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Traditionally, coronary angiography was restricted to visual estimation of contrast-filled lumen in coronary obstructive diseases. Over the previous decades, considerable development has been made in quantitatively analyzing coronary angiography, significantly improving its accuracy and reproducibility. Notably, the integration of artificial intelligence (AI) and machine learning into quantitative coronary angiography (QCA) holds promise for further enhancing diagnostic accuracy and predictive capabilities. In addition, non-invasive fractional flow reserve (FFR) indices, including computed tomography-FFR, have emerged as valuable tools, offering precise physiological assessment of coronary artery disease without the need for invasive procedures. These innovations allow for a more comprehensive evaluation of disease severity and aid in guiding revascularization decisions. This review traces the development of QCA technologies over the years, highlighting key milestones and current advancements. It also explores prospects that could revolutionize the field, such as AI integration and improved imaging techniques. By addressing both historical context and future directions, the article underscores the ongoing evolution of QCA and its critical role in the accurate assessment and management of coronary artery diseases. Through continuous innovation, QCA is poised to remain at the forefront of cardiovascular diagnostics, offering clinicians invaluable tools for improving patient care.

Background Paravalvular regurgitation (PVR) is a common complication after transcatheter aortic valve replacement, posing an increased risk of heart failure and mortality. Accurate intraprocedural quantification of PVR is challenging. Both hemodynamic indices and videodensitometry can be used for intraprocedural assessment of PVR. We compared the predictive value of the isolated versus combined use of the hemodynamic index diastolic delta (DD) and videodensitometry for the incidence of relevant PVR 1 month after transcatheter aortic valve replacement. Methods and Results In this prospective cohort study, patients underwent periprocedural PVR assessment by DD and videodensitometry (using left ventricular outflow tract—aortic regurgitation [LVOT‐AR]). Cardiac magnetic resonance served as reference modality for PVR assessment. Relevant PVR was defined as cardiac magnetic resonance–regurgitant fraction >20%. Fifty‐one patients were enrolled in this study. Mean age was 80.6±5.2 years and 45.1% of patients were men. Mean LVOT‐AR and cardiac magnetic resonance–regurgitant fraction were 8.2%±7.8% and 11.7%±9.6%, respectively. The correlation between DD and LVOT‐AR was weak (r=−0.36). DD and LVOT‐AR showed a comparable accuracy to predict relevant PVR (area under the curve 0.82, 95% CI: 0.69–0.95 versus area area under the time–density curve 0.80, 95% CI: 0.62–0.99). The combination of DD and LVOT‐AR improved the prediction of relevant PVR (area under the time–density curve, 0.90, 95% CI: 0.81–0.99), and resulted in an increased concordance (86.3%) and positive predictive value (75%) compared with DD alone (76.5% and 40%, respectively), or LVOT‐AR alone (82.3% and 50%, respectively). Conclusions DD and videodensitometry are both accurate and feasible modalities for the assessment of PVR after transcatheter aortic valve replacement. The synergistic use of both techniques increases the predictive value for relevant PVR after transcatheter aortic valve replacement. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04281771.

Abstract The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)—356 patients or percutaneous coronary intervention (PCI)—679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P

Background Coronary microvascular dysfunction (CMD) is a common complication of ST‐segment–elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. Methods and Results This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post‐STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve

Background Recently, machine learning algorithms have identified preprocedural γ‐glutamyl transferase (GGT) as a significant predictor of long‐term mortality after coronary revascularization in the SYNTAX (Synergy Between PCI [Percutaneous Coronary Intervention] With Taxus and Cardiac Surgery) trial. The aim of the present study is to investigate the impact of preprocedural GGT on 10‐year all‐cause mortality in patients with complex coronary artery disease after revascularization. Methods and Results The SYNTAX trial was a randomized trial comparing PCI with coronary artery bypass grafting in 1800 patients with complex coronary artery disease. The present report is a post hoc subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) trial, an investigator‐driven extended 10‐year follow‐up of the SYNTAX trial. The association between preprocedural GGT and 10‐year all‐cause mortality was investigated. The mean values of GGT for men and women were 43.5 (SD, 48.5) and 36.4 (SD, 46.1) U/L, respectively. In multivariable Cox regression models adjusted by traditional risk factors, GGT was an independent predictor for all‐cause death at 10‐year follow‐up, and each SD increase in log‐GGT was associated with a 1.24‐fold risk of all cause death at 10‐year follow‐up (95% CI, 1.10–1.40). According to previously reported sex‐related GGT thresholds, patients with higher GGT level had a 1.74‐fold risk of all‐cause death at 10‐year follow‐up (95% CI, 1.32–2.29) compared with patients with lower GGT level. Conclusions Preprocedural GGT is an independent predictor of 10‐year mortality after coronary revascularization in patients with complex coronary artery disease. In patients with elevated GGT, strong secondary prevention may be required after revascularization and must be studied prospectively. Registration URL: https://clinicaltrials.gov/study/NCT03417050.

Objective: We performed a post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial to determine the effect an on-versus off-pump strategy had on outcomes when compared with percutaneous coronary intervention. Methods: All randomized patients in EXCEL (n = 1905) were included. The outcomes of interest were the primary end point composite of death from any cause, stroke, or myocardial infarction; the composite study end point or ischemia-driven revascularization; and the rate of death from any cause at 5 years. Event rates were based on Kaplan–Meier estimates in time-to-first-event analyses. Results: Propensity matching resulted in groups of 1142 patients (571 each) for on-pump coronary artery bypass grafting versus percutaneous coronary intervention and 472 patients (236 each) for off-pump coronary artery bypass grafting versus percutaneous coronary intervention. In the on-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point was similar (18.0% vs 22.1%, P = .19) and the composite end point or ischemia-driven revascularization (23.3% vs 31.0%, P = .01) was lower, and mortality (7.6% vs 11.8%, P = .025) was lower in the on-pump coronary artery bypass grafting group at 5 years. In the off-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point (19.4% vs 22.2%, P = .47), composite end point or ischemia-driven revascularization (25.9% vs 34.2%, P = .07), and mortality (12.5% vs 14.2%, P = .59) were similar at 5 years. Conclusions: In the EXCEL trial, on-pump coronary artery bypass grafting was associated with a decreased 5-year rate of the composite outcome of death, stroke, myocardial infarction, or ischemia-driven revascularization, and decreased mortality when compared with percutaneous coronary intervention, whereas outcomes of off-pump coronary artery bypass grafting were similar to percutaneous coronary intervention.

Abstract Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR

Abstract Endothelial shear stress (ESS) plays a key role in the clinical outcomes in native and stented segments; however, their implications in bypass grafts and especially in a synthetic biorestorative coronary artery bypass graft are yet unclear. This report aims to examine the interplay between ESS and the morphological alterations of a biorestorative coronary bypass graft in an animal model. Computational fluid dynamics (CFD) simulation derived from the fusion of angiography and optical coherence tomography (OCT) imaging was used to reconstruct data on the luminal anatomy of a bioresorbable coronary bypass graft with an endoluminal “flap” identified during OCT acquisition. The “flap” compromised the smooth lumen surface and considerably disturbed the local flow, leading to abnormally low ESS and high oscillatory shear stress (OSI) in the vicinity of the “flap”. In the presence of the catheter, the flow is more stable (median OSI 0.02384 versus 0.02635, p

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.

Abstract More than half of heart failure (HF) patients have concomitant pulmonary hypertension, impacting symptoms and prognosis. The role of exercise in this category of patients is still unclear, probably because of the lack of a clear relationship between exercise and acute and chronic pulmonary artery pressure variations and related changes in symptoms. The limited evidence on this topic is contradictory and hardly comparable due to use of different exercise programmes and pulmonary artery pressure assessment techniques. This is further compounded by different functional and structural classes of HF making definite assessments and interpretations of exercise effect on outcomes difficult. Exercise training programmes were proven beneficial in HF patients; however, the lack of data about their pulmonary haemodynamic effects prevents clear indications on the best exercise types for patients presenting secondary pulmonary hypertension and different HF categories. Indeed, some data suggest that not all HF patients have similar responses to training, leading to either beneficial or detrimental effects, depending on the HF type. Future studies, involving modern technologies such as continuous pulmonary artery pressure monitoring implantable devices, may clarify the current gaps in this field, aiming at patient‐tailored exercise training rehabilitation programmes, in order to improve clinical outcomes, quality of life, and hopefully prognosis.

Abstract Non-ST-elevation acute coronary syndrome (NSTE-ACS) affects millions of patients. Although an invasive strategy can improve survival, the optimal treatment [i.e., percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] is not clear. We performed a meta-analysis of studies reporting outcomes between PCI and CABG in patients with NSTE-ACS. MEDLINE, EMBASE and Cochrane Library were assessed. The primary outcome was long-term mortality. Inverse variance method and random model were performed. We identified 13 observational studies (48,891 patients). No significant difference was found in the primary endpoint [CABG vs. PCI, incidence rate ratio (IRR) 0.93, 95% confidence interval (CI) 0.70; 1.23]. CABG was associated with lower long-term major adverse cardiovascular events (MACE) (IRR 0.64, 95% CI 0.54; 0.76) and lower long-term re-revascularization (IRR 0.37, 95% CI 0.30; 0.47). There was no significant difference in long-term myocardial infarction (CABG vs. PCI, IRR 0.96, 95% CI 0.50; 1.84) and peri-operative mortality (CABG vs. PCI, odds ratio 1.36, 95% CI 0.94; 1.95). For the treatment of NSTE-ACS, CABG and PCI are associated with similar rates of long-term mortality and myocardial infarction. CABG is associated with lower rates of long-term MACE and re-revascularization. Randomized comparisons in this setting are necessary.

Cessation of one component of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has been associated with increased risk of ischemic events but it is uncertain whether discontinuation of aspirin is preferable to discontinuation of the oral P2Y12 inhibitor. The GLOBAL LEADERS study compared two antiplatelet strategies following PCI, cessation of aspirin at 1 month with continued ticagrelor monotherapy for 23 months versus standard DAPT for 12 months followed by aspirin monotherapy for a further 12 months. We assessed recovery of platelet reactivity after withdrawal of either aspirin or ticagrelor at 1 month and 12 months, respectively, in this study. Platelet aggregation (PA) was assessed before cessation of DAPT (‘baseline’) and after 2, 7, and 14 days post-cessation using Multiplate whole-blood aggregometry with collagen, thrombin-receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. Following cessation of aspirin at 1 month, there was marked recovery of PA induced by AA (baseline [mean ± SD]: 11.1 ± 7.4 U vs. 14 days: 64.9 ± 19.6 U, p

Background Use of the modified American College of Cardiology (ACC)/American Heart Association (AHA) lesion classification as a prognostic tool to predict short‐ and long‐term clinical outcomes after percutaneous coronary intervention in the modern drug‐eluting stent era is uncertain. Methods and Results Patient‐level data from 7 prospective, randomized trials were pooled. Clinical outcomes of patients undergoing single lesion percutaneous coronary intervention with second‐generation drug‐eluting stent were analyzed according to modified ACC/AHA lesion class. The primary end point was target lesion failure (TLF: composite of cardiac death, target vessel myocardial infarction, or ischemia‐driven target lesion revascularization). Clinical outcomes to 5 years were compared between patients treated for noncomplex (class A/B1) versus complex (class B2/C) lesions. Eight thousand five hundred sixteen patients (age 63.1±10.8 years, 70.5% male) were analyzed. Lesions were classified as A, B1, B2, and C in 7.9%, 28.5%, 33.7%, and 30.0% of cases, respectively. Target lesion failure was higher in patients undergoing percutaneous coronary intervention of complex versus noncomplex lesions at 30 days (2.0% versus 1.1%, P=0.004), at 1 year (4.6% versus 3.0%, P=0.0005), and at 5 years (12.4% versus 9.2%, P=0.0001). By multivariable analysis, treatment of ACC/AHA class B2/C lesions was significantly associated with higher rate of 5‐year target lesion failure (adjusted hazard ratio, 1.39 [95% CI, 1.17–1.64], P=0.0001) driven by significantly higher rates of target vessel myocardial infarction and ischemia‐driven target lesion revascularization. Conclusions In this pooled large‐scale analysis, treating complex compared with noncomplex lesions according to the modified ACC/AHA classification with second‐generation drug‐eluting stent was associated with worse 5‐year clinical outcomes. This historical classification system may be useful in the contemporary era for predicting early and late outcomes following percutaneous coronary intervention.

Background Long‐term outcomes of ST‐segment–elevation myocardial infarction in patients with diabetes have been barely investigated. The objective of this analysis from the EXAMINATION‐EXTEND (10‐Years Follow‐Up of the EXAMINATION trial) trial was to compare 10‐year outcomes of patients with ST‐segment–elevation myocardial infarction with and without diabetes. Methods and Results Of the study population, 258 patients had diabetes and 1240 did not. The primary end point was patient‐oriented composite end point of all‐cause death, any myocardial infarction, or any revascularization. Secondary end points were the individual components of the primary combined end point, cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis. All end points were adjusted for potential confounders. At 10 years, patients with diabetes showed a higher incidence of patient‐oriented composite end point compared with those without (46.5% versus 33.0%; adjusted hazard ratio [HR], 1.31 [95% CI, 1.05–1.61]; P=0.016) mainly driven by a higher incidence of any revascularization (24.4% versus 16.6%; adjusted HR, 1.61 [95% CI, 1.19–2.17]; P=0.002). Specifically, patients with diabetes had a higher incidence of any revascularization during the first 5 years of follow‐up (20.2% versus 12.8%; adjusted HR, 1.57 [95% CI, 1.13–2.19]; P=0.007) compared with those without diabetes. No statistically significant differences were found with respect to the other end points. Conclusions Patients with ST‐segment–elevation myocardial infarction who had diabetes had worse clinical outcome at 10 years compared with those without diabetes, mainly driven by a higher incidence of any revascularizations in the first 5 years. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04462315.

Transcatheter aortic valve replacement (TAVR) is a recommended intervention for selected population with severe aortic stenosis (AS). Bicuspid aortic valve (BAV) anatomy has been categorized as an unfavorable anatomy for TAVR due to multiple considerations as exclusion from randomized trials in addition to the challenging and unpredictable anatomy. The anatomical constraints of BAV include the large anatomy of the annulus, sinus of Valsalva, and aorta (aortopathy), in addition to significant calcifications of the device landing zone. Most commercial transcatheter heart valves (THV) have upper dimension limits of the annulus and area in which the device can be implanted safely without significant oversizing. Myval-XL THVs (Meril Life Sciences Pvt. Ltd., India) are balloon-expandable valves (BEV) that have been developed with two new sizes, 30.5 and 32 mm, aiming to treat patients with large annulus dimensions and that exceed the upper limit of an ordinary device’s sizing matrix. This case series report describes TAVR using the XL-Myval 32 mm THV in three European patients with symptomatic severe bicuspid aortic stenosis with significant calcifications and large annular dimensions exceeding the limits of the other THVs.

Abstract Background We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study. Methods Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P=0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Patient-specific coronary endothelial shear stress (ESS) calculations using Newtonian and non-Newtonian rheological models were performed to assess whether the common assumption of Newtonian blood behavior offers similar results to a more realistic but computationally expensive non-Newtonian model. 16 coronary arteries (from 16 patients) were reconstructed from optical coherence tomographic (OCT) imaging. Pulsatile CFD simulations using Newtonian and the Quemada non-Newtonian model were performed. Endothelial shear stress (ESS) and other indices were compared. Exploratory indices including local blood viscosity (LBV) were calculated from non-Newtonian simulation data. Compared to the Newtonian results, the non-Newtonian model estimates significantly higher time-averaged ESS (1.69 (IQR 1.36)Pa versus 1.28 (1.16)Pa, p < 0.001) and ESS gradient (0.90 (1.20)Pa/mm versus 0.74 (1.03)Pa/mm, p < 0.001) throughout the cardiac cycle, under-estimating the low ESS (

Abstract Background Patients with both diabetes mellitus (DM) and chronic kidney disease (CKD) are a subpopulation characterized by ultrahigh ischemic and bleeding risk after percutaneous coronary intervention. There are limited data on the impact of ticagrelor monotherapy among these patients. Methods In this post hoc analysis of the GLOBAL-LEADERS trial, the treatment effects of the experimental (one-month dual-antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin alone) were analyzed according to DM/CKD status. The primary endpoint was a composite endpoint of all-cause death or new Q-wave myocardial infarction at 2-years. The patient-oriented composite endpoint (POCE) was defined as the composite of all-cause death, any stroke, site-reported MI and any revascularization, whereas net adverse clinical events (NACE) combined POCE with BARC type 3 or 5 bleeding events. Results At 2 years, the DM + /CKD + patients had significantly higher incidences of the primary endpoint (9.5% versus 3.1%, adjusted HR 2.16; 95% CI [1.66–2.80], p

ObjectivesTo compare the quantitative angiographic aortic regurgitation (AR) of six self-expanding valves after transcatheter aortic valve replacement (TAVR).BackgroundQuantitative videodensitometric aortography (LVOT-AR) is an accurate and reproducible tool for assessment of AR following TAVR.MethodsThis is a retrospective central core-lab analysis of 1,257 consecutive cine aortograms performed post-TAVR. The study included 107 final aortograms of consecutive patients who underwent TAVR with first-generation VitaFlow in four Chinese centers and 1,150 aortograms with five other transcatheter aortic valves (Evolut Pro, Evolut R, CoreValve, Venus A-Valve, and Acurate Neo). LVOT-AR analyses of these five valves were retrieved from a previously published pooled database.ResultsAmong 172 aortograms of patients treated with VitaFlow, 107 final aortograms (62.2%) were analyzable by LVOT-AR. In this first in man eight cases necessitated a procedural valve in valve due to inappropriate TAVR positioning and severe aortic paravalvular regurgitation. In the VitaFlow group, the mean LVOT-AR of the intermediate aortograms was 7.3 ± 7.8% and the incidence of LVOT-AR >17% was 8.6%. The mean LVOT-AR of the final aortogram was 6.1 ± 6.4% in the VitaFlow group, followed by Evolut Pro (7.3 ± 6.5%), Evolut R (7.9 ± 7.4%), Venus A-valve (8.9 ± 10.0%), Acurate Neo (9.6 ± 9.2%), and lastly CoreValve (13.7 ± 10.7%) (analysis of variance p < 0.001). Post hoc 2-by-2 testing showed that CoreValve had significantly higher LVOT-AR compared with each of the other five THVs. No statistical difference in LVOT-AR was observed between VitaFlow, Evolut Pro, Evolut R, Acurate Neo, and Venus A-valves. The VitaFlow system had the lowest proportion of patients with LVOT-AR >17% (4.7%) (AR after the final aortograms), followed by Evolut Pro (5.3%), Evolut R (8.8%), Acurate Neo (11.3%), Venus A-valve (14.2%), and CoreValve (30.1%) (chi-square p < 0.001).ConclusionCompared to other commercially available self-expanding valves, VitaFlow seems to have a low degree of AR and a low proportion of patients with ≥moderate/severe AR as assessed by quantitative videodensitometric angiography. Once the learning phase is completed, comparisons of AR between different transcatheter heart valves should be attempted in a prospective randomized trial.

A 79-year-old male with chronic coronary syndrome with complex coronary artery disease was included in the first-in-man trial of surgical revascularization guided solely by coronary computed tomography angiography (CCTA) and fractional flow reserve derived from CCTA (FFRCT). In CCTA analysis, the patient had calcified three-vessel disease, with a global anatomical SYNTAX score of 27. In contrast, in the initial FFRCT, only the ramus intermediate stenosis was physiologically significant, with no other vessels having an FFRCT ≤ 0.80 (functional SYNTAX score of 2). Discordance between the results of the CCTA and FFRCT necessitated an in-depth analysis by using both invasive and non-invasive coronary angiography. Angiography-derived fractional flow reserve (FFR) confirmed that the stenosis in the proximal left anterior descending artery (LAD) was physiologically significant, while it remained functionally negative in the second assessment of FFRCT. Extensive calcification is the most plausible explanation for the underestimation of the stenosis of proximal LAD in CCTA-derived FFR technology.

Introduction: Cyclic plaque structural stress has been hypothesized as a mechanism for plaque fatigue and eventually plaque rupture. A novel approach to derive cyclic plaque stress in vivo from optical coherence tomography (OCT) is hereby developed.Materials and Methods: All intermediate lesions from a previous OCT study were enrolled. OCT cross-sections at representative positions within each lesion were selected for plaque stress analysis. Detailed plaque morphology, including plaque composition, lumen and internal elastic lamina contours, were automatically delineated. OCT-derived vessel and plaque morphology were included in a 2-dimensional finite element analysis, loaded with patient-specific intracoronary pressure tracing data, to calculate the changes in plaque structural stress (ΔPSS) on vessel wall over the cardiac cycle.Results: A total of 50 lesions from 41 vessels were analyzed. A significant ΔPSS gradient was observed across the plaque, being maximal at the proximal shoulder (45.7 [32.3, 78.6] kPa), intermediate at minimal lumen area (MLA) (39.0 [30.8, 69.1] kPa) and minimal at the distal shoulder (35.1 [28.2, 72.3] kPa; p = 0.046). The presence of lipidic plaques were observed in 82% of the diseased segments. Larger relative lumen deformation and ΔPSS were observed in diseased segments, compared with normal segments (percent diameter change: 8.2 ± 4.2% vs. 6.3 ± 2.3%, p = 0.04; ΔPSS: 59.3 ± 48.2 kPa vs. 27.5 ± 8.2 kPa, p < 0.001). ΔPSS was positively correlated with plaque burden (r = 0.37, p < 0.001) and negatively correlated with fibrous cap thickness (r = −0.25, p = 0.004).Conclusions: ΔPSS provides a feasible method for assessing plaque biomechanics in vivo from OCT images, consistent with previous biomechanical and clinical studies based on different methodologies. Larger ΔPSS at proximal shoulder and MLA indicates the critical sites for future biomechanical assessment.

Background The optimal duration of dual antiplatelet therapy after coronary drug‐eluting stent placement in adults with stable coronary artery disease (SCAD) versus acute coronary syndromes (ACS) remains uncertain. Methods and Results This was a prespecified subgroup analysis of the GLOBAL LEADERS trial. Participants were randomly assigned 1:1 to the experimental or reference strategy, stratified by ACS (experimental, n=3750; reference, n=3737) versus SCAD (experimental, n=4230; reference, n=4251). The experimental strategy was 75 to 100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy. The reference strategy was 75 to 100 mg aspirin daily plus either 75 mg clopidogrel daily (for SCAD) or 90 mg ticagrelor twice daily (for ACS) for 12 months, followed by aspirin monotherapy for 12 months. The primary end point at 2 years was a composite of all‐cause mortality or non‐fatal centrally adjudicated new Q‐wave myocardial infarction. The key secondary safety end point was site‐reported Bleeding Academic Research Consortium grade 3 or 5 bleeding. The primary end point occurred in 147 (3.92%) versus 169 (4.52%) patients with ACS (rate ratio [RR], 0.86; 95% CI, 0.69–1.08; P=0.189), and in 157 (3.71%) versus 180 (4.23%) patients with SCAD (RR, 0.87; 95% CI, 0.71–1.08; P=0.221) with experimental and reference strategy, respectively (P‐interaction=0.926). Bleeding Academic Research Consortium grade 3 or 5 bleeding occurred in 73 (1.95%) versus 100 (2.68%) patients with ACS (RR, 0.73; 95% CI, 0.54–0.98; P=0.037), and in 90 (2.13%) versus 69 (1.62%) patients with SCAD (RR, 1.32; 95% CI, 0.97–1.81; P=0.081; P‐interaction=0.007). Conclusions While there was no evidence for differences in efficacy between treatment strategies by subgroup, the experimental strategy appeared to reduce bleeding risk in patients with ACS but not in patients with SCAD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Objectives: We aimed to compare the quantitative angiographic aortic regurgitation (AR) into the left ventricular out flow tract (LVOT-AR) of five different types of transcatheter self-expanding valves and to investigate the impact of the learning curve on post-TAVR AR. Background: Quantitative video densitometric aortography is an objective, accurate, and reproducible tool for assessment of AR following TAVR. Methods and results: This retrospective academic core-lab analysis, analyzed 1150 consecutive cine aortograms performed immediately post-TAVR. Quantitative angiographic AR of post-procedural aortography in 181 consecutive patients, who underwent TAVR with the Venus A-valve in a single Chinese center, were compared to the results of Evolut Pro, Evolut R, CoreValve, (Medtronic, Dublin, Ireland) and Acurate Neo (Boston Scientific, Massachusetts, US) transcatheter heart valves (THVs), from a previously published pooled database. Among the 181 aortograms of patients treated with the Venus A-Valve, 113 (62.4%) were analyzable for quantitative assessment of AR. The mean LVOT-AR was 8.9% ± 10.0% with 14.2% of patients having moderate or severe AR in the Venus A-valve group. No significant difference in mean LVOT-AR was observed between Evolut Pro, Evolut R, Acurate Neo, and Venus A-valve. The incidence of LVOT-AR >17%, which correlates with echocardiographic derived ≥ moderate AR, with the Evolut Pro was lower than with the Venus A-valve (5.3% vs. 14.2%, p = 0.034), but was not different from the Evolut R (5.3% vs. 8.8%, p = 0.612), or the Acurate Neo (5.3% vs. 11.3% p = 0.16) systems. A landmark analysis after recruitment of the first half of patients treated with the Venus A valve (N = 56), showed a significantly lower mean LVOT-AR in the second half of the series (11.3% ± 11.9% vs. 6.5% ± 7.1%, p = 0.011). The incidence of LVOT-AR >17% in the latest 57 cases was also numerically lower (7.0% vs. 21.4%, p = 0.857) and compared favorably with the best in class of the self-expanding valves. Conclusion: The Venus A-valve has comparable mean LVOT-AR to other self-expanding valves but has a higher rate of moderate or severe AR than the Evolut Pro THV. However, after completion of a learning phase, results improved and compared favorably with the best in class of the commercially available self-expanding valves. These findings should be confirmed in prospective randomized comparisons of AR between different THVs.

En lugar de escribir un editorial convencional, he intentado responder a la pregunta del Dr. Fernando Alfonso, editor asociado de REC: Interventional Cardiology: «¿hacia dónde vamos?» dejándome entrevistar por el experimentado cardiólogo intervencionista sudamericano, Dr. Rodrigo Modolo que en la actualidad se encuentra redactando su tesis doctoral en la ciudad de Róterdam. Pregunta: Profesor, ¿de verdad necesitamos otra revista sobre cardiología intervencionista? Respuesta: Rodrigo, atendiendo a su factor de impacto, en Estados Unidos se publican tres influyentes revistas de cardiología intervencionista: JACC: Cardiovascular Interventions, Circulation: Cardiovascular Interventions y Catheterization and Cardiovascular Interventions. En Europa, EuroIntervention es la publicación de la EAPCI. Pero tenemos una cierta tendencia a olvidar que el idioma del continente sudamericano es el español (...y el portugués, como bien me recordó el Dr. Modolo) y que a su vez, el español es una de las tres lenguas más habladas del mundo. En la actualidad Revista Española de Cardiología goza de un importante factor de impacto y se enfrenta al reto de crear una nueva revista sobre esta subespecialidad, REC: Interventional Cardiology. Supone todo un desafío, pero también una oportunidad increíble. P.: ¿Cree que la cardiología intervencionista ya ha tocado techo? R.: La cardiología intervencionista ha tocado el techo de sus 40 años de...

Instead of writing a conventional editorial I have tried to respond to the question of Dr Fernando Alfonso, Associate Editor of REC: Interventional Cardiology: “where are we going?” by letting myself be interviewed by a senior interventional cardiologist from South America, Dr Rodrigo Modolo, who is currently writing his PhD thesis in Rotterdam. QUESTION: Professor, do we need another interventional cardiology journal? ANSWER: Rodrigo, in the United States we have, ranked by their impact factors, 3 influential interventional cardiology journals: JACC: Cardiovascular Interventions, Circulation: Cardiovascular Interventions, and Catheterization and Cardiovascular Interventions. In Europe, EuroIntervention is the journal of the EAPCI (European Association of Percutaneous Intervention). But we have a tendency to forget that the language of the South American continent is Spanish (…and Portuguese, as Dr Modolo reminded me), and the Spanish language represents one of the 3 most widely spoken languages in the world. Revista Española de Cardiología currently has a major impact factor and faces the challenge of creating a new subspecialty journal, REC: Interventional Cardiology. It is a challenging decision but also a great opportunity. Q.: Do you think that interventional cardiology has reached its peak maturity? A.: Interventional cardiology has reached the peak of its 40 years of existence and it is...

A novel method for four-dimensional superficial wall strain and stress (4D-SWS) is derived from the arterial motion as pictured by invasive coronary angiography. Compared with the conventional finite element analysis of cardiovascular biomechanics using the estimated pulsatile pressure, the 4D-SWS approach can calculate the dynamic mechanical state of the superficial wall in vivo, which could be directly linked with plaque rupture or stent fracture. The validation of this approach using in silico models showed that the distribution and maximum values of superficial wall stress were similar to those calculated by conventional finite element analysis. The in vivo deformation was validated on 16 coronary arteries, from the comparison of centerlines predicted by the 4D-SWS approach against the actual centerlines reconstructed from angiograms at a randomly selected time-point, which demonstrated a good agreement of the centerline morphology between both approaches (scaling: 0.995 ± 0.018 and dissimilarity: 0.007 ± 0.014). The in silico vessel models with softer plaque and larger plaque burden presented more variation in mean lumen diameter and resulted in higher superficial wall stress. In more than half of the patients (n = 16), the maximum superficial wall stress was found at the proximal lesion shoulder. Additionally, in three patients who later suffered from acute coronary syndrome, the culprit plaque rupture sites co-localized with the site of highest superficial wall stress on their baseline angiography. These representative cases suggest that angiography-based superficial wall dynamics have the potential to identify coronary segments at high-risk of plaque rupture and fracture sites of implanted stents. Ongoing studies are focusing on identifying weak spots in coronary bypass grafts, and on exploring the biomechanical mechanisms of coronary arterial remodeling and aneurysm formation. Future developments involve integration of fast computational techniques to allow online availability of superficial wall strain and stress in the catheterization laboratory.

Objectives: The aim of the present analysis is to compare the quantitative angiographic aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) among three balloon-expandable valves. Background: Quantitative videodensitometric aortography is an objective, accurate, and reproducible tool for adjudication of AR following TAVI. Methods: This is a retrospective corelab analysis, independent from industry, of aortograms from patients treated with TAVI using the balloon-expandable Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd., India), Sapien 3, and XT THVs (Edwards Lifesciences, Irvine, CA, USA). The study comprised of 108 analyzable aortograms from consecutive patients in a multicenter European registry who underwent Myval THV implantation. The results of quantitative assessment of AR in the Sapien 3 THV (n = 397) and Sapien XT THV (n = 239) were retrieved from a published pooled database. Results: The Myval THV had the lowest proportion of patients with moderate or severe angiographic quantitative AR (2.8%) compared to the Sapien 3 THV (8.3%; p = 0.049) and Sapien XT THV (10.9%; p = 0.012). Furthermore, the Myval THV had the lowest mean angiographic quantitative AR (6.3 ± 6.3%), followed by Sapien 3 THV (7.6 ± 7.1%) and Sapien XT THV (8.8 ± 7.5%), and it was significantly lower than that of the Sapien XT THV (p = 0.006), but not significantly different from Sapien 3 THV (p = 0.246). Conclusion: The Myval THV, in comparison with other BEV’s analyzed in our database, showed a lower occurrence of moderate or severe AR after TAVI. These results should be confirmed in prospective cohorts of randomized patients with head-to-head THV comparisons.

Background: Personalized prognosis plays a vital role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease (3VD). The aim of this study is to compare the modality of revascularization chosen by the local heart team to that recommended by using individualized predictions of medium, and long-term all-cause mortality amongst patients with 3VD screened in the Multivessel TALENT trial. Methods: The SYNTAX score II (SS-II) and SS-2020 were evaluated in 200 consecutive patients by a core laboratory and compared to the decision of the “on site” heart team. Results: According to the SS-II, CABG was the recommended treatment in 51 patients (25.5%) however 34 (66.6%) of them received PCI. According to SS-2020 the predicted absolute risk differences (ARD) between PCI and CABG were significantly higher in patients receiving CABG compared to those treated by PCI for major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, stroke or myocardial infarction at 5-years (8.8 ± 4.6% vs 6.0 ± 4.0%, p < 0.001) and all-cause mortality at 5- (5.2 ± 3.5% vs 3.7 ± 3.0%, p = 0.008) and 10-years (9.3 ± 4.8% vs 6.2 ± 4.2%, p < 0.001). Based on the novel threshold of equipoise (individual absolute risk differences [ARD] 4.5%), only 19 received it. Conclusions: Despite the robustness of the risk models proposed for screening, several deviations from the recommended mode of revascularization were observed by the core laboratory among the first 200 patients with 3VD screened in the Multivessel TALENT trial. Clinical Trial Registration: ClinicalTrials.gov reference: NCT04390672.

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed and improved as both diagnostic and guidance tools for interventional procedures over the past three decades. IVUS has a resolution of 100 μm with a high tissue penetration and capability of assessing the entire structure of a coronary artery including the external elastic membrane, whereas OCT has a higher resolution of 10–20 μm to assess endoluminal structures with a limited tissue penetration compared to IVUS. Recently, two companies, CONAVI and TERUMO, integrated IVUS and OCT into a single catheter system. With their inherent strength and limitations, the combined IVUS and OCT probes are complementary and work synergistically to enable a comprehensive depiction of coronary artery. In this review, we summarize the performance of the two intracoronary imaging modalities—IVUS and OCT—and discuss the expected potential of the novel hybrid IVUS–OCT catheter system in the clinical field.

Understanding the mechanisms that regulate atherosclerotic plaque formation and evolution is a crucial step for developing treatment strategies that will prevent plaque progression and reduce cardiovascular events. Advances in signal processing and the miniaturization of medical devices have enabled the design of multimodality intravascular imaging catheters that allow complete and detailed assessment of plaque morphology and biology. However, a significant limitation of these novel imaging catheters is that they provide two-dimensional (2D) visualization of the lumen and vessel wall and thus they cannot portray vessel geometry and 3D lesion architecture. To address this limitation computer-based methodologies and user-friendly software have been developed. These are able to off-line process and fuse intravascular imaging data with X-ray or computed tomography coronary angiography (CTCA) to reconstruct coronary artery anatomy. The aim of this review article is to summarize the evolution in the field of coronary artery modeling; we thus present the first methodologies that were developed to model vessel geometry, highlight the modifications introduced in revised methods to overcome the limitations of the first approaches and discuss the challenges that need to be addressed, so these techniques can have broad application in clinical practice and research.

Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with

The objective of this study was to assess the effect of high-dose atorvastatin treatment on endothelial progenitor cell (EPC) recruitment and angiographic and clinical outcome in coronary artery disease (CAD) patients treated with the Genous ™ EPC-capturing stent. The HEALING IIB study was a multicenter, open-label, prospective trial that enrolled 100 patients. Patients were started on 80 mg atorvastatin qd, at least 2 weeks before the index procedure and continued for at least 4 weeks after the index procedure. Eighty-seven patients were included in this analysis. EPC levels significantly increased as early as 2 weeks after the start of atorvastatin. Remarkably, among this group, 31 patients proved to be nonresponders to atorvastatin treatment (i.e., no increase in EPC levels), while 56 patients were responders (i.e., rise in EPC count between week −2 and 0). Compared to responders, nonresponders had a significantly higher baseline EPC count (76 ± 10 vs. 41 ± 5, p < 0.01) with a lower late luminal loss (LLL) at 6- and 18-month follow-up (FU) (0.61 ± 0.07 vs. 0.88 ± 0.08, p < 0.05, and 0.50 ± 0.08 vs. 0.82 ± 0.08, p < 0.01 respectively). Furthermore, baseline EPC count was inversely correlated with LLL at 6-month FU ( R = −0.42, p < 0.001). Patients with a higher EPC count at baseline showed no increase in EPC recruitment in response to statin treatment but had favorable LLL at 6- and 18-month FU, whereas patients with lower EPC count were responsive to statin therapy, but EPCs might be less functional as they had higher LLL at 6- and 18-month FU. These data imply that although statin treatment can enhance EPC titer in patients with low baseline levels, there is no indication for a possible beneficial clinical effect with EPC capture stents.

Heart failure is by far the most common cause of hospitalization in Western countries, with onerous economic consequences. Cell therapy holds great promise for use in tissue regeneration and is increasingly used in an effort to improve outcomes in cardiac disease. Recently it has been shown that adipose tissue, in addition to committed adipogenic, endothelial progenitor cells and pluripotent vascular progenitor cells, also contains multipotent cell types (adipose-derived stem cells, ADSCs) that, in cell culture conditions, have shown to have an impressive developmental plasticity including the ability to undergo multilineage differentiation and self-renewal. ADSCs express multiple CD marker antigens similar to those observed on MSCs and are also capable of secreting a large number of angiogenesis-related cytokines, including vascular endothelial growth factor, granulocyte/macrophage colony stimulating factor, stromal-derived factor-1α, and hepatocyte growth factor. Adipose tissue can be harvested in large quantities with minimal morbidity in several regions of the body and, on average, 100 ml of human adipose tissue yields about 1 × 106 stem cells. Studies conducted in porcine AMI models have shown a significant LV functional improvement, with no report of any potentially fatal arrhythmias. The APOLLO trial, a prospective, double blind, randomized, placebo-controlled trial currently in the recruiting phase, is a “first-in-man” study that explores the safety and feasibility of ADSC transplantation in patients with acute MI.

Abstract Background: Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking. Objective: To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH-IVUS)-derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease. Methods: In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant. Results: In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) µg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8-4.1] µg/mL)were not associated with plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02-6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92-78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23). Conclusion: In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed.

Abstract Background: Balloon post-dilatation (BPD) is often needed for optimizing transcatheter heart valve (THV) implantation, since paravalvular leak (PVL) after transcatheter aortic valve implantation is associated with poor outcome and mortality. Quantitative assessment of PVL severity before and after BPD is mandatory to properly assess PVL, thus improving implantation results and outcomes. Objective: To investigate a quantitative angiographic assessment of aortic regurgitation (AR) by videodensitometry before and after BPD. Methods: Videodensitometric-AR assessments (VD-AR) before and after BPD were analysed in 61 cases. Results: VD-AR decreased significantly from 24.0[18.0-30.5]% to 12.0[5.5-19.0]% (p < 0.001, a two-tailed p < 0.05 defined the statistical significance). The relative delta of VD-AR after BPD ranged from -100% (improvement) to +40% (deterioration) and its median value was -46.2%. The frequency of improvement, no change, and deterioration were 70% (n = 43), 25% (n = 15) and 5% (n = 3), respectively. Significant AR (VD-AR > 17%) was observed in 47 patients (77%) before and in 19 patients (31%) after BPD. Conclusions: VD-AR after THV implantation provides a quantitative assessment of post-TAVI regurgitation and can help in the decision-making process on performing BPD and in determining its efficacy.