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).

Ten-year prognostic impact of target versus non-target vessel failure after STEMI. Insight from the EXAMINATION-EXTEND trial.

INTRODUCTION AND OBJECTIVES: After ST-segment myocardial infarction (STEMI), the impact of different adverse events on prognosis remains unknown. We aimed to assess very long-term predictors of patient-oriented composite endpoints (POCE) and investigate whether the occurrence of target vessel failure (TVF) vs a non-TVF event as the first event could potentially influence subsequent outcomes. METHODS: The EXAMINATION-EXTEND trial randomized STEMI patients to receive either an everolimus-eluting stent or a bare-metal stent. The follow-up period was 10 years. Predictors of POCE (a composite of all-cause death, any myocardial infarction, or any revascularization) were evaluated in the overall study population. The patients were stratified based on the type of first event (TVF-first vs non-TVF-first) and were compared in terms of subsequent POCE. TVF was defined as a composite of cardiac death, TV myocardial infarction, or TV revascularization. RESULTS: Out of the 1498 enrolled patients, 529 (35.3%) experienced a POCE during the 10-year follow-up. Independent predictors of POCE were age, diabetes mellitus, previous myocardial infarction, peripheral arterial disease, and multivessel coronary disease. The first event was a TVF in 296 patients and was a non-TVF in 233 patients. No significant differences were observed between TVF-first and non-TVF-first patients in terms of subsequent POCE (21.7% vs 39.3%, time ratio 1.79; 95%CI, 0.87-3.67;P=.12) or its individual components. CONCLUSIONS: At the 10-year follow-up, approximately one-third of STEMI patients had experienced at least 1 POCE. Independent predictors of these events were age, diabetes, and more extensive atherosclerotic disease. The occurrence of a TVF or a non-TVF as the first event did not seem to influence subsequent outcomes. TRIAL REGISTRATION NUMBER: NCT04462315.

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).

Functional (Re)Development of SYNTAX Score II 2020: Predictive Performance and Risk Assessment.

The present study investigates the prognostic value of the Syntax Score II 2020 corrected for flow-limiting lesions and its ability to better address treatment by benefit prediction among patients with left main or multivessel disease. We analyzed 1274 patients from the HALE-BOPP cohort and integrated the Syntax Score II 2020 with the result of the fractional flow reserve (FFR) evaluation. Absolute risk difference (ARD) between surgical and percutaneous revascularization was calculated for anatomic and functional Syntax Score II 2020 predicted mortality. The ARD allowed to stratify the population into two large categories: "coronary artery bypass graft (CABG) better" with ARD ≥ 4.5% and "CABG-percutaneous coronary intervention (PCI) equipoise" with ARD < 4.5%. The mean global anatomical Syntax Score was 15.5 ± 9.2, whereas the functional one was 9.5 ± 10 (p < 0.01). Using the anatomic Syntax Score II 2020, 881 patients had a CABG-PCI equipoise. This number increased to 1041 after considering only flow-limiting lesions by FFR (p < 0.001); therefore, 40% of CABG better patients were reclassified within the CABG-PCI equipoise category. Kaplan-Maier curves showed similar actual survival rates for patients originally with CABG-PCI equipoise and those reclassified, in both cases higher than those from CABG better patients (p < 0.01). The integration between Syntax Score II 2020 and physiology is feasible, and merging clinical, anatomic and functional data allows for better risk prediction and therapeutic guidance.

Clinical outcomes following different stenting techniques for coronary bifurcation lesions: a systematic review and network meta-analysis of randomised controlled trials.

BACKGROUND: Controversy still exists regarding the optimal treatment of coronary bifurcation lesions. AIMS: We aimed to analyse the evidence from randomised controlled trials (RCTs) to compare outcomes following different bifurcation stenting techniques. METHODS: We systematically searched for RCTs comparing different techniques published up to July 2022. We then conducted a pairwise meta-analysis to compare outcomes between provisional stenting (PS) versus upfront 2-stent techniques. Moreover, we performed a network meta-analysis (NMA) to compare all strategies with each other. The primary endpoint was major adverse cardiac events (MACE). RESULTS: Twenty-four RCTs (6,890 patients) analysed PS, T-stenting, double-kissing (DK)-crush, crush, or culotte stenting. The pairwise meta-analysis did not reveal a significant difference between the PS and 2-stent techniques. However, the prespecified sensitivity analysis, which included RCTs exclusively enrolling patients with true bifurcation lesions, showed a lower rate of MACE following 2-stent techniques, and meta-regression indicated that a longer side branch lesion was associated with a greater benefit from the 2-stent strategy, which was the most apparent in RCTs with a mean lesion length >11 mm. NMA revealed that DK-crush was associated with the lowest MACE rate (odds ratio 0.47, 95% confidence interval: 0.36-0.62; p<0.01; PS as a reference). CONCLUSIONS: Overall, 2-stent techniques were not significantly better than PS in terms of clinical outcomes. However, the results of the sensitivity analysis suggested that there might be a benefit of a 2-stent approach in selected patients with true bifurcation lesions, especially in the case of long side branch lesions. An NMA revealed that DK-crush was associated with the lowest event rates when compared with other techniques.

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).

Impact of trans-stent gradient on outcome after PCI: results from a HAWKEYE substudy.

To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR ≥ 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR ≥ 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR < 0.90, TSG = 0 (n = 37, 4.9%); G4: QFR < 0.90, TSG > 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p < 0.01). ROC analysis showed an AUC of 0.74 (95% CI: 0.67 to 0.80; p < 0.001). TSG > 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77-4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90).

Procalcitonin Predicts Bacterial Infection, but Not Long-Term Occurrence of Adverse Events in Patients with Acute Coronary Syndrome.

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09-6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97-0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

The Combination of Chest Computed Tomography and Standard Electrocardiogram Provides Prognostic Information and Pathophysiological Insights in COVID-19 Pneumonia.

AIMS: Several studies have unveiled the great heterogeneity of COVID-19 pneumonia. Identification of the "vascular phenotype" (involving both pulmonary parenchyma and its circulation) has prognostic significance. Our aim was to explore the combined role of chest computed tomography (CT) scan and electrocardiogram (ECG) at hospital admission in predicting short-term prognosis and to draw pathophysiological insights. METHODS AND RESULTS: We analyzed the chest CT scan and ECG performed at admission in 151 consecutive COVID-19 patients admitted between 20 March and 4 April 2020. All-cause mortality within 30 days was the primary endpoint. Median age was 71 years (IQR: 62-76). Severe pneumonia was present in 25 (17%) patients, and 121 (80%) had abnormal ECG. During a median follow-up of 7 days (IQR: 4-13), 54 (36%) patients died. Deceased patients had more severe pneumonia than survivors did (80% vs. 64%, p = 0.044). ECG in deceased patients showed more frequently atrial fibrillation/flutter (17% vs. 6%, p = 0.039) and acute right ventricular (RV) strain (35% vs. 10%, p < 0.001), suggesting the "vascular phenotype". ECG signs of acute RV strain (HR 2.46, 95% CIs 1.36-4.45, p = 0.0028) were independently associated with all-cause mortality in multivariable analysis, and in the likelihood ratio test, showed incremental prognostic value over chest CT scan, age, and C-reactive protein. CONCLUSIONS: Combining chest CT scan and ECG data improves risk stratification in COVID-19 pneumonia by identifying a distinctive phenotype with both parenchymal and vascular damage of the lung. Patients with severe pneumonia at chest CT scan plus ECG signs of acute RV strain have an extremely poor short-term prognosis.

Peak atrial longitudinal strain is predictive of atrial fibrillation in patients with chronic obstructive pulmonary disease and coronary artery disease.

BACKGROUND: The peak atrial longitudinal strain (PALS) has been validated in the prediction of atrial fibrillation (AF) in the general population. If this finding can be applied to patients with chronic obstructive pulmonary disease (COPD) and concomitant coronary artery disease (CAD) is unknown. METHODS AND RESULTS: We analyzed two different study populations of patients with COPD and acute CAD in SCAP trial (Clinical trial.org identifier NCT02324660) and COPD and stable CAD in the NATHAN-NEVER trial (clinical trial.org identifier NCT02519608). All patients enrolled underwent spirometry and clinical specialistic evaluation to test COPD diagnosis. During the index evaluation, all patients underwent echocardiography. The primary endpoint of the study was the occurrence of AF. Overall, 175 patients have been enrolled. PALS was significantly lower in patients with COPD compared to patients without COPD (26% ± 8% vs. 30% ± 8% for PALS4CV, P = .003). After a mean follow-up of 49 ± 15 months, 26 patients experienced at least one episode of AF. At multivariable analysis, only PALS (HR: 0.92, 95% CI: 0.86-0.98, P = .014) resulted as an independent predictor of AF in COPD patients with CAD, with the best cutoff value of 25.5% (sensitivity 87% and specificity 70%). CONCLUSION: The present study confirmed a high incidence of AF events in COPD patients and that PALS is altered and able to independently predict AF in a specific cohort of patients with CAD and COPD. This study points out the need to integrate PALS measurement in the echocardiographic workup of all COPD patients, to early identify those at high risk of AF development.

[Primary percutaneous coronary angioplasty in octogenarians and over. The experience of a high-volume hub center]. / L'angioplastica primaria nei grandi anziani. Esperienza di un centro di riferimento ad alto volume.

BACKGROUND: Primary coronary angioplasty (PCI) is the reference treatment for acute ST-elevation myocardial infarction (STEMI), but elderly patients (>80 years) are underrepresented in clinical trials that support the guideline recommendations. The aim of this study was to assess in-hospital and 1-year total mortality of octogenarians and over treated with primary PCI at a large referral center. METHODS: Single-center analysis of all consecutive patients with STEMI aged ≥80 years treated with primary PCI between 2010 and 2016. Patients were divided into three age groups: 80-84 years, 85-89 years, and ≥90 years. For each group, clinical and procedural data, in-hospital and 1-year mortality were analyzed. RESULTS: During the study period, 2127 patients were treated with primary PCI, 463 of them (22%) were aged ≥80 years (mean 85 ± 3 years). Of these, 51% were aged ≥80 and ≤84 years, 32% were aged ≥85 and ≤89 years, and 17% were aged ≥90 years. An increase of female gender prevalence and a decrease of risk factor prevalence as well as PCI success were observed with ageing. In-hospital and 1-year total death rates increased with age as well, mainly after 85 years. CONCLUSIONS: Primary PCI for STEMI among octogenarians and over is feasible and has good procedural results. Nevertheless, in-hospital and 1-year total mortality is high, with a marked deterioration after 85 years of age, when it doubles. Considering population demographics, specific studies in this very elderly population are needed to improve treatment and outcomes.

[Early invasive strategy (<24 h) in high-risk non-ST-elevation acute coronary syndrome: when the guideline recommendations need to be contextualized]. / Strategia invasiva precoce (<24 h) nelle sindromi coronariche acute senza sopraslivellamento del tratto ST ad alto rischio, ovvero quando le raccomandazioni delle linee guida dovrebbero essere contestualizzate.

The advantages of an early invasive strategy in non-ST-elevation acute coronary syndromes (NSTE-ACS) are well documented. Less clear is the ideal time to perform it (within 24 h, within 72 h, or during hospitalization after positive non-invasive testing for ischemia). In particular, the class IA recommendation for coronary angiography within 24 h in patients with high-risk NSTE-ACS is controversial. Randomized clinical trials and meta-analyses show neutral effects on mortality, while significant positive results are observed only for secondary outcomes (mainly ischemic recurrences). Favorable effects on major cardiovascular events are reported only in the subgroup analysis of a single randomized trial (TIMACS) or in several trials included in the meta-analyses. Thus, these results are far from conclusive and should stimulate new randomized clinical studies to support them. In fact, the logistical implications that this recommendation implies deserve stronger evidence. It is clear that all patients with NSTE-ACS, especially if high-risk, should have the opportunity to undergo a coronary angiogram during hospitalization. However, in the real world, the strict timeline of the international guidelines may be difficult to follow. Therefore, indications that take into account resource availability and the organizational context should be developed. Several regional indications suggest that even in high-risk patients the 24 h time limit for the invasive strategy should not be mandatory, but timing of angiography should be calibrated on clinical presentation and logistical resources, without any a priori automatism.

Diagnostic imaging for acute abdominal pain in an Emergency Department in Italy.

Imaging plays a key role in the diagnostic work-up of patients with non-traumatic acute abdominal pain (AAP) in emergency department (ED). We aimed to evaluate the use and diagnostic performance of imaging techniques in adult patients with AAP in an ED in Italy. Patients with non-traumatic AAP admitted at the ED of S. Orsola-Malpighi University Hospital of Bologna (Italy) from the 1st to the 30th November 2016 were included. Demographic and clinical data, data on radiological procedures and discharge diagnosis were collected. Sensitivity and specificity for detecting acute diseases were assessed using the discharge diagnosis from the ED as reference standard. Of the 578 patients (female 52.8%, mean age 51.3 years) admitted to the ED for AAP, 433 (74.9%) underwent abdominal imaging. The most frequent techniques used were abdominal plain radiography and ultrasonography (US), performed in 38.4% and 37.9% of patients, respectively, followed by computed tomography (CT) in 28% of patients. Plain radiography yielded a sensitivity of 28% and specificity of 91.1%; the sensitivity increased to 79.4% in patients with small bowel obstruction. Ultrasonography's sensitivity and specificity were 61.8% and 98.4%, respectively; the sensitivity of US reached 85.2% and 90% in patients with acute cholecystitis/biliary colic and urolithiasis, respectively. The sensitivity and specificity of CT were 87.8% and 92.9%, respectively. Plain radiography is still overused in the diagnostic work-up of AAP in ED in Italy, despite its unsatisfactory sensitivity. Ultrasonography and CT has a higher sensitivity and should be used as first-level imaging in most patients.