Central venus cannulation during cardiac surgery as a possible new additional risk factor for late post-operative atrial fibrillation insurgence.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most frequent cardiac arrhythmia following cardiac operations. It has been associated with an increased risk of postoperative cerebrovascular complications, morbidity and mortality. The aim of this study is to evaluate if the type of venous cannulation to institute the cardiopulmonary bypass (CPB) during major cardiac surgery procedures can influence the rate of POAF and late FA onset. METHODS: We collected data from 2087 consecutive patients who have been operated at our Institution from January 2016 to December 2018. To obtain two homogenous groups we performed a propensity match analyzes: Group 1 for whom the blood drain of the CPB has been granted via peripheral cannulation (PC) through the right common femoral vein and Group 2 with patients who underwent central cannulation (CC) with insertion of a drainage cannula in the right atrium or in the superior and inferior vein cava. RESULTS: POAF has been observed as statistically similar between the two groups. At 1250-day follow-up, While the incidence of POAF was 2.9% and 8.7% in the PC and CC groups, respectively (p = .04). CONCLUSIONS: our data seems to show that the two groups do not differ in terms of POAF, while the CC group may have a significantly higher rate of atrial fibrillation in the follow-up period.

Symptomatic post COVID patients have impaired alveolar capillary membrane function and high VE/VCO2.

BACKGROUND: Post COVID-19 syndrome is characterized by several cardiorespiratory symptoms but the origin of patients' reported symptomatology is still unclear. METHODS: Consecutive post COVID-19 patients were included. Patients underwent full clinical evaluation, symptoms dedicated questionnaires, blood tests, echocardiography, thoracic computer tomography (CT), spirometry including alveolar capillary membrane diffusion (DM) and capillary volume (Vcap) assessment by combined carbon dioxide and nitric oxide lung diffusion (DLCO/DLNO) and cardiopulmonary exercise test. We measured surfactant derive protein B (immature form) as blood marker of alveolar cell function. RESULTS: We evaluated 204 consecutive post COVID-19 patients (56.5 ± 14.5 years, 89 females) 171 ± 85 days after the end of acute COVID-19 infection. We measured: forced expiratory volume (FEV1) 99 ± 17%pred, FVC 99 ± 17%pred, DLCO 82 ± 19%, DM 47.6 ± 14.8 mL/min/mmHg, Vcap 59 ± 17 mL, residual parenchymal damage at CT 7.2 ± 3.2% of lung tissue, peakVO2 84 ± 18%pred, VE/VCO2 slope 112 [102-123]%pred. Major reported symptoms were: dyspnea 45% of cases, tiredness 60% and fatigability 77%. Low FEV1, Vcap and high VE/VCO2 slope were associated with persistence of dyspnea. Tiredness was associated with high VE/VCO2 slope and low PeakVO2 and FEV1 while fatigability with high VE/VCO2 slope. SPB was fivefold higher in post COVID-19 than in normal subjects, but not associated to any of the referred symptoms. SPB was negatively associated to Vcap. CONCLUSIONS: In patients with post COVID-19, cardiorespiratory symptoms are linked to VE/VCO2 slope. In these patients the alveolar cells are dysregulated as shown by the very high SPB. The Vcap is low likely due to post COVID-19 pulmonary endothelial/vasculature damage but DLCO is only minimally impaired being DM preserved.

Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity.

BACKGROUND: ADP-induced platelet activation leads to cell surface expression of several proteins, including TF (tissue factor). The role of ADP receptors in platelet TF modulation is still unknown. We aimed to assess the (1) involvement of P2Y1 and P2Y12 receptors in ADP-induced TF exposure; (2) modulation of TFpos-platelets in anti-P2Y12-treated patients with coronary artery disease. Based on the obtained results, we revisited the intracellular localization of TF in platelets. METHODS: The effects of P2Y1 or P2Y12 antagonists on ADP-induced TF expression and activity were analyzed in vitro by flow cytometry and thrombin generation assay in blood from healthy subjects, P2Y12-/-, and patients with gray platelet syndrome. Ex vivo, P2Y12 inhibition of TF expression by clopidogrel/prasugrel/ticagrelor, assessed by VASP (vasodilator-stimulated phosphoprotein) platelet reactivity index, was investigated in coronary artery disease (n=238). Inhibition of open canalicular system externalization and electron microscopy (TEM) were used for TF localization. RESULTS: In blood from healthy subjects, stimulated in vitro by ADP, the percentage of TFpos-platelets (17.3±5.5%) was significantly reduced in a concentration-dependent manner by P2Y12 inhibition only (-81.7±9.5% with 100 nM AR-C69931MX). In coronary artery disease, inhibition of P2Y12 is paralleled by reduction of ADP-induced platelet TF expression (VASP platelet reactivity index: 17.9±11%, 20.9±11.3%, 40.3±13%; TFpos-platelets: 10.5±4.8%, 9.8±5.9%, 13.6±6.3%, in prasugrel/ticagrelor/clopidogrel-treated patients, respectively). Despite this, 15% of clopidogrel good responders had a level of TFpos-platelets similar to the poor-responder group. Indeed, a stronger P2Y12 inhibition (130-fold) is required to inhibit TF than VASP. Thus, a VASP platelet reactivity index <20% (as in prasugrel/ticagrelor-treated patients) identifies patients with TFpos-platelets <20% (92% sensitivity). Finally, colchicine impaired in vitro ADP-induced TF expression but not α-granule release, suggesting that TF is open canalicular system stored as confirmed by TEM and platelet analysis of patients with gray platelet syndrome. CONCLUSIONS: Data show that TF expression is regulated by P2Y12 and not P2Y1; P2Y12 antagonists downregulate the percentage of TFpos-platelets. In clopidogrel good-responder patients, assessment of TFpos-platelets highlights those with residual platelet reactivity. TF is stored in open canalicular system, and its membrane exposure upon activation is prevented by colchicine.

Left ventricular functional recovery after atrial fibrillation catheter ablation in heart failure: a prediction model.

AIMS: Management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains complex. The Antwerp score, based on four parameters [QRS >120 ms (2 points), known aetiology (2 points), paroxysmal AF (1 point), severe atrial dilation (1 point)] adequately estimated the probability of left ventricular ejection fraction (LVEF) recovery after AF ablation in a single-centre cohort. The present study aims to externally validate this prediction model in a large European multi-centre cohort. METHODS AND RESULTS: A total of 605 patients (61.1 ± 9.4 years, 23.8% females, 79.8% with persistent AF) with HF and impaired LVEF (<50%) undergoing AF ablation in 8 European centres were retrospectively identified. According to the LVEF changes at 12-month echocardiography, 427 (70%) patients fulfilled the '2021 Universal Definition of HF' criteria for LVEF recovery and were defined as 'responders'. External validation of the score yielded good discrimination and calibration {area under the curve 0.86 [95% confidence interval (CI) 0.82-0.89], P < .001; Hosmer-Lemeshow P = .29}. Patients with a score < 2 had a 93% probability of LVEF recovery as opposed to only 24% in patients with a score > 3. Responders experienced more often positive ventricular remodelling [odds ratio (OR) 8.91, 95% CI 4.45-17.84, P < .001], fewer HF hospitalizations (OR 0.09, 95% CI 0.05-0.18, P < .001) and lower mortality (OR 0.11, 95% CI 0.04-0.31, P < .001). CONCLUSION: In this multi-centre study, a simple four-parameter score predicted LVEF recovery after AF ablation in patients with HF and discriminated clinical outcomes. These findings support the use of the Antwerp score to standardize shared decision-making regarding AF ablation referral in future clinical studies.

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i. METHODS: Using the health administrative databases of Lombardy, patients hospitalized with AMI from 2010 to 2019 were included. They were stratified according to DM status, then grouped into three cohorts using a propensity score matching: non-DM patients; DM patients treated with GLP-1 RA and/or SGLT-2i; DM patients not treated with GLP-1 RA/SGLT-2i. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy. RESULTS: We identified 146,798 patients hospitalized with AMI (mean age 71 ± 13 years, 34% females, 47% STEMI; 26% with DM). After matching, 3,090 AMI patients (1030 in each group) were included in the analysis. Overall, the primary endpoint rate was 16% (n = 502) and progressively increased from non-DM patients to DM patients treated with and without GLP-1 RA/SGLT-2i (13%, 16%, and 20%, respectively; P < 0.0001). Compared with non-DM patients, DM patients with GLP-1 RA/SGLT-2i had a 30% higher risk of the primary endpoint, while those not treated with GLP-1 RA/SGLT-2i had a 60% higher risk (P < 0.0001). CONCLUSION: Chronic therapy with GLP-1 RA and/or SGLT-2i has a favorable impact on the clinical outcome of DM patients hospitalized with AMI.

Prognostic Impact of Percutaneous Coronary Intervention in Chronic Dialysis Patients with Acute Myocardial Infarction: Findings from the Lombardy Health Database.

Background: Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. Methods: We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint. Results: During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 ± 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients (p < 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p < 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p < 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Conclusions: This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function.

[How to optimize Audit&Feedback: experience from the EASY-NET programme]. / Come rendere più efficace l'Audit&Feedback: riflessioni dal programma di rete EASY-NET.

This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

Uptake and effectiveness of a primary cardiovascular prevention program in an underserved multiethnic urban community.

BACKGROUND AND AIMS: Cardiometabolic risk is increased among disadvantaged people and ethnic minorities. Paradoxically, their uptake of primary cardiovascular prevention is relatively low. New strategies are needed to tackle this public health problem. Aims of this study were to assess the uptake (as well as its determinants) and effectiveness of a primary cardiovascular prevention program for communities devised to facilitate access of disadvantaged and inclusion of ethnic minorities in addition to providing a state-of-the-art interdisciplinary personalized care. METHODS AND RESULTS: Single center, hospital-based, open study. All the residents in an underserved multiethnic urban community aged 40-65 years (n = 1646, 43.6% immigrants) were proactively invited by post mail to participate in a cardiovascular prevention program and different approaches were adopted to promote accessibility and inclusiveness. Program uptake was 23% and individual features independently associated with program uptake were status of immigrant (OR [CI 95%]: 3.6 [2.6-5.1]), higher educational level (3.6 [2.8-4.7]), and female gender (1.6 [1.2-2.1]). Retention was 82% at 6 months and 69% at 12 months. A predefined outcome of global cardiovascular risk improvement at 12 months in subjects with glycaemia >126 mg/dl, LDL-C >115 mg/dl, systolic blood pressure ≥140 mmHg or BMI >28 at baseline was reached in 35%, 33%, 37% and 7% of the patients, respectively. 20% of smokers quitted and significant favorable changes were reported in diet quality, anxiety, depression and physical activity. CONCLUSION: Access inequalities to effective prevention may be counteracted, but increasing global uptake requires further upstream sensitization and awareness actions. REGISTERED IN CLINICALTRIALS.GOV: NCT03129165.

Right Ventricular Function After Minimally Invasive Mitral Valve Surgery.

OBJECTIVES: Right ventricular (RV) dysfunction is a significant cause of morbidity and mortality after cardiac surgery. Minimally invasive mitral valve surgery (MIMVS) increasingly is being performed. The authors aim was to evaluate postoperative RV function in patients who underwent MIMVS versus traditional mitral valve surgery. DESIGN: Six hundred seventy-five patients who underwent elective isolated mitral valve surgery at Centro Cardiologico Monzino from January 2016 to December 2019 were analyzed. After 1:1 propensity score matching, 60 patients were identified in the MIMVS (study group A) and 58 patients in the median sternotomy (control group B) and compared. SETTING: A university-affiliated scientific institute, monocentric. PARTICIPANTS: Patients. INTERVENTIONS: Mitral valve surgery. MEASUREMENTS AND MAIN RESULTS: No in-hospital deaths occurred. Aortic cross-clamp time (102 [87.5-119] v 83 [61-109] minutes, p = 0.0001), cardiopulmonary bypass duration (161.5 [142.5-181] v 105.5 [74-134] minutes, p < 0.0001) and intensive care unit stay (47 [44-72] v 45 [40-47] hours, p = 0.0015) were significantly longer in group A. The tricuspid annular plane systolic excursion was not different between group A and group B neither postoperatively (15 ± 3 v 14 ± 4 mm, p = 0.1) nor at three-month follow-up (18 ± 4 v 15 ± 3 mm, p = 0.3). No differences in peak postoperative lactates, inotropic score, central venous pressure, and pulmonary artery pulsatility index were observed. The length of hospital stay was significantly shorter in the minimally invasive group (ten [eight-13] v 12 [ten-17], p = 0.006). CONCLUSION: The authors study showed that the surgical strategy had no significant impact on postoperative RV function after mitral valve surgery.

The prognostic value of left ventricular dimensions at the time of transcatheter aortic valve replacement: A propensity-matched analysis.

AIMS: In the clinical practice a noteworthy proportion of severe symptomatic aortic stenosis patients presents with low-flow low-gradients features, these having reported a less favorable prognosis even when surgically or transcatheter treated. METHODS AND RESULTS: We retrospectively analyzed the prospectively collected data on 1051 consecutive patients undergone balloon-expandable transcatheter aortic valve replacement at our Institution from January 2008 to January 2020. We divided the population according with a mean aortic gradient (MAG) < or ≥40 mmHg and we performed a propensity-matched analysis based on the Society of Thoracic Surgery Score and age, obtaining two homogeneous groups of 314 patients each (Groups A and B, respectively). We then analyzed the outcomes of the two groups by implementing adjusted Cox models adjusted for significant clinical differences between the two groups, such as sex, ejection fraction, comorbidities and other variables not included in the propensity-matched analysis. The only variable associated with both cardiovascular and all-cause events was an ejection fraction ≤35%. Finally, a sensitivity analysis found that an ejection fraction ≤35% was associated with an increase cardiovascular and all-cause mortality only in patients with an indexed end-diastolic volume >97 ml/m2 (p = .0438 and .3363, respectively). CONCLUSIONS: In our series a MAG <40 mmHg was not found to be per se an independent risk factor for cardiac and all-cause mortality after transcatheter aortic valve replacement. The ejection fraction was found to be an independent risk factor only in the context of enlarged left ventricular dimensions.

"You can leave your mask on": effects on cardiopulmonary parameters of different airway protective masks at rest and during maximal exercise.

During the COVID-19 pandemic, the use of protective masks has been essential to reduce contagions. However, public opinion is that there is an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protective masks.12 healthy subjects performed three identical cardiopulmonary exercise tests, one without wearing a protective mask, one wearing a surgical mask and one with a filtering face piece particles class 2 (FFP2) mask. Dyspnoea was assessed using the Borg scale. Standard pulmonary function tests were also performed.All the subjects (40.8±12.4 years; six male) completed the protocol with no adverse events. Spirometry showed a progressive reduction of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from no mask to surgical to FFP2 (FEV1: 3.94±0.91 L, 3.23±0.81 L, 2.94±0.98 L; FVC: 4.70±1.21 L, 3.77±1.02 L, 3.52±1.21 L; p<0.001). Rest ventilation, O2 uptake (V˙ O2 ) and CO2 production (V˙ CO2 ) were progressively lower, with a reduction in respiratory rate. At peak exercise, subjects had a progressively higher Borg scale when wearing surgical and FFP2 masks. Accordingly, at peak exercise, V˙ O2 (31.0±23.4 mL·kg-1·min-1, 27.5±6.9 mL·kg-1·min-1, 28.2±8.8 mL·kg-1·min-1; p=0.001), ventilation (92±26 L, 76±22 L, 72±21 L; p=0.003), respiratory rate (42±8 breaths·min-1, 38±5 breaths·min-1, 37±4 breaths·min-1; p=0.04) and tidal volume (2.28±0.72 L, 2.05±0.60 L, 1.96±0.65 L; p=0.001) were gradually lower. There was no significant difference in oxygen saturation.Protective masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to increased airflow resistance. However, because exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.

Can the in-hospital mortality gap between STEMI patients with and without diabetes mellitus be reduced? The cardio-renal hypothesis.

BACKGROUND AND AIMS: Diabetes mellitus (DM) is a frequent comorbidity in ST-elevation-myocardial infarction (STEMI) patients and carries a higher risk of in-hospital mortality. We recently demonstrated that the higher in-hospital mortality of STEMI patients with DM, when compared to that of patients without DM, is mainly associated with their more frequent cardiac and renal dysfunction. These exploratory results prompted us to hypothesize that this higher risk in DM patients is mediated by their lower cardio-renal functional reserve. METHODS AND RESULTS: We included 5152 STEMI patients treated with primary angioplasty. By using an advanced statistical methodology (path analysis), able to clarify the putative causal paths between variables of interest, we reported that the higher in-hospital mortality of STEMI patients with DM is possibly caused by its adverse impact on cardio-renal function. CONCLUSION: This statistical approach allows to reinforce the well-known notion that DM is associated with an increased in-hospital mortality risk in STEMI and sheds lights on the causal relationship among DM, cardio-renal dysfunction, and higher in-hospital mortality. Whether the mortality gap between DM and non-DM patients with STEMI can be reduced by pharmacological strategies combining cardio-renal protective effects is an intriguing question that deserves an answer in the future.

Cardiovascular tissue banking activity during SARS-CoV-2 pandemic: evolution of national protocols and Lombardy experience.

The worldwide pandemic outbreak due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has created unprecedented challenges for public health services. Lombardy, region of the Northern Italy, has been the first area in the Western world whose organs and tissues procurement programs have had to face the virus pandemic emergency. We retrospectively collected and analyzed data about cardiovascular tissues (CT) in 2019 and in 2020. We aimed to describe the rapid evolution of SARS-CoV-2 regulation laws for tissue donor's selection and harvesting from February 2020 until January 2021. As expected the number of CT donors in 2020 was significantly lower than those of 2019 (66 vs. 99, p value 0.02). The total number of CT collected from donors have been 254 in 2019 and 206 in 2020 (p 0.28). Femoral arteries were the most required vascular tissues (55.5% in 2019 and 40% in 2020). Fifty-five and forty-eight pulmonary valves were implanted in 2019 and 2020, respectively. No differences were found for the types of CT requests between the 2 years. The median age of receivers of vascular tissues was 69.6 ± 14.6 years in the 2019 and 63.3 ± 14.9 years in 2020 (p < 0.01). The median age of receivers of pulmonary and aortic valves did not differ between the 2 years (9.32 ± 11.49 vs. 8.36 ± 10.66 and 48.67 ± 27.19 vs. 37.14 ± 31.97 respectively). Despite the dramatically reduction of donors, the number of CT collected has not decreased significantly and so far the CT distribution rate is comparable to those of 2019.

Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study.

The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10-5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (ß = 0.03 SE = 0.007, p = 4.77 × 10-5) and inversely associated with c-IMT (c-IMTmean-max ß = -0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.

Prognostic impact of admission high-sensitivity C-reactive protein in acute myocardial infarction patients with and without diabetes mellitus.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) elevation frequently occurs in acute myocardial infarction (AMI) and is associated with adverse outcomes. Since diabetes mellitus (DM) is characterized by an underlying chronic inflammation, hs-CRP may have a different prognostic power in AMI patients with and without DM. METHODS: We prospectively included 2064 AMI patients; hs-CRP was measured at hospital admission. Patients were grouped according to hs-CRP quartiles and DM status. The primary endpoint was a composite of in-hospital mortality, cardiogenic shock, and acute pulmonary edema. Two-year all-cause mortality was the secondary endpoint. RESULTS: Twenty-six percent (n = 548) of patients had DM and they had higher hs-CRP levels than non-DM patients (5.32 vs. 3.24 mg/L; P < 0.0001). The primary endpoint incidence in the overall population (7%, 9%, 13%, 22%; P for trend < 0.0001), in DM (14%, 9%, 21%, 27%; P = 0.0001), and non-DM (5%, 8%, 10%, 19%; P < 0.0001) patients increased in parallel with hs-CRP quartiles. The adjusted risk of the primary endpoint increased in parallel with hs-CRP quartiles in DM and non-DM patients but this relationship was less evident in DM patients. In the overall population, the adjusted OR of the primary endpoint associated with an hs-CRP value ≥ 2 mg/L was 2.10 (95% CI 1.46-3.00). For the same risk, hs-CRP was 7 and 2 mg/L in patients with and without DM. A similar behavior was observed for the secondary endpoint when the HR associated with an hs-CRP value ≥ 2 mg/L found in the overall population was 2.25 (95% CI 1.57-3.22). For the same risk, hs-CRP was 8 and 1.5 mg/L in DM and non-DM patients. CONCLUSIONS: This study shows that hs-CRP predicts in-hospital outcome and two-year mortality in AMI patients with and without DM. However, in DM patients, the same risk of developing events as in non-DM patients is associated to higher hs-CRP levels.

Overall dietary variety and adherence to the Mediterranean diet show additive protective effects against coronary heart disease.

BACKGROUND AND AIM: Along with the increasing evidence of the cardioprotective effects of the Mediterranean Diet (MD), the scientific interest and advocacy of dietary variety as a potentially healthy eating habit gradually faded, until its complete oblivion in the latest European cardiovascular prevention guidelines. Our study aims to investigate whether dietary variety adds to the "Mediterranean-ness" of the diet in protecting against coronary heart disease (CHD). METHODS AND RESULTS: In this case-control Italian study, data on eating habits were collected from 178 patients with CHD and 155 healthy controls, primarily males, frequency matched for age and gender, using the Food Frequency Questionnaire (FFQ) of the European Prospective Investigation into Cancer and Nutrition. Adherence to MD was estimated from FFQ by the Mediterranean Diet Score (MDS), an index developed by Trichopoulou (2003) ranging from 0 to 9, with higher scores indicating a stricter adherence. Overall dietary variety was computed from FFQ as a count of single food items consumed at least once a month. Associations between MDS or overall dietary variety and coronary status were evaluated by logistic regression models adjusted for BMI, physical activity, smoking, education, and caloric intake; the Odds Ratio (OR) for CHD for each 1.5-point increase in MDS was 0.76 [IC 95% 0.59; 0.98], whereas the OR for CHD for each 15-item increase in dietary variety was 0.62 [IC 95% 0.46; 0.84]. Remarkably, adherence to MD and overall dietary variety were independently associated with a significantly reduced chance of CHD. CONCLUSION: Dietary Mediterranean-ness and overall dietary variety exhibit additive cardioprotective effects.

12(S)-Hydroxyeicosatetraenoic acid downregulates monocyte-derived macrophage efferocytosis: New insights in atherosclerosis.

The involvement of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a 12-lipooxygenase product of arachidonic acid, has been suggested in atherosclerosis. However, its effect on macrophage functions is not completely understood, so far. The uptake of apoptotic cells (efferocytosis) by macrophages is an anti-inflammatory process, impaired in advanced atherosclerotic lesions. This process induces the release of the anti-inflammatory cytokine interleukin-10 (IL-10), and it is regulated by Rho-GTPases, whose activation involves the isoprenylation, a modification inhibited by statins. We assessed 12-HETE levels in serum of coronary artery disease (CAD) patients, and explored 12(S)-HETE in vitro effect on monocyte-derived macrophage (MDM) efferocytosis. Sixty-four CAD patients and 24 healthy subjects (HS) were enrolled. Serum 12-HETE levels were measured using a tandem mass spectrometry method. MDMs, obtained from a spontaneous differentiation of adherent monocytes, were treated with 12(S)-HETE (10-50 ng/mL). Efferocytosis and RhoA activation were evaluated by flow cytometry. IL-10 was measured by ELISA. CAD patients showed increased 12-HETE serum levels compared to HS (665.2 [438.1-896.2] ng/mL and 525.1 [380.1-750.1] ng/mL, respectively, p < 0.05) and reduced levels of IL-10. MDMs expressed the 12(S)-HETE cognate receptor GPR31. CAD-derived MDMs displayed defective efferocytosis vs HS-MDMs (9.4 [7.7-11.3]% and 11.1 [9.6-14.1]% of MDMs that have engulfed apoptotic cells, respectively, p < 0.01). This reduction is marked in MDMs obtained from patients not treated with statin (9.3 [7.4-10.6]% statin-free CAD vs HS, p = 0.01; and 9.9 [8.6-11.6]% statin-treated CAD vs HS, p = 0.07). The in vitro treatment of MDMs with 12(S)-HETE (20 ng/mL) induced 20% decrease of efferocytosis (p < 0.01) and 71% increase of RhoA activated form (p < 0.05). Atorvastatin (0.1 µM) counteracted these 12(S)-HETE-mediated effects.These results show a 12(S)-HETE pro-inflammatory effect and suggest a new potential contribution of this mediator in the development of atherosclerosis.

Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction.

RATIONALE: In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients. OBJECTIVE: To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c. METHODS AND RESULTS: We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-segment-elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20-13.38; P=0.02). CONCLUSIONS: Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI.

Prognostic significance of serum creatinine and its change patterns in patients with acute coronary syndromes.

BACKGROUND: In acute coronary syndromes (ACS), serum creatinine (sCr) levels have short- and long-term prognostic value. However, it is possible that repeated evaluations of sCr during hospitalization, rather than measuring sCr value at admission only, might improve risk assessment. We investigated the relationship between sCr baseline value, its changes, and in-hospital mortality in patients hospitalized with ACS. METHODS: In 2,756 ACS patients, sCr was measured at hospital admission and then daily, until discharge from coronary care unit. Patients were grouped according to the maximum sCr change observed: <0.3 mg/dL change from baseline (stable renal function [SRF] group), ≥0.3 mg/dL decrease (improved renal function [IRF] group), and ≥0.3 mg/dL increase (worsening renal function [WRF] group). RESULTS: Of the 2,756 patients, 2,163 (78%) had SRF, 292 (11%) had IRF, and 301 (11%) had WRF. In-hospital mortality in the 3 groups was 0.5%, 2%, and 14% (P < .001), respectively. Peak sCr value was a more powerful predictor of mortality (area under the curve 0.86, 95% CI 0.81-0.92) than the initial sCr value (area under the curve 0.69, 95% CI 0.63-0.77; P < .001). When sCr and its change patterns during coronary care unit stay were evaluated together, improved mortality risk stratification was found. CONCLUSIONS: In ACS patients, daily sCr value and its change pattern are stronger predictors of in-hospital mortality than the initial sCr value only; thus, their combined evaluation provides a more accurate and dynamic stratification of patients' risk. Finally, the intermediate mortality risk of IRF patients possibly reflects acute kidney injury started before hospitalization.

Humoral response to anti SARS-CoV2 vaccination at one and seven months is not different in shift workers and non-shift workers.

Since previous studies, mostly performed in healthy adults, show that sleep restriction around time of vaccination impairs antibody response and shift work affects sleep, aim of the study was to test the hypothesis that the antibody response to vaccination is impaired in shift workers, when compared to non-shift workers. Employees (n = 445; mean age 44 ± 11 years; 35 % men) of the Centro Cardiologico Monzino, IRCCS (Milan, Italy) were vaccinated against SARS-CoV2 in February 2021 with an mRNA-based vaccine. Antibody titers were assayed 1 and 7 months later. Differences between groups were assessed using ANOVA, after log-transformation of variables with right-skewed distribution. We report that the antibody titer was significantly higher in shift workers (33 % of employees) compared to non-shift workers at first assay [median (IQR): 2495 (1700; 4665) vs 2060 (1619; 2970) BAU/mL, p = 0.0123], as well as at the second one, and that this difference was abolished after adjustment for previous development of symptomatic COVID-19. Results were not affected by age or sex at birth. These results show that shift workers were able to mount an unimpaired antibody response to vaccination. Since vaccinations were performed during the pandemic urgency, our retrospective study has several limitations, nevertheless it underlines the need for large prospective, controlled studies on the effects of acute and chronic sleep restriction on response to vaccination in the general population and on the impact of shift work on immune response.