Background: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFR _CT ) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFR _CT on heart team’s treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. Methods: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFR _CT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFR _CT changed the treatment decision and planning. Results: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFR _CT analysis in 88%. FFR _CT was available for 1030 lesions (mean FFR _CT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFR _CT . The addition of FFR _CT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFR _CT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. Conclusions: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFR _CT changed heart team’s treatment decision-making and procedural planning in one-fifth of the patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02813473.

The number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide is increasing dramatically [1], and reports from China, Iran, Italy and other areas hit hard by SARS-CoV-2 are chilling. The metropolitan area of Milan and its surrounding region of the Lombardy are one of the worst affected in Italy, and Europe at the moment. As of 29 March 2020, there have been 97 689 cases with 10 779 fatalities due to COronaVIrus Disease 2019 (COVID-19) in whole of Italy; of these, 41 007 (6360 fatalities) have occurred in Lombardy region [2]. In order to slow down viral transmission, local authorities and the Italian government have imposed strong containment measures by quarantining initial COVID-19 clusters and followed by a complete nationwide lock-down. The exponential increase in COVID-19-positive patients and the dramatically increasing need for intensive care unit (ICU) surge capacity for the management of critically ill patients has led the emergency task force of the Lombardy region to reallocate ICU resources [3]. In addition, elective surgery has been cancelled and beds dedicated to cardiac, neurosurgery and partially coronary care units reassigned to COVID-19-patients. For this reason, 16 of the 20 cardiac surgical units in the Lombardy region have discontinued their activities, with the remaining 4 units forming ‘the hub’ for the 16 other closed units (spokes). In this hub-and-spoke system, all urgent and emergency cases are sent to these 4 units, including those that cannot be delayed for more than 60 days. Moreover, beds for critically ill patients are also obtained from the reconversion of operation and recovery rooms (A. Parolari, personal communication).

Background: CD 34 ⁺ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34 ⁺ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be “memorized” by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results: Cord‐blood–derived CD 34 ⁺ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66 ^shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal‐cell–derived factor 1 alpha and reduced protein and mRNA expression of the C‐X‐C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high‐glucose CD 34 ⁺ stem cells that negatively correlated with mRNA expression (Pearson r =−0.76; P =0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high‐glucose CD 34 ⁺ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34 ⁺ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions: CD 34 ⁺ stem cells “memorize” the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration.

The Commando procedure is challenging, and aims to replace the mitral valve, the aortic valve and the aortic mitral curtain, when the latter is severely affected by pathological processes (such as infective endocarditis or massive calcification). Given the high complexity, it is seldomly performed. We aim to review the literature on early (hospitalization and up to 30 days) and long-term (at least 3 years of follow-up) results. Bibliographical research was performed on PubMed and Cochrane with a dedicated string. Papers regarding double valve replacement or repair in the context of aortic mitral curtain disease were included. The metaprop function was used to assess early survival and complications (pacemaker implantation, stroke and bleeding). Nine papers (540 patients, median follow-up 41 (IQR 24.5–51.5) months) were included in the study. Pooled proportion of early mortality, stroke, pacemaker implant and REDO for bleeding were, respectively 16.2%, 7.8%, 25.1% and 13.1%. The long-term survival rate ranged from 50% to 92.2%. Freedom from re-intervention was as high as 90.9% when the endocarditis was not the first etiology and 78.6% in case of valvular infection (one author had 100%). Freedom from IE recurrences reached 85% at 10 years. Despite the high mortality, the rates of re-intervention and infective endocarditis recurrences following the Commando procedure are satisfactory and confirm the need for an aggressive strategy to improve long-term outcomes.

Coronary artery bypass surgery (CABG) is still one of the most frequently performed surgical procedures all over the world. The results of this procedure have been constantly improved over the years with low perioperative mortality rates, and with relatively low complication rates. To further improve these outstanding results the clinicians focused their attention at biomarkers as outcome predictors. Although biological testing for disease prediction has already been discussed many times, the role of biomarkers in outcome prediction after CABG is still controversial. In this paper we reviewed the current knowledge regarding the role of genetic and dynamic biomarkers and their possible association with the occurrence of adverse clinical outcomes after CABG. We also took into consideration the molecular pathway activation and the possible imbalance that may affect hard outcomes and graft patency. We analysed biomarkers classified in two different categories depending on their possibility to change over time: genetic markers and dynamic markers. Moreover, we evaluated these markers by dividing them, into sub-categories, such as inflammation, haemostasis, renin-angiotensin, endothelial function and other pathways. We showed that biomarkers might be associated with unfavourable outcomes after surgery, and in some cases improved outcome prediction. However, the identification of a specific panel of biomarkers or of some algorithms including biomarkers is still in an early developmental phase. Finally, larger studies are needed to analyse broad panel of biomarkers with the specific aim to evaluate the prediction of hard outcomes and graft patency.

OBJECTIVES: During the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic, Northern Italy had to completely reorganize its hospital activity. In Lombardy, the hub-and-spoke system was introduced to guarantee emergency and urgent cardiovascular surgery, whereas most hospitals were dedicated to patients with coronavirus disease 2019 (COVID-19). The aim of this study was to analyse the results of the hub-and-spoke organization system. METHODS: Centro Cardiologico Monzino (Monzino) became one of the four hubs for cardiovascular surgery, with a total of eight spokes. SARS-CoV-2 screening became mandatory for all patients. New flow charts were designed to allow separated pathways based on infection status. A reorganization of spaces guaranteed COVID-19-free and COVID-19-dedicated areas. Patients were also classified into groups according to their pathological and clinical status: emergency, urgent and non-deferrable (ND). RESULTS: A total of 70 patients were referred to the Monzino hub-and-spoke network. We performed 41 operations, 28 (68.3%) of which were emergency/urgent and 13 of which were ND. The screening allowed the identification of COVID-19 (three patients, 7.3%) and non-COVID-19 patients (38 patients, 92.7%). The newly designed and shared protocols guaranteed that the cardiac patients would be divided into emergency, urgent and ND groups. The involvement of the telematic management heart team allowed constant updates and clinical discussions. CONCLUSIONS: The hub-and-spoke organization system efficiently safeguards access to heart and vascular surgical services for patients who require ND, urgent and emergency treatment. Further reorganization will be needed at the end of this pandemic when elective cases will again be scheduled, with a daily increase in the number of operations.