Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Assessment of Non-Invasive Measurements of Oxygen Saturation and Heart Rate with an Apple Smartwatch: Comparison with a Standard Pulse Oximeter.

The most commonly used method to assess peripheral oxygen saturation (SpO2) in clinical practice is pulse oximetry. The smartwatch Apple Watch 6 was developed with a new sensor and an app that allows taking on-demand readings of blood oxygen and background readings, day and night. The present study aimed to assess the feasibility and agreement of the Apple Watch 6 compared with a standard SpO2 monitoring system to assess normal and pathological oxygen saturation. We recruited study participants with lung disease or cardiovascular disease and healthy subjects. A total of 265 subjects were screened for enrolment in this study. We observed a strong positive correlation between the smartwatch and the standard commercial device in the evaluation of SpO2 measurements (r = 0.89, p < 0.0001) and HR measurements (r = 0.98, p < 0.0001). A very good concordance was found between SpO2 (bias, −0.2289; SD, 1.66; lower limit, −3.49; and upper limit, 3.04) and HR (bias, −0.1052; SD, 2.93; lower limit, −5.84; and upper limit, 5.63) measured by the smartwatch in comparison with the standard commercial device using Bland−Altman analysis. We observed similar agreements and concordance even in the different subgroups. In conclusion, our study demonstrates that the wearable device used in the present study could be used to assess SpO2 in patients with cardiovascular or lung diseases and in healthy subjects.

Recommendations in pre-procedural imaging assessment for transcatheter aortic valve implantation intervention: Italian Society of Cardiology (SIC)-Italian Society of Medical and Interventional Radiology (SIRM) position paper part 1 (Clinical Indication and Basic Technical Aspects, Heart Team, Role of Echocardiography).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patients for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. Although advanced cardiac imaging with cardiac computed tomography is routinely used for a detailed anatomic assessment before TAVI, echocardiography remains the first imaging modality to assess aortic stenosis severity and to provide essential functional information. This document results from the collaboration between the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), aiming to produce an updated consensus statement about the pre-procedural imaging assessment in patient for TAVI. The writing committee is composed of radiologists and cardiologists, experts in the field of cardiac imaging and structural heart diseases. Part 1 of the document, after a brief overview of the clinical indication and basic technical aspects of TAVI, will focus on the role of echocardiography in TAVI pre-procedural planning.

Recommendations in pre-procedural imaging assessment for TAVI intervention: SIC-SIRM position paper part 2 (CT and MR angiography, standard medical reporting, future perspectives).

Non-invasive cardiovascular imaging owns a pivotal role in the preoperative assessment of patient candidates for transcatheter aortic valve implantation (TAVI), providing a wide range of crucial information to select the patients who will benefit the most and have the procedure done safely. This document has been developed by a joined group of experts of the Italian Society of Cardiology and the Italian Society of Medical and Interventional Radiology and aims to produce an updated consensus statement about the pre-procedural imaging assessment in candidate patients for TAVI intervention. The writing committee consisted of members and experts of both societies who worked jointly to develop a more integrated approach in the field of cardiac and vascular radiology. Part 2 of the document will cover CT and MR angiography, standard medical reporting, and future perspectives.

SIRM-SIC appropriateness criteria for the use of Cardiac Computed Tomography. Part 1: Congenital heart diseases, primary prevention, risk assessment before surgery, suspected CAD in symptomatic patients, plaque and epicardial adipose tissue characterization, and functional assessment of stenosis.

In the past 20 years, Cardiac Computed Tomography (CCT) has become a pivotal technique for the noninvasive diagnostic work-up of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Recent large multicenter randomized clinical trials documented the high prognostic value of CCT and its capability to increase the cost-effectiveness of the management of patients with suspected CAD. In the meantime, CCT, initially perceived as a simple non-invasive technique for studying coronary anatomy, has transformed into a multiparametric "one-stop-shop" approach able to investigate the heart in a comprehensive way, including functional, structural and pathophysiological biomarkers. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT.

Effects of the COVID-19 pandemic on the formation of fellows in training in cardiology.

CoronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.

Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy.

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).

Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment.

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.

Comparative assessment of "plaque/media" change on three modalities of IVUS immediately after implantation of either everolimus-eluting bioresorbable vascular scaffold or everolimus-eluting metallic stent in Absorb II study.

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.

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

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.

[Position paper on the theoretical basis, practical application and health economic evaluation of the functional assessment of coronary lesions endorsed by the Italian Society of Invasive Cardiology (SICI-GISE)]. / Documento di posizione della Società Italiana di Cardiologia Invasiva-Gruppo Italiano Studi Emodinamici (SICI-GISE) sulle basi teoriche, applicazioni pratiche e valutazione economico-sanitaria dell'utilizzo della guida di pressione intracoronarica.

Functional assessment of coronary lesions has become an integral part of routine practice in most cath labs. Such evaluation is performed using a pressure wire that allows measurement of fractional flow reserve (FFR). The latter has received a class I indication with level of evidence A according to the most recent European guidelines on myocardial revascularization for the assessment of angiographically moderate coronary lesions. The present document has the following objectives: 1) to summarize the theoretical basis of FFR; 2) to provide a guideline for vasodilator therapy; 3) to summarize scientific evidence supporting FFR; 4) to provide a model of health economy evaluation focusing on resource sparing associated with the use of FFR.

A clinical and angiographic study of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with multivessel coronary artery disease. Study design and rationale of the EXECUTIVE trial.

BACKGROUND: Myocardial revascularization with drug-eluting stents (DESs) is emerging as an alternative to conventional coronary artery bypass surgery in patients with multivessel coronary artery disease (MV-CAD). First-generation DESs have yielded equivalent safety results at mid-term compared with surgery, but inferior efficacy in preventing the recurrence of ischemic symptoms. The outcome of percutaneous coronary intervention with a second-generation everolimus DES as compared with a paclitaxel DES in patients with MV-CAD has not been established. AIM OF THE STUDY: The aim of the study is the assessment of the efficacy and performance of the XIENCE V everolimus-eluting stent in the treatment of de-novo coronary artery lesions in patients with MV-CAD. STUDY DESIGN: The study is composed of two parts: a prospective, double arm, randomized multicenter trial to assess the angiographic efficacy of the XIENCE V everolimus-eluting coronary stent system (EECSS) compared with the Taxus Liberté Paclitaxel Eluting Coronary Stent System (Taxus Liberté Stent) and a prospective, open-label, single arm, controlled registry to analyze the clinical efficacy and safety of XIENCE V EECSS at mid-term and long-term follow-up in patients treated for MV-CAD. ENDPOINTS: For the EXECUTIVE randomized trial, the primary endpoint is in-stent late lumen loss at 9 months. For the EXECUTIVE registry, the primary endpoint is a composite of all death, myocardial infarction (Q-wave and non-Q-wave), and ischemia-driven target vessel revascularization at 12 months. The study will be conducted at 30 study centers in Italy and 600 patients will be enrolled in total: 200 patients will be enrolled (1: 1) in the randomized trial and 400 patients will enter the registry. SAMPLE SIZE: It was calculated that, assuming a mean in-stent late lumen loss of 0.20 +/- 0.41 mm in the XIENCE V EECSS arm and 0.30 +/- 0.53 mm in the Taxus Liberté stent arm, and a noninferiority margin delta of 0.12 (according to the SPIRIT III results), the analysis of 81 lesions per arm would provide over 90% power. Therefore, 200 patients will be enrolled to account for dropouts. CONCLUSION: The present study is expected to provide as yet unavailable information about the performance of second-generation stents in the specific setting of patients with MV-CAD.

Comparison between four-slice computed tomography and coronary angiography for the assessment of coronary stents.

BACKGROUND: The present study aimed to evaluate the diagnostic accuracy of four-slice computed tomography for the detection, localization and patency assessment of metal coronary stents in a general population referred for coronary angiography late after coronary angioplasty. METHODS: Twenty-four consecutive patients with 34 coronary stents underwent multislice computed tomography within 24 h before a clinically driven coronary angiography performed 245 +/- 92 days after coronary stent implantation. For each patient, two independent operators were asked to evaluate the overall number of stents, the treated coronary vessels and segments, the presence of side-branches in the stented segment, the vessel patency, and the presence of binary in-stent restenosis. RESULTS: Four-slice computed tomography was feasible in 23 out of 24 patients (96%). Diagnostic accuracy was 94% for stent detection, 96% for the recognition of the stented coronary vessel and 97% for the identification of the stented segment. Accuracy in detection of side-branches in the stented segment, vessel patency and in-stent restenosis was 86%, 88% and 50%, respectively. CONCLUSIONS: Four-slice computed tomography is accurate in the identification of the stented coronary vessel and segment. By contrast, accuracy is low in the detection of vessel patency and in-stent restenosis. Such a technique does not appear to be useful as a screening tool before invasive diagnostic procedures.

Combined Abciximab REteplase Stent Study in acute myocardial infarction (CARESS in AMI).

BACKGROUND: Most patients with acute myocardial infarction (AMI) are admitted to hospitals without percutaneous transluminal coronary angioplasty (PTCA) facilities or are initially managed in a prehospital mobile unit. Thrombolysis remains the most readily available reperfusion treatment in those settings, but the optimal subsequent strategy in those patients is unclear. If a mechanical recanalization is likely to be performed in an emergency, it is probably desirable that the patient receives abciximab, the glycoprotein IIb/IIIa antagonist with the strongest evidence of benefit for angioplasty in AMI. OBJECTIVE: The aim of this trial is to compare the effects on clinical outcome and cost-effectiveness of 2 strategies after immediate treatment with abciximab and half-dose reteplase for ST-elevation AMI: to manage the patients conservatively (referring them for rescue PTCA only if needed) or to immediately send all patients for emergency coronary angioplasty. METHODS: The Combined Abciximab RE-teplase Stent Study in Acute Myocardial Infarction (CARESS in AMI) is an open, prospective, randomized, multicenter clinical trial conducted in patients with high-risk ST-segment elevation AMI treated within 12 hours from symptom onset in hospitals without PTCA facilities or in a prehospital mobile intensive care unit. Apart from contraindications to thrombolysis, the main exclusion criteria are age > or =75 years and a past history of CABG surgery or a percutaneous coronary intervention procedure involving the infarct-related artery. Enrollment will be performed in hospitals without PTCA facilities or directly in the ambulance if a dedicated system is in place for prehospital diagnosis and treatment of AMI. Patients will receive half-dose reteplase and full-dose abciximab and will subsequently be randomized to conventional medical therapy (with referral for emergency rescue PTCA allowed in selected cases) or emergency angioplasty. The primary end point is the 30-day combined incidence of mortality, reinfarction, and refractory ischemia. In order to obtain a 95% power (2-sided) to detect a 42% reduction in the primary end point, 900 patients are required in each arm of the study. Secondary end points include the 1-year composite end point of mortality, reinfarction, refractory ischemia, and hospital readmission because of heart failure; resource use at 30 days and 1 year; and the incidence of inhospital stroke and bleeding complications in the 2 groups. RESULTS: Seventy-four patients have been randomized (as of March 10, 2004); results are expected in June 2005. CONCLUSION: This study will establish whether angioplasty must be started as soon as possible in all patients who receive combined pharmacologic reperfusion with the glycoprotein IIb/IIIa inhibitor abciximab and half-dose thrombolysis or whether it can be postponed or skipped in patients with signs of successful reperfusion, with obvious organizational advantages.