Ischemic heart disease, the main clinical expression of atherosclerotic cardiovascular disease, remains a leading global health challenge. While coronary angiography is the gold standard for anatomical assessment, it has limitations in determining the functional relevance of coronary lesions. Invasive physiological techniques - such as Fractional Flow Reserve (FFR) and its resting equivalents (iFR, RFR) - enable an objective hemodynamic evaluation, particularly useful in intermediate or multivessel diseases. Emerging imaging-derived tools, including QFR and FFRCT, offer less invasive alternatives that may play an increasing role in the upstream decision-making process. This article provides a practical overview of the available modalities, their physiological rationale, and their integration into interventional practice.

Background/Objectives: Fractional flow reserve (FFR) is the reference standard for assessing the functional significance of intermediate coronary stenoses and guiding revascularization. Although a universal ischemic threshold is applied to all epicardial vessels, potential physiological differences between coronary territories remain insufficiently explored. The aim of this study was to evaluate whether the functional significance of intermediate coronary stenoses differs according to coronary artery and to assess the clinical outcomes of FFR-guided deferral across coronary territories. Methods: This single-center retrospective study included patients who underwent single-vessel FFR assessment for angiographically intermediate lesions between 2019 and 2022. Patients with left main disease or multivessel physiological assessment were excluded. Clinical characteristics, FFR values, and long-term outcomes were analyzed according to the investigated coronary artery. Major adverse cardiovascular events (MACE) were defined as a composite of death, myocardial infarction, and urgent revascularization. Results: A total of 310 patients (corresponding to 310 coronary arteries) were included: 211 LAD, 68 RCA, and 31 LCX lesions. Overall, 18.7% of lesions had a positive FFR (≤0.80). The only variable identified in univariable analysis as being associated with FFR positivity was the coronary artery evaluated (p < 0.001). Positive FFR values were observed in 24.6% of LAD lesions, compared with 8.8% in the RCA and none in the LCX. Among patients with negative FFR for whom revascularization was deferred, five-year MACE-free survival was similar across coronary territories (p = 0.12). Conclusions: The functional significance of intermediate coronary stenoses varies according to the coronary territory, with LAD lesions more frequently reaching ischemic thresholds. However, deferral of revascularization based on negative FFR is associated with favorable long-term outcomes across all vessels, supporting a vessel-specific physiological interpretation of coronary stenoses.

Background To chart the evolution of the CTO-PCI landscape in Belgium and Luxembourg, the Belgian Working Group on Chronic Total Occlusions (BWGCTO) was established in 2016. Methods Between May 2016 and December 2019, patients undergoing a CTO-PCI treatment were prospectively and consecutively enrolled. Twenty-one centres in Belgium and one in Luxembourg participated. Individual operators had mixed levels of expertise in treating CTO lesions. Demographic, angiographic, procedural parameters and incidence of major adverse cardiac and cerebrovascular events (MACCE) were systematically registered. Results Over a four-year enrolment period, 1832 procedures were performed in 1733 patients achieving technical success in 1474 cases (80%), with an in-hospital MACCE rate of 2.3%. Fifty-nine (3%) cases were re-attempt procedures of which 41 (69%) were successful. High-volume centres treated more complex lesions (mean J-CTO score: 2.15 +/- 1.21) as compared to intermediate (mean J-CTO score: 1.72 +/- 1.23;p < 0.001) and low-volume centres (mean J-CTO score: 0.99 +/- 1.21;p = 0.002). Despite this, success rates did not differ between centres (p = 0.461). Overall success rates did not differ over time (p = 0.810). High-volume centres progressively tackled more complex CTOs while keeping success rates stable. In all centres, the most applied strategy was antegrade wire escalation (83%). High-volume centres more often successfully applied antegrade dissection and re-entry and retrograde techniques in lesions with higher complexity. Conclusion With variable experience levels, operators treated CTOs with high success and relatively few complications. Although AWE remains the most used technique, it is paramount for operators to be skilled in all contemporary techniques in order to be successful in more complex CTOs.

Dobutamine stress echocardiography (DSE) is sensitive but subjective diagnostic tool to detect inducible ischemia. Nowadays, speckle tracking allows an objective quantification of regional wall function. We aimed to investigate the feasibility and accuracy of global (GLS) and regional longitudinal strain (RLS) during DSE to detect significant coronary stenosis (SCS). We conducted a prospective observational multicenter study including patients undergoing DSE for suspected SCS. 50 patients with positive DSE underwent coronary angiography. Besides visual regional wall motion score index (WMSI), GLS and RLS were determined at rest and at peak stress by Automated Function Imaging. DSE GLS feasibility was 96%. Among 35 patients with SCS, 12 patients were affected by multivessel disease, 18 had stenosis of left anterior descending artery (LAD), 18 of left circumflex (LCX) and 15 of right coronary artery (RCA). At peak stress, both GLS reduction (p = 0.037) and WMSI worsening (p = 0.04) showed significant agreement with coronary angiography for detecting SCS. When single lesion was considered, peak stress GLS and LAD RLS were lower in the obstructed LAD regions than in normo-perfused territories (17.4 ± 5.5 vs. 20.5 ± 4.4%, p = 0.03; 17.1 ± 7.6 vs. 21.6 ± 5.5%, p < 0.02, respectively). Furthermore, the addition of RLS to regional WMSI was able to improve accuracy in LAD SCS prediction (AUC 0.68, p = 0.037). Conversely, in presence of LCX or RCA SCS, LS was less accurate than WMSI at peak stress. In conclusion, DSE strain analysis is feasible and may improve prediction of LAD SCS, whereas regional WMSI assessment performs better in presence of SCS of LCX and RCA.

Aims The current study assessed the impact of COVID-19-related public containment measures (i.e. lockdown) on the ST elevation myocardial infarction (STEMI) epidemic in Belgium. Methods and results Clinical characteristics, reperfusion therapy modalities, COVID-19 status and in-hospital mortality of consecutive STEMI patients who were admitted to Belgian hospitals for percutaneous coronary intervention (PCI) were recorded during a three-week period starting at the beginning of the lockdown period on 13 March 2020. Similar data were collected for the same time period for 2017-2019. An evaluation of air quality revealed a 32% decrease in ambient NO(2)concentrations during lockdown (19.5 mu g/m(3) versus 13.2 mu g/m(3),p < .001). During the three-week period, there were 188 STEMI patients admitted for PCI during the lockdown versus an average 254 STEMI patients before the lockdown period (incidence rate ratio = 0.74,p = .001). Reperfusion strategy was predominantly primary PCI in both time periods (96% versus 95%). However, there was a significant delay in treatment during the lockdown period, with more late presentations (>12 h after onset of pain) (14% versus 7.6%,p = .04) and with longer door-to-balloon times (median of 45 versus 39 min,p = .02). Although the in-hospital mortality between the two periods was comparable (5.9% versus 6.7%), 5 of the 7 (71%) COVID-19-positive STEMI patients died. Conclusion The present study revealed a 26% reduction in STEMI admissions and a delay in treatment of STEMI patients. Less exposure to external STEMI triggers (such as ambient air pollution) and/or reluctance to seek medical care are possible explanations of this observation.

Several clinical reports indicate that the use of amphetaminic anorectic drugs or ergot derivatives could cause valvular heart disease (VHD). We sought to investigate whether valvular lesions develop in response to long-term oral administration of these drugs and to identify drug-targeted biological processes that may lead to VHD. Treatment of New Zealand White rabbits with pergolide, dexfenfluramine, or high-dose serotonin for 16 weeks induced valvular alterations characterized by extracellular matrix remodeling. Transcriptome profiling of tricuspid valves using RNA sequencing revealed distinct patterns of differentially expressed genes (DEGs) that clustered according to the different treatments. Genes that were affected by the three treatments were functionally enriched for reduced cell metabolism processes. The two drugs yielded more changes in gene expression than serotonin and shared most of the DEGs. These DEGs were mostly enriched for decreased biosynthetic processes, increased cell-matrix interaction, and cell response to growth factors, including TGF-β, which was associated with p38 MAPK activation. Treatment with pergolide specifically affected genes involved in homeostasis, which was corroborated by the activation of the master regulator of cell energy homeostasis, AMPK-α, as well as decreased levels of metabolism-related miR-107. Thus, both pergolide and dexfenfluramine may cause VHD through valve metabolic reprogramming and matrix remodeling.

Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P&lt;0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P&lt;0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.

representing deformation of myofibers during systole, is more reproducible and has previously been shown to provide superior risk prediction compared with LVEF in patients with both symptomatic and asymptomatic severe AS (3).The rationale for aortic valve intervention in patients with moderate AS and LV dysfunction stems from the high event rate in these patients.Our study shows that patients with the highest risk for mortality are those with more abnormal GLS.The TAVR UN-LOAD (Transcatheter Aortic Valve Replacement to Unload the Left Ventricle in Patients With AdvancedHeart Failure) study is a randomized study investigating whether symptomatic patients with moderate AS and LVEF <50% benefit from TAVR compared with medical therapy (4).The hypothesis is that relieving the excess afterload of moderate AS in patients with LV impairment may alleviate symptoms and improve prognosis.A hypothesis generated from our data is that intervention may more likely benefit those patients at greatest risk with more abnormal GLS.

Clinical evidence indicates that innate immune cells may contribute to acute coronary syndrome (ACS). Our prospective study aimed at investigating the association of neutrophil phenotypes with ACS. 108 patients were categorized into chronic stable coronary artery disease (n = 37), unstable angina (UA) (n = 19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n = 25), and ST-Elevation Myocardial Infarction (STEMI) (n = 27). At the time of inclusion, blood neutrophil subpopulations were analysed by flow cytometry. Differential blood cell count and plasma levels of neutrophilic soluble markers were recorded at admission and, for half of patients, at six-month follow-up. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio than stable and UA patients (p < 0.0001), which normalized at six-month post-MI. Atypical low-density neutrophils were detected in the blood of the four patient groups. STEMI patients were characterized by elevated percentages of band cells compared to the other patients (p = 0.019). Multivariable logistic regression analysis revealed that plasma levels of total myeloperoxidase was associated with STEMI compared to stable (OR: 1.434; 95% CI: 1.119–1.837; P < 0.0001), UA (1.47; 1.146–1.886; p = 0.002), and NSTEMI (1.213; 1.1–1.134; p = 0.0001) patients, while increased neutrophil side scatter (SSC) signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033–14.184; p = 0.045). Hence, changes in neutrophil phenotype are concomitant to ACS.

The onset of symptoms is a critical point in the natural history of aortic stenosis (AS) that often occurs late in the disease course, and it represents the cardinal indication for aortic valve replacement (AVR) [(1)][1]. To date, the clinical outcome significance of myocardial replacement fibrosis