Drug-Eluting Resorbable Scaffold versus Angioplasty for Infrapopliteal Artery Disease.

BACKGROUND: Among patients with chronic limb-threatening ischemia (CLTI) and infrapopliteal artery disease, angioplasty has been associated with frequent reintervention and adverse limb outcomes from restenosis. The effect of the use of drug-eluting resorbable scaffolds on these outcomes remains unknown. METHODS: In this multicenter, randomized, controlled trial, 261 patients with CLTI and infrapopliteal artery disease were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting resorbable scaffold or angioplasty. The primary efficacy end point was freedom from the following events at 1 year: amputation above the ankle of the target limb, occlusion of the target vessel, clinically driven revascularization of the target lesion, and binary restenosis of the target lesion. The primary safety end point was freedom from major adverse limb events at 6 months and from perioperative death. RESULTS: The primary efficacy end point was observed (i.e., no events occurred) in 135 of 173 patients in the scaffold group and 48 of 88 patients in the angioplasty group (Kaplan-Meier estimate, 74% vs. 44%; absolute difference, 30 percentage points; 95% confidence interval [CI], 15 to 46; one-sided P<0.001 for superiority). The primary safety end point was observed in 165 of 170 patients in the scaffold group and 90 of 90 patients in the angioplasty group (absolute difference, -3 percentage points; 95% CI, -6 to 0; one-sided P<0.001 for noninferiority). Serious adverse events related to the index procedure occurred in 2% of the patients in the scaffold group and 3% of those in the angioplasty group. CONCLUSIONS: Among patients with CLTI due to infrapopliteal artery disease, the use of an everolimus-eluting resorbable scaffold was superior to angioplasty with respect to the primary efficacy end point. (Funded by Abbott; LIFE-BTK ClinicalTrials.gov number, NCT04227899.).

Safety of metformin continuation in diabetic patients undergoing invasive coronary angiography: the NO-STOP single arm trial.

BACKGROUND: Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. METHODS: In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. RESULTS: 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3-2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3-2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR - 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43-150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. CONCLUSIONS: In diabetic patients undergoing invasive coronary angiography, metformin continuation throughout the periprocedural period does not increase lactate levels and was not associated with any decline in renal function. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov (NCT04766008).

Ultrathin bioresorbable polymer sirolimus-eluting stents in US patients undergoing coronary revascularization: 1-Year outcomes from the BIOFLOW VII trial.

BACKGROUND: Ultrathin strut coronary drug-eluting stents (DES) have demonstrated improved safety and efficacy in large contemporary trials. The evaluation of an ultrathin strut DES in a post-market United States (US) patient population was undertaken. OBJECTIVE: The purpose of this post-approval study is to confirm that the clinical performance of an ultrathin strut bioresorbable polymer sirolimus-eluting stent (BP SES) in clinical practice is similar to that observed with BP SES in the BIOFLOW V pivotal trial. METHODS: BIOFLOW VII is a prospective, multicenter, single-arm US post-market approval study to confirm the clinical performance of BP SES in a real-world setting. The primary endpoint of 1-year target lesion failure (TLF) was compared with a performance goal of 6.9% based on an adapted BIOFLOW V trial BP SES TLF rate and TLF rates from other US market-released DES utilizing the Society for Cardiovascular Angiography and Interventions definition for peri-procedural myocardial infarction (MI). Subjects undergoing percutaneous coronary intervention with BP SES were consented within 24 h post-index procedure with planned follow-up through 5 years. RESULTS: Among 556 enrolled patients, clinical demographics included: 34.7% female, 35.6% with diabetes mellitus, and 56.8% with acute coronary syndromes. The average stent length (mean ± standard deviation) was 20.2 ± 11.8 mm, and the mean number of stents per patient was 1.3 ± 0.6. Procedure success was 99.1% (551/556), and device success was 99.9% (689/690). Among 531 subjects included in the primary endpoint analysis, the 1-year rate of TLF rate was 1.7% (9/531), and the primary endpoint was met compared with the performance goal (p < 0.0001, 95% confidence interval: 0.69%, 3.43%). Rates of target vessel MI and clinically driven target lesion revascularization were 1.3% (7/531) and 0.9% (5/531), with no occurrence of cardiac death. Definite stent thrombosis was observed for two cases (0.4%; 2/556) with one acute (≤24 h) and one late (>30 days and ≤1 year) event. CONCLUSION: In a post-approval study, 1-year clinical outcomes with BP SES were consistent with prior trials supporting the safety and effectiveness of ultrathin BP SES.

Quantitative coronary three-dimensional geometry and its association with atherosclerotic disease burden and composition.

BACKGROUND: Isolate features of the coronary anatomy have been associated with the pathophysiology of atherosclerotic disease. Computational methods have been described to allow precise quantification of the complex three-dimensional (3D) coronary geometry. The present study tested whether quantitative parameters that describe the spatial 3D coronary geometry is associated with the extension and composition of the underlying coronary artery disease (CAD). METHODS: Patients with CAD scheduled for percutaneous intervention were investigated with coronary computed tomography angiography (CCTA), and invasive coronary angiography, and virtual histology intravascular ultrasound (IVUS-VH). For all target vessels, 3D centerlines were extracted from CCTA images and processed to quantify 23 geometric indexes, grouped into 3 main categories as follows: (i) length-based; (ii) curvature-based, torsion-based, and curvature/torsion-combined; (iii) vessel path-based. The geometric variables were compared with IVUS-VH parameters assessing the extent and composition of coronary atherosclerosis. RESULTS: A total of 36 coronary patients (99 vessels) comprised the study population. From the 23 geometric indexes, 18 parameters were significantly (p < 0.05) associated with at least 1 IVUS-VH parameter at a univariate analysis. All three main geometric categories provided parameters significantly related with atherosclerosis variables. The 3D geometric indexes were associated with the degree of atherosclerotic extension, as well as with plaque composition. Geometric features remained significantly associated with all IVUS-VH parameters even after multivariate adjustment for clinical characteristics. CONCLUSIONS: Quantitative 3D vessel morphology emerges as a relevant factor associated with atherosclerosis in patients with established CAD.

When coronary imaging and physiology are discordant, how best to manage coronary lesions? An appraisal of the clinical evidence.

BACKGROUND: Discordant physiology and anatomy may occur when nonsevere angiographic stenosis has positive physiology as well as the opposite situation. AIM: To underline the reasons behind the discrepancy in physiology and anatomy and to summarize the information that coronary imaging may add to physiology. METHODS: A review of the published literature on physiology and intravascular imaging assessment of intermediate lesions was carried out. RESULTS: The limitations of angiography, the possibility of an underlying diffuse disease, the presence of a "grey zone" in both techniques, the amount of myocardial mass that subtends the stenosis, and plaque vulnerability may play a role in such discrepancy. Intracoronary imaging has a poor diagnostic accuracy compared to physiology. However, it may add information about plaque vulnerability that might be useful in deciding whether to treat or not a certain lesion. CONCLUSIONS: Coronary revascularization is recommended for patients with ischemia based on physiology. Intracoronary imaging adds information on plaque vulnerability and can help on the decision whether to revascularize or not a lesion.

Optical coherence tomography assessment of acute thrombogenicity at bifurcation sites using different stenting techniques: A porcine arteriovenous shunt study.

OBJECTIVES: We aimed to compare bare-metal stents (BMS), durable-polymer everolimus-eluting stents (DP-EES), and abluminal biodegradable-polymer sirolimus-eluting stents (ABP-SES) in the bifurcation model setup. BACKGROUND: The mechanism of thrombogenicity, which differs among second-generation stents implanted using double-kissing (DK) crush or culotte stenting techniques, remains unclear. We have shown previously that setting up a porcine arteriovenous shunt model is feasible and useful to assess thrombogenicity at vessel bifurcation points. METHODS: Six porcine shunt models were prepared for the comparison between DK crush and culotte stenting techniques using BMS, DP-EES, and ABP-SES. Intracoronary imaging with high-resolution optical coherence tomography (OCT) was performed to evaluate the thrombogenicity in different stent types in the bifurcation stenting model and was evaluated by a core lab. RESULTS: Culotte stenting demonstrated more thrombogenicity at the proximal main branch (MB) with DP-EES, side branch (SB) with BMS, and the bifurcation site irrespective of the stent type, while DK crush technique exhibited thrombogenicity only at SB with BMS and ABP-SES. OCT analysis revealed malapposition of DP-EES in the proximal MB with culotte stenting. Stent expansion was generally larger in ABP-SES than BMS and DP-EES. CONCLUSIONS: The study provides hypothesis-generating findings in distinct thrombogenicity of bifurcation stenting with DP- or ABP-coated drug-eluting stents.

First in-human evaluation of a novel intravascular ultrasound and optical coherence tomography system for intracoronary imaging.

AIMS: We evaluated the first in-human performance of a novel hybrid imaging catheter that permits simultaneous and co-registered acquisition of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) images. METHODS AND RESULTS: A total of 17 patients undergoing planned percutaneous coronary intervention (PCI) were imaged between August 2018 and August 2019. Eleven patients with both pre- and post-PCI IVUS and OCT images were included in the offline image analysis. IVUS and OCT images were analyzed separately then together with co-registered images for pre-stent findings, and only separately for post-stent findings. A total of 926 frames were analyzed (218 pre-PCI, 708 post-PCI). There was substantial agreement to detect calcific plaque between co-registered IVUS-OCT and standalone IVUS (Kappa 0.72 [0.65-0.79]) and standalone OCT (Kappa 0.75 [0.68-0.81]) while standalone imaging modalities showed lower agreement to detect lipidic and fibrotic plaques compared with co-registered IVUS-OCT. There were more frames with stent underexpansion on IVUS than OCT [72 (28.7%) vs. 58 (23.1%), respectively, p = 0.039]. Detection rates of incomplete stent apposition (present on 20 OCT frames vs. 2 IVUS frames, p < 0.001) and tissue protrusion (40 vs. 27 frames, p < 0.001) were higher on OCT than IVUS. One stent edge dissection was detected in the image analysis and was seen on OCT but not IVUS. All 177 frames with image artifacts contained at least one co-registered imaging modality with interpretable diagnostic content. There were no study device-related adverse events. CONCLUSIONS: Hybrid image acquisition was safe. The availability of both IVUS and OCT changed image interpretation compared to either modality alone, suggesting a complementary role of these two techniques.

Angiography-derived versus invasively-determined index of microcirculatory resistance in the assessment of coronary microcirculation: A systematic review and meta-analysis.

BACKGROUND: The index of microvascular resistance (IMR) is an established tool to assess the status of coronary microcirculation. However, the need for a pressure wire and hyperemic agents have limited its routine use and have led to the development of angiography-derived pressure-wire-free methods (angiography-derived IMR [IMRAngio]). In this review and meta-analysis, we aim to assess the global diagnosis accuracy of IMRAngio versus IMR. METHODS: A systematic review of the literature was performed. Studies directly evaluating IMRAngio versus IMR were considered eligible. Pooled values of diagnostic test and summary receiver operator curve were calculated. RESULTS: Seven studies directly comparing IMRAngio versus IMR were included (687 patients; 807 vessels). Pooled sensitivity, specificity, +likelihood ratio (LR), and -LR were 82%, 83%, 4.5, and 0.26 respectively. Pooled accuracy was 83% while pooled positive predictive value and negative predictive value were 76% and 85%, respectively. Comparable results were obtained when analyzing by clinical scenario (acute and nonacute coronary syndromes). CONCLUSION: IMRAngio shows a good diagnostic performance for the prediction of abnormal IMR.

End-diastolic segmentation of intravascular ultrasound images enables more reproducible volumetric analysis of atheroma burden.

BACKGROUND: Volumetric intravascular ultrasound (IVUS) analysis is currently performed at a fixed frame interval, neglecting the cyclic changes in vessel dimensions occurring during the cardiac cycle that can affect the reproducibility of the results. Analysis of end-diastolic (ED) IVUS frames has been proposed to overcome this limitation. However, at present, there is lack of data to support its superiority over conventional IVUS. OBJECTIVES: The present study aims to compare the reproducibility of IVUS volumetric analysis performed at a fixed frame interval and at the ED frames, identified retrospectively using a novel deep-learning methodology. METHODS: IVUS data acquired from 97 vessels were included in the present study; each vessel was segmented at 1 mm interval (conventional approach) and at ED frame twice by an expert analyst. Reproducibility was tested for the following metrics; normalized lumen, vessel and total atheroma volume (TAV), and percent atheroma volume (PAV). RESULTS: The mean length of the analyzed segments was 50.0 ± 24.1 mm. ED analysis was more reproducible than the conventional analysis for the normalized lumen (mean difference: 0.76 ± 4.03 mm3 vs. 1.72 ± 11.37 mm3 ; p for the variance of differences ratio < 0.001), vessel (0.30 ± 1.79 mm3 vs. -0.47 ± 10.26 mm3 ; p < 0.001), TAV (-0.46 ± 4.03 mm3 vs. -2.19 ± 14.39 mm3 ; p < 0.001) and PAV (-0.12 ± 0.59% vs. -0.34 ± 1.34%; p < 0.001). Results were similar when the analysis focused on the 10 mm most diseased segment. The superiority of the ED approach was due to a more reproducible detection of the segment of interest and to the fact that it was not susceptible to the longitudinal motion of the IVUS probe and the cyclic changes in vessel dimensions during the cardiac cycle. CONCLUSIONS: ED IVUS segmentation enables more reproducible volumetric analysis and quantification of TAV and PAV that are established end points in longitudinal studies assessing the efficacy of novel pharmacotherapies. Therefore, it should be preferred over conventional IVUS analysis as its higher reproducibility is expected to have an impact on the sample size calculation for the primary end point.

Prosthetic valve endocarditis after transcatheter aortic valve replacement in low-risk patients.

OBJECTIVES: We sought to report details of the incidence, organisms, clinical course, and outcomes of prosthetic valve endocarditis (PVE) after transcatheter aortic valve replacement (TAVR) in low-risk patients. BACKGROUND: PVE remains a rare but devastating complication of aortic valve replacement. Data regarding PVE after TAVR in low-risk patients are lacking. METHODS: We performed a detailed review of all patients in the low-risk TAVR trials who underwent TAVR from 2016 to 2020 and were adjudicated to have definitive PVE by the independent Clinical Events Committee. RESULTS: We analyzed 396 low-risk patients who underwent TAVR (including 72 with bicuspid valves). PVE occurred in 11 patients at a median 379 days (210, 528) from TAVR. The incidence within the first 30 days was 0%; days 31-365, 1.5%; and after day 365, 2.8%. The most common organism identified was Streptococcus (n = 4/11). Early PVE (≤ 365 days) occurred in five patients, of whom three demonstrated evidence of embolic stroke and two underwent surgical aortic valve re-intervention. Late PVE (> 365 days) occurred in six patients, of whom thee demonstrated evidence of embolic stroke and only one underwent surgical aortic valve re-intervention. Of the six patients with evidence of embolic stroke, two died, two were discharged to rehabilitation, and two were discharged home with home care. CONCLUSIONS: PVE was infrequent following TAVR in low-risk patients but was associated with substantial morbidity and mortality. Embolic stroke complicated the majority of PVE cases, contributing to worse outcomes in these patients. Efforts must be undertaken to minimize PVE in TAVR.

Cangrelor vs. glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention.

BACKGROUND: To date, there are no real-world studies comparing cangrelor to glycoprotein IIb/IIIa inhibitors (GPI) during percutaneous coronary intervention (PCI). Thus, we performed this study to evaluate the safety and effectiveness of cangrelor compared to GPI during PCI. METHODS: We identified patients who underwent PCI at our institution who received either cangrelor or GPI during PCI. Patients already on GPI or cangrelor prior to PCI or who received both cangrelor and GPI were excluded. Baseline demographics and clinical outcomes were extracted. Major bleeding is defined as a composite of major hematoma >4 cm, hematocrit drop >15, and gastrointestinal bleeding. RESULTS: A total of 2072 patients received adjunctive antiplatelet therapy during PCI (cangrelor [n=478]; GPI [n=1594]). Patients' mean age was 61±12 years. Most (66%) presented with acute coronary syndrome. Patients who received cangrelor were older and had a higher percentage of acute coronary syndrome and lower baseline hematocrit in comparison with patients who received GPI. Procedural success was achieved in 94% of patients, with no difference between groups. Major bleeding events (1.7% vs. 5.1%, P=.001), any vascular complication rates, and hospital length of stay were significantly lower in the cangrelor group. In-hospital ischemic events did not differ between groups. On regression analysis, patients on cangrelor were noted to have significantly lower major bleeding events (OR 0.23; 95% CI, 0.09-0.59). CONCLUSIONS: Balancing ischemic and bleeding risks with adjunctive antiplatelet drugs is of prime importance during PCI. Our real-world analysis shows that cangrelor is safe and effective when compared to GPI during PCI.

National trends and 30-day readmission rates for next-day-discharge transcatheter aortic valve replacement: An analysis from the Nationwide Readmissions Database, 2012-2016.

Transcatheter aortic valve replacement (TAVR) has evolved toward a minimalist approach, resulting in shorter hospital stays. Real-world trends of next-day discharge (NDD) TAVR are unknown. This study aimed to evaluate underlying trends and readmissions of NDD TAVR. METHODS: This study was derived from the Nationwide Readmissions Database from 2012 to 2016. International Classification of Diseases, Ninth and Tenth Revisions, codes were used to identify patients. Any discharge within 1 day of admission was identified as NDD. NDD TAVR trends over the years were analyzed, and any admissions within 30 days were considered readmissions. A hierarchical logistic regression model was used to identify predictors of readmission. RESULTS: Of 49,742 TAVR procedures, 3,104 were NDD. The percentage of NDD TAVR increased from 1.5% (46/3,051) in 2012 to 12.2% (2,393/19,613) in 2016. However, the 30-day readmission rate remained the same over the years (8.6%). The patients' mean age was 80.3 ±â€¯8.4 years. Major readmission causes were heart-failure exacerbation (16%), infections (9%), and procedural complications (8%). In 2016, there were significantly higher late conduction disorder and gastrointestinal bleeding readmission rates than in 2012-2015. Significant predictors of readmission were anemia, baseline conduction disease, cardiac arrhythmias, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, neoplastic disorders, and discharge to facility. CONCLUSIONS: The percentage of NDD TAVR increased over the years; however, readmission rates remained the same, with a higher rate of conduction abnormality-related hospitalizations in 2016. Careful discharge planning that includes identification of baseline factors that predict readmission and knowledge of etiologies may further prevent 30-day readmissions.

Transcatheter aortic valve replacement in low-risk patients: 2-year results from the LRT trial.

BACKGROUND: Previous studies from the Low Risk TAVR (LRT) trial demonstrated that transcatheter aortic valve replacement (TAVR) is safe and feasible in low-risk patients, with excellent 30-day and 1-year outcomes. The objective of this study was to report clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration (SVD) 2 years after TAVR. METHODS: The LRT trial was the first Food and Drug Administration-approved Investigational Device Exemption trial in the United States to evaluate the safety and feasibility of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis (AS). Valve hemodynamics and SVD by echo were recorded 30 days, 1 year, and 2 years post-TAVR. RESULTS: The LRT trial enrolled 200 low-risk patients to receive TAVR. Their mean age was 73.6 years and 61.5% were men. At 2-year follow-up, the mortality rate was 4.2%; the cardiovascular death rate was 1.6%. The disabling stroke rate was 1.1%, permanent pacemaker implantation rate was 8.6%, and 4 patients (2.2%) presented with endocarditis (2 between years 1 and 2). Of the 14% of TAVR subjects who had evidence of HALT at 30 days, there was no impact on valve hemodynamics, endocarditis or stroke at 2 years. CONCLUSIONS: TAVR for low-risk patients with symptomatic severe tricuspid AS is safe at 2 years. The presence of HALT at 30 days did not impact the early hemodynamic improvements nor the durability of the valve structure.

Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study.

BACKGROUND: Near-infrared spectroscopy (NIRS) intravascular ultrasound imaging can detect lipid-rich plaques (LRPs). LRPs are associated with acute coronary syndromes or myocardial infarction, which can result in revascularisation or cardiac death. In this study, we aimed to establish the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions. METHODS: In this prospective, cohort study (LRP), patients from 44 medical centres were enrolled in Italy, Latvia, Netherlands, Slovakia, UK, and the USA. Patients with suspected coronary artery disease who underwent cardiac catheterisation with possible ad hoc percutaneous coronary intervention were eligible to be enrolled. Enrolled patients underwent scanning of non-culprit segments using NIRS-intravascular ultrasound imaging. The study had two hierarchal primary hypotheses, patient and plaque, each testing the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and non-culprit major adverse cardiovascular events (NC-MACE). Enrolled patients with large LRPs (≥250 maxLCBI4mm) and a randomly selected half of patients with small LRPs (<250 maxLCBI4mm) were followed up for 24 months. This study is registered with ClinicalTrials.gov, NCT02033694. FINDINGS: Between Feb 21, 2014, and March 30, 2016, 1563 patients were enrolled. NIRS-intravascular ultrasound device-related events were seen in six (0·4%) patients. 1271 patients (mean age 64 years, SD 10, 883 [69%] men, 388 [31%]women) with analysable maxLCBI4mm were allocated to follow-up. The 2-year cumulative incidence of NC-MACE was 9% (n=103). Both hierarchical primary hypotheses were met. On a patient level, the unadjusted hazard ratio (HR) for NC-MACE was 1·21 (95% CI 1·09-1·35; p=0·0004) for each 100-unit increase maxLCBI4mm) and adjusted HR 1·18 (1·05-1·32; p=0·0043). In patients with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 2·18 (1·48-3·22; p<0·0001) and adjusted HR was 1·89 (1·26-2·83; p=0·0021). At the plaque level, the unadjusted HR was 1·45 (1·30-1·60; p<0·0001) for each 100-unit increase in maxLCBI4mm. For segments with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 4·22 (2·39-7·45; p<0·0001) and adjusted HR was 3·39 (1·85-6·20; p<0·0001). INTERPRETATION: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE. NIRS-intravascular ultrasound imaging adds to the armamentarium as the first diagnostic tool able to detect vulnerable patients and plaques in clinical practice. FUNDING: Infraredx.

Paclitaxel-related balloons and stents for the treatment of peripheral artery disease: Insights from the Food and Drug Administration 2019 Circulatory System Devices Panel Meeting on late mortality.

Following the December 2018 publication of a meta-analysis by Katsanos et al reporting higher rates of long-term mortality with the utilization of paclitaxel-related devices (balloons and stents) when compared to control in femoropopliteal arteries, the US Food and Drug Administration (FDA) issued a safety alert in January 2019 and further detailed the implications for future clinical use of these devices in March 2019. The FDA convened a public meeting of the Circulatory System Devices Panel of the Medical Devices Advisory Committee in June 2019. This report summarizes the proceedings of this meeting and the panel's response to the 12 questions posed by the FDA related to the potentially increased late mortality of drug-coated balloons and drug-eluting stents with paclitaxel in patients with peripheral arterial disease.

Impact of Intravascular Ultrasound on Outcomes Following PErcutaneous Coronary InterventioN in Complex Lesions (iOPEN Complex).

BACKGROUND: Clinical data support the use of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) as being associated with improved outcomes. Nonetheless, global utilization of IVUS remains low. We hypothesize that, in the revascularization of complex lesions, IVUS use is associated with improved outcomes. METHODS: All patients with complex lesions treated with PCI at a single center from 2003 to 2016 were stratified by use of IVUS. Complex lesions were defined as follows: American College of Cardiology/American Heart Association type C lesions, in-stent restenosis, long lesions, bifurcations, severe calcification, left main lesions, and chronic total occlusions. The primary end point was the rate of major adverse cardiac events (MACE) at 1-year follow-up, defined as the composite of all-cause mortality, Q-wave myocardial infarction, and target vessel revascularization. Inverse probability weighting was used in the adjusted analysis. RESULTS: A total of 6,855 patients were included in the final analysis, of whom 67.3% had IVUS and 32.7% had angiography alone. The primary end point occurred in 13.4% of patients treated with IVUS and 18.3% of patients treated with angiography alone (P < .001). Inverse probability weighting-adjusted 1-year MACE rates demonstrated significant reduction with IVUS for each complex lesion type. CONCLUSIONS: Among patients with complex lesions, the use of IVUS was associated with lower MACE 1 year after PCI than angiography alone was. Because of the increased procedural risk in complex lesions, routine utilization of IVUS-guided PCI should be considered in this subset of patients.

The IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact (IMPROVE) trial: Study design and rationale.

Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) has been shown in clinical trials, registries, and meta-analyses to reduce recurrent major adverse cardiovascular events after PCI. However, IVUS utilization remains low. An increasing number of high-risk or complex coronary artery lesions are treated with PCI, and we hypothesize that the impact of IVUS in guiding treatment of these complex lesions will be of increased importance in reducing major adverse cardiovascular events while remaining cost-effective. The "IMPact on Revascularization Outcomes of intraVascular ultrasound-guided treatment of complex lesions and Economic impact" trial (registered on clinicaltrials.gov: NCT04221815) is a multicenter, international, clinical trial randomizing subjects to IVUS-guided versus angiography-guided PCI in a 1:1 ratio. Patients undergoing PCI involving a complex lesion are eligible for enrollment. Complex lesion is defined as involving at least 1 of the following characteristics: chronic total occlusion, in-stent restenosis, severe coronary artery calcification, long lesion (≥28 mm), or bifurcation lesion. The clinical investigation will be conducted at approximately 120 centers in North America and Europe, enrolling approximately 2,500 to 3,100 randomized subjects with an adaptive design. The primary clinical end point is the rate of target vessel failure at 12 months, defined as the composite of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization. The co-primary imaging end point is the final post-PCI minimum stent area assessed by IVUS. The primary objective of this study is to assess the impact of IVUS guidance on the PCI treatment of complex lesions.

Assessment of residual thrombus burden in patients with ST-segment elevation myocardial infarction undergoing bivalirudin versus unfractionated heparin infusion: The MATRIX (minimizing adverse hemorrhagic events by transradial access site and angioX) OCT study.

BACKGROUND: Residual stent strut thrombosis after primary percutaneous coronary intervention (PCI), negatively affects myocardial perfusion, may increase stent thrombosis risk, and it is associated with neointima hyperplasia at follow-up. OBJECTIVES: To study the effectiveness of any bivalirudin infusion versus unfractionated heparin (UFH) infusion in reducing residual stent strut thrombosis in patients with ST-elevation myocardial infarction (STEMI). METHODS: Multi-vessel STEMI patients undergoing primary PCI and requiring staged intervention were selected among those randomly allocated to two different bivalirudin infusion regimens in the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and angioX) Treatment-Duration study. Those receiving heparin only were enrolled into a registry arm. Optical coherence tomography (OCT) of the infarct-related artery was performed at the end of primary PCI and 3-5 days thereafter during a staged intervention. The primary endpoint was the change in minimum flow area (ΔMinFA) defined as (stent area + incomplete stent apposition [ISA] area) - (intraluminal defect + tissue prolapsed area) between the index and staged PCI. RESULTS: 123 patients in bivalirudin arm and 28 patients in the UFH arm were included. Mean stent area, percentage of malapposed struts, and mean percent thrombotic area were comparable after index or staged PCI. The ΔMinFA in the bivalirudin group was 0.25 versus 0.05 mm2 in the UFH group, which resulted in a between-group significant difference of 0.36 [95% CI: (0.05, 0.71); p = .02]. This was mostly related to a decrease in tissue protrusion in the bivalirudin group (p = .03). There was a trend towards more patients in the bivalirudin group who achieved a 5% difference in the percentage of OCT frames with the area >5% (p = .057). CONCLUSIONS: The administration of bivalirudin after primary PCI significantly reduces residual stent strut thrombosis when compared to UFH. This observation should be considered hypothesis-generating since the heparin-treated patients were not randomly allocated.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC).

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.