher in Asian than in Western countries. In this study, we aim to determine the prognostic impact of underweight in patients with HFpEF in Asian population.We enrolled 846 consecutive patients from the PURSUIT-HFpEF registry. We then divided them into three groups by BMI, namely, underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 23), and overweight (23 ≤ BMI). The underweight group consisted of 187 patients (22%). Over a mean follow-up of 407 days, 105 deaths were reported as all-cause mortality. On multivariable Cox analysis, the underweight group was determined to be significantly associated with higher risk of all-cause mortality than the normal and overweight groups (Hazard ratios [HR]: 2.33; 95% confidence intervals [CI]: 1.45-3.75, P < 0.001; HR: 3.54; 95% CI: 1.99-6.29, P < 0.001, respectively), after adjustment for age, sex, vital signs, and comorbidities.Underweight is a useful predictor of poor prognosis in patients with HFpEF in Asian population.

Impact of diabetes mellitus on the early-phase arterial healing after drug-eluting stent implantation.

BACKGROUND: Early arterial healing after drug-eluting stent (DES) implantation may enable short dual-antiplatelet therapy (DAPT) strategy. The impact of diabetes mellitus (DM) on this healing has not been elucidated. We used coronary angioscopy (CAS) to compare intravascular status of DM and non-DM patients in the early phase after DES implantation. METHODS: This study was a multicenter retrospective observational study. We analyzed CAS findings of 337 lesions from 270 patients evaluated 3-5 months after DES implantation. We divided the lesion into two groups: DM (n = 149) and non-DM (n = 188). We assessed neointimal coverage (NIC) grades (dominant, maximum and minimum), thrombus adhesion and maximum yellow color grade. NIC was graded as follows: grade 0, stent struts were not covered; grade 1, stent struts were covered by thin layer; grade 2, stent struts were buried under neointima. Yellow color was graded as grade 0, white; grade 1, light yellow; grade 2, yellow; grade 3, intensive yellow. RESULTS: Minimum NIC grade was significantly lower in DM than in non-DM groups (p = 0.002), whereas dominant and maximum NIC grades were similar between them (p = 0.59 and p = 0.94, respectively), as were thrombus adhesion (44.3% vs. 38.8%, p = 0.32) and maximum yellow color grade (p = 0.78). A multivariate analysis demonstrated that DM was an independent predictor of minimum NIC of grade 0 (odds ratio: 2.14, 95% confidence interval: 1.19-3.86, p = 0.011). CONCLUSIONS: DM patients showed more uncovered struts than non-DM patients 3-5 months after DES implantation, suggesting that the recent ultra-short DAPT strategy might not be easily applied to DM patients.

Persistent Systemic Inflammation Is Associated With Bleeding Risk in Atrial Fibrillation Patients.

BACKGROUND: This study investigated the impact of systemic inflammation on bleeding risk in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOAC).Methods and Results:We conducted a single-center prospective registry of 2,216 NVAF patients treated with DOAC: the DIRECT registry (UMIN000033283). High-sensitivity C-reactive protein (hsCRP) was measured ≤3 months before (pre-DOAC hsCRP) and 6±3 months after initiation of DOAC (post-DOAC hsCRP). Multivariate logistic regression model was used to assess the influence of systemic inflammation and conventional bleeding risk factors on major bleeding according to International Society on Thrombosis and Haemostasis criteria. Based on the findings, we created a new bleeding risk assessment score: the ORBIT-i score, which included post-DOAC hsCRP >0.100 mg/dL and all components of the ORBIT score. A total of 1,848 patients had both pre- and post-DOAC hsCRP data (follow-up duration, 460±388 days). Post-DOAC hsCRP was associated with major bleeding (OR, 2.770; 95% CI: 1.687-4.548, P<0.001). Patients with post-DOAC hsCRP >0.100 mg/dL more frequently had major bleeding than those without (log-rank test, P<0.001). ORBIT-i score had the highest C-index of 0.711 (95% CI, 0.654-0.769) compared with the ORBIT and HAS-BLED scores. CONCLUSIONS: Persistent systemic inflammation was associated with major bleeding risk. ORBIT-i score had a higher discriminative performance compared with the conventional bleeding risk scores.

Bioresorbable Scaffold: The Emerging Reality and Future Directions.

In the era of drug-eluting stents, large-scale randomized trials and all-comer registries have shown excellent clinical results. However, even the latest-generation drug-eluting stent has not managed to address all the limitations of permanent metallic coronary stents, such as the risks of target lesion revascularization, neoatherosclerosis, preclusion of late lumen enlargement, and the lack of reactive vasomotion. Furthermore, the risk of very late stent, although substantially reduced with newer-generation drug-eluting stent, still remains. These problems were anticipated to be solved with the advent of fully biodegradable devices. Fully bioresorbable coronary scaffolds have been designed to function transiently to prevent acute recoil, but have retained the capability to inhibit neointimal proliferation by eluting immunosuppressive drugs. Nevertheless, long-term follow-up data of the leading bioresorbable scaffold (Absorb) are becoming available and have raised a concern about the relatively higher incidence of scaffold thrombosis. To reduce the rate of clinical events, improvements in the device, as well as implantation procedure, are being evaluated. This review will focus on the current CE-mark approved bioresorbable scaffolds, their basic characteristics, and clinical results. In addition, we summarize the current limitations of bioresorbable scaffold and their possible solutions.

Serial Optical Coherence Tomography at Baseline, 7 Days, and 1, 3, 6 and 12 Months After Bioresorbable Scaffold Implantation in a Growing Porcine Model.

BACKGROUND: Little is known about serial changes in lumen and device dimensions after bioresorbable scaffold implantation in a growing animal model. Methods and Results: ABSORB (n=14) or bare metal stents (ICROS amg [Abbott Vascular, Santa Clara, CA, USA], Winsen-Luhe, Germany; n=15) were implanted in the coronary arteries of domestic swine (a hybrid of Finnish-Norwegian Landrace swine) weighing 30-35 kg. Angiography and optical coherence tomography (OCT) were performed immediately after implantation and repeated at 7 days, 1, 3, 6 and 12 months after the index procedure. One month after implantation, mean lumen area decreased relative to baseline in both groups (relative area change from baseline, -41.4±15.6% for ABSORB vs. -20.9±18.6% for ICROS) while mean device area decreased only in the ABSORB group (relative area change: -11.1±9.4% vs. +0.14±7.95%, respectively). At 12 months, mean lumen area increased relative to baseline in both groups (relative area change from baseline, +55.6±22.4% vs. +32.3±83.6%, respectively) in accordance with the swine growth weighing up to 260-300 kg. Mean device area in the ICROS group remained stable whereas that in the ABSORB group began to increase between 3 and 6 months along with the vessel growth (relative area change: +107.8±25.7% vs. +0.14±7.95%). CONCLUSIONS: In the growing porcine model, ABSORB was associated with greater extent of recoil 1 month after implantation compared with ICROS but demonstrated substantial adaptability to vessel growth in late phase.

Endothelial shear stress 5 years after implantation of a coronary bioresorbable scaffold.

Aims: As a sine qua non for arterial wall physiology, local hemodynamic forces such as endothelial shear stress (ESS) may influence long-term vessel changes as bioabsorbable scaffolds dissolve. The aim of this study was to perform serial computational fluid dynamic (CFD) simulations to examine immediate and long-term haemodynamic and vascular changes following bioresorbable scaffold placement. Methods and results: Coronary arterial models with long-term serial assessment (baseline and 5 years) were reconstructed through fusion of intravascular optical coherence tomography and angiography. Pulsatile non-Newtonian CFD simulations were performed to calculate the ESS and relative blood viscosity. Time-averaged, systolic, and diastolic results were compared between follow-ups. Seven patients (seven lesions) were included in this analysis. A marked heterogeneity in ESS and localised regions of high blood viscosity were observed post-implantation. Percent vessel area exposed to low averaged ESS (<1 Pa) significantly decreased over 5 years (15.92% vs. 4.99%, P < 0.0001) whereas moderate (1-7 Pa) and high ESS (>7 Pa) did not significantly change (moderate ESS: 76.93% vs. 80.7%, P = 0.546; high ESS: 7.15% vs. 14.31%, P = 0.281), leading to higher ESS at follow-up. A positive correlation was observed between baseline ESS and change in lumen area at 5 years (P < 0.0001). Maximum blood viscosity significantly decreased over 5 years (4.30 ± 1.54 vs. 3.21± 0.57, P = 0.028). Conclusion: Immediately after scaffold implantation, coronary arteries demonstrate an alternans of extremely low and high ESS values and localized areas of high blood viscosity. These initial local haemodynamic disturbances may trigger fibrin deposition and thrombosis. Also, low ESS can promote neointimal hyperplasia, but may also contribute to appropriate scaffold healing with normalisation of ESS and reduction in peak blood viscosity by 5 years.

Hemodynamic analysis of a novel bioresorbable scaffold in porcine coronary artery model.

BACKGROUND: The shear stress distribution assessment can provide useful insights for the hemodynamic performance of the implanted stent/scaffold. Our aim was to investigate the effect of a novel bioresorbable scaffold, Mirage on local hemodynamics in animal models. METHOD: The main epicardial coronary arteries of 7 healthy mini-pigs were implanted with 11 Mirage Microfiber sirolimus-eluting Bioresorbable Scaffolds (MMSES). Optical coherence tomography (OCT) was performed post scaffold implantation and the obtained images were fused with angiographic data to reconstruct the coronary artery anatomy. Blood flow simulation was performed and Endothelial Shear Stress(ESS) distribution was estimated for each of the 11 scaffolds. ESS data were extracted in each circumferential 5-degree subunit of each cross-section in the scaffolded segment. The generalized linear mixed-effect analysis was implemented for the comparison of ESS in two scaffold groups; 150-µm strut thickness MMSES and 125-µm strut thickness MMSES. RESULTS: ESS was significantly higher in MMSES (150 µm) [0.85(0.49-1.40) Pa], compared to MMSES (125 µm) [0.68(0.35-1.18) Pa]. Both MMSES (150 µm) and MMSES (125 µm) revealed low recirculation zone percentages per luminal surface area [3.17% ± 1.97% in MMSES (150 µm), 2.71% ± 1.32% in MMSES (125 µm)]. CONCLUSION: Thinner strut Mirage scaffolds induced lower shear stress due to the small size vessels treated as compared to the thick strut version of the Mirage which was implanted in relatively bigger size vessels. Vessel size should be taken into account in planning BRS implantation. Small vessels may not get benefit from BRS implantation even with a streamlined strut profile. This pilot study warrants comparative assessment with commercially available bioresorbable scaffolds.