First description and validation of a new method for estimating aortic stenosis burden and predicting the functional response to TAVI.

Background: Up to one-fifth of patients continue to have poor quality of life after transcatheter aortic valve implantation (TAVI), with an additional similar proportion not surviving 1 year after the procedure. We aimed to assess the value of a new method based on an integrated analysis of left ventricular outflow tract flow velocity and aortic pressure to predict objective functional improvement and prognosis after TAVI. Methods: In a cohort of consecutive patients undergoing TAVI, flow velocity-pressure integrated analysis was obtained from simultaneous pressure recordings in the ascending aorta and flow velocity recordings in the left ventricular outflow tract by echocardiography. Objective functional improvement 6 months after TAVI was assessed through changes in a 6-min walk test and NT-proBNP levels. A clinical follow-up was conducted at 2 years. Results: Of the 102 patients studied, 82 (80.4%) showed objective functional improvement. The 2-year mortality of these patients was significantly lower (9% vs. 44%, p = 0.001). In multivariate analysis, parameter "(Pressure at Vmax - Pressure at Vo)/Vmax" was found to be an independent predictor for objective improvement. The C-statistic was 0.70 in the overall population and 0.78 in the low-gradient subgroup. All echocardiographic parameters and the valvuloarterial impedance showed a C-statistic of <0.6 for the overall and low-gradient patients. In a validation cohort of 119 patients, the C-statistic was 0.67 for the total cohort and 0.76 for the low-gradient subgroup. Conclusion: This new method allows predicting objective functional improvement after TAVI more precisely than the conventional parameters used to assess the severity of aortic stenosis, particularly in low-gradient patients.

Intraprocedural delayed reassessment of paravalvular regurgitation in TAVR significantly reduces the use of postdilatation.

OBJECTIVES: We sought to investigate the effect of a 15-min delayed intraprocedural reassessment of paravalvular aortic regurgitation (PVR) after an immediate evaluation of posttranscatheter aortic valve replacement (TAVR) on the regurgitation grading and usage of postdilatation. BACKGROUND: PVR after TAVR is associated with poor prognosis, but postdilatation may increase the risk of other complications. METHODS: In a prospective cohort of consecutive patients treated with balloon-expandable valve ES-3 ultra, the degree of PVR was assessed immediately and 15 min after that first evaluation (excluded severe cases), with the indication of postdilatation based on the delayed assessment. As a control group, the previous consecutive series of patients also treated with the same model of valve prosthesis was used. RESULTS: A total of 180 patients were included in the prospective study cohort and 152 in the retrospective control group. In the study group, the immediate PVR assessment showed none-trace 27.5%, mild 52%, moderate 19%, and severe 1.5%, and the delayed re-evaluation graded PVR as none-trace 83%, mild 15.6%, and moderate 1.2% (p < 0.001 as compared to immediate). In the control group, the immediate PVR assessment showed none-trace 33.5%, mild 52%, moderate 13%, and severe 1.5%. The rate of postdilatation was 2.8% in the study group versus 10.5% in the control group (p = 0.006). At discharge, no differences were observed between groups in PVR echocardiographic grading. CONCLUSIONS: A post-TAVR delayed intraprocedural reassessment of the PVR shows a clearly lower degree of regurgitation as compared to immediate evaluation, which significantly decreased the indication of postdilatation.

A new integrative approach to assess aortic stenosis burden and predict objective functional improvement after TAVR.

Background: A non-negligible rate of patients undergoing transcatheter aortic valve replacement (TAVR) do not report symptomatic improvement or even die in the short-midterm. We sought to assess the degree of objective functional recovery after TAVR and its prognostic implications and to develop a predictive model. Methods: In a cohort of patients undergoing TAVR, a prospective evaluation of clinical, anatomical, and physiological parameters was conducted before and after the procedure. These parameters were derived from echocardiography, non-invasive analysis of arterial pulse waves, and cardiac tomography. Objective functional improvement 6 months after TAVR was assessed using a 6-min walk test and nitro-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The derived predictive model was prospectively validated in a different cohort. A clinical follow-up was conducted at 2 years. Results: Among the 212 patients included, objective functional improvement was observed in 169 patients (80%) and subjective improvement in 187 (88%). Patients with objective functional improvement showed a much lower death rate at 2 years (9% vs. 31% p = 0.0002). Independent predictors of improvement were as follows: mean aortic gradient of ≥40 mmHg, augmentation index75 of ≥45%, the posterior wall thickness of ≤12 mm, and absence of atrial fibrillation. A simple integer-based point score was developed (GAPA score), which showed an area under the curve of 0.81 for the overall cohort and 0.78 for the low-gradient subgroup. In a validation cohort of 216 patients, these values were 0.75 and 0.76, respectively. Conclusion: A total of 80% of patients experienced objective functional improvement after TAVR, showing a significantly lower 2-year mortality rate. A predictive score was built that showed a good discriminative performance in overall and low-gradient populations.

Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study.

AIMS: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial. METHODS AND RESULTS: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35). CONCLUSIONS: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

Procedural Results and One-Year Clinical Outcomes of Treatment of Bioresorbable Vascular Scaffolds Restenosis (from the RIBS VII Prospective Study).

Currently, both drug-eluting stents (DES) and drug-eluting balloons are recommended in patients with in-stent restenosis (ISR) of metallic stents. However, the clinical results of repeated interventions in patients with restenosis of bioresorbable vascular scaffolds (BVS) remain unsettled. We sought to assess the results of interventions in patients with BVS-ISR as compared with those obtained in patients with ISR of DES and bare-metal stents (BMS). Restenosis Intrastent: Treatment of Bioresorbable Vascular Scaffolds Restenosis (RIBS VII) is a prospective multicenter study (23 Spanish sites) that included 117 consecutive patients treated for BVS-ISR. Inclusion/exclusion criteria were similar to those of previous RIBS studies. Patients in the RIBS IV (DES-ISR, n = 309) and RIBS V (BMS - ISR, n = 189) randomized trials, were used as controls. Most patients with BVS-ISR were treated with DES (76%). Patients with BVS-ISR were younger, had larger vessels, and after interventions had higher in-segment residual diameter stenosis (19 ± 13%, 15 ± 11%, 15 ± 12%, p <0.001) than those treated for DES-ISR and BMS-ISR, respectively. At 1-year clinical follow-up (obtained in 100% of patients) target lesion revascularization (6%) was similar to that seen in patients with DES-ISR and BMS-ISR (8.7% and 3.7%, p = 0.32). Freedom from death, myocardial infarction, and target vessel revascularization (primary clinical end point) was 8.5%, also similar to that found in patients with DES-ISR and BMS-ISR (14.2% and 7.4%, p = 0.09). Results were also similar when only patients treated with DES in each group were compared and remained unchanged after adjusting for potential confounders in baseline characteristics. Time to BVS-ISR did not influence angiographic or clinical results. This study demonstrates the safety and efficacy of coronary interventions for patients presenting with BVS-ISR. One-year clinical results in these patients are comparable to those seen in patients with ISR of metallic stents (ClinicalTrials.gov ID:NCT03167424).

Validation study to determine the accuracy of central blood pressure measurement using the SphygmoCor XCEL cuff device in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Central aortic blood pressure could be helpful in the evaluation of patients with aortic stenosis (AS). The SphygmoCor XCEL device estimates central blood pressure (BP) measurement with its easy-to-use, operator-independent procedure. However, this device has not been properly validated against invasive measurement in patients with severe AS. We evaluated the relationship between cuff-brachial BP, transfer function-estimated and invasively measured central aortic pressure in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Agreement between techniques was analyzed and, according to the ARTERY Society recommendations, the minimum acceptable error was a mean difference ± SD ≤5 ± ≤8 mm Hg. A total of 94 patients with AS undergoing TAVR had simultaneous non-invasive and invasive measurements of central BP before and after the procedure. Before TAVR central systolic BP was in average slightly underestimated, though with wide variability, when using the default calibration of brachial-cuff SBP (mean difference ± SD, -3 ± 15 mm Hg), and after TAVR the degree of underestimation increased (mean difference ± SD, -9 ± 13 mm Hg). The agreement tended to improve for those patients with low aortic gradient stenosis compared to those with high gradient at baseline (mean difference ± SD, -2 ± 11 mm Hg vs. -4 ± 17, respectively, p = .3). The cuff-brachial systolic BP yielded numerically lower degree of agreement and weaker correlation with invasive measurements than SphygmoCor XCEL. In patients with severe AS the SphygmoCor XCEL cuff device, despite showing strong correlation, does not meet the ARTERY Society accuracy criteria for non-invasive measurement of central SBP.

First-in-Man Evaluation of a Sirolimus-Eluting Stent With Abluminal Fluoropolymeric/Triflusal Coating With Ultrathin Struts by OCT at 9 Months' Follow-Up: The PROMETHEUS Study.

OBJECTIVES: We sought to investigate stent healing and neointimal hyperplasia with ihtDEStiny drug-eluting stent (DES) by optical coherence tomography (OCT) examination conducted 9 months after implantation. BACKGROUND: The currently used DES present certain features that have been linked separately to their better performance in terms of efficacy and safety. METHODS: First-in-man, prospective and multicenter study including patients treated with ihtDEStiny stent undergoing OCT examination at 9 months follow up. The ihtDEStiny stent is a sirolimus eluting stent with an oval shape ultrathin struts (68 µm) and an abluminal coating of a fluoropolymer containing the antiplatelet agent triflusal. Primary endpoint was the percentage of obstruction of the in-stent volume by the neointima. RESULTS: In 58 patients (63 lesions) in-stent late lumen loss was 0.11 ± 0.23 mm (95% CI 0.05-0.16) with only in 6% of stents being > 0.5 mm and in-segment binary stenosis was 1.6%. In OCT mean neointima volume obstruction was 10.5 ± 6.9% with a mean neointima thickness of 110.9 ± 89.8 µm. The proportion of uncovered struts was 2.5%, malapposed struts 1.1% and malapposed/uncovered struts 0.7% and no subclinical thrombi detected. Mean incomplete stent apposition area was 0.1 ± 0.1 mm2. At 12 months target lesion revascularization rate was 3% and no stent thrombosis was reported. CONCLUSIONS: In this study the ihtDEStiny stent has shown a very low degree of neointimal proliferation associated with a low rate of uncovered/malapposed struts and total absence of subclinical thrombi at 9 months follow up.

Scoring balloon predilation before bioresorbable vascular scaffold implantation in patients with in-stent restenosis: the RIBS VI 'scoring' study.

BACKGROUND: Currently drug-eluting stents (DES) and drug-eluting balloons are recommended in patients with in-stent restenosis (ISR). However, the efficacy of bioresorbable vascular scaffolds (BVS) after scoring balloon (SCB) predilation in these patients is unknown. METHODS: RIBS VI (NCT02672878) and RIBS VI 'Scoring' (NCT03069066) are prospective multicentre studies assessing the value of BVS in patients with ISR. Inclusion and exclusion criteria were identical in both studies. Results of conventional BVS implantation (112 patients) were compared with those obtained with systematic SCB therapy before BVS (108 patients). Angiographic follow-up was scheduled for all patients. RESULTS: On late angiography (93% of eligible patients) the in-segment minimal lumen diameter (primary end-point) (1.88 ± 0.5 vs. 1.90 ± 0.4 mm, P = 0.81), % diameter stenosis (28 ± 17 vs. 29 ± 15%), late lumen loss (0.23 ± 0.4 vs. 0.22 ± 0.4 mm) and binary restenosis rate (8.5 vs. 9.3%) were similar in the conventional BVS and SCB + BVS groups, respectively. At 1-year follow-up (100% of patients) target lesion revascularization (TLR) requirement (9.8 vs. 11.1%) was similar with the two strategies. Freedom from cardiac death, myocardial infarction and TLR was 88% and 87%, respectively. Results remained unchanged after adjusting for potential baseline confounders and were consistent in 10 prespecified subgroups. CONCLUSION: This study suggests that results of conventional BVS implantation in patients with ISR are not improved by systematic predilation with SCB. ClinicalTrials.gov ID: NCT02672878 (RIBS VI) and NCT03069066 (RIBS VI 'Scoring').

Outcomes of predefined optimisation criteria for intravascular ultrasound guidance of left main stenting.

AIMS: This study sought to investigate the prognostic effect of a protocol with optimisation targets for intravascular ultrasound (IVUS)-guided left main (LM) revascularisation. METHODS AND RESULTS: A protocol was prospectively applied for IVUS-guided LM revascularisation (IVUS-PRO group) including predefined optimisation targets. Using propensity score matching, we selected as control groups patients with angiography-guided PCI (ANGIO group) and IVUS-guided PCI (IVUS group) from a large multicentre registry. The primary endpoint was a composite of cardiac death, LM-related infarction and LM revascularisation at 12 months. In each group, 124 patients with comparable characteristics were included. The incidence of the primary outcome was significantly higher in the ANGIO group compared to the IVUS-PRO group (12.9% vs 4.8%, HR 0.35, 95% CI: 0.15 to 0.82, p=0.02), but not with respect to the IVUS group (12.9% vs 8%, HR 0.51, 95% CI: 0.20 to 1.22, p=0.1), driven by a lower rate of LM revascularisation (8% in the ANGIO group, 6.4% in the IVUS group and 3.2% in the IVUS-PRO group). IVUS-PRO resulted in being an independent risk predictor (HR 0.45, 95% CI: 0.15 to 0.98; p=0.041). CONCLUSIONS: IVUS guidance of LM stenting provides prognostic benefit with respect to the use of angiography alone, particularly when following a protocol with these predefined optimisation criteria.

Angiography and Optical Coherence Tomography Assessment of the Drug-Coated Balloon ESSENTIAL for the Treatment of In-Stent Restenosis.

OBJECTIVES: This study sought to assess the efficacy of the drug-coated balloon (DCB) ESSENTIAL for the treatment of in-stent restenosis (ISR). BACKGROUND: DCBs have proven a valid therapeutic option for the management of ISR in several clinical trials, yet no class effect can be claimed. Accordingly, every new DCB model has to be individually evaluated through clinical studies. METHODS: This is a prospective, multicenter study including consecutive patients undergoing percutaneous coronary intervention for ISR with the ESSENTIAL DCB. A 6-month quantitative coronary angiography (QCA)/optical coherence tomography (OCT) follow-up was scheduled. The primary endpoint was OCT-derived in-segment maximal area stenosis. Secondary endpoints included QCA-derived in-segment late lumen loss (LLL) and target lesion failure (TLF) rates at 6, 12, and 24 months. TLF was defined as the composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS: A total of 31 patients were successfully treated with DCB, with 67% of ISR corresponding to drug-eluting stents (DES). At 6 months, 26 patients underwent the scheduled angiographic follow-up. The mean value for in-segment maximal area stenosis was 51.4 ±â€¯13% and the median value was 53% (IQR 46.4-59.5). In the DES-ISR subgroup, these parameters were 52.6 ±â€¯10% and 55.2% (IQR 49.3-58.5), respectively. In-segment LLL was 0.25 ±â€¯0.43 mm with only 2 (7.7%) patients showing binary restenosis (>50%). The incidence of TLF was 10% at 6 months, 13.3% at 12 months, and 13.3% at 24 months. CONCLUSIONS: In this study, the ESSENTIAL DCB showed sustained efficacy in the prevention of recurrent restenosis after treatment of ISR. SUMMARY: We sought to assess the efficacy of the drug-coated balloon ESSENTIAL for the treatment of in-stent restenosis through a prospective, multicenter study including QCA and OCT assessment at 6-month follow-up. The primary endpoint was in-segment maximal area stenosis. Among the 31 patients successfully treated with the ESSENTIAL DCB, an angiographic follow-up was conducted in 26. Mean in-segment maximal area stenosis was 51.4 ±â€¯13% and the median value was 53% (IQR 46.4-59.5). In the DES-ISR subgroup, corresponding values were 52.6 ±â€¯10% and 55.2% (IQR 49.3-58.5), respectively. The observed in-segment LLL was 0.25 ±â€¯0.43 mm and binary restenosis rate was 7.7%. TLF was 10% at 6 months and 13.3% at 12 and 24 months.

First-in-man randomised comparison of the Angiolite durable fluoroacrylate polymer-based sirolimus-eluting stent versus a durable fluoropolymer-based everolimus-eluting stent in patients with coronary artery disease: the ANGIOLITE trial.

AIMS: The durable fluoroacrylate polymer-based sirolimus-eluting stent (Angiolite SES) has shown promising preclinical and clinical results regarding inflammatory vascular reaction and neointimal healing. We aimed to compare performance between the Angiolite SES and an everolimus-eluting stent (EES) in patients with coronary artery disease. METHODS AND RESULTS: The ANGIOLITE trial, a prospective, randomised, multicentre trial, compared the restenosis parameters of both stents in de novo coronary lesions. The primary endpoint was late lumen loss at six-month angiographic follow-up. In-stent healing was assessed by optical coherence tomography (OCT). The main clinical endpoint was target lesion failure (TLF) evaluated up to 24 months. A total of 223 patients were randomised 1:1 to EES or SES. At six months, in-stent late lumen loss was 0.08 mm (±0.38) for EES vs 0.04 mm (±0.39) for SES (difference=-0.04 mm, 95% CI: -0.15, 0.07, p for non-inferiority=0.002). By OCT, the rate of uncovered to total number of struts score >30% was comparable between the groups whereas neointimal thickness was reduced in the SES arm (9.0% [7.6, 10.6] vs 9.9% [8.5, 11.3], p=0.41; and 86.4 [81.6, 91.2] µm vs 72.1 [68.2, 76.0] µm, p<0.01, respectively). At 24 months, TLF occurred in eight patients (7.6% [3.3, 14.5]) in the EES arm and in seven patients (7.1% [2.9, 14.0]) in the SES arm (p=0.88). The definite/probable stent thrombosis rate was comparable between the groups (1.9% [0.2, 6.7] vs 1.0% [0.0, 5.5] EES vs SES, respectively; p=0.59). CONCLUSIONS: This trial demonstrates similar antirestenotic efficacy at midterm follow-up of the Angiolite SES vs an EES. Clinical endpoints were comparable between the groups at two-year follow-up. Visual summary. Main results of the ANGIOLITE trial.

Safety of drug-eluting stents compared to bare metal stents in patients with an indication for long-term oral anticoagulation: A propensity score matched analysis.

BACKGROUND: Drug-eluting stents (DES) reduce stent restenosis compared with bare-metal stents (BMS). However, their use in patients requiring long-term oral anticoagulation (OAC) is controversial owing to increased risk of bleeding associated with OAC plus antiplatelet treatment over time. OBJECTIVE: To assess the safety of DES vs BMS in patients requiring long-term OAC for any reason. METHODS: Prospective observational multicenter study conducted at 6 teaching centers of patients undergoing percutaneous coronary intervention who required OAC for any reason. Adverse outcomes were analyzed at 1 year of follow-up. RESULTS: We identified 1002 patients requiring OAC (mean age: 72 years, male 72%). Six- hundred and thirteen patients (61.2%) received BMS and 389 (38.8%) DES. Diabetes, previous PCI, myocardial infarction and acute coronary syndrome at admission (P < 0.0001) were more common in patients with DES. Antithrombotic prescribing was similar at discharge between groups (TT: 51.5% vs 50.9%, clopidogrel plus OAC: 7.0% vs 5.0% and DAPT: 41.4% vs 42.7%, p = 0.52). DES and BMS patients showed similar rates of total bleeding (15.2% vs 13.4%, adjusted HR 0.82 [0.58-1.17, p = 0.82 and major bleeding (6.2% vs 6.0%; adjusted HR 1.22 [0.71-2.09], p = 0.46) and MACE (15.2% vs 18.6%, adjusted HR: 0.82 [0.57-1.17], p = 0.28, while restenosis was lower in patients with DES (5.3% vs 8.5%, adjusted HR. (0.52 [0.29-0.92], p = 0.02. Cox analysis after propensity score selection of 368 matched pairs demonstrated that DES use was not associated with a higher incidence of total bleeding or major bleeding. CONCLUSION: DES use is safe in patients with an indication for long-term OAC.

Angiography-Derived Fractional Flow Reserve in the SYNTAX II Trial: Feasibility, Diagnostic Performance of Quantitative Flow Ratio, and Clinical Prognostic Value of Functional SYNTAX Score Derived From Quantitative Flow Ratio in Patients With 3-Vessel Disease.

OBJECTIVES: The aims of the present study were to investigate the applicability of quantitative flow ratio (QFR) in patients with 3-vessel disease and to demonstrate the impact of functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score derived from QFR (fSSQFR) on clinical outcomes. BACKGROUND: The applicability of QFR in patients with 3-vessel disease and the feasibility of fSSQFR have not yet been investigated. METHODS: All lesions interrogated using instantaneous wave-free ratio and/or fractional flow reserve in the SYNTAX II trial were retrospectively screened and analyzed for QFR. The diagnostic performance of QFR was investigated using hybrid wire-derived pressure assessment (instantaneous wave-free ratio and fractional flow reserve), used in the trial as a reference. Patients with analyzable QFR in 3 vessels were stratified according to fSSQFR to evaluate its clinical prognostic value on the basis of 2-year patient-oriented composite endpoint. RESULTS: QFRs were analyzable in 71.0% of lesions (836 lesions). The diagnostic performance of QFR to predict binary wire-based ischemia was substantial (area under the curve 0.81, accuracy 73.8%), with a positive predictive value of 85.9%. Independent predictors of diagnostic discordance were lesions in side branches, involvement of bifurcation or trifurcation, and small vessel. According to the 2-year patient-oriented composite endpoint, fSSQFR reclassified 26.1% of the patients (36 of 138) in the high- to intermediate-risk group into the low-risk group appropriately (net reclassification improvement 0.32; p < 0.001). The area under the curve for fSSQFR to predict the 2-year patient-oriented composite endpoint was higher than that of the classic anatomic SYNTAX score (0.68 vs. 0.56; p = 0.002). CONCLUSIONS: QFR demonstrated substantial applicability in patients with 3-vessel disease. The fSSQFR has the potential to further refine prognostic risk estimation compared with the classic anatomic SYNTAX score.

3-Year Clinical Follow-Up of the RIBS IV Clinical Trial: A Prospective Randomized Study of Drug-Eluting Balloons Versus Everolimus-Eluting Stents in Patients With In-Stent Restenosis in Coronary Arteries Previously Treated With Drug-Eluting Stents.

OBJECTIVES: This study sought to compare the long-term safety and efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with in-stent restenosis (ISR) of drug-eluting stents (DES). BACKGROUND: Treatment of patients with DES-ISR remains a challenge. METHODS: The RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents) trial is a prospective multicenter randomized clinical trial comparing DEB and EES in patients with DES-ISR. The pre-specified comparison of the 3-year clinical outcomes obtained with these interventions is the main objective of the present study. RESULTS: A total of 309 patients with DES-ISR were randomized to DEB (n = 154) or EES (n = 155). At angiographic follow-up, the in-segment minimal lumen diameter was larger in the EES arm (2.03 ± 0.7 mm vs. 1.80 ± 0.6 mm; p < 0.01). Three-year clinical follow-up was obtained in all enrolled patients (100%). The combined clinical outcome measure of cardiac death, myocardial infarction and target lesion revascularization was significantly reduced in the EES arm (19 [12.3%] vs. 31 [20.1%]; p = 0.04; hazard ratio: 0.57 [95% confidence interval: 0.34 to 0.96]), driven by a lower need for target lesion revascularization (11 [7.1%] vs. 24 [15.6%]; p = 0.015; hazard ratio: 0.43 [95% confidence interval: 0.21 to 0.87]). The need for "late" (>1 year) target lesion revascularization (2.6% vs. 4%) and target vessel revascularization (4% vs. 6.6%) was similar in the 2 arms. Rates of cardiac death (3.9% vs. 3.2%), myocardial infarction (2.6% vs. 4.5%), and stent thrombosis (1.3% vs. 2.6%) at 3 years were also similar in both arms. CONCLUSIONS: The 3-year clinical follow-up of this randomized clinical trial demonstrates that in patients with DES-ISR, EES reduce the need for repeat interventions compared with DEB. (Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloons vs Everolimus-Eluting Stents [RIBS IV]; NCT01239940).

Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with de novo three vessel disease: 1-year results of the SYNTAX II study.

Aims: To investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease. Methods and results: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39-0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11-0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37-0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27-1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10-4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07-0.97, P = 0.045). Conclusion: At one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted. ClinicalTrials.gov Identifier: NCT02015832.

Bioresorbable Vascular Scaffolds for Patients With In-Stent Restenosis: The RIBS VI Study.

OBJECTIVES: This study sought to assess the value of bioresorbable vascular scaffolds (BVS) in patients with in-stent restenosis (ISR). BACKGROUND: Currently both drug-eluting stents (DES) and drug-eluting balloons (DEB) are recommended in patients with ISR. However, the value of BVS in this setting remains unclear. METHODS: RIBS VI (Restenosis Intra-stent: drug-eluting Balloon vs everolimus-eluting Stent) was a prospective multicenter study (19 Spanish sites) that included 141 patients treated with BVS for either bare-metal stent (BMS) ISR or DES-ISR. Late angiography was scheduled at 6 to 9 months. Inclusion/exclusion criteria were similar to those used in the RIBS IV (patients with DES-ISR) and RIBS V (patients with BMS-ISR) trials, where DEB (n = 249) was compared with everolimus (EES)-DES (n = 249). Results of BVS in RIBS VI were compared with those obtained with DEB and EES in the RIBS IV and V trials. RESULTS: On late angiography (n = 134; 95% of eligible) the in-segment minimal lumen diameter (primary endpoint) was 1.87 ± 0.5 mm, late lumen loss was 0.23 ± 0.4 mm, and restenosis rate was 11%. At 1-year follow-up (100% of patients) no patient died, 4 (2.8%) experienced a myocardial infarction, and 16 (11.3%) required target lesion revascularization. One patient (0.7%) who discontinued antiplatelet therapy experienced definitive BVS thrombosis. Freedom from cardiac death, myocardial infarction, and target lesion revascularization was 86%. The minimal lumen diameter at follow-up after BVS was similar to that obtained with DEB (1.88 ± 0.6 mm; p = NS) but smaller than that achieved after EES (2.16 ± 0.7 mm; p < 0.001). Likewise, target lesion revascularization rates after BVS were similar to those seen with DEB (10.4%) but higher than with EES (3.2%; p < 0.001). Results remained unchanged after adjusting for potential confounders in baseline characteristics. CONCLUSIONS: This study suggests the safety and efficacy of BVS in patients with ISR. In this challenging anatomic scenario BVS obtained late angiographic and clinical results similar to DEB but inferior to EES. (Restenosis Intrastent: Bioresorbable Vascular Scaffolds Treatment [RIBS VI]; NCT02672878).

Usefulness of Drug-Eluting Balloons for Bare-Metal and Drug-Eluting In-Stent Restenosis (from the RIBS IV and V Randomized Trials).

Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is particularly challenging. We sought to compare results of drug-eluting balloons in patients with DES-ISR with those in patients with bare-metal stent (BMS) ISR. A pooled analysis of the Restenosis Intra-Stent: Drug-Eluting Balloon versus Everolimus-Eluting Stent IV and V randomized trials was performed. Both trials had identical inclusion and exclusion criteria. Results of drug-eluting balloons in 95 patients with BMS-ISR and 154 patients with DES-ISR were compared. Patients with DES-ISR were more frequently diabetics, presented more often as an acute coronary syndrome and had more severe lesions and more frequently a focal pattern, including edge-ISR. Late angiographic findings (92% of eligible patients), including minimal lumen diameter (1.80 ± 0.6 vs 2.01 ± 0.6 mm, p = 0.001; absolute mean difference 0.21 mm; 95% confidence interval 0.04 to 0.38; p = 0.014) and restenosis rate (19% vs 9.5%, p <0.05) were poorer in DES-ISR. Results were consistent across 10 prespecified subgroups. Moreover, on multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR after adjusting for potential confounders (adjusted absolute mean difference 0.17 mm; 95% confidence interval 0.04 to 0.41; p = 0.019). Finally, at 1-year clinical follow-up (100% of patients), rates of target vessel revascularization (16% vs 6%, p = 0.02) and of the main combined clinical end point (18% vs 8%, p = 0.03) were significantly higher in patients treated for DES-ISR. In conclusion, this study confirms the efficacy of DEB for patients with ISR. However, the long-term clinical and angiographic results of DEB are poorer in patients with DES-ISR than in those with BMS-ISR. (ClinicalTrials.govIdentifier:NCT01239953&NCT01239940).

Everolimus-Eluting Stents in Patients With Bare-Metal and Drug-Eluting In-Stent Restenosis: Results From a Patient-Level Pooled Analysis of the RIBS IV and V Trials.

BACKGROUND: Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is more challenging than that of patients with bare-metal stent ISR. However, the results of everolimus-eluting stents (EES) in these distinct scenarios remain unsettled. METHODS AND RESULTS: A pooled analysis of the RIBS IV (Restenosis Intra-Stent of Drug-Eluting Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) and RIBS V (Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent) randomized trials was performed using patient-level data to compare the efficacy of EES in bare-metal stent ISR and DES-ISR. Inclusion and exclusion criteria were identical in both trials. Results of 94 patients treated with EES for bare-metal stent ISR were compared with those of 155 patients treated with EES for DES-ISR. Baseline characteristics were more adverse in patients with DES-ISR, although they presented later and more frequently with a focal pattern. After intervention, minimal lumen diameter (2.22±0.5 versus 2.38±0.5 mm, P=0.01) was smaller in the DES-ISR group. Late angiographic findings (89.3% of eligible patients), including minimal lumen diameter (2.03±0.7 versus 2.36±0.6 mm, P<0.001) and diameter stenosis (23±22 versus 13±17%, P<0.001) were poorer in patients with DES-ISR. Results were consistent in the in-segment and in-lesion analyses. On multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR. Finally, at 1-year clinical follow-up (100% of patients), mortality (2.6 versus 0%, P<0.01) and need for target vessel revascularization (8 versus 2%, P=0.03) were higher in the DES-ISR group. CONCLUSIONS: This patient-level pooled analysis of the RIBS IV and RIBS V randomized clinical trials suggests that EES provide favorable outcomes in patients with ISR. However, the results of EES are less satisfactory in patients with DES-ISR than in those with bare-metal stent ISR. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01239953 and NCT01239940.

Puncture Versus Surgical Cutdown Complications of Transfemoral Aortic Valve Implantation (from the Spanish TAVI Registry).

Vascular complications in transcatheter aortic valve implantation using transfemoral approach are related to higher mortality. Complete percutaneous approach is currently the preferred technique for vascular access. However, some centers still perform surgical cutdown. Our purpose was to determine complications related to vascular access technique in the population of the Spanish TAVI National Registry. From January 2010 to July 2015, 3,046 patients were included in this Registry. Of them, 2,465 underwent transfemoral approach and were treated with either surgical cutdown and closure (cutdown group, n = 632) or percutaneous approach (puncture group, n = 1,833). Valve Academic Research Consortium-2 definitions were used to assess vascular and bleeding complications. Propensity matching resulted in 615 matched pairs. Overall, 30-day vascular complications were significantly higher in the puncture group (109 [18%] vs 42 [6.9%]; relative risk [RR] 2.60; 95% confidence interval [CI] 1.85 to 3.64, p <0.001) due mostly by minor vascular events (89 [15%] vs 25 [4.1%], RR 3.56, 95% CI 2.32 to 5.47, p <0.001). Bleeding rates were lower in the puncture group (18 [3%] vs 40 [6.6%], RR 0.45, 95% CI 0.26 to 0.78, p = 0.003) mainly driven by major bleeding (9 [1.5%] vs 21 [3.4%], RR 0.43, 95% CI 0.20 to 0.93, p = 0.03). At a mean follow-up of 323 days, complication rates remained significantly different between groups (minor vascular complications 90 [15%] vs 31 [5.1%], hazard ratio 2.99, 95% CI 1.99 to 4.50, p <0.001 and major bleeding 10 [1.6%] vs 21 [3.4%], hazard ratio 0.47, 95% CI 0.22 to 1.0, p = 0.04, puncture versus cutdown group, respectively). In conclusion, percutaneous approach yielded higher rates of minor vascular complications but lower rates of major bleeding compared with the surgical cutdown, both at 30-day and at mid-term follow-up in our population.

Long-Term Results of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With Bare-Metal In-Stent Restenosis: 3-Year Follow-Up of the RIBS V Clinical Trial.

OBJECTIVES: The aim of this study was to compare the long-term efficacy of everolimus-eluting stents (EES) and drug-eluting balloons (DEB) in patients with bare-metal stent in-stent restenosis (ISR). BACKGROUND: The relative long-term clinical efficacy of current therapeutic modalities in patients with ISR remains unknown. METHODS: The 3-year clinical follow-up (pre-specified endpoint) of patients included in the RIBS V (Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent Implantation) randomized clinical trial was analyzed. All patients were followed yearly using a pre-defined structured questionnaire. RESULTS: A total of 189 patients with bare-metal stent ISR were allocated to either EES (n = 94) or DEB (n = 95). Clinical follow-up at 1, 2, and 3 years was obtained in all patients (100%). Compared with patients treated with DEB, those treated with EES obtained better angiographic results, including larger minimal luminal diameter at follow-up (primary study endpoint; 2.36 ± 0.6 mm vs. 2.01 ± 0.6 mm; p < 0.001). At 3 years, the rates of cardiac death (2% vs. 1%), myocardial infarction (4% vs. 5%) and target vessel revascularization (9% vs. 5%) were similar in the DEB and EES arms. Importantly, however, at 3 years, the rate of target lesion revascularization was significantly lower in the EES arm (2% vs. 8%; p = 0.04; hazard ratio: 0.23; 95% confidence interval: 0.06 to 0.93). The need for "late" (>1 year) target vessel (3 [3.2%] vs. 3 [3.2%]; p = 0.95) and target lesion (1 [1%] vs. 2 [2.1%]; p = 0.54) revascularization was low and similar in the 2 arms. Rates of definite or probable stent thrombosis (1% vs. 0%) were also similar in the 2 arms. CONCLUSIONS: The 3-year clinical follow-up of the RIBS V clinical trial confirms the sustained safety and efficacy of EES and DEB in patients treated for bare-metal stent ISR. In this setting, EES reduce the need for target lesion revascularization at very long-term follow-up. (RIBS V [Restenosis Intra-Stent of Bare Metal Stents: Paclitaxel-Eluting Balloon vs Everolimus-Eluting Stent] [RIBS V]; NCT01239953).