Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

High iliac calcium score is associated with increased severity and complexity of peripheral arterial disease and predicts global atherosclerotic burden.

BACKGROUND: The role of vascular calcifications in iliac arteries for predicting global atherosclerotic burden in still unknown. The aim of this study was to investigate whether iliac calcium score (ICS), a new computed tomographic angiography (CTA) derived biomarker of vascular calcification, can predict the severity and complexity of peripheral arterial disease (PAD) as well as the global atherosclerotic burden. PATIENTS AND METHODS: This was a single centre, non-randomized, observational prospective study on 84 consecutive patients with symptomatic peripheral arterial disease, undergoing peripheral CTA examination of the lower limbs, divided into high (n = 42) and low ICS (n = 42) groups with a median value for ICS of 3934 HU. RESULTS: Patients with high ICS were significantly older (66.2 ± 8.0 vs. 62.8 ± 11.2, p < 0.0001) and were more frequently diabetic (61.9 vs. 38.1 %, p = 0.04). ICS was significantly higher in patients with Rutherford stage 5-6 vs. 1-2 (p = 0.03) and in TASC D or TASC C vs. TASC B class (p = 0.01). Mean iliac intima-media thickness (i-IMT) was significantly higher in the high ICS group compared to the low ICS group (1.3 ± 0.2 vs. 0.9 ± 0.2, p < 0.0001). Linear regression analysis demonstrated a very good correlation between ICS and i-IMT (r = 0.59, p < 0.0001 for right, r = 0.57, p < 0.0001 for left and r = 0.67, p < 0.0001 for both iliac arteries averaged). Patients with high ICS presented a significantly lower left ventricular ejection fraction compared to those with low ICS (45.3 ± 4.3 vs. 53.8 ± 4.8, p < 0.0001). Linear regression analysis demonstrated significant inverse correlation between ICS and left ventricular EF (r = -0.54, p < 0.0001). CONCLUSIONS: Increased values of ICS, a new CTA marker of vascular calcification, are associated with a higher severity and complexity of PAD and a more depressed left ventricular function. High ICS values are also associated with increased i-IMT. Both can represent new surrogate markers of an increased atherosclerotic burden.

CT-Assessment of Epicardial Fat Identifies Increased Inflammation at the Level of the Left Coronary Circulation in Patients with Atrial Fibrillation.

Background: Atrial fibrillation (AF) can often be triggered by an inflammatory substrate. Perivascular inflammation may be assessed nowadays using coronary computed tomography angiography (CCTA) imaging. The new pericoronary fat attenuation index (FAI HU) and the FAI Score have prognostic value for predicting future cardiovascular events. Our purpose was to investigate the correlation between pericoronary fat inflammation and the presence of AF among patients with coronary artery disease. Patients and methods: Eighty-one patients (mean age 64.75 ± 7.84 years) who underwent 128-slice CCTA were included in this study and divided into two groups: group 1 comprised thirty-six patients with documented AF and group 2 comprised forty-five patients without a known history of AF. Results: There were no significant differences in the absolute value of fat attenuation between the study groups (p > 0.05). However, the mean FAI Score was significantly higher in patients with AF (15.53 ± 10.29 vs. 11.09 ± 6.70, p < 0.05). Regional analysis of coronary inflammation indicated a higher level of this process, especially at the level of the left anterior descending artery (13.17 ± 7.91 in group 1 vs. 8.80 ± 4.75 in group 2, p = 0.008). Conclusions: Patients with AF present a higher level of perivascular inflammation, especially in the region of the left coronary circulation, and this seems to be associated with a higher risk of AF development.

Acute-Phase Inflammatory Reaction Predicts CMR Myocardial Scar Pattern and 2-Year Mortality in STEMI Patients Undergoing Primary PCI.

(1) Background: The inflammatory response following MI plays an important role in the healing, scar formation, and left ventricle (LV) remodeling. Cardiac magnetic resonance (CMR) imaging can accurately quantify the extent of myocardial scarring. The study aimed to investigate: (a) the relationship between acute inflammatory response and the CMR parameters of the scarring extent, and (b) the predictive power of inflammatory biomarkers and myocardial scarring for 2-year mortality. (2) Methods: The study included 202 STEMI patients, who underwent pPCI. Serum hs-CRP, IL-6, P-selectin, E-selectin, I-CAM, and V-CAM levels were determined at admission, and hs-CRP on the fifth day. Patients underwent LGE-CMR after 1 month, for LV volumes, ejection fraction (EF), infarct size (IS), and transmurality. Subjects were divided into tertiles according to the IS, and 2-year all-cause mortality was determined. (3) Results: IL-6 was associated with IS (r = 0.324, p = 0.01), increased transmurality index (r = 0.3, p = 0.01), and lower LVEF (r = −0.3, p = 0.02). Admission hs-CRP levels were not associated with IS, transmurality, or mortality, while hs-CRP at day 5 was a significant predictor for IS (AUC = 0.635, p = 0.05) as well as IL-6 levels (AUC = 0.685, p < 0.001). Mortality was significantly higher in the upper IS tertiles (6% vs. 8.7% vs. 24.52%, p = 0.005). IS was a significant predictor of 2-year mortality (AUC = 0.673, p = 0.002), with a cut-off value of 28.81 g, as well as high transmurality (AUC = 0.641, p = 0.013), with a cut off value of 18.38 g. (4) Conclusions: The serum levels of IL-6 and day-5 hs-CRP predict IS and transmurality, and day-5 hs-CRP levels are independent predictors of 2-year mortality in STEMI patients treated with pPCI. The CMR pattern of myocardial scarring after 1 month, as expressed by the magnitude of IS and transmurality, is a significant predictor for 2-year mortality after revascularized STEMI.

Imaging Cardiovascular Inflammation in the COVID-19 Era.

Cardiac complications are among the most frequent extrapulmonary manifestations of COVID-19 and are associated with high mortality rates. Moreover, positive SARS-CoV-2 patients with underlying cardiovascular disease are more likely to require intensive care and are at higher risk of death. The underlying mechanism for myocardial injury is multifaceted, in which the severe inflammatory response causes myocardial inflammation, coronary plaque destabilization, acute thrombotic events, and ischemia. Cardiac magnetic resonance (CMR) imaging is the non-invasive method of choice for identifying myocardial injury, and it is able to differentiate between underlying causes in various and often challenging clinical scenarios. Multimodal imaging protocols that incorporate CMR and computed tomography provide a complex evaluation for both respiratory and cardiovascular complications of SARS-CoV2 infection. This, in relation to biological evaluation of systemic inflammation, can guide appropriate therapeutic management in every stage of the disease. The use of artificial intelligence can further improve the diagnostic accuracy of these imaging techniques, thus enabling risk stratification and evaluation of prognosis. The present manuscript aims to review the current knowledge on the possible modalities for imaging COVID-related myocardial inflammation or post-COVID coronary inflammation and atherosclerosis.

Systemic Vulnerability, as Expressed by I-CAM and MMP-9 at Presentation, Predicts One Year Outcomes in Patients with Acute Myocardial Infarction-Insights from the VIP Clinical Study.

(1) Background: The prediction of recurrent events after acute myocardial infarction (AMI) does not sufficiently integrate systemic inflammation, coronary morphology or ventricular function in prediction algorithms. We aimed to evaluate the accuracy of inflammatory biomarkers, in association with angiographical and echocardiographic parameters, in predicting 1-year MACE after revascularized AMI. (2) Methods: This is an extension of a biomarker sub-study of the VIP trial (NCT03606330), in which 225 AMI patients underwent analysis of systemic vulnerability and were followed for 1 year. Hs-CRP, MMP-9, IL-6, I-CAM, V-CAM and E-selectin were determined at 1 h after revascularization. The primary end-point was the 1-year MACE rate. (3) Results: The MACE rate was 24.8% (n = 56). There were no significant differences between groups in regard to IL-6, V-CAM and E-selectin. The following inflammatory markers were significantly higher in MACE patients: hs-CRP (11.1 ± 13.8 vs. 5.1 ± 4.4 mg/L, p = 0.03), I-CAM (452 ± 283 vs. 220.5 ± 104.6, p = 0.0003) and MMP-9 (2255 ± 1226 vs. 1099 ± 706.1 ng/mL p = 0.0001). The most powerful predictor for MACE was MMP-9 of >1155 ng/mL (AUC-0.786, p < 0.001) even after adjustments for diabetes, LVEF, acute phase complications and other inflammatory biomarkers. For STEMI, the most powerful predictors for MACE included I-CAM > 239.7 ng/mL, V-CAM > 877.9 ng/mL and MMP-9 > 1393 ng/mL. (4) Conclusions: High levels of I-CAM and MMP-9 were the most powerful predictors for recurrent events after AMI for the overall study population. For STEMI subjects, the most important predictors included increased levels of I-CAM, V-CAM and MMP-9, while none of the analyzed parameters had proven to be predictive. Inflammatory biomarkers assayed during the acute phase of AMI presented a more powerful predictive capacity for MACE than the LVEF.

Impact of COVID-19 Pandemic on STEMI Networks in Central Romania.

The COVID-19 pandemic has had a major impact on cardiovascular emergencies. The aim of this study was to investigate the impact of the COVID-19 pandemic on a regional network for management of ST-segment elevation acute myocardial infarction (STEMI). METHODS: We report a single center's experience of patients hospitalized for ACS in a high-volume hub of a STEMI network during the lockdown (in the first pandemic trimester), compared with the same time interval of the previous year and including all consecutive patients referred for an AMI during the second trimester of 2020 (from April to June) or during the same time interval of the previous year, 2019. RESULTS: The absolute number of hospital admissions for AMI decreased by 22.3%, while the non-AMI hospitalizations decreased by 77.14% in Q2-2020 compared to Q2-2019 (210 vs. 48, p < 0.0001). As a consequence, the percentage of AMI cases from the total number of hospital admission increased from 38% to 68% (p < 0.0001), AMI becoming the dominant pathology. In the STEMI group there was a significant reduction of 55% in the absolute number of late STEMI presentations. Functionality of the STEMI network at the hub level did not present a significant alteration with only a minor increase in the door-to-balloon time, from 34 min to 41 min. However, at the level of the network we recorded a lower number of critical cases transferred to the interventional center, with a dramatic reduction of 56.1% in the number of critical STEMI cases arriving in the acute cardiac care unit (17.0% vs. 7.3%, p-0.04 for KILLIP class III, and 21.17% vs. 11.11%, p = 0.08 for resuscitated out of hospital cardiac arrest). CONCLUSIONS: The COVID-19 outbreak did not have a major impact on the interventional center's functionality, but it limited the capacity of the regional STEMI network to bring the critical patient with complicated STEMI to the cathlab in time during the first months of the lockdown. Even a very well-functioning STEMI network like the one in Central Romania had difficulties bringing the most critical STEMI cases to the cathlab in time.

Cardiovascular Imaging for Guiding Interventional Therapy in Structural Heart Diseases.

Development of interventional methods has revolutionized the treatment of structural cardiac diseases. Given the complexity of structural interventions and the anatomical variability of various structural defects, novel imaging techniques have been implemented in the current clinical practice for guiding the interventional procedure and for selection of the device to be used. Three- dimensional echocardiography is the most used imaging method that has improved the threedimensional assessment of cardiac structures, and it has considerably reduced the cost of complications derived from malalignment of interventional devices. Assessment of cardiac structures with the use of angiography holds the advantage of providing images in real time, but it does not allow an anatomical description. Transesophageal Echocardiography (TEE) and intracardiac ultrasonography play major roles in guiding Atrial Septal Defect (ASD) or Patent Foramen Ovale (PFO) closure and device follow-up, while TEE is the procedure of choice to assess the flow in the Left Atrial Appendage (LAA) and the embolic risk associated with a decreased flow. On the other hand, contrast CT and MRI have high specificity for providing a detailed description of structure, but cannot assess the flow through the shunt or the valvular mobility. This review aims to present the role of modern imaging techniques in pre-procedural assessment and intraprocedural guiding of structural percutaneous interventions performed to close an ASD, a PFO, an LAA or a patent ductus arteriosus.

Stem cell-derived exosomes - an emerging tool for myocardial regeneration.

Cardiovascular diseases (CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction (AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cells that can generate new myocardial tissue to replace the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosome-based therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

Right Ventricle Remodeling and Function in Scleroderma Patients.

Scleroderma, known also as systemic sclerosis (SSc), is a severe disease associated with high mortality rates, and right ventricular (RV) remodeling and dysfunction, along with pulmonary artery hypertension (PAH), are among the most important internal organ manifestations of this disease. PAH has a higher prevalence in patients with SSc compared to the general population and represents a significant predictor of mortality in SSc. In patients with SSc, the morphological remodeling and alteration of RV function begin even before the setting of PAH and lead to development of a specific adaptive pattern of the RV which is different from the one recorded in patients with IAPH. These alterations cause worse outcomes and increased mortality rates in SSc patients. Early detection of RV dysfunction and remodeling is possible using modern imaging tools currently available and can indicate the initiation of specific therapeutic measures before installation of PAH. The aim of this review is to summarize the current knowledge related to mechanisms involved in the remodeling and functional alteration of the RV in SSc patients.

Impact of coronary plaque geometry on plaque vulnerability and its association with the risk of future cardiovascular events in patients with chest pain undergoing coronary computed tomographic angiography-the GEOMETRY study: Protocol for a prospective clinical trial.

INTRODUCTION: Coronary computed tomography angiography (CCTA) has emerged as a valuable noninvasive imaging tool for assessing atheromatous plaque morphology and composition, and several CCTA features have been validated as reliable indicators of the plaque-associated risk. However, the role of lesion geometry as a CCTA feature of plaque vulnerability has not been investigated so far. MATERIAL AND METHODS: Here we present the study protocol of the GEOMETRY trial, a prospective, single center, cohort study in which we aim to investigate the relationship between plaque geometry (as expressed by cross-sectional and longitudinal plaque eccentricity) and the risk for major adverse cardiac events (MACE) during 2 years of follow-up, in order to validate plaque eccentricity as a new CCTA marker of coronary plaque vulnerability. One thousand patients with suspected coronary artery disease (CAD) and pretest probability of CAD between 15% and 85%, who undergo CCTA and in whom CCTA identifies the presence of at least 1 significant coronary plaque (producing a luminal narrowing of at least 50%) will be enrolled in the study. Based on the results of complex image post-processing and plaque analysis, patients will be divided into 2 groups: group 1-patients in whom CCTA analysis identifies only non-eccentric coronary plaque; and group 2-patients in whom CCTA analysis reveals the presence of at least 1 eccentric significant coronary plaque producing a significant luminal narrowing. Study outcomes will consist in the rate of major cardiovascular events and the rate of plaque progression during follow-up.The study is funded by the Romanian Ministry of European Funds, the Romanian Government and the European Union, as part of the research grant number 103544/2016 - PlaqueIMAGE (contract number 26/01.09.2016). CONCLUSION: In conclusion, GEOMETRY will be the first CCTA-based study that will investigate the impact of geometric distribution of coronary atheromatous plaque on the future risk of cardiovascular events and on the rate of plaque progression, introducing and validating a new potential feature of plaque vulnerability represented by plaque geometry.

Predictors of Mortality in Patients with ST-Segment Elevation Acute Myocardial Infarction and Resuscitated Out-of-Hospital Cardiac Arrest.

INTRODUCTION: In patients with out-of-hospital cardiac arrest (OHCA) complicating an ST-segment elevation myocardial infarction (STEMI), the survival depends largely on the restoration of coronary flow in the infarct related artery. The aim of this study was to determine clinical and angiographic predictors of in-hospital mortality in patients with OHCA and STEMI, successfully resuscitated and undergoing primary percutaneous intervention (PCI). METHODS: From January 2013 to July 2015, 78 patients with STEMI presenting OHCA, successfully resuscitated, transferred immediately to the catheterization unit and treated with primary PCI, were analyzed. Clinical, laboratory and angiographic data were compared in 28 non-survivors and 50 survivors. RESULTS: The clinical baseline characteristics of the study population showed no significant differences between the survivors and non-survivors in respect to age (p=0.06), gender (p=0.8), the presence of hypertension (p=0.4), dyslipidemia (p=0.09) obesity (p=1), smoking status (p=0.2), presence of diabetes (p=0.2), a clinical history of acute myocardial infarction (p=0.7) or stroke (p=0.17). Compared to survivors, the non-survivor group exhibited a significantly higher incidence of cardiogenic shock (50% vs 24%, p=0.02), renal failure (64.3% vs 30.0%, p=0.004) and anaemia (35.7% vs 12.0%, p=0.02). Three-vessel disease was significantly higher in the non-survivor group (42.8% vs. 20.0%, p=0.03), while there was a significantly higher percentage of TIMI 3 flow postPCI in the infarct-related artery in the survivor group (80.% vs. 57.1%, p=0.03). The time from the onset of symptoms to revascularization was significantly higher in patients who died compared to those who survived (387.5 +/- 211.3 minutes vs 300.8 +/- 166.1 minutes, p=0.04), as was the time from the onset of cardiac arrest to revascularization (103.0 +/- 56.34 minutes vs 67.0 +/- 44.4 minutes, p=0.002). Multivariate analysis identified the presence of cardiogenic shock (odds ratio [OR]: 3.17, p=0.02), multivessel disease (OR: 3.0, p=0.03), renal failure (OR: 4.2, p=0.004), anaemia (OR: 4.07, p=0.02), need for mechanical ventilation >48 hours (OR: 8.07, p=0.0002) and a duration of stay in the ICU longer than 5 days (OR: 9.96, p=0.0002) as the most significant independent predictors for mortality in patients with OHCA and STEMI. CONCLUSION: In patients surviving an OHCA in the early phase of a myocardial infarction, the presence of cardiogenic shock, renal failure, anaemia or multivessel disease, as well as a longer time from the onset of symptoms or of cardiac arrest to revascularization, are independent predictors of mortality. However, the most powerful predictor of death is the duration of stay in the ICU and the requirement of mechanical ventilation for more than forty-eight hours.