Future of invasive and non-invasive hemodynamic assessment for coronary artery disease management.

Coronary artery disease represents a global health challenge. Accurate diagnosis and evaluation of hemodynamic parameters are crucial for optimizing patient management and outcomes. Nowadays a wide range of both non-invasive and invasive methods are available to assess the hemodynamic impact of both epicardial coronary stenosis and vasomotor disorders. In fact, over the years, important developments have reshaped the nature of both invasive and non-invasive diagnostic techniques, and the future holds promises for further innovation and integration. Non-invasive techniques have progressively evolved and currently a broad spectrum of methods are available, from cardiac magnetic resonance imaging with pharmacological stress and coronary computed tomography (CT) to the newer application of FFR-CT and perfusion CT. Invasive methods, on the contrary, have developed to a full-physiology approach, able not only to identify functionally significant lesions but also to evaluate microcirculation and vasospastic disease. The aim of this review is to summarize the current state-of-the-art of invasive and non-invasive hemodynamic assessment for CAD management.

Effect of physical activity on left ventricular dimensions and function after myocardial infarction: a systematic review.

INTRODUCTION: Coronary artery disease is the major pathophysiological driver of ventricular remodeling. A multimodal intervention is the key strategy to promote a positive left ventricular remodeling with improvement in volumes and ejection fraction, known as "reverse remodeling." The aim of this review was to highlight the effect of physical activity (PA) on echocardiographic and cardiac magnetic resonance parameters of left ventricle in patients with myocardial infarction. EVIDENCE ACQUISITION: We performed a systematic review of the literature to summarize current evidence about the efficacy (in terms of improvement in chamber dimensions, ejection fraction, speckle tracking and diastolic function) of physical activity in patients with myocardial infarction, supported by echocardiographic or magnetic resonance data. Articles were searched in Pubmed, Cochrane Library and Biomed Central. EVIDENCE SYNTHESIS: Only papers published in English and in peer-reviewed journals up to November 2022 were selected. After an initial evaluation, 1029 records were screened; the literature search identified 20 relevant articles. From this data, some PA protocols appeared to favor left ventricular reverse remodeling. CONCLUSIONS: PA provides beneficial effects on left ventricular parameters analyzed by echocardiography and cardiac magnetic resonance.

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.

1,3,8-Triazaspiro[4.5]decane Derivatives Inhibit Permeability Transition Pores through a FO-ATP Synthase c Subunit Glu119-Independent Mechanism That Prevents Oligomycin A-Related Side Effects.

Permeability transition pore (PTP) molecular composition and activity modulation have been a matter of research for several years, especially due to their importance in ischemia reperfusion injury (IRI). Notably, c subunit of ATP synthase (Csub) has been identified as one of the PTP-forming proteins and as a target for cardioprotection. Oligomycin A is a well-known Csub interactor that has been chemically modified in-depth for proposed new pharmacological approaches against cardiac reperfusion injury. Indeed, by taking advantage of its scaffold and through focused chemical improvements, innovative Csub-dependent PTP inhibitors (1,3,8-Triazaspiro[4.5]decane) have been synthetized in the past. Interestingly, four critical amino acids have been found to be involved in Oligomycin A-Csub binding in yeast. However, their position on the human sequence is unknown, as is their function in PTP inhibition. The aims of this study are to (i) identify for the first time the topologically equivalent residues in the human Csub sequence; (ii) provide their in vitro validation in Oligomycin A-mediated PTP inhibition and (iii) understand their relevance in the binding of 1,3,8-Triazaspiro[4.5]decane small molecules, as Oligomycin A derivatives, in order to provide insights into Csub interactions. Notably, in this study we demonstrated that 1,3,8-Triazaspiro[4.5]decane derivatives inhibit permeability transition pores through a FO-ATP synthase c subunit Glu119-independent mechanism that prevents Oligomycin A-related side effects.

Multi-domain lifestyle intervention in older adults after myocardial infarction: rationale and design of the PIpELINe randomized clinical trial.

BACKGROUND: Traditional cardiac rehabilitation (CR) is effective in improving physical performance and prognosis after myocardial infarction (MI). Anyway, it is not consistently recommended to older adults, and its attendance rate is low. Previous studies suggested that alternative, early and tailored exercise interventions are feasible and effective in improving physical performance in older MI patients. Anyway, the demonstration that they are associated also with a significant reduction of hard endpoints is lacking. AIM: To describe rationale and design of the "Physical activity Intervention in Elderly patients with myocardial Infarction" (PIpELINe) trial. METHODS: The PIpELINe trial is a prospective, randomized, multicentre study with a blinded adjudicated evaluation of the outcomes. Patients aged ≥ 65 years, admitted to hospital for MI and with a low physical performance one month after discharge, as defined as short physical performance battery (SPPB) value between 4 and 9, will be randomized to a multi-domain lifestyle intervention (including dietary counselling, strict management of cardiovascular and metabolic risk factors, and exercise training) or health education. The primary endpoint is the one-year occurrence of the composite of cardiovascular death or re-hospitalization for cardiovascular causes. RESULTS: The recruitment started in March 2020. The estimated sample size is 456 patients. The conclusion of the enrolment is planned for mid-2023. The primary endpoint analysis will be available for the end of 2024. CONCLUSIONS: The PIpELINe trial will show if a multi-domain lifestyle intervention is able to reduce adverse events in older patients with reduced physical performance after hospitalization for MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT04183465.

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).

Neural interfaces to monitor Interventional Cardiologists' mental workload: GAME-ON SAGA.

BACKGROUND: Interventional cardiologists' mental workload may impact on their performance as well as on patients' outcome. Nevertheless, little attention is paid to the monitoring and optimization of their mental status. Electroencephalogram (EEG)-based neural-interfaces can estimate mental fatigue and sleepiness through spectral analysis techniques and the amplitude of alpha waves is a widely validated indicator of mental engagement's level. METHODS: The present study aims to describe mental fatigue and sleepiness through variation of psychometrics and neurometrics during a work shift in a population of 7 interventional cardiologists. Neurometrics have been acquired at the beginning of the shift, before and after each procedure performed during 127 valid Alpha Attenuation Protocols (AAP), a practical test to quantify sleepiness measuring alpha power during 2 cycle of eye opening/closing protocol. We collected alpha waves' power measures obtained during resting condition (AA Coefficient-eyes open [AAC-eo], AAC-eyes closed [AAC-ec] and AAC-mean), related to fatigue, and AAC-ec/AAC-eo (AAC-ratio), related to sleepiness. RESULTS: From a two-months observation, the first interesting preliminary results emerged: 1) AAC-mean showed an upward trend during the working day, reflecting an increase in mental fatigue (P=0.01); 2) population-level psychometrics trend confirms the same tendency described by neurometrics, possibly reflecting a reduced awareness of the operator of his/her actual mental status. CONCLUSIONS: Developing a low cost and high feasibility device to monitor and analyze operator's mental engagement level could be extremely appealing, considering the lack of data in literature for interventional disciplines and recent technology developments.

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.

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).

Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.

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.