Continuation versus Interruption of Oral Anticoagulation during TAVI.

BACKGROUND: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism. METHODS: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI. RESULTS: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6). CONCLUSIONS: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.).

Graft Failure After Coronary Artery Bypass Grafting and Its Association With Patient Characteristics and Clinical Events: A Pooled Individual Patient Data Analysis of Clinical Trials With Imaging Follow-Up.

BACKGROUND: Graft patency is the postulated mechanism for the benefits of coronary artery bypass grafting (CABG). However, systematic graft imaging assessment after CABG is rare, and there is a lack of contemporary data on the factors associated with graft failure and on the association between graft failure and clinical events after CABG. METHODS: We pooled individual patient data from randomized clinical trials with systematic CABG graft imaging to assess the incidence of graft failure and its association with clinical risk factors. The primary outcome was the composite of myocardial infarction or repeat revascularization occurring after CABG and before imaging. A 2-stage meta-analytic approach was used to evaluate the association between graft failure and the primary outcome. We also assessed the association between graft failure and myocardial infarction, repeat revascularization, or all-cause death occurring after imaging. RESULTS: Seven trials were included comprising 4413 patients (mean age, 64.4±9.1 years; 777 [17.6%] women; 3636 [82.4%] men) and 13 163 grafts (8740 saphenous vein grafts and 4423 arterial grafts). The median time to imaging was 1.02 years (interquartile range [IQR], 1.00-1.03). Graft failure occurred in 1487 (33.7%) patients and in 2190 (16.6%) grafts. Age (adjusted odds ratio [aOR], 1.08 [per 10-year increment] [95% CI, 1.01-1.15]; P=0.03), female sex (aOR, 1.27 [95% CI, 1.08-1.50]; P=0.004), and smoking (aOR, 1.20 [95% CI, 1.04-1.38]; P=0.01) were independently associated with graft failure, whereas statins were associated with a protective effect (aOR, 0.74 [95% CI, 0.63-0.88]; P<0.001). Graft failure was associated with an increased risk of myocardial infarction or repeat revascularization occurring between CABG and imaging assessment (8.0% in patients with graft failure versus 1.7% in patients without graft failure; aOR, 3.98 [95% CI, 3.54-4.47]; P<0.001). Graft failure was also associated with an increased risk of myocardial infarction or repeat revascularization occurring after imaging (7.8% versus 2.0%; aOR, 2.59 [95% CI, 1.86-3.62]; P<0.001). All-cause death after imaging occurred more frequently in patients with graft failure compared with patients without graft failure (11.0% versus 2.1%; aOR, 2.79 [95% CI, 2.01-3.89]; P<0.001). CONCLUSIONS: In contemporary practice, graft failure remains common among patients undergoing CABG and is strongly associated with adverse cardiac events.

The impact of stroke and bleeding on mortality and quality of life during the first year after TAVI: A POPular TAVI subanalysis.

BACKGROUND: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited. AIM: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI. METHODS: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI. RESULTS: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke. CONCLUSION: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI.

Non-invasive physiological assessment of coronary artery obstruction on coronary computed tomography angiography.

Computed tomography-derived fractional flow reserve (CT-FFR) enhances the specificity of coronary computed tomography angiography (CCTA) to that of the most specific non-invasive imaging techniques, while maintaining high sensitivity in stable coronary artery disease (CAD). As gatekeeper for invasive coronary angiography (ICA), use of CT-FFR results in a significant reduction of negative ICA procedures and associated costs and complications, without increasing cardiovascular events. It is expected that CT-FFR algorithms will continue to improve, regarding accuracy and generalisability, and that introduction of new features will allow further treatment guidance and reduced invasive diagnostic testing. Advancements in CCTA quality and artificial intelligence (AI) are starting to unfold the incremental diagnostic and prognostic capabilities of CCTA's attenuation-based images in CAD, with future perspectives promising additional CCTA parameters which will enable non-invasive assessment of myocardial ischaemia as well as CAD activity and future cardiovascular risk. This review discusses practical application, interpretation and impact of CT-FFR on patient care, and how this ties into the CCTA 'one stop shop' for coronary assessment and patient prognosis. In this light, selective adoption of the most promising, objective and reproducible techniques and algorithms will yield maximal diagnostic value of CCTA without overcomplicating patient management and guideline recommendations.

Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation.

BACKGROUND: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied. METHODS: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31). CONCLUSIONS: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.).

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

Association of Dual Antiplatelet Therapy With Ticagrelor With Vein Graft Failure After Coronary Artery Bypass Graft Surgery: A Systematic Review and Meta-analysis.

Importance: The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. Objective: To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery. Data Sources: MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction. Study Selection: Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure. Data Extraction and Synthesis: Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used. Main Outcomes and Measures: The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin. Results: A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46). Conclusions and Relevance: Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.

Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Approximately 15% of saphenous vein grafts (SVGs) occlude during the first year after coronary artery bypass graft surgery (CABG) despite aspirin use. The POPular CABG trial (The Effect of Ticagrelor on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting Surgery) investigated whether ticagrelor added to standard aspirin improves SVG patency at 1 year after CABG. METHODS: In this investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial, patients with ≥1 SVGs were randomly assigned (1:1) after CABG to ticagrelor or placebo added to standard aspirin (80 mg or 100 mg). The primary outcome was SVG occlusion at 1 year, assessed with coronary computed tomography angiography, in all patients that had primary outcome imaging available. A generalized estimating equation model was used to perform the primary analysis per SVG. The secondary outcome was 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. RESULTS: Among 499 randomly assigned patients, the mean age was 67.9±8.3 years, 87.1% were male, the indication for CABG was acute coronary syndrome in 31.3%, and 95.2% of procedures used cardiopulmonary bypass. Primary outcome imaging was available in 220 patients in the ticagrelor group and 223 patients in the placebo group. The SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). CONCLUSIONS: In this randomized, placebo-controlled trial, the addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02352402.

Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment.

BACKGROUND: Life expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population. METHODS: A cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors. RESULTS: The study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings. CONCLUSION: Neither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.

Outcomes of newly diagnosed atrial fibrillation in patients with acute coronary syndromes.

BACKGROUND: Acute coronary syndrome (ACS) is frequently accompanied by newly diagnosed atrial fibrillation (AF). AIMS: We aimed to compare the risk of major adverse cardiovascular events (MACE) in ACS patients presenting with known, newly diagnosed, or no AF. METHODS: In our multicentre, prospective registry study, we included patients with confirmed ACS. Patients are classified as having known, newly diagnosed or no AF. Newly diagnosed AF is subdivided according to the duration of the episode, time of onset, post-coronary artery bypass graft (CABG) or spontaneous occurrence, and treatment with oral anticoagulants (OAC). The primary endpoint is MACE at 1 year. Key secondary endpoints include ischaemic stroke and bleeding complications. RESULTS: Amongst 4,433 patients with confirmed ACS, 3,598 (81.2%) had no AF, 438 (9.9%) had newly diagnosed AF, and 397 (9.0%) had known AF. The rates of OAC treatment at discharge were 53.4% in patients with newly diagnosed AF and 89.2% in patients with known AF. After adjusting for baseline imbalances, only new AF was independently associated with increased rates of MACE, whereas known AF was not (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.19-1.90 and HR 0.93, 95% CI: 0.70-1.23). For ACS patients with newly diagnosed AF, episodes lasting >24 hours were associated with a higher risk of MACE compared to episodes <24 hours (HR 1.99, 95% CI: 1.36-2.93). Episodes of new AF occurring post-CABG had more favourable outcomes compared to spontaneously occurring new AF (HR for MACE 0.52, 95% CI: 0.31-0.86). OAC treatment rates were higher in the new AF subcategories with higher rates of MACE and ischaemic stroke. CONCLUSIONS: Newly diagnosed AF in ACS patients was associated with higher rates of MACE and ischaemic stroke compared to ACS patients without or with known AF. Among the ACS patients with new AF, an episode lasting >24 hours was associated with worse outcomes than shorter episodes, while post-CABG occurrence of AF showed relatively better outcomes compared to spontaneously occurring AF. Only 53% of new AF patients were discharged on OAC therapy versus 89% with known AF.

Coronary Artery Bypass Graft Failure in Women: Incidence and Clinical Implications.

BACKGROUND: Women have worse outcomes after coronary artery bypass surgery (CABG) than men. OBJECTIVES: This study aimed to determine the incidence of CABG graft failure in women, its association with cardiac events, and whether it contributes to sex-related differences in outcomes. METHODS: A pooled analysis of individual patient data from randomized clinical trials with systematic imaging follow-up was performed. Multivariable logistic regression models were used to assess the association of graft failure with myocardial infarction and repeat revascularization between CABG and imaging (primary outcome) and death after imaging (secondary outcome). Mediation analysis was performed to evaluate the effect of graft failure on the association between female sex and risk of death. RESULTS: Seven randomized clinical trials (N = 4,413, 777 women) were included. At a median imaging follow-up of 1.03 years, graft failure was significantly more frequent among women than men (37.3% vs 32.9% at the patient-level and 20.5% vs 15.8% at the graft level; P = 0.02 and P < 0.001, respectively). In women, graft failure was associated with an increased risk of myocardial infarction and repeat revascularization (OR: 3.94; 95% CI: 1.79-8.67) and death (OR: 3.18; 95% CI: 1.73-5.85). Female sex was independently associated with the risk of death (direct effect, HR: 1.84; 95% CI: 1.35-2.50) but the association was not mediated by graft failure (indirect effect, HR: 1.04; 95% CI: 0.86-1.26). CONCLUSIONS: Graft failure is more frequent in women and is associated with adverse cardiac events. The excess mortality risk associated with female sex among CABG patients is not mediated by graft failure.

Complications of Balloon Pulmonary Angioplasty: A Comprehensive Analysis Based on the Latest ESC Consensus Statement.

Background/Objectives: The literature reports high complication rates in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), especially in patients with poor pulmonary hemodynamics. Here, we describe the complications of BPA based on the new definitions. Methods: All patients with CTEPH who completed BPA treatment before 15 September 2023 were selected from the CTEPH database. Peri-procedural complications were collected and classified according to the 2023 consensus paper on BPA treatment. Complications were analyzed in subgroups of patients with pulmonary vascular resistance (PVR), ≤ or >6.6 WU, and mean pulmonary artery pressure (mPAP), ≤ or >45 mmHg, at first BPA. Results: In this analysis, 87 patients (63% women; mean age 61.1 ± 14.0 years; 62% on dual PH targeted medical therapy) underwent 426 (mean 4.9 ± 1.6 per patient) BPAs. Only non-severe complications occurred in 14% of BPA treatments and in 47% of the patients; 31% patients had a thoracic complication. The thoracic complications were mild (71%) or moderate (29%). Patients with a PVR > 6.6 WU (n = 8) underwent more BPA treatments (6.6 ± 1.5 versus 4.6 ± 1.5, p = 0.002), had more complications (88% versus 41% of patients, p = 0.020), and had more thoracic complications (17% vs. 7% of BPAs, p = 0.013) than patients with PVR ≤ 6.6 WU. Patients with mPAP > 45 mmHg (n = 13) also had more BPA treatments (6.5 ± 1.7 versus 4.6 ± 1.4, p < 0.001), more complications (77% versus 44% of patients, p = 0.027) and more thoracic complications (14% versus 8% of BPAs, p = 0.039) than patients with mPAP ≤ 45 mmHg. Conclusions: Complications occurred in 14% of BPAs and were mostly mild. Patients with severe pulmonary hemodynamics suffered more (thoracic) complications.

Association between overweight and obesity with coronary artery bypass graft failure: an individual patient data analysis of clinical trials.

OBJECTIVES: The association between obesity and graft failure after coronary artery bypass grafting has not been previously investigated. METHODS: We pooled individual patient data from randomized clinical trials with systematic postoperative coronary imaging to evaluate the association between obesity and graft failure at the individual graft and patient levels. Penalized cubic regression splines and mixed-effects multivariable logistic regression models were performed. RESULTS: Six trials comprising 3928 patients and 12 048 grafts were included. The median time to imaging was 1.03 (interquartile range 1.00-1.09) years. By body mass index (BMI) category, 800 (20.4%) patients were normal weight (BMI 18.5-24.9), 1668 (42.5%) were overweight (BMI 25-29.9), 983 (25.0%) were obesity class 1 (BMI 30-34.9), 344 (8.8%) were obesity class 2 (BMI 35-39.9) and 116 (2.9%) were obesity class 3 (BMI 40+). As a continuous variable, BMI was associated with reduced graft failure [adjusted odds ratio (aOR) 0.98 (95% confidence interval (CI) 0.97-0.99)] at the individual graft level. Compared to normal weight patients, graft failure at the individual graft level was reduced in overweight [aOR 0.79 (95% CI 0.64-0.96)], obesity class 1 [aOR 0.81 (95% CI 0.64-1.01)] and obesity class 2 [aOR 0.61 (95% CI 0.45-0.83)] patients, but not different compared to obesity class 3 [aOR 0.94 (95% CI 0.62-1.42)] patients. Findings were similar, but did not reach significance, at the patient level. CONCLUSIONS: In a pooled individual patient data analysis of randomized clinical trials, BMI and obesity appear to be associated with reduced graft failure at 1 year after coronary artery bypass grafting.

Real-World Implementation of a Genotype-Guided P2Y12 Inhibitor De-Escalation Strategy in Acute Coronary Syndrome Patients.

BACKGROUND: CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel may optimize the balance between ischemic and bleeding risk in patients with acute coronary syndrome (ACS). OBJECTIVES: This study sought to compare bleeding and ischemic event rates in genotyped patients vs standard care. METHODS: Since 2015, ACS patients in the multicenter FORCE-ACS (Future Optimal Research and Care Evaluation in Patients with Acute Coronary Syndrome) registry received standard dual antiplatelet therapy (DAPT). Since 2021, genotype-guided P2Y12 inhibitor de-escalation was recommended at a single center, switching noncarriers of the loss-of-function allele CYP2C19∗3 or CYP2C19∗2 from ticagrelor or prasugrel to clopidogrel, whereas loss-of-function carriers remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction, or stroke, and the primary bleeding endpoint, Bleeding Academic Research Consortium 2, 3, or 5 bleeding, were compared between a genotyped cohort and a cohort treated with standard DAPT after 1 year. RESULTS: Among 5,321 enrolled ACS patients, 406 underwent genotyping compared with 4,915 nongenotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n = 265) were noncarriers, 88.7% (n = 235) of whom were switched to clopidogrel. The primary ischemic endpoint occurred in 5.2% (n = 21) of patients in the genotyped cohort compared to 6.9% (n = 337) in the standard care cohort (adjusted HR: 0.82; 95% CI: 0.53-1.28). The primary bleeding rate was significantly lower in the genotyped cohort compared to the standard care cohort (4.7% vs 9.8%; adjusted HR: 0.47; 95% CI: 0.30-0.76). CONCLUSIONS: The implementation of a CYP2C19 genotype-guided P2Y12 inhibitor de-escalation strategy in a real-world ACS population resulted in lower bleeding rates without an increase in ischemic events compared to a standard DAPT regimen.

Left Atrial Appendage Occlusion in Patients With Anticoagulation Failure vs Anticoagulation Contraindication.

BACKGROUND: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO. OBJECTIVES: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data. METHODS: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores. RESULTS: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT. CONCLUSIONS: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT.

Non-invasive Angiographic-based Fractional Flow Reserve: Technical Development, Clinical Implications, and Future Perspectives.

New non- and less-invasive techniques have been developed to overcome the procedural and operator related burden of the fractional flow reserve (FFR) for the assessment of potentially significant stenosis in the coronary arteries. Virtual FFR-techniques can obviate the need for the additional flow or pressure wires as used for FFR measurements. This review provides an overview of the developments and validation of the virtual FFR-algorithms, states the challenges, discusses the upcoming clinical trials, and postulates the future role of virtual FFR in the clinical practice.

Periprocedural continuation versus interruption of oral anticoagulant drugs during transcatheter aortic valve implantation: rationale and design of the POPular PAUSE TAVI trial.

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.

Effects of CYP3A4*22 and CYP3A5 on clinical outcome in patients treated with ticagrelor for ST-segment elevation myocardial infarction: POPular Genetics sub-study.

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients. Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43-7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58-1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39-2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73-1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45-2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27-1.30) p = 0.20]. Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01761786.