Biodegradable-Polymer or Durable-Polymer Stents in Patients at High Bleeding Risk: A Randomized, Open-Label Clinical Trial.

BACKGROUND: Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI. METHODS: The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha. RESULTS: A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P<0.0001 for noninferiority for both tests). CONCLUSIONS: Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04137510.

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes.

BACKGROUND: The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain. METHODS: In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding. RESULTS: A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P = 0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P = 0.46). CONCLUSIONS: Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups. (Funded by the German Center for Cardiovascular Research and Deutsches Herzzentrum München; ISAR-REACT 5 ClinicalTrials.gov number, NCT01944800.).

Efficacy of drug-coated balloon angioplasty in early versus late occurring drug-eluting stent restenosis: A pooled analysis from the randomized ISAR DESIRE 3 and DESIRE 4 trials.

BACKGROUND: Whether there exist differences concerning clinical outcomes between patients presenting with early versus late DES-ISR undergoing treatment with drug-coated balloons (DCB) remains a scientific knowledge gap. METHODS: This is a pooled analysis including patients with DES-ISR assigned to treatment with DCB in the setting of the ISAR DESIRE 3 and 4 trials. Clinical outcomes were evaluated according to time of occurrence of ISR after DES implantation, in patients presenting with early (≤12 months) versus late DES-ISR (>12 months) undergoing treatment with DCB. The primary endpoint of this analysis was major adverse cardiac event (MACE), defined as the combined incidence of death, myocardial infarction and target lesion revascularization (TLR) at 12 months after DCB treatment. Secondary endpoints included the incidence of death, myocardial infarction, TLR and target lesion thrombosis at 12 months after DCB treatment. RESULTS: This analysis included 352 patients, 199 patients presented with early-ISR, 153 patients with late-ISR. Concerning the primary endpoint, patients with early-DES-ISR as compared those with late-DES-ISR showed significant higher risk (25.9% vs. 17.0%; p = .04). In a multivariate analysis including diabetic status, clinical presentation, previous coronary bypass graft and diameter stenosis after DCB-treatment, the adjusted hazard ratio showed significant higher risk for MACE of early-DES-ISR as compared to late-DES-ISR (HRadj = 1.8, [95% CI = 1.1-3.0], p = .02). CONCLUSION: Clinical outcome at 12 months after treatment of DES-ISR with DCB, showed significant higher clinical event rates in patients presenting with early DES restenosis, as compared with patients presenting with late DES restenosis.

Safety and clinical performance of a drug eluting absorbable metal scaffold in the treatment of subjects with de novo lesions in native coronary arteries: Pooled 12-month outcomes of BIOSOLVE-II and BIOSOLVE-III.

OBJECTIVES: Based on outcomes of the BIOSOLVE-II study, a novel second generation drug-eluting absorbable metal scaffold gained CE-mark in 2016. The BIOSOLVE-III study aimed to confirm these outcomes and to obtain additional 12-month angiographic data. BACKGROUND: Bioresorbable scaffolds are intended to overcome possible long-term effects of permanent stents such as chronic vessel wall inflammation, stent crushing, and fractures. METHODS: The prospective, multicenter BIOSOLVE-II and BIOSOLVE-III studies enrolled 184 patients with 189 lesions (123 patients in BIOSOLVE-II and 61 patients in BIOSOLVE-III). Primary endpoints were in-segment late lumen loss at 6 months (BIOSOLVE-II) and procedural success (BIOSOLVE-III). RESULTS: Mean patient age was 65.5 ± 10.8 years and mean lesion reference diameter was 2.70 ± 0.43 mm. In BIOSOLVE-III, there were significantly more type B2/C lesions than in BIOSOLVE-II (80.3% versus 43.4%, P < 0.0001) and significantly more moderate-to-severe calcifications (24.2% versus 10.7%, P = 0.014). At 12 months, there was no difference in late lumen loss between the two studies; in the overall population, it was 0.25 ± 0.31 mm in-segment and 0.39 ± 0.34 mm in-scaffold. Target lesion failure occurred in six patients (3.3%) and included two cardiac deaths, one target-vessel myocardial infarction, and three clinically driven target lesion revascularizations. No definite or probable scaffold thrombosis was observed. CONCLUSION: The pooled outcomes of BIOSOLVE-II and BIOSOLVE-III provide further evidence on the safety and performance of a novel drug-eluting absorbable metal scaffold with constant clinical and angiographic performance parameters at 12 months and no definite or probable scaffold thrombosis.

Effect of strut distribution on neointimal coverage of everolimus-eluting bioresorbable scaffolds: an optical coherence tomography study.

The thick struts of bioresorbable vascular scaffolds (BRS) are associated with changes in wall shear stress and contribute to neointimal proliferation. We aimed to evaluate the relationship between the BRS strut distribution and the neointimal proliferation. 50 lesions underwent optical coherence tomography, 12 months after BRS implantation. Scaffold area and neointimal thickness were evaluated in each cross-sectional area (CSA). Scaffold eccentricity was defined as follows: (maximum diameter - minimum diameter) × 100/maximum diameter. CSAs of BRS were divided into four quadrants. The maximal neointimal thickness (Maximal-NIT), Minimal-NIT and the number of struts in each quadrant were measured. The number of struts were classified as 1, 2, 3 and ≥ 4. Furthermore, the mean-NIT acquired in each quadrant was divided by the average-NIT of all struts in the same CSA, which was defined as the unevenness score. In addition, Maximal-NIT minus Minimal-NIT was divided by the average-NIT of all struts in the same CSA, which was defined as heterogenicity of neointimal proliferation. There was a significant difference in the association between the number of struts and not only the unevenness score (no. of strut = 1 (N = 440), unevenness score 1.04 ± 0.34; 2 (N = 696), 0.98 ± 0.27; 3 (N = 994), 0.96 ± 0.23; ≥4 (N = 1202), 1.04 ± 0.22, P < 0.01) but also Maximal-NIT and Minimal-NIT. Furthermore, a significant correlation was observed between scaffold eccentricity in each CSA and the heterogeneity of neointimal proliferation in the same CSA (N = 892, R = 0.38, p = 0.01). Crowding of struts is associated with increased neointimal proliferation after BRS implantation. The scaffold eccentricity causes heterogeneity of neointimal proliferation.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction.

AIMS: Whether prasugrel plus bivalirudin is a superior strategy to unfractionated heparin plus clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has never been assessed in specifically designed randomized trials. METHODS AND RESULTS: The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is an investigator-initiated, randomized, open-label, multicentre trial, designed to test the hypothesis that in STEMI patients with planned primary PCI a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus heparin in terms of net clinical outcome. Owing to slow recruitment, the trial was stopped prematurely after enrolment of 548 of 1240 planned patients. At 30 days, the primary composite endpoint of death, myocardial infarction, unplanned revascularization of the infarct related artery, stent thrombosis, stroke, or bleeding was observed in 42 patients (15.6%) randomized to prasugrel plus bivalirudin and 40 patients (14.5%) randomized to clopidogrel plus heparin [relative risk, 1.09; one-sided 97.5% confidence interval (CI) 0-1.79, P = 0.680]. The composite ischaemic endpoint of death, myocardial infarction, unplanned revascularization of the infarct-related artery, stent thrombosis, or stroke occurred in 13 patients (4.8%) in the prasugrel plus bivalirudin group and 15 patients (5.5%) in the clopidogrel plus heparin group (relative risk, 0.89; 95% CI 0.40-1.96, P = 0.894). Bleeding according to the HORIZONS-AMI definition was observed in 38 patients (14.1%) in the prasugrel plus bivalirudin group and 33 patients (12.0%) in the clopidogrel plus heparin group (relative risk, 1.18; 95% CI 0.74-1.88, P = 0.543). Results were consistent across various subgroups of patients. CONCLUSION: In this randomized trial of STEMI patients, we were unable to demonstrate significant differences in net clinical outcome between prasugrel plus bivalirudin and clopidogrel plus heparin. Neither the composite of ischaemic complications nor bleeding were favourably affected by prasugrel plus bivalirudin compared with a regimen of clopidogrel plus unfractionated heparin. However, the results must be interpreted in view of the premature termination of the trial. CLINICAL TRIAL REGISTRATION INFORMATION: Unique identifier NCT00976092 (www.clinicaltrials.gov).

Comparison of balloon-expandable vs self-expandable valves in patients undergoing transcatheter aortic valve replacement: the CHOICE randomized clinical trial.

IMPORTANCE: Transcatheter aortic valve replacement (TAVR) is an effective treatment option for high-risk patients with severe aortic stenosis. Different from surgery, transcatheter deployment of valves requires either a balloon-expandable or self-expandable system. A randomized comparison of these 2 systems has not been performed. OBJECTIVE: To determine whether the balloon-expandable device is associated with a better success rate than the self-expandable device. DESIGN, SETTING, AND PATIENTS: The CHOICE study was an investigator-initiated trial in high-risk patients with severe aortic stenosis and an anatomy suitable for the transfemoral TAVR procedure. One hundred twenty-one patients were randomly assigned to receive a balloon-expandable valve (Edwards Sapien XT) and 120 were assigned to receive a self-expandable valve (Medtronic CoreValve). Patients were enrolled between March 2012 and December 2013 at 5 centers in Germany. INTERVENTIONS: Transfemoral TAVR with a balloon-expandable or self-expandable device. MAIN OUTCOMES AND MEASURES: The primary end point was device success, which is a composite end point including successful vascular access and deployment of the device and retrieval of the delivery system, correct position of the device, intended performance of the heart valve without moderate or severe regurgitation, and only 1 valve implanted in the proper anatomical location. Secondary end points included cardiovascular mortality, bleeding and vascular complications, postprocedural pacemaker placement, and a combined safety end point at 30 days, including all-cause mortality, major stroke, and other serious complications. RESULTS: Device success occurred in 116 of 121 patients (95.9%) in the balloon-expandable valve group and 93 of 120 patients (77.5%) in the self-expandable valve group (relative risk [RR], 1.24, 95% CI, 1.12-1.37, P < .001). This was attributed to a significantly lower frequency of residual more-than-mild aortic regurgitation (4.1% vs 18.3%; RR, 0.23; 95% CI, 0.09-0.58; P < .001) and the less frequent need for implanting more than 1 valve (0.8% vs 5.8%, P = .03) in the balloon-expandable valve group. Cardiovascular mortality at 30 days was 4.1% in the balloon-expandable valve group and 4.3% in the self-expandable valve group (RR, 0.97; 95% CI, 0.29-3.25; P = .99). Bleeding and vascular complications were not significantly different, and the combined safety end point occurred in 18.2% of those in the balloon-expandable valve group and 23.1% of the self-expandable valve group (RR, 0.79; 95% CI, 0.48-1.30; P = .42). Placement of a new permanent pacemaker was less frequent in the balloon-expandable valve group (17.3% vs 37.6%, P = .001). CONCLUSIONS AND RELEVANCE: Among patients with high-risk aortic stenosis undergoing TAVR, the use of a balloon-expandable valve resulted in a greater rate of device success than use of a self-expandable valve. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01645202.

Incidence and pattern of urgent revascularization in acute coronary syndromes treated with ticagrelor or prasugrel.

BACKGROUND: The ISAR-REACT 5 trial compared the efficacy and safety of ticagrelor and prasugrel in patients with ACS managed invasively. The present study sought to investigate the impact of ticagrelor and prasugrel on the incidence and pattern of urgent revascularization in acute coronary syndromes (ACS) patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This post-hoc analysis of the ISAR-REACT 5 trial included all ACS patients who underwent PCI. The primary endpoint for this analysis was the incidence of urgent revascularization at 12-month follow-up. Secondary outcome was the pattern of urgent revascularization procedures (namely, urgent target vessel/non-target vessel revascularization - TVR/NTVR). Among 3,377 ACS patients who underwent PCI, 1,676 were assigned to ticagrelor and 1,701 to prasugrel before PCI. After 12 months, the incidence of urgent revascularization was higher among patients assigned to ticagrelor as compared to prasugrel (6.8% vs. 5.2%; hazard ratio [HR] = 1.32, 95% confidence interval [CI] 1.00-1.75; p = 0.051), mostly attributable to significantly more urgent NTVR in the ticagrelor group (3.8% vs. 2.4%; HR = 1.62 [1.09-2.41]; p = 0.017). The risk of urgent TVR did not differ between treatment groups (3.3% vs. 3.0%; HR = 1.13 [0.77-1.65]; p = 0.546). CONCLUSIONS: In ACS patients treated with PCI, the cumulative rate of urgent revascularizations after 12 months is higher with ticagrelor compared to prasugrel, due to a significant increase in urgent revascularizations involving remote coronary vessels.

Clinical Safety and Efficacy of New-Generation Single-Layer Polytetrafluorethylene Covered Coronary Stents.

BACKGROUND: Early-generation "sandwich-design" polytetrafluorethylene (PTFE) covered coronary stents (CS) are associated with a high frequency of adverse events. New-generation single layer PTFE-CS offers the potential to enhanced procedural efficacy and improves clinical safety. Data from a dedicated study, concerning outcomes after treatment with single-layer PTFE-CS in patients undergoing percutaneous coronary intervention are scant. METHODS: This is a retrospective multicenter registry including 30 patients undergoing implantation of 39 single-layer PTFE-CS (BeGraft-coronary Stent Graft System, Bentley InnoMed GmbH, Hechingen, Germany) in native coronary arteries or saphenous bypass grafts, in 3 centers in Europe, between May 2013 and May 2019. Endpoints of interest were procedural success (placement of covered stent), binary-angiographic restenosis (BAR), percent diameter stenosis (% DS) and late-lumen loss at 6-8 months follow-up angiography, rates of target lesion revascularization (TLR), myocardial infarction (MI), stent thrombosis (ST) and mortality at 12 months. RESULTS: 28 patients underwent implantation of 37 CS due to coronary artery perforation 2 patients due to coronary artery aneurysm. Technical success was achieved in all patients (100 %). More than one stent was implanted in 7 patients (25 %) all in the perforation group. Follow-up angiography was available in 23 patients (77 %) showing favorable results: BAR = 21.8 %, %DS = 30.3 ± 27.5; LLL = 0.16 ± 0.81 mm. At 12 months all patients were alive, rates of TLR were low (3 patients, 10.0 %), there was one case of late stent thrombosis (3.3 %) and one MI (3.3 %). CONCLUSIONS: In this dedicated study, implantation of a new single layer PTFE-CS for the treatment of native coronary arteries or saphenous vein grafts after perforation or due to aneurysm showed high technical success rates and favorable angiographic and clinical efficacy. Clinical safety outcomes are encouraging, but larger prospective studies are needed to determine long-term safety of this device.

Design and Rationale of the BIOFLOW-DAPT Trial: a Prospective, Randomized, Multicenter Study to Assess the Safety of the Orsiro Mission Stent Compared to the Resolute Onyx Stent in Subjects at High Risk for Bleeding in Combination with 1-Month Dual Antiplatelet Therapy.

The optimal duration of dual antiplatelet therapy (DAPT) in high bleeding risk (HBR) patients undergoing percutaneous coronary intervention (PCI) with implantation of the Orsiro Mission stent remains unclear. The BIOFLOW-DAPT (clinicaltrials.gov, NCT04137510) trial is a prospective, multi-center, randomized controlled study designed to assess the safety of the Orsiro Mission versus the Resolute Onyx stent in HBR patients. Patients are treated with DAPT (aspirin and a P2Y12 inhibitor) for 1 month, followed by a single antiplatelet therapy (SAPT). The primary endpoint is the composite of cardiac death, myocardial infarction, and definite or probable stent thrombosis at 1 year. With a final sample size of 1948 HBR patients, this study is powered to assess the noninferiority of the Orsiro Mission stent with respect to the primary study endpoint. The BIOFLOW-DAPT is the first randomized clinical trial investigating 1-month DAPT duration in HBR patients after implantation of the Orsiro Mission stent.Trial Registration: ClinicalTrials.gov number, NCT04137510 Study design and key features. Patient selection starts before the index PCI, when consented patients will be randomized to the Orsiro Mission or the Resolute Onyx stent with mandated 1-month DAPT. At 1 month, eligibility is reassessed and if met, patients will discontinue DAPT and continue with P2Y12 inhibitor or aspirin monotherapy. PCI, percutaneous coronary intervention; DAPT, dual antiplatelet therapy; DES, drug-eluting stent; HBR, high bleeding risk; P2Y12i, P2Y12 inhibitor; ST, stent thrombosis.

Design and rationale of a prospective, randomized, non-inferiority trial to determine the safety and efficacy of the Biolimus A9™ drug coated balloon for the treatment of in-stent restenosis: First-in-man trial (REFORM).

BACKGROUND: Drug-coated balloon (DCB) angioplasty with paclitaxel-eluting devices is an established treatment for coronary in-stent restenosis (ISR). Biolimus A9™ (BA9), a sirolimus analogue with enhanced lipophilicity, may facilitate enhanced local drug delivery into vascular tissue. A novel DCB coated with Biolimus A9™ represents an alternative to traditional paclitaxel- and sirolimus-coated devices. Hence, we sought to investigate the safety and efficacy of this novel DCB in the treatment of coronary ISR. METHODS AND DESIGN: REFORM (NCT04079192) is a prospective, multicenter, single blind, randomized controlled trial comparing the BA9-DCB (Biosensors Europe SA, Morges, Switzerland) to the paclitaxel-coated SeQuent® Please DCB (Braun Melsungen AG, Germany) in the treatment of coronary ISR. A total of 201 patients with coronary artery disease and an indication for interventional treatment of ISR in a bare-metal stent (BMS) or drug-eluting stent (DES) have been randomized 2:1 to receive treatment with the BA9- or the paclitaxel-DCB comparator. Patients were enrolled across 24 investigational centers in Europe and Asia. The primary endpoint is percent diameter stenosis (%DS) of the target segment as assessed by quantitative coronary angiography (QCA) at 6 months. Key secondary endpoints are in-stent late lumen loss, binary restenosis, target lesion failure, target vessel failure, myocardial infarction and death at 6 months. Subjects will be followed for 24 months from enrolment. IMPLICATIONS: The REFORM trial will seek to prove that the BA9-DCB is non-inferior to the standard paclitaxel-DCB comparator in the treatment of coronary ISR with respect to %DS at 6 months and has similar safety characteristics.

Ablation of typical atrial flutter as therapeutic component in carcinoid heart disease: a case report.

BACKGROUND: Carcinoid heart disease is the cardiac manifestation of carcinoid syndrome. There is limited research on rhythm management in patients with carcinoid heart disease. The association of typical atrial flutter and carcinoid heart disease in particular is poorly described. CASE PRESENTATION: Here we present a case of a 77-year-old German woman with carcinoid heart disease and recurrent typical atrial flutter complicating the postoperative course after tricuspid valve replacement and its successful long-term rhythm control by ablation therapy. CONCLUSION: There is limited evidence on rhythm management in patients with the rare diagnosis of carcinoid heart disease. Typical atrial flutter repeatedly complicated the postoperative course of our patient with carcinoid heart disease and could finally be treated curatively by ablation. Radiofrequency ablation should be considered as a valuable therapeutic component in the challenging therapy of this disease.

Impact of Endothelial Shear Stress on Absorption Process of Resorbable Magnesium Scaffold: A BIOSOLVE-II Substudy.

BACKGROUND/PURPOSE: Local hemodynamic forces such as endothelial shear stress (ESS) may have an influence on appropriate neointimal healing, vessel remodeling, and struts' absorption process following second-generation drug-eluting resorbable magnesium scaffold (RMS, Magmaris, Biotronik AG, Buelach, Switzerland) placement. The aim of this study was to investigate the impact of ESS assessed by optical coherence tomography (OCT)-based computational fluid dynamic (CFD) simulations on absorption process and coronary lumen dimension after Magmaris implantation. METHODS AND RESULTS: A total of 22 patients who were enrolled in the BIOSOLVE-II trial and underwent serial OCT assessment immediately after Magmaris implantation and at 6- and 12-month follow-up were included. We evaluated qualitative OCT findings frame by frame, and CFD simulations were performed to calculate the ESS at 3-dimensional (3D) reconstructed arteries. For quantitative calculation, the average ESS within each 1-mm section was classified into three groups: low (<1.0 Pa), intermediate (1.0-2.5 Pa), or high (>2.5 Pa). A significant difference of percentage remnants of scaffold was observed among the 3 groups at 12-month follow-up (P = 0.001) but not at 6-month follow-up. Low-ESS segment at baseline resulted in a greater lumen change of -1.857 ± 1.902 mm2 at 1 year compared to -1.277 ± 1.562 mm2 in the intermediate-ESS segment (P = 0.017) and - 0.709 ± 1.213 mm2 in the high-ESS segment (P = 0.001). CONCLUSION: After Magmaris implantation, the presence of higher ESS might be associated with slower strut absorption process but less luminal loss.

Early hemodynamic and neurohormonal response after transcatheter aortic valve implantation.

BACKGROUND: The conventional surgical aortic bioprostheses used for treatment of aortic stenosis (AS) are inherently stenotic in nature. The more favorable mechanical profile of the Medtronic CoreValve bioprosthesis may translate into a better hemodynamic and neurohormonal response. PATIENTS AND METHODS: The early hemodynamic and neurohormonal responses of 56 patients who underwent successful transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve bioprosthesis for severe symptomatic AS were compared with those of 36 patients who underwent surgical aortic valve replacement (SAVR) using tissue valves in the same period. RESULTS: At baseline, patients in the TAVI and SAVR group had comparable indexed aortic valve area (0.33 ± 0.1 vs 0.34 ± 0.1 cm² , respectively; P = .69) and mean transvalvular gradient (51.1 ± 16.5 vs 53.1 ± 14.3 mm Hg, respectively; P = .56). At 30-day follow-up, mean transvalvular gradient was lower in the TAVI group than in the SAVR group (10.3 ± 4 vs 13.1 ± 6.2 mm Hg, respectively; P = .015), and the indexed aortic valve area was larger in the TAVI group (1.0 ± 0.14 vs 0.93 ± 0.13 cm²/m²; P = .017). There was a trend toward a higher incidence of moderate patient-prosthesis mismatch in the surgical group compared with the TAVI group (30.5% vs 17.8%, respectively; P = .11). The overall incidence of prosthetic regurgitation (any degree) was higher in the TAVI group than in the SAVR group (85.7% vs 16.7%, respectively; P < .00001). The left ventricular mass index decreased after TAVI (175.1 ± 61.8 vs 165.6 ± 57.2 g/m²; P = .0003) and remained unchanged after SAVR (165.1 ± 50.6 vs 161 ± 64.8 g/m²; P = .81). Similarly, NT-ProBNP decreased after TAVI (3,479 ± 2,716 vs 2,533 ± 1,849 pg/mL; P = .033) and remained unchanged after SAVR (1,836 ± 2,779 vs 1,689 ± 1,533 pg/mL; P = .78). There was a modest correlation between natriuretic peptides and left ventricular mass index in the whole cohort (r = 0.4, P = .013). CONCLUSION: In patients with severe AS, TAVI resulted in lower transvalvular gradients and higher valve areas than SAVR. Such hemodynamic performance after TAVI may have contributed to early initiation of a reverse cardiac remodeling process and a decrease in natriuretic peptides.

Serial 3-Dimensional Optical Coherence Tomography Assessment of Jailed Side-Branch by Second-Generation Drug-Eluting Absorbable Metal Scaffold (from the BIOSOLVE-II Trial).

Second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) is used for treating coronary lesions. However, the natural history of the jailed side-branch (SB) after DREAMS 2G implantation remains to be elucidated. The aim of this study is to investigate the effect of scaffold struts on jailed SBs as assessed by 3-dimensional (3D) optical coherence tomography (OCT) after implantation of DREAMS 2G. We enrolled the patients who received a DREAMS 2G implantation and where OCT was performed at postprocedure and 12-month follow-up in the BIOSOLVE-II trial. The area of the ostium of jailed SBs and number of compartments divided by scaffold struts were assessed by cut-plane analysis using 3D OCT. A total of 24 patients with 61 jailed SBs were analyzed in this study. The number of compartments was significantly decreased (postprocedure; 1.98 ± 0.84 vs 12 months; 1.10 ± 0.30, p <0.001) during the 12 months. Since most of the struts disappeared, the ostium area was increased in 62% of jailed SBs at 12 months, however, not significantly different from postprocedure (postprocedure; 0.74 [0.34 to 1.46] mm2 vs 12 months; 0.78 [0.41 to 1.68] mm2, p = 0.055). The number of compartments created by scaffold struts and branching angle at postprocedure had no effect on the changes of SB ostium area. DREAMS 2G has a favorable absorption process in the jailed SBs up to 12 months and may be considered as an optional therapy for treating lesions that involve SBs.

Impact of procedural characteristics on coronary vessel wall healing following implantation of second-generation drug-eluting absorbable metal scaffold in patients with de novo coronary artery lesions: an optical coherence tomography analysis.

AIMS: Second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) is an alternative novel device for treating coronary lesions. However, the relationship between in-scaffold dimensions after implantation of DREAMS 2G and vessel healing and luminal results at follow-up is unknown. The aim of this study is, therefore, to investigate whether the expansion index after implantation of DREAMS 2G as assessed by optical coherence tomography (OCT) impacts late luminal status and healing of the vessel wall. METHODS AND RESULTS: This study comprises of a total 65 out of 123 patients who were enrolled in the BIOSOLVE-II trial. We assessed both qualitative and quantitative OCT findings and the expansion index of DREAMS 2G after implantation frame by frame using OCT. Expansion index was defined as minimum scaffold area/mean reference lumen area. The over-expansion group was also defined with expansion index >1.0. The total number of analysed frames at post-procedure and 6-month follow-up was 8243 and 8263 frames, respectively. At 6-month follow-up, in-scaffold healing was documented by the reduction of 82% in dissections, 93% in attached intra-luminal mass (ILM), 65% in non-attached ILM, and 76% in jailed side branch. The over-expansion group had significantly greater in-scaffold luminal volume loss (LVL) compared with the non-over-expansion group [over-expansion: 35.0 (18.5-52.1) mm3 vs. non-over-expansion: 21.0 (11.6-37.9) mm3, P = 0.039]. CONCLUSION: Excellent in vivo healing process after implantation of DREAMS 2G was observed at 6 months. We found that higher expansion indices were associated with higher in-scaffold LVL at 6 months assessed by OCT.

Simvastatin and ezetimibe in addition to nonpharmacological risk factor modification for achieving new low-density lipoprotein cholesterol targets.

BACKGROUND: Though guidelines emphasize low-density lipoprotein cholesterol (LDL-C) lowering as an essential strategy for cardiovascular risk reduction, achieving target levels may be difficult. PATIENTS AND METHODS: The authors conducted a prospective, controlled, open-label trial examining the effectiveness and safety of high-dose fluvastatin or a standard dosage of simvastatin plus ezetimibe, both with an intensive guideline-oriented cardiac rehabilitation program, in achieving the new ATP III LDL-C targets in patients with proven coronary artery disease. 305 consecutive patients were enrolled in the study. Patients were divided into two groups: the simvastatin (40 mg/d) plus ezetimibe (10 mg/d) and the fluvastatin-only group (80 mg/d). Patients in both study groups received the treatment for 21 days in addition to nonpharmacological measures, including advanced physical, dietary, psychosocial, and educational activities. RESULTS: After 21 days of treatment, a significant reduction in LDL-C was found in both study groups as compared to the initial values, however, the reduction in LDL-C was significantly stronger in the simvastatin plus ezetimibe group: simvastatin plus ezetimibe treatment decreased LDL-C to a mean level of 57.7 +/- 1.7 mg/ml, while fluvastatin achieved a reduction to 84.1 +/- 2.4 mg/ml (p < 0.001). In the simvastatin plus ezetimibe group, 95% of the patients reached the target level of LDL-C < 100 mg/dl. This percentage was significantly higher than in patients treated with fluvastatin alone (75%; p < 0.001). The greater effectiveness of simvastatin plus ezetimibe was more impressive when considering the optional goal of LDL-C < 70 mg/dl (75% vs. 32%, respectively; p < 0.001). There was no difference in occurrence of adverse events between both groups. CONCLUSION: Simvastatin 40 mg/d plus ezetimibe 10 mg/d, on the background of a guideline-oriented standardized intensive cardiac rehabilitation program, can reach 95% effectiveness in achieving challenging goals (LDL < 100 mg/dl) using lipid-lowering medication in patients at high cardiovascular risk.

Dual Antithrombotic Therapy with Clopidogrel and Novel Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Real-world Study.

INTRODUCTION: For patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), proper antithrombotic therapy is equivocal. Current guidelines recommend triple therapy, which carries a high risk of bleeding. Recent large trials suggest that dual therapy (DT) with novel oral anticoagulant (NOAC) plus P2Y12 inhibitor can be an appropriate alternative, but real-world data for this alternative are scarce and the optimal duration of DT has not yet been established. METHODS: This analysis was performed in a single-center prospective cohort. We investigated 216 PCI patients with indication for anticoagulation due to AF. After PCI patients received DT with reduced doses NOAC plus P2Y12 inhibitor for 6 months, which was followed by standard dose NOAC monotherapy. Efficacy endpoints were defined as cardiac death, myocardial infarction (MI), stent thrombosis (ST), and stroke. Safety endpoints were bleeding events as defined by Bleeding Academic Consortium (BARC). RESULTS: Baseline characteristics of our study population were described by a CHA2DS2-VASc score of greater than 4 and a HAS-BLED score of greater than 3. After a mean follow-up of 18.7 months, efficacy events occurred in 12 patients (5.6%). We observed three (1.4%) cardiac deaths, two (0.9%) MIs, six (2.8%) strokes, and one (0.5%) definite ST. After switching from DT to NOAC monotherapy after 6.3 ± 1.7 months, there was no rebound of ischemic events. Bleeding events occurred in 34 patients (15.7%) mainly under DT, while bleeding was less during NOAC monotherapy. CONCLUSIONS: In this long-term study of high-risk and real-world AF-patients with PCI, DT with NOAC and P2Y12 inhibitor (6 months) followed by NOAC monotherapy was safe and effective.

In vivo serial invasive imaging of the second-generation drug-eluting absorbable metal scaffold (Magmaris - DREAMS 2G) in de novo coronary lesions: Insights from the BIOSOLVE-II First-In-Man Trial.

RATIONALE: Bioresorbable scaffolds may confer clinical benefit in long-term studies; early mechanistic studies using intravascular imaging have provided insightful information about the immediate and mid-term local serial effects of BRS on the coronary vessel wall. OBJECTIVES: We assessed baseline, 6- and 12-month imaging data of the drug-eluting absorbable metal scaffold (DREAMS 2G). METHODS AND RESULTS: The international, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to 2 de novo lesions (in vessels of 2.2 to 3.7mm). Angiographic based vasomotion, curvature and angulation were assessed; intravascular ultrasound (IVUS) derived radiofrequency (RF) data analysis and echogenicity were evaluated; optical coherence tomography (OCT) attenuation and backscattering analysis were also performed. There was hardly any difference in curvature between pre-procedure and 12months (-0.0019; p=0.48). The change in angulation from pre- to 12months was negligible (-3.58°; 95% CI [-5.97, -1.20]), but statistically significant. At 6months, the change in QCA based minimum lumen diameter in response to high dose of acetylcholine and IVUS-RF necrotic core percentage showed an inverse relationship (estimate of -0.489; p=0.055) and with fibrous volume a positive relationship (estimate of 0.53, p=0.035). Bioresorption analysis by OCT showed that the maximum attenuation values decreased significantly from post-procedure at 6months (Δ 6months vs. post-proc. is -13.5 [95% CI -14.6, -12.4]) and at 12months (Δ 12months vs. post-proc. is -14.0 [95% CI -15.4, -12.6]). By radiofrequency data, the percentage of dense calcium decreased significantly from post-procedure at 6months and at 12months. Likewise, by echogenicity, hyperechogenic structures decreased significantly from post-procedure at 6months; thereafter, they remained unchanged. CONCLUSION: Following implantation of DREAMS 2G, restoration of the vessel geometry, vasomotion and bioresorption signs were observed at up to 12months; importantly, these changes occurred with preservation of the lumen size between 6 and 12months. NCT01960504.