Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

BACKGROUND: The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. METHODS: In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. RESULTS: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). CONCLUSIONS: Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).

Clinical Performance and Persistence on Dual Pathway Inhibition with Rivaroxaban and Aspirin in Real-World Setting.

ABSTRACT: The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.

Integrating platelet reactivity in the age, creatinine and ejection fraction score to predict clinical outcomes following percutaneous coronary intervention in patients with chronic coronary syndrome: the PR-ACEF score.

To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up.

Angio-Based Fractional Flow Reserve, Functional Pattern of Coronary Artery Disease, and Prediction of Percutaneous Coronary Intervention Result: a Proof-of-Concept Study.

PURPOSE: Wire-based coronary physiology pullback performed before percutaneous coronary intervention (PCI) discriminates coronary artery disease (CAD) distribution and extent, and is able to predict functional PCI result. No research investigated if quantitative flow ratio (QFR)-based physiology assessment is able to provide similar information. METHODS: In 111 patients (120 vessels) treated with PCI, QFR was measured both before and after PCI. Pre-PCI QFR trace was used to discriminate functional patterns of CAD (focal, serial lesions, diffuse disease, combination). Functional CAD patterns were identified analyzing changes in the QFR virtual pullback trace (qualitative method) or after computation of the QFR virtual pullback index (QVPindex) (quantitative method). QVPindex calculation was based on the maximal QFR drop over 20 mm and the length of epicardial coronary segment with QFR most relevant drop. Then, the ability of the different functional patterns of CAD to predict post-PCI QFR value was tested. RESULTS: By qualitative method, 51 (43%), 20 (17%), 15 (12%), and 34 (28%) vessels were classified as focal, serial focal lesions, diffuse disease, and combination, respectively. QVPindex values >0.71 and ≤0.51 predicted focal and diffuse patterns, respectively. Suboptimal PCI result (post-PCI QFR value ≤0.89) was present in 22 (18%) vessels. Its occurrence differed across functional patterns of CAD (focal 8% vs. serial lesions 15% vs. diffuse disease 33% vs. combination 29%, p=0.03). Similarly, QVPindex was correlated with post-PCI QFR value (r=0.62, 95% CI 0.50-0.72). CONCLUSION: Our results suggest that functional patterns of CAD based on pre-PCI QFR trace can predict the functional outcome after PCI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02811796. Date of registration: June 23, 2016.

Prediction of type 4a myocardial infarction with the angiography-derived hemodynamic (ADDED) index.

Percutaneous coronary intervention (PCI) is frequently complicated by type 4a myocardial infarction (MI), which is associated with an increased risk of mortality. We assessed the usefulness of the angiography-derived hemodynamic index (ADDED), which is based on the extent of myocardium at risk and on the anatomical lesion severity, in predicting type 4a MI in patients with chronic coronary syndrome (CCS) undergoing PCI. We enrolled 442 patients treated with single-vessel PCI. The ADDED index was calculated as the ratio of the Duke Jeopardy Score to the minimum lumen diameter assessed with quantitative angiography analysis. Type 4a MI was defined according to the 4th Universal Definition of MI. The overall population was divided into tertiles of ADDED index. Type 4a MI occurred in 5 patients (3.3%) in the ADDED-low tertile, 8 (5.5%) in the ADDED-mid tertile, and 26 (17.7%) in the ADDED-high tertile (p < 0.0001). At ROC curve analysis, the ADDED index could significantly discriminate between patients with and without type 4a MI (area under the curve 0.745). At multivariate analysis, an ADDED index value > 5.25 was the strongest independent predictor type 4a MI. Our results support the role of the ADDED index as a predictor of type 4a MI in patients with CCS treated with elective PCI of a single vessel. Whether a selective use of additional preventive measures in patients considered at high risk based on ADDED index values may improve peri-procedural and long-term outcomes remains to be tested in dedicated investigations.

Fractional flow reserve in patients with reduced ejection fraction.

AIMS: Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes. METHODS AND RESULTS: From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion. In the FFR-guided group, 433 patients were matched with 866 contemporary patients of the Angiography-guided group. For outcome comparison, 617 control patients with LVEF >50% were included. After FFR, stenotic vessels per patient were significantly downgraded compared with the Angiography-guided group (1.43 ± 0.98 vs. 1.97 ± 0.84; P < 0.001). This was associated with lower revascularization rate (52% vs. 62%; P < 0.001) in the FFR-guided vs. the Angiography-guided group. All-cause death at 5 years of follow-up was significantly lower in the FFR-guided as compared with Angiography-guided group [22% vs. 31%. HR (95% CI) 0.64 (0.51-0.81); P < 0.001]. Similarly, rate of major adverse cardiovascular and cerebrovascular events (MACCE: composite of all-cause death, myocardial infarction, revascularization, and stroke) was significantly lower in the FFR-guided group [40% vs. 46% in the Angiography-guided group. HR (95% CI) 0.81 (0.67-0.97); P = 0.019]. Higher rates of death and MACCE were observed in patients with reduced LVEF compared with the control cohort. CONCLUSIONS: In patients with reduced LVEF and CAD, FFR-guided revascularization was associated with lower rates of death and MACCE at 5 years as compared with the Angiography-guided strategy. This beneficial impact was observed in parallel with less coronary artery bypass grafting and more patients deferred to percutaneous coronary intervention or medical therapy.

Physiology-guided revascularization versus optimal medical therapy of nonculprit lesions in elderly patients with myocardial infarction: Rationale and design of the FIRE trial.

BACKGROUND: Myocardial infarction (MI) in elderly patients is associated with unfavorable prognosis, and it is becoming an increasingly prevalent condition. The prognosis of elderly patients is equally impaired in ST-segment elevation (STE) or non-STE (NSTE), and it is markedly worsened by the common presence of multivessel disease (MVD). Given the limited evidence available for elderly patients, it has not yet been established whether, as for younger patients, a complete revascularization strategy in MI patients with MVD should be advocated. We present the design of a dedicated study that will address this research gap. METHODS AND DESIGN: The FIRE trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients aged 75 years and older, with MI (either STE or NSTE), MVD at coronary artery angiography, and a clear culprit lesion will be randomized to culprit-only treatment or to physiology-guided complete revascularization. The primary end point will be the patient-oriented composite end point of all-cause death, any MI, any stroke, and any revascularization at 1 year. The key secondary end point will be the composite of cardiovascular death and MI. Quality of life and physical performance will be evaluated as well. All components of the primary and key secondary outcome will be tested also at 3 and 5 years. The sample size for the study is 1,400 patients. IMPLICATIONS: The FIRE trial will provide evidence on whether a specific revascularization strategy should be applied to elderly patients presenting MI and MVD to improve their clinical outcomes.

Interrupted versus uninterrupted novel oral anticoagulant peri-implantation of cardiac device: A single-center randomized prospective pilot trial.

BACKGROUND: Many patients requiring cardiac implantable electronic device (CIED) implantation are on long-term oral anticoagulant therapy. While continuation of warfarin has been shown to be safe and reduce bleeding complications compared to interruption of warfarin therapy and heparin bridging, it is not known which novel oral anticoagulants (NOAC) regimen (interrupted vs uninterrupted) is better in this setting. METHODS: One-hundred and one patients were randomized to receive CIED implantation with either interrupted or uninterrupted/continuous NOAC therapy before surgery. No heparin was used in either treatment arm. The primary end-point was the presence of a clinically significant pocket hematoma after CIED implantation. The secondary end-point was a composite of other major bleeding events, device-related infection, thrombotic events, and device-related admission length postdevice implantation. RESULTS: Both treatment groups were equally balanced for baseline variables and concomitant medications. One clinically significant pocket hematoma occurred in the uninterrupted NOAC group and none in the interrupted group (P  =  0.320). There was no difference in other bleeding complications. No thrombotic events were observed in either of the two groups. CONCLUSIONS: Despite the paucity of bleeding events, data from this pilot study suggest that uninterrupted NOAC therapy for CIED implantation appears to be as safe as NOAC interruption and does not increase bleeding complications.

Impact of platelet reactivity on 5-year clinical outcomes following percutaneous coronary intervention: a landmark analysis.

We investigated the impact of suboptimal platelet reactivity on clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients with stable coronary artery disease undergoing elective PCI. Platelet reactivity was measured before PCI using the VerifyNow P2Y12 assay. Primary endpoint was the incidence of ischemic or bleeding events at 1 month and 5 years. Patients with high platelet reactivity (HPR) showed significantly higher rates of ischemic events both during the 1st month after PCI (HR 2.06, 95% CI 1.02-4.06), and beyond 1 month compared with patients without HPR (HR 1.73, 95% CI 1.02-2.95). Conversely, compared with patients without low platelet reactivity (LPR), patients with LPR presented significantly higher rates of bleeding only during the 1st month (HR 3.67, 95% CI 1.68-8.02). In conclusion, pre-procedural HPR is associated with ischemic events even beyond the 1st month after PCI. The association of LPR with bleeding events seems to be confined to the periprocedural period.

Impact of the high-frequency cutoff of bandpass filtering on ECG quality and clinical interpretation: A comparison between 40Hz and 150Hz cutoff in a surgical preoperative adult outpatient population.

BACKGROUND: In 1990 the American Heart Association (AHA) established a standard 0.05 to 150Hz bandwidth for the routine recording of 12-lead electrocardiograms (ECGs). However, subsequent studies have indicated a very high prevalence of deviations from the recommended cutoffs. OBJECTIVE: This prospective observational study investigates the impact of 40Hz compared to 150Hz high-frequency cutoffs on ECG quality and clinical interpretation in a single-center surgical outpatient population. METHODS: 1582 consecutive adult patients underwent two standard 12-lead ECG tracings using different high-frequency cutoffs (40Hz and 150Hz). Two blinded cardiologists randomly reviewed and interpreted the recordings according to pre-defined parameters (PR and ST segment, Q and T wave abnormalities). An arbitrary score, ranging from 1 to 3, was established to evaluate the perceived quality of the recordings and the non-interpretable ECGs were noted. The tracings were then matched to compare interpretations between 40 and 150Hz filters. RESULTS: A 40Hz high-frequency cutoff resulted in an increased rate of optimal quality ECGs compared to the 150Hz cutoff (93.4% vs 54.6%; p<0.001) and a lower rate of non-interpretable traces (0.25% vs 4.80%; p<0.001). Analyzing the morphologic parameters, no significant differences between the filter settings were found, except for a higher incidence of the J-point elevation in the 40Hz high-frequency cutoff (p=0.007) and a higher incidence of left ventricular hypertrophy in the 150Hz high-frequency cutoff (7.4% vs 5.4%, p<0.001). The latter was noted only in ECGs with borderline QRS amplitudes (between 3.3 and 3.7mV; p<0.001). CONCLUSION: Despite current recommendations, the large deviation from standard high-frequency cutoff in clinical practice does not seem to significantly affect ECG clinical interpretation and a 40Hz high-frequency cutoff of the band-pass filtering may be acceptable in a low risk population, allowing for a better quality of tracings.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial.

BACKGROUND: The debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. OBJECTIVES: The primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. METHODS: Patients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. RESULTS: A total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). CONCLUSIONS: In CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952).

Natural History of Coronary Atherosclerosis in Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement: The Role of Quantitative Flow Ratio.

BACKGROUND: The prognostic impact of functionally significant coronary artery disease, as assessed with quantitative flow ratio (QFR), in patients with severe aortic stenosis treated with transcatheter aortic valve replacement is unknown. METHODS: This is a retrospective study with blind analysis of angiographic data, enrolling consecutive patients with severe aortic stenosis treated with transcatheter aortic valve replacement at 4 Italian centers. None of the patients enrolled received pre-transcatheter aortic valve replacement or concomitant coronary revascularization, either for the absence of significant coronary stenoses or by clinical decision. Visual estimation of diameter stenosis and QFR analysis were performed in all coronary arteries. The end point was all-cause mortality at a 3-year follow-up. RESULTS: A total of 318 patients were enrolled. At visual estimation, 140 patients (44%) presented a diameter stenosis ≥50% in at least 1 coronary artery, whereas 78 patients (24.5%) had at least 1 vessel with QFR <0.80 and, therefore, included in the positive QFR group. Overall, 69 (21.7%) patients died during the follow-up. In the Kaplan-Meier analysis, patients with positive QFR experienced significantly higher rates of death during follow-up compared with those without (51.1% versus 12.1%; P<0.001), whereas no significant difference was evident in terms of death between patients with or without significant coronary artery disease according to angiographic evaluation (24.3% versus 19.7%; P=0.244). In a multivariate regression model, positive QFR was an independent predictor of all-cause death during follow-up (hazard ratio, 5.31 [95% CI, 3.21-8.76]). CONCLUSIONS: Coronary QFR can predict mortality in patients with severe aortic stenosis treated with transcatheter aortic valve replacement without revascularization.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation.

BACKGROUND: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI). OBJECTIVES: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI. METHODS: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year. RESULTS: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654). CONCLUSIONS: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743).

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

AIMS: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients. METHODS AND RESULTS: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year. Secondary endpoints included the composite of cardiovascular death or MI, as well as single components of the primary endpoint. Pre-admission physical activity was categorized into three groups: (i) absent (sedentary), (ii) light, and (iii) vigorous. Among 1445 patients, 692 (48%) were sedentary, whereas 560 (39%) and 193 (13%) performed light and vigorous physical activity, respectively. Patients engaging in light or vigorous pre-admission physical activity exhibited a reduced risk of the primary outcome compared with sedentary individuals [light hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.55-0.91 and vigorous HR 0.14, 95% CI 0.07-0.91, respectively]. These trends were also observed for death, cardiovascular death, or MI. When comparing physiology-guided complete revascularization vs. culprit-only strategy, no significant interaction was observed for primary and secondary endpoints when stratified by sedentary or active status. CONCLUSION: In older patients with MI, pre-admission physical activity emerges as a robust and independent prognostic determinant. Physiology-guided complete revascularization stands out an effective strategy in reducing ischaemic adverse events, irrespective of pre-admission physical activity status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03772743.

The Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial has shown that physiology-guided complete revascularization reduces ischaemic adverse events in older patients with myocardial infarction (MI) and multivessel disease. Older patients who engage in light or vigorous physical activity before hospitalization for MI have a reduced risk of the primary composite outcome of death, MI, stroke, or ischaemia-driven revascularization. These benefits extend to all secondary cardiovascular outcomes as well. In the present subanalysis of the FIRE trial, we find that the positive prognosis associated with physiology-guided complete revascularization holds true even for patients with a sedentary lifestyle. This means that this type of revascularization can effectively reduce ischaemic adverse events in older patients with MI and multivessel disease, regardless of their physical activity levels.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk: A Randomized Clinical Trial.

Importance: Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). Objective: To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. Design, Setting, and Participants: This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Interventions: Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. Main Outcomes and Measures: The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Results: Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. Conclusions and Relevance: HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. Trial Registration: ClinicalTrials.gov Identifier: NCT03772743.

QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial.

BACKGROUND: The role of quantitative flow ratio (QFR) in the treatment of nonculprit vessels of patients with myocardial infarction (MI) is a topic of ongoing discussion. OBJECTIVES: This study aimed to investigate the predictive capability of QFR for adverse events and its noninferiority compared to wire-based functional assessment in nonculprit vessels of MI patients. METHODS: The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial randomized 1,445 older MI patients to culprit-only (n = 725) or physiology-guided complete revascularization (n = 720). In the culprit-only arm, angiographic projections of nonculprit vessels were prospectively collected, centrally reviewed for QFR computation, and associated with endpoints. In the complete revascularization arm, endpoints were compared between nonculprit vessels investigated with QFR or wire-based functional assessment. The primary endpoint was the vessel-oriented composite endpoint (VOCE) at 1 year. RESULTS: QFR was measured on 903 nonculprit vessels from 685 patients in the culprit-only arm. Overall, 366 (40.5%) nonculprit vessels showed a QFR value ≤0.80, with a significantly higher incidence of VOCEs (22.1% vs 7.1%; P < 0.001). QFR ≤0.80 emerged as an independent predictor of VOCEs (HR: 2.79; 95% CI: 1.64-4.75). In the complete arm, QFR was used in 320 (35.2%) nonculprit vessels to guide revascularization. When compared with propensity-matched nonculprit vessels in which treatment was guided by wire-based functional assessment, no significant difference was observed (HR: 0.57; 95% CI: 0.28-1.15) in VOCEs. CONCLUSIONS: This prespecified subanalysis of the FIRE trial provides evidence supporting the safety and efficacy of QFR-guided interventions for the treatment of nonculprit vessels in MI patients. (Functional Assessment in Elderly MI Patients With Multivessel Disease [FIRE]; NCT03772743).

Effects of ticagrelor and prasugrel on coronary microcirculation in elective percutaneous coronary intervention.

OBJECTIVE: To compare the effects of ticagrelor and prasugrel on absolute coronary blood flow (Q) and microvascular resistance (R) in patients with stable coronary artery disease (CAD) treated with elective percutaneous coronary intervention (PCI) (NCT05643586). Besides being at least as effective as prasugrel in inhibiting platelet aggregation, ticagrelor has been shown to have additional properties potentially affecting coronary microcirculation. METHODS: We randomly assigned 50 patients to ticagrelor (180 mg) or prasugrel (60 mg) at least 12 hours before intervention. Continuous thermodilution was used to measure Q and R before and after PCI. Platelet reactivity was measured before PCI. Troponin I was measured before, 8 and 24 hours after PCI. RESULTS: At baseline, fractional flow reserve, Q and R were similar in two study groups. Patients in the ticagrelor group showed higher post-PCI Q (242±49 vs 205±53 mL/min, p=0.015) and lower R values (311 (263, 366) vs 362 (319, 382) mm Hg/L/min, p=0.032). Platelet reactivity showed a negative correlation with periprocedural variation of Q values (r=-0.582, p<0.001) and a positive correlation with periprocedural variation of R values (r=0.645, p<0.001). The periprocedural increase in high-sensitivity troponin I was significantly lower in the ticagrelor compared with the prasugrel group (5 (4, 9) ng/mL vs 14 (10, 24) ng/mL, p<0.001). CONCLUSIONS: In patients with stable CAD undergoing PCI, pretreatment with a loading dose of ticagrelor compared with prasugrel improves post-procedural coronary flow and microvascular function and seems to reduce the related myocardial injury.

Impact of Endothelial Dysfunction on Long-Term Clinical Outcomes in Patients With Chronic Coronary Syndromes Treated With Second Generation Drug-Eluting Stent Implantation.

BACKGROUND: Studies investigating clinical outcomes of patients with or without endothelial disfunction (ED) treated with percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) using second generation drug eluting stents (DES) are lacking. METHODS: We prospectively collected data from 109 patients undergoing PCI with second generation DES due to stable CAD between December 2014 and September 2016. ED was evaluated evaluating the flow mediated dilation (FMD) at the brachial artery level and defined by an FMD < 7 %. Primary outcome were major adverse cardiovascular events (MACE), secondary outcomes were target vessel failure (TVR), myocardial infarction (MI) and all-cause death. RESULTS: Five-year follow-up was available in all patients. Median FMD didn't significantly differ between patients who experienced the outcome and those who didn't [no TVR vs. TVR: p = 0.358; no MI vs. MI: p = 0.157; no death vs. death: p = 0.355; no MACE vs. MACE: p = 0.805]. No association between ED and an increased risk for the primary outcome as well as for the secondary ones was evident [MACE: 17.0 % vs. 14.3 %, HR 0.87 (0.33-2.26), log rank p = 0.780; TVR: 9.4 % vs. 5.4 %, HR 0.53 (0.12-2.24), log rank p = 0.384; MI: 3.7 % vs. 8.9 %, HR 2.46 (0.47-12.76), log rank p = 0.265; death: 7.5 % vs. 3.6 %, HR 0.53 (0.09-2.90), log rank p = 0.458]. These findings were confirmed using a lower threshold of FMD to define ED and at one-year landmark analysis. CONCLUSIONS: ED is not associated with an increased risk of adverse events at long-term follow-up in a contemporary cohort of patients undergoing PCI with second generation DES.

Quantitative flow ratio-based outcomes in patients undergoing transcatheter aortic valve implantation quaestio study.

Background: Coronary artery disease (CAD) is common in patients with aortic valve stenosis (AS) ranging from 60% to 80%. The clinical and prognostic role of coronary artery lesions in patients undergoing Transcatheter Aortic Valve Implantation (TAVI) remains unclear. The aim of the present observational study was to estimate long-term clinical outcomes by Quantitative Flow Ratio (QFR) characterization of CAD in a well-represented cohort of patients affected by severe AS treated by TAVI. Methods: A total of 439 invasive coronary angiographies of patients deemed eligible for TAVI by local Heart Teams with symptomatic severe AS were retrospectively screened for QFR analysis. The primary endpoint of the study was all-cause mortality. The secondary endpoint was a composite of cardiovascular mortality, stroke/transient ischemic attack (TIA), acute myocardial infarction (AMI), and any hospitalization after TAVI. Results: After exclusion of patients with no follow-up data, coronary angiography not feasible for QFR analysis and previous surgical myocardial revascularization (CABG) 48/239 (20.1%) patients had a QFR value lower or equal to 0.80 (QFR + value), while the remaining 191/239 (79.9%) did not present any vessel with a QFR positive value. In the adjusted Cox regression analysis, patients with positive QFR were independently associated with an increased risk of all-casual mortality (Model 1, HR 3.47, 95% CI, 2.35-5.12; Model 2, HR 5.01, 95% CI, 3.17-7.90). In the adjusted covariate analysis, QFR+ involving LAD (37/48, 77,1%) was associated with the higher risk of the composite outcome compared to patients without any positive value of QFR or non-LAD QFR positive value (11/48, 22.9%). Conclusions: Pre-TAVI QFR analysis can be used for a safe, simple, wireless functional assessment of CAD. QFR permits to identify patients at high risk of cardiovascular mortality or MACE, and it could be considered by local Heart Teams.

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial.

BACKGROUND: Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values ≥0.90 are associated with a low incidence of adverse events. OBJECTIVES: The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results. METHODS: The AQVA trial is an investigator-initiated, randomized, controlled, parallel-group clinical trial. A total of 300 patients (356 study vessels) undergoing PCI were randomized 1:1 to receive either QFR-based virtual PCI or angiography-based PCI (standard of care). The primary outcome was the rate of study vessels with a suboptimal post-PCI QFR value, which was defined as <0.90. Secondary outcomes were procedure duration, stent length/lesion, and stent number/patient. RESULTS: Overall, 38 (10.7%) study vessels missed the prespecified optimal post-PCI QFR target. The primary outcome occurred significantly more frequently in the angiography-based group (n = 26, 15.1%) compared with the QFR-based virtual PCI group (n = 12 [6.6%]; absolute difference = 8.5%; relative difference = 57%; P = 0.009). The main cause of a suboptimal result in the angiography-based group is the underestimation of a diseased segment outside the stented one. There were no significant differences among secondary endpoints, although stent length/lesion and stent number/patient were numerically lower in the virtual PCI group (P = 0.06 and P = 0.08, respectively), whereas procedure length was higher in the virtual PCI group (P = 0.06). CONCLUSIONS: The AQVA trial demonstrated the superiority of QFR-based virtual PCI over angiography-based PCI with regard to post-PCI optimal physiological results. Future larger randomized clinical trials that demonstrate the superiority of this approach in terms of clinical outcomes are warranted. (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR [AQVA]; NCT04664140).