Fifteen-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation.

BACKGROUND: Clinical outcomes after percutaneous coronary intervention have improved with the use of drug-eluting stents, but data beyond 10 years are limited. The purpose of this study was to evaluate the clinical outcomes of patients undergoing sirolimus-eluting stent implantation with follow-up beyond 10 years and to determine the impact of clinical and angiographic characteristics on long-term prognosis.Methods and Results: The clinical outcomes of 885 patients who had undergone sirolimus-eluting stent implantation at a single institution were retrospectively reviewed. Primary endpoints included in the analysis were clinically driven target lesion revascularization (cTLR) and target lesion revascularization (TLR). Univariate and multivariate nominal logistic regression was used for data analysis. The incidence rates of cTLR and TLR beyond 10 years after sirolimus-eluting stent implantation were 16.4% and 36.8%, respectively, with cTLR tending to decrease beyond 10 years. Acute coronary syndrome was a predominant trigger for cTLR. Age, statin use, and stent restenosis emerged as predictors of cTLR within 10 years, but no significant predictors other than age were identified beyond 10 years. CONCLUSIONS: Events continue to occur beyond 10 years after sirolimus-eluting stent implantation, with a trend toward an increase in acute coronary syndromes. It is important to be vigilant about the occurrence of acute coronary syndromes during long-term follow-up.

Predictors of success and puncture site complications in the distal radial approach.

The distal radial approach (DRA) has been proposed as an alternative approach for coronary angiography (CAG) and percutaneous coronary intervention (PCI); however, the predictors of DRA failure and puncture site complications are unclear. Among 7153 consecutive patients undergoing CAG or PCI between November 2018 and January 2021, 3610 patients undergoing CAG or PCI with DRA were analyzed. The primary endpoint of this study was the procedural success, and the secondary endpoint of this study was puncture site complications during procedure. Puncture site complications during procedure were defined as a composite of major bleeding, minor bleeding, arteriovenous fistula, pseudoaneurysm, and neuropathy. The DRA success rate and the puncture site complication rate were 90.4% and 7.7%, respectively. The predictors of DRA failure were low body weight and dual antiplatelet therapy; those of DRA success were PCI and ultrasonography-guided DRA; those of puncture site complications during procedure were low body weight, peripheral arterial disease, dual antiplatelet therapy, anticoagulant therapy, and PCI; and that of no puncture site complications were previous PCI and ultrasonography-guided DRA. The negative predictors of DRA success with no puncture site complication during procedure were low body weight and dual antiplatelet therapy. The positive predictor of DRA success with no puncture site complication during procedure was ultrasonography-guided DRA. We identified the predictors of DRA failure and puncture site complications during procedure in patients undergoing CAG and PCI with DRA. Ultrasonography-guided DRA was associated with a high DRA success rate and a low puncture site complication rate in patients undergoing CAG or PCI with DRA.

Comparison and Validation of Long-Term Bleeding Events for Academic Bleeding Risk (ARC-HBR) Criteria and Contemporary Risk Scores for Percutaneous Coronary Intervention With a Second-Generation Drug Eluting Stent.

BACKGROUND: The Academic Research Consortium for High Bleeding Risk (ARC-HBR) defined a consensus clinical criterion for patients at HBR undergoing percutaneous coronary intervention (PCI). This study aimed to validate and compare the ARC-HBR criteria and the contemporary risk score for long-term bleeding outcomes using a cohort of patients undergoing PCI.Methods and Results: This study analyzed 3,410 patients who underwent PCI between 2010 and 2013. The endpoint was defined as incidence of The Bleeding Academic Research Consortium 3 or 5 bleeding events. In addition to ARC-HBR, this study validated the predictability of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score, Patterns of non-adherence to Anti-platelet Regimens In Stented patients (PARIS) bleeding score, and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) bleeding scores for bleeding events. There was a trend toward an increase in bleeding events, as the risk score increased for all bleeding risk scores used in this study. The ARC-HBR criteria had higher diagnostic sensitivity for bleeding events than other bleeding risk scores. CONCLUSIONS: Patients with a higher number of risk factors in each of the four bleeding risk scores had a higher risk of long-term bleeding events. In comparison to other contemporary risk scores, the ARC-HBR criteria were more sensitive in the identification of patients with bleeding events in the long-term.

Gastrointestinal and Intracranial Bleeding Events After Second-Generation Drug-Eluting Stent Implantation　- Their Association With High Bleeding Risk, Predictors, and Clinical Outcomes.

BACKGROUND: Gastrointestinal bleeding (GIB) and intracranial bleeding (ICB) are frequently observed as major bleeding events after percutaneous coronary intervention (PCI); however, there are few reports on these predictors and their association with the Academic Research Consortium for High Bleeding Risk (ARC-HBR).Methods and Results: The study included 3,453 patients who underwent PCI with second-generation drug-eluting stents between 2010 and 2013. Mean follow up was 2,663±596 days. The cumulative incidences of GIB and ICB were significantly higher in the HBR group than in the non-HBR group (6.3% vs. 1.9%, P<0.001, 5.5% vs. 2.3%, P<0.001). Older age, oral anticoagulant (OAC), and severe chronic kidney disease were independent predictors of GIB (hazard ratios [HR], 1.64; 95% confidence intervals [CI], 1.11-2.41; P=0.012; HR, 1.94; 95% CI, 1.23-3.05; P=0.004; HR, 1.80; 95% CI, 1.02-3.19, P=0.043 respectively), and low body weight, OAC, and left main coronary artery stenting were independent predictors of ICB by multivariate logistic regression analysis (HR, 1.83; 95% CI, 1.20-2.80; P=0.005; HR, 2.04; 95% CI, 1.31-3.19; P=0.002; HR, 1.79; 95% CI, 1.18-2.70; P=0.006 respectively). CONCLUSIONS: ARC-HBR was consistently associated with GIB and ICB within a 7-year period. GIB and ICB had three predictors each. Of these, only OAC administration was common, and the other two were different.

Delayed stenosis regression after drug-coated balloon angioplasty for femoropopliteal artery lesions.

Paclitaxel has the potential for inducing lumen enlargement by vessel enlargement, healing of dissection, and plaque regression. This study was carried out to determine the possibility of and the relevant factors of delayed stenosis regression after drug-coated balloon (DCB) angioplasty for femoropopliteal (FP) artery lesions. A total 105 de novo FP lesions were finalized with DCB angioplasty in our institute between May 2018 and June 2020. Among them, cases in which residual stenosis was detected by duplex ultrasonography (DUS) after the procedure were included in this study. Significant stenosis was defined as peak systolic velocity ratio ≥ 2.4 by DUS. Follow-up DUS was routinely performed 6 months after the procedure, and we defined cases without stenosis as cases of delayed stenosis regression according to the follow-up DUS. DUS showed that 26 (25.5%) of 102 lesions had residual stenosis after DCB angioplasty, and delayed stenosis regression was observed in 12 (57.1%) of 21 lesions 6 months after the procedure. The percentage of lesions containing calcified plaque as detected by intravascular ultrasound analysis was significantly higher in the non-regression group than in the regression group (18.2% vs. 77.8%, p = 0.02). Vessel remodeling and dissection patterns were not associated with delayed stenosis regression. The results of our analyses indicate that delayed stenosis regression may occur after DCB angioplasty for FP lesions in more than half of cases with residual stenosis. Delayed stenosis regression may be difficult in cases of calcified lesions.

Impact of Guidewire Route on Severe Dissection After Balloon Angioplasty for Femoropopliteal Chronic Total Occlusion Lesions: An Intravascular Ultrasound Analysis.

OBJECTIVE: To determine the impact of the guidewire route on severe dissection after balloon angioplasty for femoropopliteal chronic total occlusion (CTO) lesions using a new intravascular ultrasound (IVUS) assessed classification scheme corresponding to a conventional angiographic classification scheme. METHODS: Images for 21 femoropopliteal CTO lesions treated endovascularly between May 2018 and December 2019 were used for analysis. IVUS images after guidewire passage and those after balloon angioplasty were evaluated at 1 cm intervals. Cross sectional images were obtained (n = 219) and divided into two groups by the guidewire route: those in which the guidewire passed through the inner half of the luminal radius (central wiring group, 139 cross sectional images) and those in which the guidewire passed through the outer half of the luminal radius (eccentric wiring group, 80 cross sectional images). Angiographically severe dissection was defined as Type C or greater according to the National Heart, Lung, and Blood Institute classification, to which six dissection morphology patterns were applied based on IVUS images (Types A - E2). RESULTS: Central wiring was achieved in an average of 69.6 ± 28.0% of the CTO length from per limb analysis. Among the IVUS assessed dissection morphology patterns, Types D - E2 were more frequently correlated with angiographically severe dissection than were Types A - C (57.5% vs. 13.7%, p < .001). Multivariable analysis showed that soft plaque was a predictive factor for (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.007 - 4.72; p = .048) and central wiring was a protective factor (OR 0.27; 95% CI 0.14 - 0.49; p < .001) against Type D - E2 dissection patterns assessed by IVUS after balloon angioplasty. CONCLUSION: Lesions with Type D - E2 dissection patterns assessed by IVUS were correlated with angiographically severe dissection. Central wiring may be useful for preventing severe dissection after balloon angioplasty for femoropopliteal CTO lesions.

Academic Research Consortium for High Bleeding Risk Definitions for Early, Late, and Very Late Bleeding Events.

BACKGROUND: The validity of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definitions of early (<1 year), late (1-4 years), and very late (>4 years) bleeding events is unknown.Methods and Results:This study was performed on patients (n=3,453) implanted with second-generation drug-eluting stents (DES) between 2010 and 2013. Data on all criteria of the ARC-HBR definition were collected retrospectively. The primary endpoint was Bleeding Academic Research Consortium Type 3 or 5 bleeding events; the ischemic endpoint was a composite of cardiac death, myocardial infarction, and ischemic stroke. The mean follow-up period was 7.5 years. Compared with non-high bleeding risk (HBR) patients, HBR patients (n=1,840; 53.3%) had an increased risk of the primary endpoint (early events, 3.6% vs. 0.5% [P<0.0001]; late events, 5.3% vs. 2.5% [P<0.0001]; very late events, 5.5% vs. 2.1% [P<0.0001]) and of ischemic events during follow-up. The discrimination ability of the ARC-HBR definition for late and very late bleeding events was comparable to that of early bleeding events (C statistics 0.679, 0.621, and 0.620, respectively) with high negative predictive value (96.6%, 95.1%, and 93.1%, respectively). Multivariate analysis revealed the different effects of individual criteria on bleeding events in each follow-up period. CONCLUSIONS: The ARC-HBR definition consistently identified patients at risk of long-term bleeding and ischemic events after second-generation DES implantation.

Outcomes at 1 Year of Non-Left Main Trunk Bifurcation Lesions Treated With a 2-Stent Strategy Using Newer-Generation Everolimus-Eluting Stents.

BACKGROUND: Percutaneous coronary intervention (PCI) for coronary bifurcation lesions using the 2-stent strategy remains a challenging procedure for interventionalists because of the higher incidence of in-stent restenosis (ISR) and adverse events. ISR predictors in patients treated with newer-generation everolimus-eluting stents (EES) and the 2-stent strategy remain unknown. Hence, we aimed to evaluate the 1-year clinical and angiographic outcomes of non-left main trunk (LMT) bifurcation lesions treated with the 2-stent strategy using newer-generation EES.Methods and Results:The study sample consisted of 262 non-LMT bifurcation lesions treated using culotte or T-stenting with EES between 2010 and 2018. One-year post-procedural angiographic and clinical examinations were conducted in 208 (79.4%) and 260 (99.2%) lesions, respectively. The primary outcome measure was the 1-year post-procedural ISR rate, which was found to be 15.9%. Independent predictors of 1-year post-procedural ISR were long side branch lesions (adjusted odds ratio [aOR] 2.31; 95% confidence interval [CI] 1.02-5.23; P=0.04) and 3-link EES implantation (aOR 2.45; 95% CI 1.07-5.61; P=0.03). The 1-year cumulative incidence of target lesion revascularization was 3.5%. CONCLUSIONS: The 1-year clinical outcomes of non-LMT bifurcation lesions treated with the 2-stent strategy using EES were acceptable. Long side branch lesions and lesions treated with 3-link EES were independent predictors of 1-year post-procedural ISR.

Impact of high-dose statin on cardiovascular outcomes in real-world patients with ST-elevation acute myocardial infarction.

Little is known about the impact of a high-dose statin on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) in real-world Japanese patients. Between July 2011 and June 2017, 1110 consecutive STEMI patients underwent primary percutaneous coronary intervention at our hospital and were discharged. A high-dose statin was administered in 117 patients (10.5%) and non-high-dose statin was administered in 947 patients (85.3%). The low-density lipoprotein cholesterol level was significantly higher in the high-dose statin group at admission (129.8 ± 44.9 vs. 110.4 ± 32.7, p < 0.0001), but the levels were not significantly different at follow-up (86.7 ± 25.7 vs. 85.0 ± 25.0, p = 0.52). The cumulative 2-year incidence of a composite of cardiac death, myocardial infarction, ischemic stroke, and any unplanned coronary revascularization was significantly lower in the high-dose statin group (6.2% vs. 16.9%, log-rank p = 0.004). Propensity score matched analysis indicated similar results. Among the types of coronary revascularization, a high-dose statin was significantly correlated with a lower rate of de novo lesion revascularization (hazard ratio 0.31; 95% confidence interval 0.08-0.83; p = 0.02). The results of our analyses indicate that administration of a high-dose statin may result in better cardiovascular outcomes after STEMI mainly by reducing the rate of revascularization for de novo lesions regardless of the achieved low-density lipoprotein cholesterol level in real-world patients.

Clinical Characteristics and Social Frailty of Super-Elderly Patients With Heart Failure　- The Kitakawachi Clinical Background and Outcome of Heart Failure Registry.

BACKGROUND: Social background is important in preventing admission/readmission of heart failure (HF) patients. However, few clinical studies have been conducted to assess the social background of these patients, especially elderly patients.Methods and Results:The Kitakawachi Clinical Background and Outcome of Heart Failure (KICKOFF) Registry is a prospective multicenter community-based cohort of HF patients, established in April 2015. We compared the clinical characteristics and social background of the super-elderly group (≥85 years old) and the non-super-elderly group (<85 years old). This study included 647 patients; 11.8% of the super-elderly patients were living alone, 15.6% were living with only a partner, and of these, only 66.7% had the support of other family members. The super-elderly group had less control over their diet and drug therapies than the non-super-elderly group. Most patients in the super-elderly group were registered for long-term care insurance (77.4%); 73.5% of the super-elderly patients could walk independently before admission, but only 55.5% could walk independently at discharge, whereas 94% of the non-super-elderly patients could walk independently before admission and 89.4% could walk independently at discharge. CONCLUSIONS: The KICKOFF Registry provides unique detailed social background information of Japanese patients with HF. Super-elderly patients are at serious risk of social frailty; they need the support of other people and their ability to perform activities of daily living decline when hospitalized.

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.

AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n = 24) and AMPK-DN (n = 24) mice were randomly divided into two groups: an untreated preexperimental control group (n = 12 in each group) and an unloading (n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system.

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells.

5'-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock transcription factor 1 in myotubes. Protein content and diameter were less in the AICAR-treated myotubes in those without treatment. AICAR-induced suppression of myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated AMPKα knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of HSP72, and the increase of miR-1 was not induced in AMPKα knockdown condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICAR-induced inhibition of myotube hypertrophy. AICAR upregulated the gene expression of muscle Ring-finger 1, and this alteration was suppressed in either AMPKα or HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr(389) was downregulated by AICAR, whereas this was attenuated in AMPKα, but not in HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy through, in part, an HSP72-associated mechanism via miR-1 and protein degradation pathways in skeletal muscle cells.

Two-year outcomes of endovascular therapy for femoropopliteal arterial lesions for patients with high bleeding risk.

The Academic Research Consortium (ARC) recently published a definition of patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. However, the prevalence of the ARC-HBR criteria in patients undergoing endovascular therapy (EVT) for femoropopliteal arterial lesions has not been thoroughly investigated. The study population comprised 165 patients undergoing initial EVT for femoropopliteal lesions between June 2018 and June 2020. They were divided into two groups according to the ARC-HBR criteria. The primary end point was a composite of all-cause death, Bleeding Academic Research Consortium type 3 or 5 bleeding, and target lesion revascularization (TLR) within 2 years of EVT. The 165 patients were divided into two groups: 125 (75.8%) patients at HBR (HBR group) and 40 (24.2%) patients at no HBR (non-HBR group). The cumulative incidence of the primary endpoint was significantly higher in the HBR group than in the non-HBR group (40.6% vs. 0%, log-rank p < 0.001). The HBR group had a significantly higher risk of all-cause death, major bleeding, and TLR than the non-HBR group (25.2% vs. 0%, log-rank p = 0.004, 13.9% vs. 0%, log-rank p = 0.047, 16.8% vs. 0%, log-rank p = 0.035). Most patients with peripheral artery disease were classified as HBR patients, and HBR patients were at higher risk of death, major bleeding, and TLR than non-HBR patients.

An aspiration catheter stuck in a patient with acute coronary syndrome: an unanticipated complication.

A 62-year-old man presented with ST-elevation myocardial infarction. Thrombectomy using an aspiration catheter was performed, but the wire lumen of the catheter had been torn during the catheter was removed. The aspiration catheter could not be retrieved into the guide catheter, and the entire system along with the guide catheter was removed.

Long-term outcomes of balloon-expandable transcatheter aortic valve replacement in Japanese patients.

BACKGROUND: Data on long-term outcomes of transcatheter aortic valve replacement (TAVR) in Japanese patients beyond 5 years are limited. METHODS: Between June 2010 and December 2014, 55 consecutive inoperable or high surgical risk patients underwent TAVR with SAPIEN XT valves (Edwards Lifesciences, Irvine, CA, USA) for severe aortic stenosis at our institution. Among them, 2 patients were excluded from the analysis because one was converted to open surgery during the TAVR procedure and the other could not undergo TAVR due to device delivery failure. We retrospectively analyzed long-term clinical outcomes of these 53 patients (mean age: 84.1 years; mean STS score: 8.4) who had at least a 7-year follow-up after TAVR. RESULTS: The rates of freedom from all-cause and cardiovascular deaths at 7 years were 35.8 % and 79.3 %, respectively. The moderate or severe structural valve deterioration (SVD) rate at 5 and 7 years was 7.2 % and 11.4 %, respectively. The rate of bioprosthetic valve failure (BVF) at 7 years was 6.2 %. CONCLUSIONS: The 7-year mortality rate of inoperable or high surgical risk patients treated with SAPIEN XT was high, while the cardiovascular mortality rate was acceptable. Although the poor survival rate limited the long-term assessment of SAPIEN XT valve durability, the incidence of SVD and BVF was not rare.

Impact of serum haemoglobin-to-creatinine ratio after transcatheter aortic valve implantation.

OBJECTIVE: The association between a combined anaemia and renal failure index and 1-year prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) is unexplored. We aimed to investigate a simple risk score in patients undergoing TAVI. METHODS: A total of 469 consecutive patients undergoing TAVI between 2015 and 2021 were enrolled. After excluding patients undergoing dialysis, the remaining 458 patients were classified according to three tertiles of the serum haemoglobin-to-creatinine (Hgb/Cr) ratio 1 day before TAVI. The primary clinical outcome measure was all-cause mortality and heart failure hospitalisation 1 year after TAVI. RESULTS: In the first, second and third tertiles, the 1-year cumulative incidence of all-cause mortality was 16.9% versus 7.2% versus 2.0%, respectively (p<0.01), and that of heart failure hospitalisation was 10.7% versus 3.4% versus 0.7%, respectively (p<0.01). The indexes of the area under the curve of the Hgb/Cr ratio for all-cause mortality and heart failure hospitalisation 1 year after TAVI were both 0.73. Cut-off values were 10.1 for all-cause mortality 1 year after TAVI (OR, 4.78; 95% CI 2.43 to 9.74; p<0.01) and 10.4 for heart failure hospitalisation 1 year after TAVI (OR, 5.3; 95% CI 2.21 to 14.1; p<0.01). In the multivariate analysis, the Hgb/Cr ratio was an independent predictor of all-cause mortality and heart failure hospitalisation 1 year after TAVI. CONCLUSIONS: Hgb/Cr ratio calculation 1 day before TAVI may help predict midterm all-cause mortality and heart failure hospitalisation in patients with severe aortic valve stenosis undergoing TAVI. TRIAL REGISTRATION NUMBER: 4143 (The Institutional Review Board of Kurashiki Central Hospital).

Modified percutaneous coronary intervention-derived risk models (PARIS and CREDO-Kyoto integer scoring systems) applied to Japanese transcatheter aortic valve replacement patients.

OBJECTIVE: Postprocedural ischaemic and bleeding risks after transcatheter aortic valve replacement (TAVR) remain a major concern. Nevertheless, no reliable risk models incorporating both possibilities are currently available. We aimed to assess the accuracy of percutaneous coronary intervention (PCI)-derived models and the performance of a recalibrated model that included variables more applicable to TAVR. METHODS: This study included 26 869 patients who had been enrolled in a national registry. Ischaemic events were defined as myocardial infarction, stroke, transient ischaemic attack or peripheral embolism at 1 year. Bleeding events were defined as any bleeding based on the Valve Academic Research Consortium-2 consensus document at 1 year. Patterns of Non-adherence to Anti-Platelet Regimen in Stented Patients (PARIS) and Coronary Revascularisation Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) integer scoring systems were tested. The models were recalibrated by applying new variables using the Fine and Gray method. RESULTS: The 1-year cumulative incidences for ischaemic and bleeding events were 2.7% and 3.1%. Patients with high PARIS and CREDO-Kyoto risk scores had higher incidences of both ischaemic (3.3% vs 2.4% vs 2.4%, p<0.001 and 2.8% vs 2.0% vs 0.8%, p<0.001) and bleeding events (3.3% vs 2.5% vs 0.8%, p<0.001 and 3.7% vs 3.0% vs 2.4%, p<0.001) when compared with intermediate and low-risk patients. The receiver operating characteristic area under the curves for these models were 0.53, 0.58, 0.56 and 0.55, respectively. After the models were recalibrated to incorporate variables more applicable to TAVR, the performance of ischaemic and bleeding models modestly improved (0.58 and 0.61, respectively). CONCLUSIONS: The PCI-derived models demonstrated modest accuracy but was inadequate for risk stratification of TAVR patients at 1-year follow-up. TRIAL REGISTRATION NUMBER: 3395.

Clinical impacts of CT-derived fractional flow reserve under insurance reimbursement: Results from multicenter, prospective registry.

BACKGROUND: Although computed tomography-derived fractional flow reserve (FFRCT) has been reimbursed in a few countries, its impacts on daily practice of coronary artery diseases are not fully elucidated. We evaluated the clinical impacts of FFRCT under the real Japanese insurance reimbursement. METHODS: In the multicenter prospective registry: DYNAMIC-FFRCT study, a total of 410 patients who underwent FFRCT analysis under reimbursement were prospectively enrolled at 6 Japanese sites from October 2019 to November 2021. Coronary CT angiography and FFRCT findings, treatment plans, and 90-day outcomes were recorded. The primary endpoint was the redirection rate from the tests that might be expected without FFRCT [invasive coronary angiography (ICA)-selected group, myocardial perfusion single photon emission CT (MPS)-selected group, optimal medical therapy (OMT)-selected group, and others-selected group] to those that were actually performed based on FFRCT. RESULTS: ICA could be avoided in 39.5 % in the ICA-selected group (N = 233). In particular, in 94.3 % of patients with an FFRCT value of >0.80, additional examinations, such as ICA, were avoided. In addition, in the MPS-selected group (N = 133), 92.6 % had no additional tests with FFRCT > 0.80, while only 2 cases with FFRCT ≤ 0.80 underwent additional MPS examination. On the contrary, 33.3 % of the OMT-selected group (N = 33) had FFRCT ≤ 0.80. Approximately, 35 % medical cost reduction was also finally expected. CONCLUSION: Introduction of FFRCT could not only reduce unnecessary ICA and be a test that replaces the conventional non-invasive functional assessment modality but also result in medical cost reduction even when used under real Japanese insurance reimbursement.

Effects of heat stress on muscle mass and the expression levels of heat shock proteins and lysosomal cathepsin L in soleus muscle of young and aged mice.

Effects of heat stress on skeletal muscle mass in young and aged mice were investigated. Young (7-week) and aged (106-week) male C57BL/6J mice were randomly assigned to control and heat-stressed groups in each age. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anesthesia. Seven days after the exposure, soleus muscles were dissected from both hindlimbs. Protein content and the relative composition of Type II fibers in aged soleus were lower than those in young muscle. In aged soleus, higher baseline expression levels of HSP25, HSP72, and cathepsin L were observed compared with those in young muscle (p < 0.05). However, there were no significant differences in the expression levels of phosphorylated p70 S6 kinase (p-p70S6K), calpain 1, and calpain 2 of soleus between two age groups. A significant increase in muscle mass of both age groups was induced by heat stress (p < 0.05). Heat stress also upregulated the expressions of HSP25, HSP72, and p-p70S6K in both ages (p < 0.05). On the other hand, a significant decrease in cathepsin L expression by heating was observed in aged soleus, but not in young (p < 0.05). Both the percentage of Type I fibers and the expression of calpains in both age groups were unchanged following heat stress. Heat stress-associated downregulation of cathepsin L may be attributed to the upregulation of HSP72, which stabilizes lysosomal membranes (p < 0.05). Upregulations of HSP25, HSP72, and p-p70S6K and/or the downregulation of cathepsin L may play a role in heat stress-associated muscle hypertrophy in aged soleus muscle.

Impact of Late Lumen Loss on Clinical Outcomes of Side-Branch Bifurcation Lesions Treated by Drug-Coated Balloon Angioplasty With Main-Branch Stenting.

BACKGROUND: Drug-coated balloon (DCB) angioplasty for side branches with main branch stenting is effective for bifurcation lesions and reduces late lumen loss (LLL) in side branches. However, the predictors and clinical implications of LLL after DCB angioplasty are largely unexplored. METHODS: Among 181 patients undergoing DCB angioplasty for side branches with drug-eluting stent implantation for main branches between 2016 and 2018, we enrolled 138 patients (138 lesions) undergoing follow-up coronary angiography within 1 year. The 1-year cumulative rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE: defined as a composite of all-cause death, myocardial infarction, and TLR) were compared between patients with late lumen gain (LLG) (LLG group) and those with LLL (LLL group). RESULTS: The binary restenosis rate of the side branch was 8.0% (11 lesions), mean LLL was -0.14 ± 0.43 mm, and LLG was observed in 99 lesions (71.7%). The DCB size/reference vessel diameter ratio showed mild discrimination (area under the curve, 0.60; 95% confidence interval, 1.2-65.0; p = 0.03) for predicting the side branch progression. The 1-year cumulative rates of MACE and TLR were not significantly different but numerically lower in the LLG group than in the LLL group (2.0% vs. 7.8%, p = 0.11 and 2.0% vs. 7.7%, p = 0.11, respectively). Lumen regression after DCB angioplasty for side branches are associated with improved clinical outcomes. CONCLUSIONS: The DCB size relative to the reference vessel diameter is a predictor of late lumen enlargement in side branches.