De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.

BACKGROUND: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation. METHODS: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083). FINDINGS: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy. INTERPRETATION: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation. FUNDING: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

Single-center experience with self-expanding transcatheter aortic valve system for symptomatic high-risk patients with severe aortic regurgitation: One-year outcomes.

AIMS: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) for the treatment of aortic regurgitation (AR). METHODS: From September 2019 to February 2022, 62 patients who underwent transfemoral TAVI procedure for pure, symptomatic severe AR with the VitaFlow system were enrolled in the current study. The outcomes were assessed according to the Valve Academic Research Consortium 3 criteria. Procedural results and clinical outcomes for 1 year were analyzed. RESULTS: The mean age was 71.56 ± 7.34 years and 58.1% were male. The mean Society of Thoracic Surgeons score was 5.44 ± 3.22%. The device success rate was 79.0%. Only one patient was converted to open surgery. The in-hospital mortality rate was 1.6%. The 1-year all-cause mortality rate was 6.5%. The new permanent pacemaker implantation rate was 29.0% in-hospital and 30.7% at 1-year follow-up. The second valve implantation rate was 14.5%. No patient developed more than moderate paravalvular leakage during follow-up. The mean ejection fraction improved from 54.05 ± 10.83% at baseline to 59.32 ± 8.70% (p < 0.001 compared with baseline) at 12 months. Left ventricular end-diastolic diameter decreased from 61.62 ± 5.58 mm at baseline to 55.20 ± 4.51 mm (p < 0.001 compared with the baseline) at 12 months. CONCLUSIONS: Transfemoral TAVI procedure shows efficacy in treating patients with severe pure native AR. The safety is improved with the development of the VitaFlow system.

Angiographic Findings and Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated. Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation. Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023. Exposures: Angiographic parameters and post-PCI FFR. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years. Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group). Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Intravascular Ultrasound vs Angiography-Guided Drug-Coated Balloon Angioplasty: The ULTIMATE â ¢ Trial.

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).

Pulmonary artery denervation versus conventional therapies for PAH: a systematic review and updated network meta-analysis.

AIMS: A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta-analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies. METHODS AND RESULTS: According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta-analyses. Data were extracted and curated for Bayesian network meta-analysis. The primary outcome was the change in the 6-min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (-77.76 m, 95% CI: -102.04 to -54.34 m), Macitentan (-65.32 m, 95% CI: -95.34 to -36.1 m), Bosentan (-64.5 m, 95% CI: -94.7 to -35.07 m), Iloprost (-62.66 m, 95% CI: -99.48 to -27.13 m), Oxygen (-62.42 m, 95% CI: -100.01 to -25.78 m), Treprostinil (-62.01 m, 95% CI: -89.04 to -35.61 m), Riociguat (-60.59 m, 95% CI: -86.11 to -35.98 m), Selexipag (-47.2 m, 95% CI: -85.61 to -10.19 m), Sildenafil (-44.92 m, 95% CI: -74.43 to -16.15 m), or Sitaxsentan (-39.53 m, 95% CI: -78.99 to -0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re-hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions. CONCLUSIONS: Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual-drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Differential Impact of Fractional Flow Reserve Measured After Coronary Stent Implantation by Left Ventricular Dysfunction.

Background: Both left ventricular systolic function and fractional flow reserve (FFR) are prognostic factors after percutaneous coronary intervention (PCI). However, how these prognostic factors are inter-related in risk stratification of patients after PCI remains unclarified. Objectives: This study evaluated differential prognostic implication of post-PCI FFR according to left ventricular ejection fraction (LVEF). Methods: A total of 2,965 patients with available LVEF were selected from the POST-PCI FLOW (Prognostic Implications of Physiologic Investigation After Revascularization with Stent) international registry of patients with post-PCI FFR measurement. The primary outcome was a composite of cardiac death or target-vessel myocardial infarction (TVMI) at 2 years. The secondary outcome was target-vessel revascularization (TVR) and target vessel failure, which was a composite of cardiac death, TVMI, or TVR. Results: Post-PCI FFR was independently associated with the risk of target vessel failure (per 0.01 decrease: HRadj: 1.029; 95% CI: 1.009-1.049; P = 0.005). Post-PCI FFR was associated with increased risk of cardiac death or TVMI (HRadj: 1.145; 95% CI: 1.025-1.280; P = 0.017) among patients with LVEF ≤40%, and with that of TVR in patients with LVEF >40% (HRadj: 1.028; 95% CI: 1.005-1.052; P = 0.020). Post-PCI FFR ≤0.80 was associated with increased risk of cardiac death or TVMI in the LVEF ≤40% group and with that of TVR in LVEF >40% group. Prognostic impact of post-PCI FFR for the primary outcome was significantly different according to LVEF (Pinteraction = 0.019). Conclusions: Post-PCI FFR had differential prognostic impact according to LVEF. Residual ischemia by post-PCI FFR ≤0.80 was a prognostic indicator for cardiac death or TVMI among patients with patients with LVEF ≤40%, and it was associated with TVR among patients with patients with LVEF>40%. (Prognostic Implications of Physiologic Investigation After Revascularization with Stent [POST-PCI FLOW]; NCT04684043).

Transfemoral transcatheter aortic valve replacement with VitaFlowTM valve for pure native aortic regurgitation in patients with high surgical risk: Rationale and design of a prospective, multicenter, and randomized SEASON-AR trial.

BACKGROUND: Previous studies primarily demonstrated that transfemoral transcatheter aortic valve replacement (TAVR) with self-expanding valve appeared to be a safe and feasible treatment for patients with pure native aortic regurgitation (AR). However, the routine application of transfemoral TAVR for pure AR patients lacks support from randomized trials. TRIAL DESIGN: SEASON-AR trial is a prospective, multicenter, randomized, controlled, parallel-group, open-label trial, involving at least 20 sites in China, aiming to enroll 210 patients with pure native severe AR and high surgical risk. All enrolled patients are randomly assigned in a 1:1 fashion to undergo transfemoral TAVR with VitaFlowTM valve and receive guideline-directed medical therapy (GDMT) or to receive GDMT alone. The primary endpoint is the rate of major adverse cardiac events (MACE) at 12 months after the procedure, defined by the composite of all-cause mortality, disabling stroke, and rehospitalization for heart failure. The major secondary endpoints encompass various measures, including procedure-related complications, device success, 6-minute walk distance, and the occurrence of each individual component of the primary endpoint. After hospital discharge, follow-up was conducted through clinical visits or telephone contact at 1, 6, and 12 months. The follow-up will continue annually until 5 years after the index procedure to assess the long-term outcomes. CONCLUSION: SEASON-AR trial is the first study designed to investigate the clinical efficacy and safety of transfemoral TAVR with a self-expanding valve in patients with pure native severe AR with inoperable or high-risk, as compared to medical treatment only.

The first reported case of intravascular ultrasound-guided reverse overlapping stenting of a long calcified lesion using ultra-low contrast and metallic roadmaps: case report.

Background: Percutaneous coronary intervention (PCI) of a long calcified coronary lesion in patients with chronic kidney disease (CKD) is challenging and can lead to stent under-expansion and contrast-induced acute kidney injury (CI-AKI). We described the first case of intravascular ultrasound (IVUS)-guided reverse overlapping stenting of long calcified left anterior descending (LAD) coronary lesion using ultra-low contrast and the metallic roadmaps to prevent CI-AKI after PCI. Case summary: A 77-year-old man with a history of hypertension, type 2 diabetes, and CKD was admitted with angina class 4 and ruled in for non-ST-elevation myocardial infarction. His ejection fraction was 40%. He was referred for cardiac catheterization and PCI. Coronary angiography showed a long calcified stenosis of the LAD. IVUS catheter was advanced at least 10 mm distal to the lesion or stent edge. IVUS images were obtained with automated pullback (1 mm/s) using a commercially available IVUS system with a 60-MHz mechanical transducer (Boston Scientific, Natick, Massachusetts). IVUS showed calcified plaque fractures after balloon angioplasty and intracoronary lithotripsy. The first stent was deployed proximally using the guidewire in the diagonal branch as a metallic roadmap, and the second stent was deployed distally overlapping at the distal edge of the first stent as a roadmap with no contrast injection. Percutaneous coronary intervention was completed successfully using only 12 mL contrast. Glomerular filtration rate remained stable after PCI. Glomerular filtration rate and ejection fraction improved at 12-month follow-up. Discussion: We described the first case of the reverse overlapping stenting technique guided by IVUS with no contrast in a patient with CKD and a long calcified LAD lesion. Conventionally, in long lesions, the first stent is deployed distally and the second stent proximally, which requires contrast injection for stent deployment. We demonstrated that the above technique resulted in preventing CI-AKI and improving creatinine as well as ejection fraction at follow-up.

Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P<0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P<0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P=0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P=0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P<0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P=0.07). CONCLUSIONS: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension. METHODS AND RESULTS: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

TAX1BP1 downregulation by STAT3 in cardiac fibroblasts contributes to diabetes-induced heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is now the most common form of HF and has been reported to be closely related to diabetes. Accumulating evidence suggests that HFpEF patients exhibit cardiac fibrosis. This study investigates whether direct targeted inhibition of the activation of cardiac fibroblasts (CFs), the main effector cells in cardiac fibrosis, improves diabetes-induced HFpEF and elucidates the underlying mechanisms. Twenty-week-old db/db mice exhibited HFpEF, as confirmed by echocardiography and hemodynamic measurements. Proteomics was performed on CFs isolated from the hearts of 20-week-old C57BL/6 and db/db mice. Bioinformatic prediction was used to identify target proteins. Experimental validation was performed in both high glucose (HG)-treated neonatal mouse CFs (NMCFs) and diabetic hearts. TAX1 binding protein 1 (TAX1BP1) was identified as the most significantly differentially expressed protein between 20-week-old C57BL/6 and db/db mice. TAX1BP1 mRNA and protein were markedly downregulated in CFs from diabetic hearts and HG-cultured NMCFs. Overexpression of TAX1BP1 profoundly inhibited HG/diabetes-induced NF-κB nuclear translocation and collagen synthesis in CFs, improved cardiac fibrosis, hypertrophy, inflammation and HFpEF in diabetic mice. Mechanistically, signal transducer and activator of transcription 3 (STAT3), which is phosphorylated and translocated from the cytoplasm into the nucleus under hyperglycemic conditions, bound to TAX1BP1 promoter and blocked TAX1BP1 transcriptional activity, consequently promoting NF-κB nuclear translocation and collagen synthesis in CFs, aggravating cardiac fibrosis, hypertrophy and inflammation, leading to HFpEF in db/db mice. Taken together, our findings demonstrate that targeting regulation of STAT3-TAX1BP1-NF-κB signaling in CFs may be a promising therapeutic approach for diabetes-induced HFpEF.

Machine-learning-based prediction of fractional flow reserve after percutaneous coronary intervention.

BACKGROUND AND AIMS: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated. METHODS: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated. RESULTS: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0. CONCLUSIONS: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event.

Clinical prognostic value of a novel quantitative flow ratio from a single projection in patients with coronary bifurcation lesions treated with the provisional approach.

Background: A novel quantitative flow ratio (µQFR) for bifurcated coronary vessels, derived from a single projection, has been recently reported. Provisional stenting is effective for most bifurcation lesions. However, the clinical value of the side branch (SB) µQFR in patients with coronary bifurcation lesions undergoing provisional stenting remains unclear. Aims: This study aims to determine the clinical predictive value of the SB µQFR after provisional stenting in patients with coronary bifurcation lesions. Methods: Between June 2015 and May 2018, 288 patients with true coronary bifurcation lesions who underwent a provisional approach without SB treatment (including predilation, kissing balloon inflation or stenting) were classified by an SB µQFR <0.8 (n=65) and ≥0.8 (n=223) groups. The primary endpoint was the three-year composite of target vessel failure (TVF), including cardiac death, target vessel myocardial infarction (TVMI), and revascularisation (TVR). Results: Three years after the procedures, there were 43 (14.9%) TVFs, with 19 (29.2%) in the SB µQFR <0.8 and 24 (10.8%) in the SB µQFR ≥0.8 groups (adjusted hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.39-5.54; p=0.003), mainly driven by increased TVMI (16.9% vs 5.4%, adjusted HR 3.29, 95% CI: 1.15-6.09; p=0.030) and TVR (15.4% vs 2.2%, adjusted HR 6.39, 95% CI: 2.04-13.48; p=0.007). Baseline diameter stenosis at the ostial SB and SB lesion length were the two predictors of an SB µQFR <0.8 immediately after stenting the main vessel, whereas previous percutaneous coronary intervention and an SB µQFR <0.8 were the two independent factors of 3-year TVF. Conclusions: An SB µQFR <0.8 immediately after the provisional approach is strongly associated with clinical events. Further randomised studies with large patient populations are warranted.

Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications.

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P<0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P=0.03) and vice versa (area under the curve 0.68 versus 0.78; P=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.

A sham-controlled randomised trial of pulmonary artery denervation for Group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial.

BACKGROUND: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported. AIMS: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH. METHODS: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death. RESULTS: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (pinteraction=0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone. CONCLUSIONS: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.