Prognostic Value of Microvascular Resistance Reserve After Percutaneous Coronary Intervention in Patients With Myocardial Infarction.

BACKGROUND: The microvascular resistance reserve (MRR) has recently been introduced as a novel index to assess the vasodilatory capacity of the microcirculation, independent of epicardial disease. The prognostic value of MRR in ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: The aim of this analysis was to investigate the prognostic value of MRR in patients with STEMI and to compare MRR with cardiovascular magnetic resonance imaging parameters. METHODS: From a pooled analysis of individual patient data from 6 cohorts that measured the index of microcirculatory resistance (IMR) directly after primary percutaneous coronary intervention in patients with STEMI (n = 1,265), a subgroup analysis was performed in patients in whom both MRR and IMR were available. The primary endpoint was the composite of all-cause mortality or hospitalization for heart failure. RESULTS: Both MRR and IMR could be calculated in 446 patients. The optimal cutoff of MRR to predict the primary endpoint in this STEMI population was 1.25. During a median follow-up of 3.1 years (Q1-Q3: 1.5-6.1 years), the composite of all-cause mortality or hospitalization for heart failure occurred in 27.3% and 5.9% of patients (HR: 4.16; 95% CI: 2.31-7.50; P < 0.001) in the low MRR (≤1.25) and high MRR (>1.25) groups, respectively. Both IMR and MRR were independent predictors of the composite of all-cause mortality or hospitalization for heart failure. CONCLUSIONS: MRR measured directly after primary percutaneous coronary intervention was an independent predictor of the composite of all-cause mortality or hospitalization for heart failure during long-term follow-up.

Risk Burden of Cancer in Patients Treated With Abbreviated Dual Antiplatelet Therapy After PCI: Analysis of Multicenter Controlled High-Bleeding Risk Trials.

BACKGROUND: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals. METHODS: Patient-level data from 4 high-bleeding risk coronary drug-eluting stent studies (ONYX One, LEADERS FREE, LEADERS FREE II, and SENIOR trials) treated with short DAPT were analyzed. The comparison focused on patients with high-bleeding risk with and without cancer, assessing 1-year rates of net adverse clinical events (all-cause death, myocardial infarction, stroke, revascularization, and Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and major adverse clinical events (all-cause death, myocardial infarction, stroke). RESULTS: A total of 5232 patients were included, of whom 574 individuals had cancer, and 4658 were at high-bleeding risk without previous cancer. Despite being younger with fewer risk factors, patients with cancer had higher net adverse clinical event (HR, 1.25; P=0.01) and major adverse clinical event (HR, 1.26; P=0.02), primarily driven by all-cause mortality and major bleeding (BARC 3-5), but not myocardial infarction, stroke, stent thrombosis, or repeat revascularization. Cancer was an independent predictor of net adverse clinical event (P=0.005), major adverse clinical event (P=0.01), and major bleeding (P=0.03). CONCLUSIONS: The present work is the first report on abbreviated DAPT dedicated to patients with cancer. Cancer is a major marker of adverse outcomes and these events had high lethality. Despite short DAPT, patients with cancer experienced higher rates of major bleeding compared with patients without cancer with high-bleeding risk, which occurred mainly after DAPT discontinuation. These findings reinforce the need for a more detailed and individualized stratification of those patients. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03344653, NCT01623180, NCT02843633, NCT0284.

Validation of a new non-hyperemic physiological index: the constant-resistance ratio (cRR).

OBJECTIVES: The instantaneous wave-free ratio (iwFR) has limited availability. A new resting index called the constant-resistance ratio (cRR), which dynamically identifies cardiac intervals with constant and minimum resistance, has been developed; however, its diagnostic performance is unknown. The aim of this study was to validate the cRR by retrospectively calculating the cRR values from raw pressure waveforms of 2 publicly available datasets and compare them with those of the iwFR. METHODS: Waveform data from the CONTRAST and VERIFY 2 studies were used. The primary endpoint was Bland-Altman bias between cRR and iwFR. Secondary endpoints included diagnostic agreement, correlation, receiver operating characteristic (ROC) analysis, and success rates of cRR and iwFR. RESULTS: Among the 1036 waveforms, 871 were successful in determining paired cRR and iwFR values, while cRR was 6% more successful than iwFR (P less than .0001). The mean bias between cRR and iwFR was 0.003, with 95% limits of agreement [-0.021,0.028]. These 2 indices were highly correlated (r = 0.991; P less than .0001). Using an iwFR of 0.89 or less as the reference standard, the optimal cRR cutoff was 0.89, with an area under the ROC curve of 0.991 (P less than .001) and a diagnostic accuracy of 96.9% (95% CI [96%, 98%]). CONCLUSIONS: The cRR, a new resting index for identifying dynamic cardiac intervals with constant and minimum resistance, demonstrated high numerical agreement, diagnostic consistency, and a higher success rate than the iwFR based on the 2 publicly available datasets.

Performance of drug-coated balloons in coronary and below-the-knee arteries: Anatomical, physiological and pathological considerations.

Below-the-knee (infrapopliteal) atherosclerotic disease, which presents as chronic limb-threatening ischemia (CLTI) in nearly 50% of patients, represents a treatment challenge when it comes to the endovascular intervention arm of management. Due to reduced tissue perfusion, patients usually experience pain at rest and atrophic changes correlated to the extent of the compromised perfusion. Unfortunately, the prognosis remains unsatisfactory with 30% of patients requiring major amputation and a mortality rate of 25% within 1 year. To date, randomized multicentre trials of endovascular intervention have shown that drug-eluting stents (DES) increase patency rate and lower target lesion revascularization rate compared to plain balloon angioplasty and bare-metal stents. The majority of these trials recruited patients with focal infrapopliteal lesions, while most patients requiring endovascular intervention have complex and diffuse atherosclerotic disease. Moreover, due to the nature of the infrapopliteal arteries, the use of long DES is limited. Following recent results of drug-coated balloons (DCBs) in the treatment of femoropopliteal and coronary arteries, it was hoped that similar effective results would be achieved in the infrapopliteal arteries. In reality, multicentre trials have failed to support the proposed hypothesis and no advantage was found in using DCBs in comparison to plain balloon angioplasty. This review aims to explore anatomical, physiological and pathological differences between lesions of the infrapopliteal and coronary arteries to explain the differences in outcome when using DCBs.

Current spectrum and outcomes of infarct-related cardiogenic shock: insights from the CULPRIT-SHOCK registry and randomized controlled trial.

AIMS: We analysed consecutive patients with acute myocardial infarction complicated by cardiogenic shock (CS) who were enrolled into the CULPRIT-SHOCK randomized controlled trial (RCT) and those with exclusion criteria who were included into the accompanying registry. METHODS AND RESULTS: In total, 1075 patients with infarct-related CS were screened for CULPRIT-SHOCK in 83 specialized centres in Europe; 369 of them had exclusion criteria for the RCT and were enrolled into the registry. Patients were followed over 1 year. The mean age was 68 years and 260 (25%) were women. 13.5%, 30.9%, and 55.6% had one-vessel, two-vessel, and three-vessel coronary artery disease (CAD), respectively. Significant left main (LM) coronary artery stenosis was present in 8.0%. 54.2% of the patients had cardiac arrest before admission. Thrombolysis in myocardial infarction (TIMI) 3 patency of the infarct vessel after percutaneous coronary intervention was achieved in 83.6% of all patients. Mechanical circulatory support was applied in one-third of patients. Total mortality after 30 days and 1 year was 47.6% and 52.9%. Mortality after 1 year was highest in patients with LM coronary artery stenosis (63.5%), followed by three-vessel (56.6%), two-vessel (49.8%), and one-vessel CAD (38.6%), respectively. Mechanical complications were rare (21/1008; 2.1%) but associated with a high mortality of 66.7% after 1 year. CONCLUSION: In specialized centres in Europe, short- and long-term mortality of patients with infarct-related CS treated with an invasive strategy is still high and mainly depends on the extent of CAD. Therefore, there is still a need for improvement of care to improve the prognosis of infarct-related CS.

Patient-Specific Commissural Alignment With a Self-Expanding Transcatheter Heart Valve.

A simple and reproducible technique to achieve commissural alignment during transcatheter aortic valve replacement with the Allegra valve is described. Slight rotation of the system before system insertion is necessary. Moreover, thanks to its permaflow system (Biosensors) and its radiopaque markings, small adjustments before valve deployment can be made to reassess correct alignment.

Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial.

Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data.

BACKGROUND: Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. OBJECTIVES: The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. METHODS: In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. RESULTS: In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. CONCLUSIONS: In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.

Impact of Post-PCI FFR Stratified by Coronary Artery.

BACKGROUND: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated. OBJECTIVES: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery. METHODS: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization. RESULTS: Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005). CONCLUSIONS: The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels.

Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial.

BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Fractional Flow Reserve-Guided Stent Optimisation in Focal and Diffuse Coronary Artery Disease.

Assessing coronary physiology after stent implantation facilitates the optimisation of percutaneous coronary intervention (PCI). Coronary artery disease (CAD) patterns can be characterised by the pullback pressure gradient (PPG) index. The impact of focal vs. diffuse disease on physiology-guided incremental optimisation strategy (PIOS) is unknown. This is a sub-study of the TARGET-FFR randomized clinical trial (NCT03259815). The study protocol directed that optimisation be attempted for patients in the PIOS arm when post-PCI FFR was <0.90. Overall, 114 patients (n = 61 PIOS and 53 controls) with both pre-PCI fractional flow reserve (FFR) pullbacks and post-PCI FFR were included. A PPG ≥ 0.74 defined focal CAD. The PPG correlated significantly with post-PCI FFR (r = 0.43; 95% CI 0.26 to 0.57; p-value < 0.001) and normalised delta FFR (r = 0.49; 95% CI 0.34 to 0.62; p-value < 0.001). PIOS was more frequently applied to vessels with diffuse CAD (6% focal vs. 42% diffuse; p-value = 0.006). In patients randomized to PIOS, those with focal disease achieved higher post-PCI FFR than patients with diffuse CAD (0.93 ± 0.05 vs. 0.83 ± 0.07, p < 0.001). There was a significant interaction between CAD patterns and the randomisation arm for post-PCI FFR (p-value for interaction = 0.004). Physiology-guided stent optimisation was applied more frequently to vessels with diffuse disease; however, patients with focal CAD at baseline achieved higher post-PCI FFR.

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

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

Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors.

BACKGROUND: Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches to treatment. METHODS: Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life-5 dimension-5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was performed to compare clinical and procedural characteristics among patients with and without post-PCI angina (defined by follow-up SAQ-angina frequency score <100). RESULTS: Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59, P<0.001) and EQ-5D-5L health index scores (0.84±0.15 versus 0.69±0.22, P<0.001). Pre-PCI fractional flow reserve (FFR) was lower among patients who had no post-PCI angina (0.56±0.15 versus 0.62±0.13, P=0.003). Percentage change in FFR after PCI had a moderate correlation with angina frequency score at follow-up (r=0.36, P<0.0001). Patients with post-PCI angina had less improvement in FFR (43.1±33.5% versus 67.0±50.7%, P<0.001). There were no between-group differences in post-PCI FFR, coronary flow reserve, or corrected index of microcirculatory resistance. Patients with post-PCI angina had lower SAQ-summary scores (64.01±22 versus 95.16±8.72, P≤0.001) and EQ-5D-5L index scores (0.69±0.26 versus 0.91±0.17, P≤0.001) at follow-up. CONCLUSIONS: Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriateness of PCI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03259815.

Comparison of outcomes in patients with or without ARC-HBR criteria undergoing PCI with polymer-free biolimus coated stents: The BioFreedom France study.

BACKGROUND: The polymer-free biolimus coated stent (BioFreedom) was shown to be superior to bare metal stents in the LEADERS FREE randomized trial in high bleeding risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT). However, there is limited outcome data with this device in an all-comers' population. METHODS: We conducted a prospective single-arm study of patients undergoing percutaneous coronary intervention with the polymer-free biolimus coated stent in 25 centers in France with wide inclusion criteria including multivessel disease, complex lesions, and acute coronary syndromes. The primary endpoint was the incidence of target lesion failure (TLF), a composite of cardiac death or target-vessel myocardial infarction (MI) or clinically indicated target lesion revascularization (ci-TLR) at 1-year. The patient population was classified according to the presence (or not) of HBR criteria according to the recent ARC-HBR definition. RESULTS: Between April 2019 and April 2020, 1497 patients were enrolled. TLF occurred in 101 (6.9%) patients, including cardiac death in 35 (2.4%), target vessel MI in 20 (1.4%) and ci-TLR in 65 (4.5%) of them. There were 491 HBR patients (32.8%) and 1006 non-HBR patients. The median duration of DAPT was 74 days in the HBR group versus 348 days in the non-HBR group (p < 0.0001). TLF occurred in 44 (9.2%) of the HBR group and in 57 (5.8%) of the non-HBR group (relative risk 1.62 [95% confidence interval: 1.10-2.41], p = 0015). Compared to the non-HBR group, HBR patients had higher rates of cardiac death (4.4% vs. 1.4%, p = 0.0005) and target vessel MI (2.9% vs. 0.6%, p = 0.0003), but similar rates of ci-TLR. BARC 3-5 bleeding occurred in 6.2% of the HBR group versus 1.4% of the non-HBR group (p < 0.0001). CONCLUSION: In this multicenter all-comers study, HBR patients treated with a polymer-free biolimus coated stent had, compared to non-HBR patients, an increased risk of cardiac death and MI, and despite a shorter duration of DAPT, continued to have higher rates of BARC 3-5 bleeding.

Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial.

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease.

BACKGROUND: An increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief. OBJECTIVES: The aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG). METHODS: This is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques-Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100. RESULTS: A total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020). CONCLUSIONS: Residual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques-Fractional Flow Reserve [TARGET-FFR]; NCT03259815).

Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index.

BACKGROUND: There is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories. OBJECTIVES: The aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial. METHODS: The TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m2], overweight [BMI 25-29.99 kg/m2], and obese [BMI ≥30 kg/m2]) and by median BMI, as prespecified in the protocol. RESULTS: Among 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI. CONCLUSIONS: Among high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.

Coronary Artery Perforations: Glasgow Natural History Study of Covered Stent Coronary Interventions (GNOCCI) Study.

Background The objective of the GNOCCI (Glasgow Natural History Study of Covered Stent Coronary Interventions) Study was to report the incidence and outcomes of coronary artery perforations over an 18-year period at a single, high-volume percutaneous coronary intervention center. We considered both the temporal trends and long-term outcomes of covered stent deployment. Methods and Results We evaluated procedural and long-term clinical outcomes following coronary perforation in a cohort of 43,343 consecutive percutaneous coronary intervention procedures. Procedural major adverse cardiac events were defined as a composite of death, myocardial infarction, stroke, target vessel revascularization, or cardiac surgery within 24 hours. A total of 161 (0.37%) procedures were complicated by coronary perforation of which 57 (35%) were Ellis grade III. Incidence increased with time over the study period (r=0.73; P<0.001). Perforation severity was linearly associated with procedural mortality (median 2.9-year follow-up): Ellis I (0%), Ellis II (1.7%), Ellis III/IIIB (21%), P<0.001. Procedural major adverse cardiac events occurred in 47% of patients with Ellis III/IIIB versus 13.5% of those with Ellis I/II perforations (odds ratio, 5.8; 95% CI, 2.7-12.5; P<0.001). Covered stents were associated with an increased risk of stent thrombosis at 2.9-year follow-up (Academic Research Consortium definite or probable; 9.1% versus 0.9%; risk ratio, 10.5; 95% CI, 1.1-97; P=0.04). Conclusions The incidence of coronary perforation increased between 2001 and 2019. Severe perforation was associated with higher procedural major adverse cardiac events and was an independent predictor of long-term mortality. Although covered stents are a potentially lifesaving treatment, the generation of devices used during the study period was limited by their efficacy and high risk of stent thrombosis. Registration Information Clinicaltrials.gov. Identifier: NCT03862352.