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.

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.

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.

Assessment of lesion-associated myocardial ischemia based on fusion coronary CT imaging - the FUSE-HEART study: A protocol for non-randomized clinical trial.

INTRODUCTION: Multimodality assessment of coronary artery lesions has demonstrated superior effectiveness compared to the conventional approach, for assessing both anatomical and functional significance of a coronary stenosis. Multiple imaging modalities can be integrated into a fusion imaging tool to better assess myocardial ischemia. MATERIAL AND METHODS: The FUSE-HEART trial is a single center, prospective, cohort study that will assess the impact of a coronary artery stenosis on myocardial function and viability, based on advanced fusion imaging technics derived from Cardiac Computed Tomography Angiography (CCTA). Moreover, the study will investigate the correlation between morphology and composition of the coronary plaques and myocardial ischemia in the territory irrigated by the same coronary artery. At the same time, imaging parameters will be correlated with inflammatory status of the subjects. The trial will include 100 subjects with coronary lesions found on CCTA examination. The study population will be divided into 2 groups: first group will consist of subjects with anatomically significant coronary lesions on native coronary arteries and the second one will include subjects surviving an acute myocardial infarction. The vulnerability score of the subjects will be calculated based on presence of CCTA vulnerability markers of the coronary plaques: napkin ring sign, positive remodeling, spotty calcifications, necrotic core, and low-density plaques. 3D fusion images of the coronary tree will be generated, integrating the images reflecting wall motion with the ones of coronary circulation. The fusion models will establish the correspondence between plaque composition and wall motion in the subtended myocardium of the coronary artery. The study primary outcome will be represented by the rate of major adverse cardiac events related to myocardial ischemia at 1-year post assessment, in correlation with the degree of coronary artery stenosis and myocardial ischemia or viability.The secondary outcomes are represented by the rate of re-hospitalization, rate of survival and rate of major adverse cardiovascular events (including cardiovascular death or stroke), in correlation with the morphology and composition of atheromatous plaques located in a coronary artery, and myocardial ischemia in the territory irrigated by the same coronary artery. CONCLUSION: In conclusion, FUSE-HEART will be a study based on modern imaging tools that will investigate the impact of a coronary artery stenosis on myocardial function and viability, using advanced fusion imaging technics derived from CCTA, sighting to validate plaque composition and morphology, together with inflammatory biomarkers, as predictors to myocardial viability.

Impact of cardiac rehabilitation programs on left ventricular remodeling after acute myocardial infarction: Study Protocol Clinical Trial (SPIRIT Compliant).

INTRODUCTION: While the role of early mobilization in the immediate postinfarction period has been well demonstrated, little is known in present about the link between early mobilization and reduction of systemic inflammation. At the same time, the impact of early mobilization on regression of left ventricular remodeling has not been elucidated so far. MATERIAL AND METHODS: Here we present the study protocol of the REHAB trial, a clinical descriptive, prospective study, conducted in a single-center, with the purpose to analyze the impact of early mobilization in reducing left ventricular remodeling, the complication rates and mortality in patients who had suffered a recent acute myocardial infarction (AMI). At the same time, the study aims to demonstrate the contribution of early mobilization to reduction of systemic inflammation, thus reducing the inflammation-mediated ventricular remodeling. 100 patients with AMI in the last 12 hours, and successful revascularization of the culprit artery within the first 12 hours after the onset of symptoms in ST-segment elevation acute myocardial infarction or within first 48 hours in non ST-segment elevation AMI will be enrolled in the study. Based on the moment of mobilization after AMI patients will be distributed in 2 groups: group 1 - patients with early mobilization (<2 days after the onset of symptoms) and; group 2 - subjects with delayed mobilization after AMI (>2 days after the onset of symptoms). Study outcomes will consist in the impact of early mobilization after AMI on the ventricular remodeling in the post-infarction period, as assessed by cardiac magnetic resonance imaging, the rate of in-hospital mortality, the rate of repeated revascularization or MACE and the effect of early mobilization on systemic inflammation in the immediate postinfarction phase. CONCLUSION: In conclusion, REHAB will be the first trial that will elucidate the impact of early mobilization in the first period after AMI, as a first step of a complex cardiac rehabilitation program, to reduce systemic inflammation and prevent deleterious ventricular remodeling in patients who suffered a recent AMI.

Altered nutritional status, inflammation and systemic vulnerability in patients with acute myocardial infarction undergoing percutaneous coronary revascularisation: A prospective study in a level 3 cardiac critical care unit.

AIM: The aim of the present study was to assess the influence of nutritional status, as expressed by Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) scores, on the inflammatory response following acute myocardial infarction (AMI) and the impact of an altered nutritional status and increased systemic inflammation on immediate evolution following AMI. METHODS: This was an observational prospective study in which we used the CONUT score and GNRI on 86 consecutive patients with AMI receiving primary revascularisation, divided into a well-nourished group (CONUT score 0-2, n = 68) and moderate-to-severe nutritional deficit group (CONUT score ≥ 3, n = 18). Inflammatory status was assessed on the basis of highly sensitive C-reactive protein (hs-CRP) at baseline and on day 5. RESULTS: Malnourished patients presented significantly higher levels of serum hs-CRP at baseline (33.6 ± 35.02 mg/dL vs 10.26 ± 25.93 mg/dL, P < 0.0001) and day 5 (52.8 ± 46.25 mg/dL vs 17.04 ± 24.78 mg/dL, P < 0.0001). GNRI values showed a weak but significant correlation with serum hs-CRP at baseline (r = -0.26, P = 0.01) and day 5 (r = -0.44, P < 0.0001). Patients with altered nutritional status presented more frequent deterioration of their haemodynamical status, requiring inotropic support (P = 0.002) and longer hospitalisation in the acute cardiac care unit (4.27 ± 2.60 vs 2.85 ± 0.73 days, P = 0.005). Patients requiring intravenous inotropics had a higher CONUT score (2.31 ± 1.7 vs 1.17 ± 1.27, P = 0.01), lower GNRI (102.0 ± 5.31 vs 98.56 ± 5.2, P = 0.02) and higher hs-CRP levels at baseline and day 5 (31.40 ± 46.57 vs 18.52 ± 32.98, P = 0.04 and 46.04 ± 51.50 vs 19.60 ± 46.05, P = 0.006). CONCLUSIONS: Malnourished patients with AMI had more expressed inflammation, increased blood vulnerability and worse outcomes.

Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis.

Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress.

Impact of inflammation-mediated response on pan-coronary plaque vulnerability, myocardial viability and ventricular remodeling in the postinfarction period - the VIABILITY study: Protocol for a non-randomized prospective clinical study.

INTRODUCTION: While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree, on the extension of ventricular remodeling and scaring, has not been clarified yet. MATERIALS AND METHODS: The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study. The main purpose of this trial is to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). One hundred patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms will be enrolled in the study. The level of systemic inflammation will be evaluated based on the serum biomarker levels (hs-CRP, matrix metalloproteinases, interleukin-6) in the acute phase of the myocardial infarction (MI) and at 1 month. Pan-coronary plaque vulnerability will be assessed based on serum biomarkers known to be associated with increased plaque vulnerability (V-CAM or I-CAM) and at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features of all coronary plaques. Myocardial viability and remodeling will be assessed based on 3D speckle tracking echocardiography associated with dobutamine infusion and LGE-CMR associated with post-processing imaging methods. The study population will be categorized in 2 subgroups: subgroup 1 - subjects with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl), and subgroup 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP < 3 mg/dl). Study outcomes will consist in the rate of post-infarction heart failure development and the major adverse events (MACE) rate. CONCLUSION: VIABILITY is the first prospective study designed to evaluate the influence of infarct-related inflammatory response on several major determinants of post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling.

Impact of inflammation-mediated myocardial fibrosis on the risk of recurrence after successful ablation of atrial fibrillation - the FIBRO-RISK study: Protocol for a non-randomized clinical trial.

INTRODUCTION: Interventional ablation has been demonstrated to represent an effective therapy in patients with atrial fibrillation (AF), leading to restoration and maintenance of sinus rhythm in the majority of cases. However, recurrence of AF is encountered in 35% to 40% of cases, and the causes for this frequent complication have not been elucidated so far. MATERIAL AND METHODS: Here we present the study protocol of the FIBRO-RISK trial, a prospective, single-center, cohort study which aims to investigate the impact of inflammatory-mediated myocardial fibrosis on the risk of recurrence after successful catheter ablation of atrial fibrillation. The level of systemic inflammation in the pre-ablation and immediate post-ablation period will be assessed on the basis of serum levels of inflammatory biomarkers (hsCRP, matrix metalloproteases, interleukin-6), while the level of cardiac fibrosis will be determined based on cardiac magnetic resonance imaging associated with complex post-processing techniques for mapping myocardial fibrosis at the level of left atrium and left ventricle. At the same time, the amount of epicardial fat will serve as an indirect marker of localized inflammation and will be determined at different levels in the heart (surrounding left atrium, right atrium or the entire heart), while ventricular function will be assessed on the basis of serum levels of NT-proBNP prior to the procedure. All these parameters will be investigated in patients with successful ablation of AF, who will be divided into 2 groups: group 1 - patients who develop AF recurrence at 1-year, and group 2 - patients with no recurrence of AF at 1-year. In all patients, the following biomarkers will be determined: serum levels of inflammatory biomarkers and NT-proBNP at 24 hours and 1-year post procedure, the amount of myocardial fibrosis at the level of left atrium and left ventricle at baseline +/- 7 days, and the amount of epicardial fat surrounding left atrium, right atrium and the entire heart at baseline +/- 7 days.The primary endpoint of the study will be represented by the rate of AF recurrence at 1-year post ablation, documented by either ECG or Holter monitoring. The secondary endpoints of the study will consist in:In conclusion, FIBRO-RISK will be the first CMR-based study that will investigate the impact of inflammation-mediated myocardial fibrosis and ventricular remodeling on the risk of recurrence after successful ablation of AF, aiming to validate inflammatory biomarkers and myocardial fibrosis as predictors for AF recurrence.