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.).

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Complete Versus Culprit-Only Revascularization in Older Patients With ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis.

BACKGROUND: Complete revascularization is the standard treatment for patients with ST-segment-elevation myocardial infarction and multivessel disease. The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit (>1 year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in patients with ST-segment-elevation myocardial infarction ≥75 years of age enrolled in randomized clinical trials investigating complete versus culprit-only revascularization strategies. METHODS: PubMed, Embase, and the Cochrane database were systematically searched to identify randomized clinical trials comparing complete versus culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary end point was death, myocardial infarction, or ischemia-driven revascularization. The secondary end point was cardiovascular death or myocardial infarction. RESULTS: Data from 7 randomized clinical trials encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization) were analyzed. The median age was 79 [interquartile range, 77-83] years. Of the patients, 595 (34%) were female. Follow-up ranged from a minimum of 6 months to a maximum of 6.2 years (median, 2.5 [interquartile range, 1-3.8] years). Complete revascularization reduced the primary end point up to 4 years (hazard ratio, 0.78 [95% CI, 0.63-0.96]) but not at the longest available follow-up (hazard ratio, 0.83 [95% CI, 0.69-1.01]). Complete revascularization significantly reduced the occurrence of cardiovascular death or myocardial infarction at the longest available follow-up (hazard ratio, 0.76 [95% CI, 0.58-0.99]). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. CONCLUSIONS: In this individual patient data meta-analysis of older patients with ST-segment-elevation myocardial infarction and multivessel disease, complete revascularization reduced the primary end point of death, myocardial infarction, or ischemia-driven revascularization up to 4 years. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or myocardial infarction but not the primary end point. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022367898.

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.

Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial.

BACKGROUND: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy. METHODS: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial comparing a QFR-based with an FFR-based diagnostic strategy for patients with intermediate coronary stenosis. Enrolment was performed in 34 centres across 11 European countries. Patients aged 18 years or older with either chronic coronary syndrome or stabilised acute coronary syndrome, and with at least one intermediate non-culprit stenosis (40-90% diameter stenosis by visual estimate; referred to here as a study lesion), were randomly assigned (1:1) to the QFR-guided or the FFR-guided group. Randomisation was done using a concealed web-based system and was stratified by diabetes and presence of a left anterior descending coronary artery study lesion. The primary endpoint was a composite of death, myocardial infarction, and unplanned revascularisation at 12 months. The predefined non-inferiority margin was 3·4% and the primary analysis was performed in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03729739) and long-term follow-up is ongoing. FINDINGS: Between Nov 6, 2018, and July 21, 2023, 2000 patients were enrolled and randomly assigned to the QFR-guided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67·3 years (IQR 59·9-74·7); 1538 (76·9%) patients were male and 462 (23·1%) were female. Median follow-up time was 365 days (IQR 365-365). At 12 months, a primary endpoint event had occurred in 67 (6·7%) patients in the QFR group, and in 41 (4·2%) patients in the FFR group (hazard ratio 1·63 [95% CI 1·11-2·41]). The event proportion difference was 2·5% (90% two-sided CI 0·9-4·2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3·4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1·8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1·0%) patients in the QFR group and seven (0·7%) in the FFR group. One patient in the QFR group died in relation to the index procedure. INTERPRETATION: The results of the FAVOR III Europe trial do not support the use of QFR if FFR is available to guide revascularisation decisions in patients with intermediate coronary stenosis. This finding could have implications for current clinical guidelines recommending QFR for this purpose. FUNDING: Medis Medical Imaging Systems and Aarhus University.

Coronary artery disease management in older adults: revascularization and exercise training.

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Relationship between stent length and very long-term target lesion failure following percutaneous coronary intervention for ST-elevation myocardial infarction in the drug-eluting stents era: insights from the EXAMINATION-EXTEND study.

BACKGROUND: Little data exist on the relationship between total stent length (TSL) and cardiovascular outcomes at very-long follow-up in patients with ST-elevation myocardial infarction (STEMI) in the 2nd generation drug-eluting stents (DES) era. AIM: To analyze the relationship between TSL and 10-year target-lesion failure (TLF) in STEMI patients treated with percutaneous coronary intervention enrolled in the EXAMINATION-EXTEND. METHODS: The EXAMINATION-EXTEND was an extended-follow-up study of the EXAMINATION trial, which randomized 1:1 STEMI patients to receive DES or bare metal stent (BMS). The primary endpoint was TLF, defined as a composite of target lesion revascularization (TLR), target vessel myocardial infarction (TVMI), or definite/probable stent thrombosis (ST). Relationship between stent length and TLF was evaluated in the whole study group in a multiple-adjusted Cox regression model with TSL as a quantitative variable. Subgroup analysis was also performed according to stent type, diameter, and overlap. RESULTS: A total of 1,489 patients with a median TSL of 23 mm (Q1-Q318-35 mm) were included. TSL was associated with TLF at 10 years (adjusted HR per 5 mm increase of 1.07; 95% CI, 1.01-1.14; P = .02). This effect was mainly driven by TLR and was consistent regardless of stent type, diameter, or overlap. There was no significant relationship between TSL and TV-MI or ST. CONCLUSIONS: In STEMI patients, there is a direct relationship between TSL implanted in the culprit vessel and the risk of TLF at 10 years, mainly driven by TLR. The use of DES did not modify this association.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Clinical Outcome of FFR-Guided Revascularization Strategy of Coronary Lesions: The HALE-BOPP Study.

Background: Recently, questions around the efficacy and effectiveness of Fractional Flow Reserve (FFR) have arisen in various clinical settings. Methods: The Clinical Outcome of FFR-guided Revascularization Strategy of Coronary Lesions (HALE-BOPP) study is an investigator-initiated, multicentre, international prospective study enrolling patients who underwent FFR measurement on at least one vessel. In accordance with the decision-making workflow and treatment, the vessels were classified in three subgroups: (i) angio-revascularized, (ii) FFR-revascularized, (iii) FFR-deferred. The primary endpoint was the occurrence of target vessel failure (TVF, cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization). The analysis was carried out at vessel- and patient-level. Results: 1305 patients with 2422 diseased vessels fulfilled the criteria for the present analysis. Wire-related pitfalls and transient adenosine-related side effects occurred in 0.8% (95% CI: 0.4%-1.4%) and 3.3% (95% CI: 2.5%-4.3%) of cases, respectively. In FFR-deferred vessels, the overall incidence rate of TVF was 0.024 (95% CI: 0.019-0.031) lesion/year. After a median follow-up of 3.6 years, the occurrence of TVF was 6%, 7% and 11.7% in FFR-deferred, FFR-revascularized and angio-revascularized vessels, respectively. Compared to angio-revascularized vessels, FFR-guided vessels (both FFR-revascularized and FFR-deferred vessels) showed a lower TVF incidence rate lesion/year (0.029, 95% CI: 0.024-0.034 vs. 0.049, 95% CI: 0.040-0.061 respectively, p = 0.0001). The result was consistent after correction for confounding factors and across subgroups of clinical interest. The patient-level analysis confirmed the lower occurrence of TVF in negative-FFR vs. positive-FFR subgroups. Conclusions: In a large prospective observational study, an FFR-based strategy for the deferral of coronary lesions is a reliable and safe tool, associated with good outcomes. Clinical Trial Registration: NCT03079739.

Unsolved Questions in the Revascularization of Older Myocardial Infarction Patients with Multivessel Disease.

Background: In cardiology, the global phenomenon of population ageing poses new major challenges, ranging from more comorbid and frail patients to the presence of complex, calcified and multiple coronary lesions. Considering that elderly patients are under-represented in randomized clinical trials (RCT), the aim of this systematic review is to summarize the current knowledge on the revascularization of the elderly patient with myocardial infarction and multivessel coronary artery disease. Methods: A systematic review following PRISMA guidelines has been performed. The search was conducted on Pubmed (Medline), Cochrane library, Google Scholar and Biomed Central databases between January and February 2022. We selected the articles focusing on patients hospitalized for myocardial infarction (MI) with multivessel disease and aged 75 years or older. A total of 36 studies have been included. Results: Multivessel coronary artery disease is present in around 50-60% of older patients with MI. The in-hospital mortality rate of patients older than 75 years is double compared to their younger counterpart, and the most prevalent complications after revascularization are bleeding and renal failure. In the treatment of patients with ST elevation MI (STEMI), primary percutaneous coronary intervention should be the first choice over fibrinolysis. However, it is not clear whether this population would benefit from complete revascularization or not. In patients with non-ST elevation MI (NSTEMI), an invasive approach with either percutaneous coronary intervention or coronary artery bypass graft may be chosen, but a conservative strategy is also accepted. There are no data from large trials about the comparison of possible revascularization strategies in NSTEMI patients. Conclusions: This systematic review shows that this field of research lacks randomized clinical trials to guide revascularization strategy in older STEMI or NSTEMI patients with MI. New results are expected from ongoing trials.

Complete versus culprit-only strategy in older MI patients with multivessel disease.

AIMS: The revascularization strategy to pursue in older myocardial infarction (MI) patients with multivessel disease (MVD) is currently unknown. For this reason, while waiting for the results of dedicated trials, we sought to compare a complete versus a culprit-only strategy in older MI patients by merging data from four registries. METHODS AND RESULTS: The inclusion criteria for the target population of the present study were (i) age ≥ 75 years; (ii) MI (STE or NSTE); (iii) MVD; (iv) successful treatment of culprit lesion. Propensity scores (PS) were derived using logistic regression (backward stepwise selection, p < 0.2). The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) death, MI, and major bleeding. Multivariable adjustment included the PS and inverse probability of treatment weighting (IPTW). The Kaplan-Meier plots were weighted for IPT. Among 2087 patients included, 1362 (65%) received culprit-only treatment whereas 725 (35%) complete revascularization. The mean age was 81.5 years, while the mean follow-up was 419 ± 284 days. Seventy-four patients (10%) died in the complete group and 223 in the culprit-only one (16%). The adjusted cumulative 1-year mortality was 9.7% in the complete and 12.9% in the culprit-only group (adjusted HR: 0.67, 95% CI: 0.50-0.89). Complete revascularization was associated with lower incidence of CV death (adjusted HR: 0.68, 95% CI: 0.48-0.95) and MI (adjusted HR 0.67, 95% CI: 0.48-0.95). CONCLUSIONS: Culprit-only is the default strategy in older MI patients with MVD. In our analysis, complete revascularization was associated with lower all-cause and CV mortality and with a lower MI rate.

Shedding Light on Treatment Options for Coronary Vasomotor Disorders: A Systematic Review.

PURPOSE: Coronary vasomotor dysfunction embraces two specific clinical entities: coronary (micro)vascular spasm and microvascular dysfunction. The clinical manifestations of these entities are respectively called vasospastic angina (VSA) and microvascular angina (MVA). Over the years, these diseases have become more and more prominent and several studies aimed to investigate the best diagnostic and therapeutic strategies. Patients with coronary vasomotor disorders are often undertreated due to the absence of evidence-based guidelines. The purpose of this overview is to illustrate the various therapeutic options available for the optimized management of these patients. METHODS: A Medline search of full-text articles published in English from 1980 to April 2022 was performed. The main analyzed aspects of vasomotor disorders were treatment options. We also performed research on "Clinicaltrial.gov" for ongoing trials. CONCLUSION: Coronary (micro)vascular spasm and microvascular dysfunction are clinical entities characterized by high prevalence and clinical representation. Several therapeutic strategies, both innovative and established, are available to optimize treatment and improve the quality of life of these patients.

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.

Acute myocardial infarction and large coronary thrombosis in a patient with COVID-19.

This is a case report of a 60-year-old male, without any cardiovascular risk factor and no cardiac history admitted to hospital with a diagnosis of interstitial pneumonia caused by coronavirus disease 2019 (COVID-19). After 7 days, the blood tests showed a significant rise of inflammatory and procoagulant markers, along with a relevant elevation of high-sensitivity Troponin I. Electrocardiogram and transthoracic echocardiogram (TTE) were consistent with a diagnosis of infero-posterolateral acute myocardial infarction and the patient was transferred to the isolated Cath Lab for primary percutaneous coronary intervention (PCI). The angiography showed an acute massive thrombosis of a dominant right coronary artery without clear evidence of atherosclerosis. Despite the optimal pharmacological therapies and different PCI techniques, the final TIMI flow was 0/1 and after 3 hr the clinical condition evolved in cardiac arrest for pulseless electric activity. Acute coronary syndrome-ST-elevation myocardial infarction is a relevant complication of COVID-19. Due to high levels of proinflammatory mediators, diffuse coronary thrombosis could occur even in patients without cardiac history or comorbidities. This clinical case suggests that coronary thrombosis in COVID-19 patients may be unresponsive to optimal pharmacological (GP IIb-IIIa infusion) and mechanical treatment (PCI).

Comparison of quantitative flow ratio, Pd/Pa and diastolic hyperemia-free ratio versus fractional flow reserve in non-culprit lesion of patients with non ST-segment elevation myocardial infarction.

OBJECTIVES: To investigate the correlation between quantitative flow ratio (QFR), Pd/Pa, diastolic hyperemia-free ratio (DFR) and fractional flow reserve (FFR, gold standard) in non-culprit lesion (NCL) of patients with non ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND: The non-hyperemic pressure ratio (NHPR) and the angiography-based indexes have been developed to overcome the limitation of the use of the FFR. METHODS: Between January and December 2019, 184 NCL from 116 NSTEMI patients underwent physiologic assessment and were included in the study. NCLs were investigated with QFR, Pd/Pa, DFR, and FFR. Mean values of QFR, Pd/Pa, DFR and FFR were 0.85 ± 0.10, 0.92 ± 0.07, 0.93 ± 0.05 and 0.84 ± 0.07, respectively. RESULTS: DFR and FFR showed a good correlation (r = 0.76). Bland and Altman plot showed a mean difference of 0.080. DFR Diagnostic accuracy was 88%. The area under the ROC curve (AUC) for DFR was 0.946 (95%CI 0.90-0.97, p = .0001). Similar findings were reported for Pd/Pa (r = 0.73; mean difference 0.095, diagnostic accuracy 84%, AUC 0.909 [95%CI 0.85-0.94, p = .0001]) and QFR (r = 0.68; mean difference 0.01; diagnostic accuracy 88%, AUC 0.964 [95% CI 0.91-0.98, p = .0001]). FFR, QFR, Pd/Pa and DFR identified 31%, 32%, 30% and 32% potentially flow-limiting lesions, respectively. CONCLUSIONS: In NSTEMI patients, QFR, Pd/Pa and DFR showed equivalence as compared to gold standard FFR in the discrimination of non-culprit lesions requiring revascularization.

Over time relationship between platelet reactivity, myocardial injury and mortality in patients with SARS-CoV-2-associated respiratory failure.

The aim of this study (NCT04343053) is to investigate the relationship between platelet activation, myocardial injury, and mortality in patients affected by Coronavirus disease 2019 (COVID-19). Fifty-four patients with respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were enrolled as cases. Eleven patients with the same clinical presentation, but negative for SARS-CoV-2 infection, were included as controls. Blood samples were collected at three different time points (inclusion [T1], after 7 ± 2 days [T2] and 14 ± 2 days [T3]). Platelet aggregation by light transmittance aggregometry and the circulating levels of soluble CD40 ligand (sCD40L) and P-selectin were measured. Platelet biomarkers did not differ between cases and controls, except for sCD40L which was higher in COVID-19 patients (p = .003). In COVID-19 patients, P-selectin and sCD40L levels decreased from T1 to T3 and were higher in cases requiring admission to intensive care unit (p = .004 and p = .008, respectively). Patients with myocardial injury (37%), as well as those who died (30%), had higher values of all biomarkers of platelet activation (p < .05 for all). Myocardial injury was an independent predictor of mortality. In COVID-19 patients admitted to hospital for respiratory failure, heightened platelet activation is associated with severity of illness, myocardial injury, and mortality.ClinicalTrials.gov number: NCT04343053.

Complete revascularization reduces cardiovascular death in patients with ST-segment elevation myocardial infarction and multivessel disease: systematic review and meta-analysis of randomized clinical trials.

AIMS: The aim of this work was to investigate the prognostic impact of revascularization of non-culprit lesions in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease by performing a meta-analysis of available randomized clinical trials (RCTs). METHODS AND RESULTS: Data from six RCTs comparing complete vs. culprit-only revascularization in STEMI patients with multivessel disease were analysed with random effect generic inverse variance method meta-analysis. The endpoints were expressed as hazard ratio (HR) with 95% confidence interval (CI). The primary outcome was cardiovascular death. Main secondary outcomes of interest were all-cause death, myocardial infarction (MI), and repeated coronary revascularization. Overall, 6528 patients were included (3139 complete group, 3389 culprit-only group). After a follow-up ranging between 1 and 3 years (median 2 years), cardiovascular death was significantly reduced in the group receiving complete revascularization (HR 0.62, 95% CI 0.39-0.97, I2 = 29%). The number needed to treat to prevent one cardiovascular death was 70 (95% CI 36-150). The secondary endpoints MI and revascularization were also significantly reduced (HR 0.68, 95% CI 0.55-0.84, I2 = 0% and HR 0.29, 95% CI 0.22-0.38, I2 = 36%, respectively). Needed to treats were 45 (95% CI 37-55) for MI and 8 (95% CI 5-13) for revascularization. All-cause death (HR 0.81, 95% CI 0.56-1.16, I2 = 27%) was not affected by the revascularization strategy. CONCLUSION: In a selected study population of STEMI patients with multivessel disease, a complete revascularization strategy is associated with a reduction in cardiovascular death. This reduction is concomitant with that of MI and the need of repeated revascularization.

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.