Impact of patient selection in clinical trials: application of ROCKET AF and ARISTOTLE criteria in GARFIELD-AF.

BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.

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

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

A case report of a rapidly growing giant coronary pseudoaneurysm: challenges and lessons learned.

Background: Coronary pseudoaneurysm is a rare, potentially fatal, complication of coronary intervention. A challenging management case of a giant right coronary pseudoaneurysm is presented. Case summary: A 56-year-old man presented with an atypical presentation for ST-elevation myocardial infarction. Initial angiogram showed a crescent-shaped ostial lesion with probable connection to the aorta, which disappeared after placing a drug-eluting stent. A few hours later, patient was found to have staph aureus bacteraemia and infective endocarditis for which he received a prolonged antibiotic course. Patient presented a few weeks later with second degree heart block. Echocardiography showed a large cystic lesion adjacent to the right coronary cusp suspicious for a coronary pseudoaneurysm, which was confirmed with angiography. Attempts to treat it with a covered stent were unsuccessful and patient ultimately underwent surgical resection. Discussion: Coronary pseudoaneurysm develops when there is a contained breach of all three layers of the vessel. It may develop from direct iatrogenic trauma to the vessel wall but can be infectious in aetiology. The treatment approach remains uncertain due to limited evidence. Here, we present the diagnostic and technical challenges of managing such an uncommon entity and discuss an algorithm for management.

Do We Still Need Aspirin in Coronary Artery Disease?

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization.

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

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

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

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

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique.

INTRODUCTION: Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI). METHODS: A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented. RESULTS: SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients. CONCLUSIONS: This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.

Procedural Time and Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention.

Chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) can be lengthy procedures. We sought to investigate the effect of procedural time on CTO PCI outcomes. We examined the procedural time required for the various steps of CTO PCI in 6,442 CTO PCIs at 40 US and non-US centers between 2012 and 2022. The mean and median procedure times were 129 ± 76 and 112 minutes, respectively, with no significant change over time. The median times from access to wire insertion, guidewire manipulation time, and post crossing were 20, 32, and 53 minutes, respectively. Lesions crossed in <30 minutes were less complex, as reflected by lower Japanese CTO score (1.89 ± 1.19, p <0.001) than lesions that were not successfully crossed (2.88 ± 1.22) and lesions that were crossed in ≥30 minutes (2.85 ± 1.13). The likelihood of successful crossing if crossing was not achieved after 30, 90, and 180 minutes were a 76.7%, 60.7%, and 42.7%, respectively. The parameters independently associated with ≥30 minutes guidewire manipulation time in patients with a primary antegrade approach included left anterior descending target vessel, proximal cap ambiguity, blunt/no stump, occlusion length, previous failed attempt, medium/severe calcification, and medium/severe tortuosity. The mean duration of CTO PCI is approximately 2 hours (∼20% of time for access to wire insertion, ∼30% wire manipulation time, and ∼50% postwiring time). Guidewire crossing time was shorter in less complex lesions and in cases without complications.

Selected inflammatory and coagulation biomarkers pre-viral suppression in people with human immunodeficiency virus (HIV) infection without overt cardiovascular disease: Is there a need to redefine reference indices?

BACKGROUND: Human immunodeficiency virus (HIV) infection is prevalent in Africa and causes morbidity and mortality despite antiretroviral therapy (ART). Non-communicable complications of HIV infection include cardiovascular disease (CVD) with thromboses throughout the vascular tree. Ongoing inflammation and endothelial dysfunction in people living with HIV (PLWH) probably contribute significantly to HIV-related CVD. OBJECTIVES: A systematic review was conducted to inform interpretation of 5 biomarkers commonly measured in PLWH namely interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), D-dimers, and soluble intracellular and vascular adhesion molecules-1 (sICAM-1 and sVCAM-1) to attempt to define a range for these values in ART naïve PLWH without overt CVD or additional comorbid diseases. METHODS: A systematic search was conducted for all studies documenting the levels of the above biomarkers in ART naïve PLWH published on the PubMed database from 1994 to 2020. RESULTS: The number of publications that reported medians above the assay values was: 4/15 for D-dimer; 0/5 for TNF-α, 8/16 for IL-6, 3/6 for sVCAM-1, and 4/5 for sICAM-1. CONCLUSION: The clinical utility of biomarkers is reduced by the lack of standardisation of the measurement of these parameters, absence of normal reference indices and the lack of uniformity of study protocols in different research centres. This review supports the ongoing use of D-dimers to predict thrombotic and bleeding events in PLWH since the weighted averages across study assays suggest that the median levels do not exceed the reference range. The role of inflammatory cytokine monitoring and measurement of endothelial adhesion markers is less clear.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention After a Previous Failed Attempt.

The impact of a previous failure on procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We examined the clinical and angiographic characteristics and procedural outcomes of 9,393 patients who underwent 9,560 CTO PCIs at 42 United States and non-United States centers between 2012 and 2022. A total of 1,904 CTO lesions (20%) had a previous failed PCI attempt. Patients who underwent reattempt CTO PCI were more likely to have a family history of coronary artery disease (37% vs 31%, p <0.001) and dyslipidemia (87.9% vs 84.3%, p <0.001) but were less likely to have heart failure (25.1% vs 29.5%; p <0.001) and cerebrovascular disease (8.7% vs 10.4%, p = 0.04). Patients with previous failure had a higher Japanese CTO (3.33 ± 1.16 vs 2.12 ± 1.19, p <0.001) score and required longer procedure (120 vs 111 minutes, p <0.001) and fluoroscopy (46.9 vs 40.4 minutes, p <0.001) times and higher air kerma radiation dose (2.3 vs 2.1 gray, p = 0.013). Technical success rates (84.3% vs 86.5%, p = 0.011) were lower in patients with a previous failure compared with patients who underwent first-attempt CTO PCI with no significant difference in in-hospital major adverse cardiac events. After adjusting for potential confounders, a previous failure was not associated with technical failure. Operators performing >30 CTO PCIs annually were more likely to achieve technical success in patients with previous failure. In conclusion, a previous failed CTO PCI attempt was associated with higher lesion complexity, longer procedure time, and lower technical success; however, the association with lower technical success did not remain significant in multivariable analysis.

Use of Bivalirudin for Chronic Total Occlusion Percutaneous Intervention: Insights From the PROGRESS-CTO Registry.

BACKGROUND: There are limited data on the use of bivalirudin for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We compared CTO-PCIs performed using bivalirudin vs unfractionated heparin in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO; NCT02061436). The primary endpoint was net adverse cardiac events (NACE), defined as major adverse cardiac events (MACE) and vascular complications. RESULTS: Between 2012 and 2022, a total of 73 of 9723 procedures (0.75%) were performed using bivalirudin. The J-CTO score (2.4 ± 1.2 vs 2.4 ± 1.3; P=.73) and the PROGRESS-CTO score (1.4 ± 0.9 vs 1.2 ± 1.0; P=.31) were similar in both groups, and the retrograde approach was used less often in the bivalirudin group (15% vs 30%; P<.01). Procedural success (89% vs 85%; P=.35), in-hospital NACE (1.4% vs 2.1%; P>.99), incidence of MACE (0% vs 0.76%; P=.64), and vascular access complications (1.4% vs 0.9%; P=.48) were not different between the 2 groups. On multivariable analysis, use of bivalirudin was not associated with an increased risk of NACE (odds ratio, 0.99; 95% confidence interval, 0.13-7.27). CONCLUSION: Bivalirudin is infrequently used during retrograde CTO-PCI. While the incidence of adverse events was similar with unfractionated heparin, larger studies are needed to assess the safety of bivalirudin.

Impact of lesion length on the outcomes of chronic total occlusion percutaneous coronary intervention: Insights from the PROGRESS-CTO registry.

BACKGROUND: The impact of occlusion length on the procedural techniques and outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. METHODS: We examined the clinical and angiographic characteristics and procedural outcomes of 10,335 CTO PCIs at 42 US and non-US centers between 2012 and 2022. The cohort was divided into two groups based on lesion length (≥20 mm vs. <20 mm). RESULTS: Long lesions were present in 7208 (70%) patients. Comorbidities were more common in patients with long CTOs. Compared with short lesions, long lesions had higher J-CTO score (2.8 ± 1.1 vs. 1.3 ± 1; p < 0.001) and retrograde wiring was more often the initial (15.5% vs. 4.0%; p < 0.001) and successful (22.8% vs. 8.2%; p < 0.001) crossing strategy. Long lesions were more likely to require longer procedure (123 vs. 91 min; p < 0.001) and fluoroscopy (47.1 vs. 32.2 min; p < 0.001) time, larger contrast volume (218 vs. 200 mL; p < 0.001) and higher air kerma radiation dose (2.4 vs. 1.7 Gy; p < 0.001). After adjusting for potential confounders, long lesions were associated with lower technical success (odds ratio [OR]: 0.91 per 10 mm increase; 95% confidence interval [CI]: 0.88, 0.94) and higher major adverse cardiovascular events (MACE) (OR: 1.08 per 10 mm increase; 95% CI: 1.02, 1.15). CONCLUSIONS: CTO PCI of long occlusions is independently associated with lower rates of technical success and higher rates of in-hospital MACE.