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Structural and functional abnormalities of coronary microvasculature are highly prevalent in several clinical settings and often associated with worse clinical outcomes. Therefore, there is a growing interest in the detection and treatment of this, often overlooked, disease. Coronary angiography allows the assessment of the Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR). However, the measurement of these parameters is not always feasible because of limited technical availability and the need for a cardiac catheterization with a small but real risk of potential complications. Recent advances in non-invasive imaging techniques allow the assessment of coronary microvascular function with good accuracy and reproducibility. The objective of this review is to discuss the strengths and weaknesses of alternative non-invasive approaches used in the diagnosis of coronary microvascular dysfunction (CMD), highlighting the most recent advances for each imaging modality., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Cardiovascular diseases are among the main causes of morbidity, disability, and mortality. Most of them occur because of an atherosclerotic plaque developing within a coronary artery, which can cause a narrowing of the vessel lumen (coronary stenosis) or even break it. It is, therefore, useful to evaluate the role of the stress state of the endothelial layer of the arterial tissue, both for the maintenance of the blood circulation and for the implications in presence of a pathology that can lead to thromboembolic complications. The aim of the following study was to develop and test an application that is able to evaluate specific hemodynamic shear stress indicators in coronary arteries at different percentages of stenosis and in different patients' specific conditions. The application, based on Java, allows users to view the results of simulations performed on a coronary anatomy that can be customized with a stenosis of different degrees and positions. Being in possession of a predictive tool for disturbed flow factors may be important for the location and development of atherosclerotic plaque. Moreover, the application can be a valid tool to help in the evaluation of the condition and in the follow-up of the coronary affected by pathology.

Objectives: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies., Background: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes., Methods: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization., Results: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919)., Conclusions: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR)., Objectives: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial., Methods: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex., Results: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06)., Conclusions: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Circulating levels of microRNAs (miRNAs) are emergent promising biomarkers for cardiovascular disease. Altered expression of miRNAs has been related to heart failure (HF) and cardiac remodelling. We measured the concentration gradients across the coronary circulation to assess their usefulness to diagnose HF of different aetiologies., Methods and Results: Circulating miRNAs were measured in plasma samples simultaneously obtained from the aorta and the coronary venous sinus in patients with non-ischaemic HF (NICM-HF, n = 23) ischaemic HF (ICM-HF, n = 41), and in control patients (n = 11). A differential modulation of circulating levels of miR-423, -34a, -21-3p, -126, -199 and -30a was found across the aetiology groups. Interestingly, a positive transcoronary gradient was found for miR-423 (P < 0.001) and miR-34a (P < 0.001) only in the ICM-HF group. On the contrary, a positive gradient was found for miR-21-3p (P < 0.001) and miR-30a (P = 0.030) only in the NICM-HF group. Finally, no significant variations were observed in the transcoronary gradient of miR-126 or miR-199., Conclusions: The present findings suggest that circulating levels of miRNAs are differentially expressed in patients with HF of different aetiologies. The presence of a transcoronary concentration gradient suggests a selective release of miRNAs by the failing heart into the coronary circulation. The presence of aetiology-specific transcoronary concentration gradients in HF patients might provide important information to better understand their role in HF, and suggests they could be useful biomarkers to distinguish HF of different aetiologies., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Objectives: The authors sought to evaluate the accuracy of instantaneous wave-Free Ratio (iFR) pullback measurements to predict post-percutaneous coronary intervention (PCI) physiological outcomes, and to quantify how often iFR pullback alters PCI strategy in real-world clinical settings., Background: In tandem and diffuse disease, offline analysis of continuous iFR pullback measurement has previously been demonstrated to accurately predict the physiological outcome of revascularization. However, the accuracy of the online analysis approach (iFR pullback) remains untested., Methods: Angiographically intermediate tandem and/or diffuse lesions were entered into the international, multicenter iFR GRADIENT (Single instantaneous wave-Free Ratio Pullback Pre-Angioplasty Predicts Hemodynamic Outcome Without Wedge Pressure in Human Coronary Artery Disease) registry. Operators were asked to submit their procedural strategy after angiography alone and then after iFR-pullback measurement incorporating virtual PCI and post-PCI iFR prediction. PCI was performed according to standard clinical practice. Following PCI, repeat iFR assessment was performed and the actual versus predicted post-PCI iFR values compared., Results: Mean age was 67 ± 12 years (81% male). Paired pre- and post-PCI iFR were measured in 128 patients (134 vessels). The predicted post-PCI iFR calculated online was 0.93 ± 0.05; observed actual iFR was 0.92 ± 0.06. iFR pullback predicted the post-PCI iFR outcome with 1.4 ± 0.5% error. In comparison to angiography-based decision making, after iFR pullback, decision making was changed in 52 (31%) of vessels; with a reduction in lesion number (-0.18 ± 0.05 lesion/vessel; p = 0.0001) and length (-4.4 ± 1.0 mm/vessel; p < 0.0001)., Conclusions: In tandem and diffuse coronary disease, iFR pullback predicted the physiological outcome of PCI with a high degree of accuracy. Compared with angiography alone, availability of iFR pullback altered revascularization procedural planning in nearly one-third of patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aim of the present study was to perform a meta-analysis of all available studies comparing the instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR)., Methods and Results: Published trials comparing the iFR with FFR were searched for in PubMed, Google Scholar, and Scopus electronic databases. A total of 23 studies were available for the analysis, including 6381 stenoses. First, a meta-analysis of all studies was performed exploring the correlation between FFR and iFR. Interestingly, we found good correlation (0.798 [0.78-0.82]) between the 2 indices ( P <0.001). In addition, to evaluate the diagnostic performance of iFR to identify FFR-positive coronary stenoses, we performed an additional meta-analysis, summarizing the results of receiver operating characteristics analyses from individual studies reporting the area under the curve. Summing the results of these studies, we found that iFR has a good diagnostic performance for the identification of FFR-positive stenoses (area under the curve=0.88 [0.86-0.90]; P <0.001). Furthermore, our search results included 5 studies that compared iFR and FFR to a third independent reference standard. Interestingly, no significant differences between iFR and FFR were reported in those studies., Conclusions: The present meta-analysis shows that iFR significantly correlates with standard FFR and shows a good diagnostic performance in identifying FFR-positive coronary stenoses. Finally, iFR and FFR have similar diagnostic efficiency for detection of ischemia-inducing stenoses when tested against a third comparator., (© 2018 American Heart Association, Inc.)

The purpose of the study to assess the comparability of immediate changes in plaque/media volume (PV) on three modalities of intravascular ultrasound (IVUS) after implantation of either bioresorbable vascular scaffold (BVS) or everolimus-eluting metallic stent (EES) in Absorb II Study. The two devices have different device volume and ultrasound backscattering that may interfere with the "plaque/media" assessed by three modalities on IVUS: grayscale, backscattering of radiofrequency and brightness function. In a multicenter randomized controlled trial, 501 patients with stable or unstable angina underwent documentary IVUS pre- and post- implantation. The change in plaque/media volume (PV) was categorized into three groups according to the relative PV change in device segment: PV "increased" >+5% (PVI), PV unchanged ±5% (PVU), and PV decreased <-5% (PVD). The change in PV was re-evaluated three times: after subtraction of theoretical device volume, after analysis of echogenicity based on brightness function. In 449 patients, 483 lesions were analyzed pre- and post-implantation. "PVI" was more frequently observed in BVS (53.8%) than EES group (39.4%), p = 0.006. After subtraction of the theoretical device volume, the frequency of "PVI" decreased in both BVS (36.2%) and EES (32.1%) groups and became comparable (p = 0.581). In addition, the percentage of "PVI" was further reduced in both device groups after correction for either radiofrequency backscattering (BVS 34.4% vs. EES 22.6%) or echogenicity (BVS 25.2% vs. EES 9.7%). PV change in device segment was differently affected by BVS and EES devices implantation due to their differences in device volume and ultrasound backscattering. It implies that the lumen volume was also artifactually affected by the type of device implanted. Comparative IVUS assessment of lumen and plaque/media volume changes following implantation of BVS and EES requires specific methodological adjustment.

Background: The effect of optical coherence tomography (OCT) guidance on the implantation strategy during all phases of percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVSs) in a real-world scenario has been poorly investigated., Methods: Consecutive patients undergoing BVS implantation at our institution were included in this registry. Frequency-domain OCT pullbacks were performed at the operator's discretion during all phases of BVS implantation procedures to optimize preparation of lesions, confirm BVS size, and optimize expansion and apposition of scaffolds., Results: Between September 2012 and July 2015, 203 BVSs were implanted in 101 consecutive patients at our institution (2.01 BVSs/patient). In 66 patients, the procedure was performed under OCT guidance. In the OCT subgroup, 66 (77.6%) of the 85 treated lesions were complex (B2/C AHA/ACC type). Overall, 147 OCT pullbacks were performed and 72/147 (49.0%) pullbacks indicated the need for changing strategy. After angiography-only-guided optimisation of BVS in 27 (31.8%) lesions, an OCT examination prompted performance of a second post-expansion. This resulted in an increase in the minimal scaffold area (5.5 to 6.3mm(2), p=0.004) and a decrease in the incomplete scaffold apposition area (1.1 to 0.6mm(2), p=0.082), with no new stent fractures. When the population was divided according to the time of BVS implantation, an initial learning adaptation became evident, with the number of OCT-guided changes in strategy significantly decreasing between the initial and final time periods (p=0.017)., Conclusions: OCT guidance for BVS implantation significantly affects the procedural strategy, with favourable effects on acute results and the learning curve., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients., Methods: COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A., Conclusion: COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Background: Aim of the present study was to evaluate all randomized trials, comparing intracoronary adenosine versus placebo in STEMI patients undergoing primary PCI., Methods and Results: PubMed, the Cochrane Library and ISI Web of Knowledge electronic databases were scanned for eligible studies up to February 23rd 2015. The summary measure used was risk ratio (RR) with 95% confidence intervals. A total of 13 studies were eligible, including 1487 patients. Incidence of ST resolution was significantly higher in the IC adenosine group than in the placebo group (RR = 1.20 [1.05–1.38]; p = 0.008). At metaregression, a significant correlation was found between the magnitude of the adenosine-related effect on ST resolution and the mean ischemic time (p = 0.011) or the percentage of patients with the LAD as the infarct-related artery (p = 0.03). Furthermore, we found a larger increase in LVEF (p = 0.02) with a parallel reduction in the incidence of heart failure (HF) (RR = 0.50 [0.28–0.89]; p = 0.02) in the IC adenosine group. Finally, IC adenosine administration was associated with a significantly lower incidence of major adverse cardiac events (MACE) both at short- (RR = 0.62 [0.39–0.98] p = 0.04) and long-term (RR = 0.61 [0.39–0.95] p = 0.03)., Conclusions: This is the first meta-analysis demonstrating a clinical benefit for IC adenosine in hard endpoints, such as adverse cardiovascular events, in patients undergoing primary PCI.

Background: Adequate expansion is critical to achieve optimal Bioresorbable Vascular Scaffolds (BVS) apposition to the vessel wall. However, compared to metallic stents, BVS present different mechanical properties. Hence, slow deployment and maintenance of balloon inflation for at least 30" is recommended for BVS implantation. However, since no evidences are available demonstrating the superiority of a longer balloon dilatation time, the implantation technique is highly variable among different centers., Methods: A total of 24 BVS-treated lesions were included in the present analysis. After BVS deployment at 12 atmosphere (ATM) the balloon was rapidly deflated and scaffold expansion was documented with an angiogram. The same balloon was then inflated again and kept at 12 ATM for 30". Finally, a further angiogram was obtained to evaluate BVS expansion. Quantitative coronary angiography (QCA) was performed at each step., Results: A significant increase of minimal luminal diameter (MLD)-to-reference scaffold diameter (RSD) ratio (MLD to RSD Ration, MR-Ratio) from 0.70 ± 0.10 after initial stent deployment to 0.79 ± 0.10 after the 30"-long balloon dilation was observed (p < 0.001). Of note, this result was consistent across all sub-segments, as well as across almost all lesion subgroups. A substantial reduction in the prevalence of residual stenosis from 29 % to 17 % was registered after the 30"-long dilation., Conclusions: Our results strongly support the maintenance of balloon inflation for at least 30" during BVS deployment to achieve optimal scaffold expansion and minimize the occurrence of residual stenosis.

Aims: To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R., Methods and Results: All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group., Conclusions: In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Aim: There is lack of information on the outcome of patients treated with primary angioplasty for lesions located in an ectatic coronary artery segment in the setting of acute myocardial infarction. The aim of this study was to analyse the 2-year follow-up of this specific patient population., Methods: By means of a systematic review of the databases and cine-films of 5912 primary angioplasties performed in eight Italian cardiac centers we identified 101 patients with infarct-related coronary artery ectasia. Ectasia was defined as a dilatation exceeding the 1.5-fold of normal adjacent segment and was classified according to its severity. The primary end point was the composite rate of cardiac death, recurrence of acute myocardial infarction and a new revascularisation at 2-year., Results: The procedure was successful in 70.3% of cases, unsuccessful or complicated in 29.7%. The primary endpoint was met in 6.9% of cases during hospitalization (95% CI: 2.0-11.8), in 17.8% (95% CI: 10.3-25.3) at 1 year, and in 38.5% (95% CI: 29.0-48.0) at 2 years. Nine patients had a stent thrombosis: 3 acute and 6 sub-acute. A statistically significant correlation between the dimensions of the stent and stent thrombosis was observed (P=0.005)., Conclusion: In subjects undergoing primary angioplasty for acute myocardial infarction the rate of patients treated on lesions located in an ectatic coronary artery segment is very small (1.7%). The procedural success was low, whereas the rate of events at follow-up was quit high reflecting the complexity of this disease.

Objectives: This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD)., Background: Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery., Methods: Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months., Results: The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30)., Conclusions: The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011)., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease., Background: In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI)., Methods: Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging., Results: The IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI., Conclusions: In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Direct stenting (DS) was attempted in 99 coronary lesions in 94 patients while standard stenting (SS) was attempted in 113 lesions in 103 patients matched for clinical characteristics, stenosis type, and location and stent type. The angiographic result was also evaluated according to TIMI frame count method (TFC) before and after procedure. A clinical follow-up was performed 1 year after the procedure. Before the procedure, TIMI grade 3 flow was detected in 42 cases (42.4%), grade 2 in 40 cases (40.4%), grade 1 in 5 cases (5.1%), and grade 0 in 12 cases (12.1%) in the DS group; these data were similar in SS group. After the procedure, TIMI grade flow was 3 in 90 cases (92.8%) in DS group and in 87 (77.0%) in SS group (P < 0.005); grade 2 was observed in 7 case (7.2%) in DS group and in 25 (22.1%) in SS group (P < 0.005). Major adverse cardiac events during hospitalization and at follow-up were similar in two groups. Radiation exposure time and procedure costs per lesion were significantly reduced in DS group compared to SS group (10.1 +/- 8 min vs. 13.9 +/- 4.7 min, P < 0.001; and 1901 +/- 687 Euro vs. 2352 +/- 743 Euro, P < 0.001, respectively). This study confirms that, in selected patients, direct stenting is a safe and successful procedure, allowing a significant reduction in radiation exposure time and procedural costs compared to standard stenting technique. The angiographic success is confirmed by the improvement in TFC in all cases., (Copyright 2001 Wiley-Liss, Inc.)

The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of alpha-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of alpha-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to alpha-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both alpha(1)- and alpha(2)-adrenoceptors in epicardial conduit arteries and microvessels. Such augmented alpha-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of alpha(2)-adrenergic coronary constriction.

Percutaneous transluminal coronary angioplasty is associated with spontaneous transient vasoconstriction. The mechanisms by which coronary vasoconstriction occurs distally to a successful dilated stenosis after coronary artery angioplasty are still unknown. The present study was planned to investigate the effect of successful coronary artery angioplasty on coronary vasomotion distal to a dilated stenosis and in the control vessel and the role of alpha-adrenergic receptors on coronary vasomotion after successful coronary artery angioplasty. We prospectively studied 32 consecutive patients scheduled for elective single coronary artery angioplasty of the left anterior descending coronary artery. Only aspirin, 325 mg, or nitroglycerin was allowed in the week before the study; no premedication with diazepam or other drugs was given. In group 1 (control patients, n = 20), quantitative coronary angiography was performed in the control state; 5 and 15 minutes after coronary artery angioplasty; and after intracoronary nitroglycerin infusion, 300 micrograms. In group 2 (n = 12), intracoronary phentolamine, 2 mg, was infused regionally through the balloon catheter before the coronary artery angioplasty, and coronary angiography was performed at baseline, 15 minutes after balloon deflation, and after nitroglycerin infusion. In group 1, constriction of the coronary segment distal to a dilated stenosis (2.4 +/- 0.8 to 2.1 +/- 0.6 mm, -14.6% vs baseline; p < 0.05) and of the circumflex coronary artery segment (2.8 +/- 0.7 to 2.5 +/- 0.6 mm, -10.7% vs baseline, p < 0.05) occurred 15 minutes after coronary artery angioplasty. The degree of vasoconstriction was not correlated with the lesion severity before coronary artery angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

This study evaluated the effects of digoxin infusion (0.014 mg/kg in 10 min i.v.) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (aged 47 +/- 12), divided in 3 groups were studied. The effects of digoxin infusion (after 10 and 20 min) and sublingual administration of isosorbide dinitrate were investigated in Group I (patients with angiographically normal coronary arteries, n = 9) and in Group II (patients with atherosclerotic coronary arteries, n = 8). In Group III (n = 5) to determine whether or not the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiographies were performed after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, i.v.). In Group I, 10 min after the end of digoxin infusion, cross-sectional area decreased from 7.7 +/- 4.1 mm2 to 6.0 +/- 2.2 mm2, and after 20 min to 5.6 +/- 2.6 mm2 (p < 0.05). Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (NS versus baseline). By 20 min after digoxin infusion heart rate was significantly reduced from 79 +/- 16 to 74 +/- 13 b/min (p < 0.01). Peripheral vascular resistances increased significantly 10 min after digoxin infusion (from 1396 +/- 693 to 1693 +/- 984 dyne*s*cm-5, p < 0.05), whereas cardiac output did not change. In Group II, minimal stenosis diameter decreased significantly 20 min after digoxin infusion from 1.6 +/- 0.5 mm to 1.4 +/- 0.5 mm (p < 0.05). Again, isosorbide dinitrate reverted digoxin-induced vasoconstriction as minimal stenosis diameter increased (NS versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

This study evaluated the effect of bolus infusion of digoxin (0.014 mg/kg in 10 minutes, intravenously) on large coronary arteries measured by quantitative digital angiography. Twenty-two patients (mean age +/- standard deviation 47 +/- 12 years) divided into 3 groups were studied. The effects of digoxin infusion (after 10 and 20 minutes) and sublingual administration of isosorbide dinitrate were investigated in group I (patients with angiographically normal coronary arteries, n = 9) and in group II (patients with atherosclerotic coronary arteries, n = 8). To determine whether the effects of digoxin were mediated by activation of alpha-adrenergic receptors, coronary angiography was performed in group III after alpha-adrenoceptor blockade (phentolamine 0.11 mg/kg, intravenously) (n = 5). Ten minutes after the end of digoxin infusion, the cross-sectional area decreased from 7.7 +/- 4.1 to 6.0 +/- 2.2 mm2, and after 20 minutes to 5.6 +/- 2.6 mm2 (p less than 0.05) in group I. Isosorbide dinitrate reverted digoxin-induced vasoconstriction as cross-sectional area increased to 8.5 +/- 3.4 mm2 (p = not significant versus baseline). Twenty minutes after digoxin infusion, heart rate significantly decreased from 79 +/- 16 to 74 +/- 13 beats/min (p less than 0.01). Ten minutes after digoxin infusion, peripheral vascular resistance increased significantly from 1,396 +/- 693 to 1,693 +/- 984 dynes.s.cm-5 (p less than 0.05), whereas cardiac output did not change. Twenty minutes after digoxin infusion, minimal stenosis diameter decreased significantly from 1.6 +/- 0.5 to 1.4 +/- 0.5 mm (p less than 0.05) in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease., Methods: We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium., Results: In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than 0.01). The effect was significantly potentiated by administration of ketanserin. In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P less than 0.001). Ketanserin prevented this effect., Conclusions: Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect. When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.