Prasugrel Monotherapy After Percutaneous Coronary Intervention With Biodegradable-Polymer Platinum-Chromium Everolimus Eluting Stent for Japanese Patients With Chronic Coronary Syndrome (ASET-JAPAN).

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

Ten-Year All-Cause Death According to Completeness of Revascularization in Patients With Three-Vessel Disease or Left Main Coronary Artery Disease: Insights From the SYNTAX Extended Survival Study.

BACKGROUND: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). METHODS: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR. RESULTS: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15-1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0-4 versus 28.9% for rSS>4-8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13-5.43]). CONCLUSIONS: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS<8) revascularization can be achieved with PCI in patients with 3-vessel disease, CABG should be considered. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417050.

Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease.

AIMS: The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes. METHODS AND RESULTS: The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227). CONCLUSIONS: The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials. TRIAL REGISTRATION: SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.

Redevelopment and validation of the SYNTAX score II to individualise decision making between percutaneous and surgical revascularisation in patients with complex coronary artery disease: secondary analysis of the multicentre randomised controlled SYNTAXES trial with external cohort validation.

BACKGROUND: Randomised controlled trials are considered the gold standard for testing the efficacy of novel therapeutic interventions, and typically report the average treatment effect as a summary result. As the result of treatment can vary between patients, basing treatment decisions for individual patients on the overall average treatment effect could be suboptimal. We aimed to develop an individualised decision making tool to select an optimal revascularisation strategy in patients with complex coronary artery disease. METHODS: The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension follow-up of a multicentre, randomised controlled trial done in 85 hospitals across 18 North American and European countries between March, 2005, and April, 2007. Patients with de-novo three-vessel and left main coronary artery disease were randomly assigned (1:1) to either the percutaneous coronary intervention (PCI) group or coronary artery bypass grafting (CABG) group. The SYNTAXES study ascertained 10-year all-cause deaths. We used Cox regression to develop a clinical prognostic index for predicting death over a 10-year period, which was combined, in a second stage, with assigned treatment (PCI or CABG) and two prespecified effect-modifiers, which were selected on the basis of previous evidence: disease type (three-vessel disease or left main coronary artery disease) and anatomical SYNTAX score. We used similar techniques to develop a model to predict the 5-year risk of major adverse cardiovascular events (defined as a composite of all-cause death, non-fatal stroke, or non-fatal myocardial infarction) in patients receiving PCI or CABG. We then assessed the ability of these models to predict the risk of death or a major adverse cardiovascular event, and their differences (ie, the estimated benefit of CABG versus PCI by calculating the absolute risk difference between the two strategies) by cross-validation with the SYNTAX trial (n=1800 participants) and external validation in the pooled population (n=3380 participants) of the FREEDOM, BEST, and PRECOMBAT trials. The concordance (C)-index was used to measure discriminative ability, and calibration plots were used to assess the degree of agreement between predictions and observations. FINDINGS: At cross-validation, the newly developed SYNTAX score II, termed SYNTAX score II 2020, showed a helpful discriminative ability in both treatment groups for predicting 10-year all-cause deaths (C-index=0·73 [95% CI 0·69-0·76] for PCI and 0·73 [0·69-0·76] for CABG) and 5-year major adverse cardiovascular events (C-index=0·65 [0·61-0·69] for PCI and C-index=0·71 [0·67-0·75] for CABG). At external validation, the SYNTAX score II 2020 showed helpful discrimination (C-index=0·67 [0·63-0·70] for PCI and C-index=0·62 [0·58-0·66] for CABG) and good calibration for predicting 5-year major adverse cardiovascular events. The estimated treatment benefit of CABG over PCI varied substantially among patients in the trial population, and the benefit predictions were well calibrated. INTERPRETATION: The SYNTAX score II 2020 for predicting 10-year deaths and 5-year major adverse cardiovascular events can help to identify individuals who will benefit from either CABG or PCI, thereby supporting heart teams, patients, and their families to select optimal revascularisation strategies. FUNDING: The German Heart Research Foundation and the Patient-Centered Outcomes Research Institute.

Usefulness of updated logistic clinical SYNTAX score based on MI-SYNTAX score in patients with ST-elevation myocardial infarction.

OBJECTIVES: To compare the predictive performances of the prewiring, postwiring MI-SYNTAX scores, prewiring, and postwiring Updated Logistic Clinical SYNTAX score (LCSS) for 2-year all-cause mortality post percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: In patients with STEMI and undergoing primary PCI, coronary stenosis(es) distal to the culprit lesion is often observed after the restoration of coronary flow. To address comprehensively the complex coronary anatomy in these patients, prewiring and postwiring MI-SYNTAX scores have been reported in the literature. Furthermore, to enable individualized risk estimation for long-term all-cause mortality, the Updated LCSS has been developed by combining the anatomical SYNTAX score and clinical factors. METHODS: In the randomized GLOBAL LEADERS trial, anatomical SYNTAX score analysis was performed by an independent angiographic corelab for the first 4,000 consecutive patients as a prespecified analysis; of these, 545 presented with STEMI. The efficacy of the mortality predictions of the four scores at 2 years were evaluated based on their discrimination and calibration abilities. RESULTS: Complete data was available in 512 patients (93.9%). When the patients were stratified into two groups based on the median of the scores, the prewiring and postwiring Updated LCSSs demonstrated that the high-score groups were associated with higher rates of 2-year all-cause mortality compared to the low-score groups (6.6 vs. 1.2%; log-rank p = .001 and 6.6 vs. 1.2%; log-rank p = .001, respectively). There were no statistically significant differences for predicting the mortality between the prewiring (area under the curve [AUC] 0.625), postwiring MI-SYNTAX score (AUC 0.614), prewiring (AUC 0.755), and postwiring Updated LCSS (AUC 0.757). In the integrated discrimination improvement (IDI), the prewiring MI-SYNTAX score had a better discrimination for the mortality than the postwiring MI-SYNTAX score (IDI -0.0082; p = .029). The four scores had acceptable calibration abilities for 2-year all-cause mortality. CONCLUSIONS: The prewiring Updated LCSS predicts long-term all-cause mortality with clearly useful discrimination and acceptable calibration. Since the postwiring MI-SYNTAX score does not improve mortality prediction, the prewiring MI-SYNTAX score may be preferred for the 2-year mortality prediction using the Updated LCSS.

Predicting 2-year all-cause mortality after contemporary PCI: Updating the logistic clinical SYNTAX score.

AIMS: We aimed to update the logistic clinical SYNTAX score to predict 2 year all-cause mortality after contemporary percutaneous coronary intervention (PCI). METHODS AND RESULTS: We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2 year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population. CONCLUSIONS: The new model of the logistic clinical SYNTAX score better predicts 2 year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.

Ticagrelor monotherapy in patients with concomitant diabetes mellitus and chronic kidney disease: a post hoc analysis of the GLOBAL LEADERS trial.

BACKGROUND: Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. METHODS: In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. RESULTS: At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66-2.80], p < 0.001), BARC type 3 or 5 bleeding events, stroke, site-reported myocardial infraction, all revascularization, POCE, and NACE, compared with the DM-/CKD- patients. Among the DM + /CKD + patients, after adjustment, there were no significant differences in the primary endpoints between the experimental and reference regimen; however, the experimental regimen was associated with lower rates of POCE (20.6% versus 25.9%, HR 0.74; 95% CI [0.55-0.99], p = 0.043, pinteraction = 0.155) and NACE (22.7% versus 28.3%, HR 0.75; 95% CI [0.56-0.99], p = 0.044, pinteraction = 0.310), which was mainly driven by a lower rate of all revascularization, as compared with the reference regimen. The landmark analysis showed that while the experimental and reference regimen had similar rates of all the clinical endpoints during the first year, the experimental regimen was associated with significantly lower rates of POCE (5.8% versus 11.0%, HR 0.49; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.040) and NACE (5.8% versus 11.2%, HR 0.48; 95% CI [0.29-0.82], p = 0.007, pinteraction = 0.013) in the second year. CONCLUSION: Among patients with both DM and CKD, ticagrelor monotherapy was not associated with lower rates of all-cause death or new Q-wave, or major bleeding complications; however, it was associated with lower rates of POCE and NACE. These findings should be interpreted as hypothesis-generating. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01813435).

Two years clinical outcomes with the state-of-the-art PCI for the treatment of bifurcation lesions: A sub-analysis of the SYNTAX II study.

BACKGROUND: Bifurcation PCI is associated with a lower rate of procedural success, especially in multivessel disease patients. We aimed to determine the impact of bifurcation treatment on 2-years clinical outcomes when a state-of-the-art PCI strategy (heart team decision-making using the SYNTAX score II, physiology guided coronary stenosis assessment, thin strut bioresorbable polymer drug-eluting stent, and intravascular ultrasound guidance) is followed. METHODS: Three-vessel disease patients enrolled in the SYNTAX II trial (n = 454) were categorized in patients with (a) ≥1 treated bifurcation (n = 126), and (b) without bifurcation (n = 281). The primary endpoint was the occurrence of major adverse cardio and cerebrovascular events (MACCE-a composite of all-cause death, stroke, any myocardial infarction, or any revascularization) at 2 years. Secondary endpoints were the occurrence of target lesion failure (TLF) defined as cardiac death, target-vessel myocardial infarction and ischemia-driven target lesion revascularization, and the individual components of the composite primary endpoint, as well as stent thrombosis. RESULTS: A total of 145 bifurcation were treated in 126 patients. At 2 years, MACCE occurred in 75/407 patients (20.7% for bifurcation versus 17.5% for nonbifurcation, hazard ratio [HR] of 1.28, CI95% 0.78-2.08, p = .32). TLF presented a trend toward higher occurrence in bifurcation (16.8% vs. 10.8%, HR 1.75, CI95% 0.99-3.09, p = .053). Definite stent thrombosis did not differ at 2-year between groups (0.8% for the bifurcation vs. 0.7% for the nonbifurcation, p = .92). CONCLUSION: Bifurcation treatment in patients with three-vessel disease undergoing state-of-the-art PCI had similar event rate of MACCE but was associated with a trend toward higher incidence of TLF compared with nonbifurcation lesions.

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial.

BACKGROUND: The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. RESULTS: Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. CONCLUSIONS: After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial.

Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial.

OBJECTIVES: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). BACKGROUND: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. METHODS: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. RESULTS: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p < .001) and integrated discrimination improvement (0.121, p < .001). CONCLUSIONS: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.

Impact of established cardiovascular disease on outcomes in the randomized global leaders trial.

OBJECTIVE: To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD). METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events. RESULTS: Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models. CONCLUSIONS: The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.

Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial.

AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Impact of post-procedural minimal stent area on 2-year clinical outcomes in the SYNTAX II trial.

OBJECTIVES: To investigate the impact of minimal stent area (MSA) evaluated by post-procedural intravascular ultrasound (IVUS) on clinical outcomes after contemporary PCI in patients with three-vessel disease (TVD). BACKGROUND: The impact of post-procedural MSA on clinical outcomes has not yet been extensively studied in patients with TVD. METHODS: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a state-of-the-art PCI strategy on clinical outcomes in patients with TVD (454 patients with 1,559 lesions). The relationships between post-procedural MSA and lesion-level outcomes at 2 years were investigated. Clinical events adjudicated per patient by clinical event committee were assessed per lesion. Lesion-oriented composite endpoint (LOCE) was defined as the composite of cardiac death, target-vessel myocardial infarction, and ischemia-driven target lesion revascularization. RESULTS: Eight hundred and nineteen lesions with post-procedural MSA available in 367 patients were included in the analysis. The post-procedural MSA per lesion was divided into terciles (smallest tercile: ≤5.0 mm2 , intermediate tercile: 5.0-6.7 mm2 , and largest tercile: >6.7 mm2 ). LOCE was observed in 16/288 (5.6%), 15/265 (5.7%), and 8/266 (3.0%) (P = 0.266). Target lesion revascularization (TLR) was observed in 16/288(5.6%), 12/265 (4.5%), and 4/266 (1.5%) (P = 0.042). The multivariate analysis demonstrated that smaller post-procedural MSA, as well as creatinine clearance, history of previous stroke, chronic total occlusion, and lesion SYNTAX Score was an independent predictor of TLR. CONCLUSIONS: In the SYNTAX II trial, larger post-procedural MSA was independently associated with the lower rate of TLR at 2 years.

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.

Angiographic late lumen loss revisited: impact on long-term target lesion revascularization.

Aim: In current device trials, the values of angiographic late lumen loss (LLL) have become extremely low and the relationship between LLL and clinical endpoints has not been recently re-evaluated. The impact of LLL on target lesion revascularization (TLR) in a patient- and study-level analysis of contemporary coronary devices was investigated. Methods and results: We performed a patient-level meta-analysis of seven randomized controlled trials including 2426 patients treated with first- and second-generation drug-eluting stents (DES) and a study-level meta-analysis of 40 studies including 19 199 patients treated with CE-marked DES. In the patient-level analysis, the probability regression curve showed an exponential relationship between in-stent LLL and 2-year incidence of TLR. The optimal cut-off value of LLL based on Youden's index for 2-year TLR event was 0.50 mm. In the Cox proportional hazard model, LLL >0.50 mm was independently associated with an increased incidence of TLR up to 4 years after angiographic follow-up {adjusted hazard ratio (HR) 6.62 [95% confidence interval (95% CI) 4.67-9.39], P < 0.001}. In the meta-regression analysis of the DES studies, pooled mean value of LLL was as low as 0.23 mm (95% CI 0.20-0.26), and there was a moderate correlation between the 1- and 5-year incidence of TLR and the percentage of the lesions with LLL >0.50 mm (R2 = 0.44, P < 0.001 at 1 year, R2 = 0.40, P < 0.001 at 5 years). Conclusion: An angiographic LLL ≤0.50 mm was not predictive of the incidence of TLR whereas a LLL >0.50 mm was. Low LLL in contemporary device trials may not be a sufficiently discriminating parameter for the comparative evaluation of devices.

Angioplasty of the Occluded Persistent Sciatic Artery Using the Retrograde Approach from Superficial Femoral Artery.

Persistent sciatic artery is a rare developmental anomaly prone to atherosclerotic disease. We present a case of successful endovascular therapy for left persistent sciatic artery that was occluded at the distal site. The angioplasty was performed with both antegrade approach from contralateral common femoral artery and retrograde approach from ipsilateral superficial femoral artery. The guidewire was advanced via collateral channel and crossed through the lesion retrogradely. Rendez-vous technique was performed, and the lesion was successfully dilated by balloon inflation. Angioplasty of occluded sciatic artery can be performed successfully and effectively using the collateral channel.

Thoracolumbar intradural disc herniation in eight dogs: clinical, low-field magnetic resonance imaging, and computed tomographic myelography findings.

Intradural disc herniation is a rarely reported cause of neurologic deficits in dogs and few published studies have described comparative imaging characteristics. The purpose of this retrospective cross sectional study was to describe clinical and imaging findings in a group of dogs with confirmed thoracolumbar intradural disc herniation. Included dogs were referred to one of four clinics, had acute mono/paraparesis or paraplegia, had low field magnetic resonance imaging (MRI) and/or computed tomographic myelography, and were diagnosed with thoracolumbar intradural disc herniation during surgery. Eight dogs met inclusion criteria. The prevalence of thoracolumbar intradural disc herniation amongst the total population of dogs that developed a thoracolumbar intervertebral disc herniation and that were treated with a surgical procedure was 0.5%. Five dogs were examined using low-field MRI. Lesions that were suspected to be intervertebral disc herniations were observed; however, there were no specific findings indicating that the nucleus pulposus had penetrated into the subarachnoid space or into the spinal cord parenchyma. Thus, the dogs were misdiagnosed as having a conventional intervertebral disc herniation. An intradural extramedullary disc herniation (three cases) or intramedullary disc herniation (two cases) was confirmed during surgery. By using computed tomographic myelography (CTM) for the remaining three dogs, an intradural extramedullary mass surrounded by an accumulation of contrast medium was observed and confirmed during surgery. Findings from this small sample of eight dogs indicated that CTM may be more sensitive for diagnosing canine thoracolumbar intradural disc herniation than low-field MRI.

Differential Effect of Aortic Valve Replacement for Severe Aortic Stenosis on Hyperemic and Resting Epicardial Coronary Pressure Indices.

BACKGROUND: Coronary pressure indices to assess coronary artery disease are currently underused in patients with aortic stenosis due to many potential physiological effects that might hinder their interpretation. Studies with varying sample sizes have provided us with conflicting results on the effect of transcatheter aortic valve replacement (TAVR) on these indices. The aim of this meta-analysis was to study immediate and long-term effects of TAVR on fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs). METHODS AND RESULTS: Lesion-specific coronary pressure data were extracted from 6 studies, resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Lesion data were pooled and compared with paired t tests. Immediately after TAVR, FFR decreased significantly (-0.0130±0.0406 SD, P: 0.0002) while NHPR remained stable (0.0003±0.0675, P: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230±0.0747, P: 0.0038) while NHPR increased nonsignificantly (0.0166±0.0699, P: 0.0543). When only borderline NHPR lesions were considered, this increase became significant (0.0249±0.0441, P: 0.0015). Sensitivity analysis confirmed our results in borderline lesions. CONCLUSIONS: TAVR resulted in small significant, but opposite, changes in FFR and NHPR. Using the standard cut-offs in patients with severe aortic stenosis, FFR might underestimate the physiological significance of a coronary lesion while NHPRs might overestimate its significance. The described changes only play a clinically relevant role in borderline lesions. Therefore, even in patients with aortic stenosis, an overtly positive or negative physiological assessment can be trusted.