Clinical Characteristics, Management, and Outcomes in Cardiogenic Shock: Insights From a High-Volume Italian Cardiac Intensive Care Unit.

ABSTRACT: Cardiogenic shock (CS) is a life-threatening condition. The aim of this study is to evaluate the clinical characteristics, management, and complication rate of patients with CS admitted to a high-volume hospital in Italy. We retrospectively reviewed the clinical, echocardiographic, and laboratory data, therapeutic management, and outcomes of patients with CS admitted to the Policlinico Gemelli (Rome) between January 1, 2020, and January 1, 2023. We included 96 patients [median age 71 years, interquartile range 60-79; 65 (68%) males], of whom 49 patients (51%) presented CS secondary to acute myocardial infarction and 60 (63%) with a de novo presentation of CS. Dobutamine was the most frequently used inotrope and noradrenaline the most frequently used vasopressor (adopted in 56% and 82% of cases, respectively). Forty-five (47%) patients died during the hospitalization. Nonsurvivors were older and had a higher inflammatory burden at admission, elevated lactate levels, a greater increase in lactate levels, higher left ventricular filling pressures, and worse right ventricular function. C-reactive protein levels [odds ratio (OR) 1.03, 95% confidence interval (CI) (1.00-1.04), P = 0.027], lactate levels at admission (OR 3.49, 95% CI, 1.59-7.63, P = 0.02), and increase in lactate levels (OR 2.8, 95% CI, 1.37-5.75, P = 0.005) were independent predictors of in-hospital all-cause death. Our data contribute to the assessment of the regional variations in the management and outcomes of patients with CS. We observed a high mortality and complication rate. Lactate acidosis and C-reactive protein measured at admission may help in identifying patients at higher risk of adverse in-hospital outcomes.

Molecular Hallmarks of Ischemia with Non-Obstructive Coronary Arteries: The "INOCA versus Obstructive CCS" Challenge.

Up to 4 million patients with signs of myocardial ischemia have no obstructive coronary artery disease (CAD). The absence of precise guidelines for diagnosis and treatment in non-obstructive CAD encourages the scientific community to fill the gap knowledge, to provide non-invasive and less expensive diagnostic tools. The aim of our study was to explore the biological profile of Ischemia with Non-Obstructive Coronary Arteries (INOCA) patients with microvascular dysfunction compared to patients presenting with obstructive chronic coronary syndrome (ObCCS) in order to find specific hallmarks of each clinical condition. We performed a gene expression array from peripheral blood mononuclear cells (PBMCs) isolated from INOCA (n = 18) and ObCCS (n = 20) patients. Our results showed a significantly reduced gene expression of molecules involved in cell adhesion, signaling, vascular motion, and inflammation in INOCA as compared to the ObCCS group. In detail, we found lower expression of Platelet and Endothelial Cell Adhesion Molecule 1 (CD31, p < 0.0001), Intercellular Adhesion Molecule-1 (ICAM1, p = 0.0004), Tumor Necrosis Factor (TNF p = 0.0003), Transferrin Receptor (TFRC, p = 0.002), and Vascular Endothelial Growth Factor A (VEGFA, p = 0.0006) in the INOCA group compared with ObCCS. Meanwhile, we observed an increased expression of Hyaluronidase (HYAL2, p < 0.0001) in INOCA patients in comparison to ObCCS. The distinct expression of molecular biomarkers might allow an early and non-invasive differential diagnosis between ObCCS and INOCA, improving clinical management and treatment options, in the era of personalized medicine.

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture.

The evaluation of monocyte subset distribution among acute coronary syndrome (ACS) patients according to culprit coronary plaque morphology has never been explored. We evaluated whether there were significant differences in frequency of circulating monocyte subsets isolated from ACS patients according to optical coherence tomography (OCT) investigation of plaque erosion and rupture. We enrolled 74 patients with non-ST-elevation ACS (NSTE-ACS), 21 of them underwent OCT investigation of the culprit coronary plaque and local macrophage infiltration (MØI) assessment. As control, we enrolled 30 chronic coronary syndrome (CCS) patients. We assessed the frequency of monocyte subsets in the whole study population, in reliance on their CD14 and CD16 expression (classical, CM: CD14++CD16-; intermediates, IM: CD14++CD16+; non-classical, NCM: CD14+CD16++). Then, we tested the effect of lipopolysaccharide (LPS) (a CD14 ligand) on peripheral blood mononuclear cells (PBMCs) of NSTE-ACS patients, quantifying the inflammatory cytokine levels in cell-culture supernatants. Our data proved that monocyte subsets isolated from NSTE-ACS patients represent a peculiar biological signature of the pathophysiological mechanism lying beneath atherosclerotic plaque with a ruptured fibrous cap (RFC) as compared with plaque erosion. Moreover, the magnitude of LPS-mediated effects on IL-1ß, IL-6, and IL-10 cytokine release in cell-culture supernatants appeared to be greater in NSTE-ACS patients with RFC. Finally, we described a fourth monocyte population never explored before in this clinical setting (pre-classical monocytes, PCM: CD14+CD16-) that was prevalent in NSTE-ACS patients as compared with CCS and, especially, in patients with RFC and culprit plaque with MØI.

Monocyte-Platelet Aggregates Triggered by CD31 Molecule in Non-ST Elevation Myocardial Infarction: Clinical Implications in Plaque Rupture.

Despite the recent innovations in cardiovascular care, atherothrombosis is still a major complication of acute coronary syndromes (ACS). We evaluated the involvement of the CD31 molecule in thrombotic risk through the formation of monocyte-platelet (Mo-Plt) aggregates in patients with ACS with no-ST-segment elevation myocardial infarction (NSTEMI) on top of dual anti-platelet therapy (DAPT). We enrolled 19 control (CTRL) subjects, 46 stable angina (SA), and 86 patients with NSTEMI, of which, 16 with Intact Fibrous Cap (IFC) and 19 with Ruptured Fibrous Cap (RFC) as assessed by the Optical Coherence Tomography (OCT). The expression of CD31 on monocytes and platelets was measured. Following the coronary angiography, 52 NSTEMIs were further stratified according to thrombus grade (TG) evaluation. Finally, a series of ex vivo experiments verified whether the CD31 participates in Mo-Plt aggregate formation. In patients with NSTEMI, CD31 was reduced on monocytes and was increased on platelets, especially in NSTEMI presented with RFC plaques compared to those with IFC lesions, and in patients with high TG compared to those with zero/low TG. Ex vivo experiments documented an increase in Mo-Plt aggregates among NSTEMI, which significantly decreased after the CD31 ligation, particularly in patients with RFC plaques. In NSTEMI, CD31 participates in Mo-Plt aggregate formation in spite of optimal therapy and DAPT, suggesting the existence of alternative thrombotic pathways, as predominantly displayed in patients with RFC.

Multiple Arterial Thrombosis in Seronegative Antiphospholipid Syndrome: Need for New Diagnostic Criteria?

BACKGROUND: Antiphospholipid syndrome (APS) is defined as thromboembolic complications and/or pregnancy morbidity in the presence of persistent increased titres of antiphospholipid antibodies. Nevertheless, some patients with clinical signs suggestive of APS are negative for diagnostic antibodies and may be classified as having seronegative-APS (SN-APS). Among the 'non-diagnostic' antibodies, a few studies have suggested that the IgG anti-vimentin/cardiolipin antibodies (AVA/CL) may be associated with risk of thrombosis. AIMS: The aim of this case report is to encourage the assessment of non-conventional antibodies in APS.Patient and methods: We report the case of a 69-year-old male patient with rapid onset of apparently unexplained multiple exclusively arterial thrombotic events in both coronary and peripheral vascular beds. RESULTS: The patient did not meet the diagnostic criteria for APS but was positive for AVA/CL, which result persisted on further testing at 3 and 6 months. DISCUSSION: Ongoing research has revealed the existence of non-criteria antibodies which may be relevant for the diagnosis of SN-APS and should be included in the classification criteria for the disease. LEARNING POINTS: In patients with unexplained multiple thrombosis without the conventional antibodies of antiphospholipid syndrome, the assessment of non-conventional antibodies should be considered.IgG anti-vimentin/cardiolipin antibodies may be associated with risk of thrombosis.Arterial thrombosis could be the only manifestation of antiphospholipid syndrome.

Time to therapeutic range (TtTR), anticoagulation control, and cardiovascular events in vitamin K antagonists-naive patients with atrial fibrillation.

BACKGROUND: Vitamin K antagonists (VKAs) reduce cardiovascular events (CVEs) in atrial fibrillation (AF) when a time in therapeutic range (TiTR) >70% is achieved. Factors affecting the time to achieve the TR (TtTR) are unknown. METHODS: Prospective observational study including 1,406 nonvalvular AF patients starting VKAs followed for a mean of 31.3months (3,690 patient/year); TiTR, TtTR, and SAMe-TT2R2 score were calculated, and CVEs were recorded. RESULTS: Median TtTR was 8.0days (interquartile range 5.0-18.0). Patients with high TtTR (ie, >75th percentile) were more likely to be in AF than in sinus rhythm at entry (odds ratio [OR]: 1.423, P=.011). Median TiTR was 60.0%; low TiTR (below median) was associated with SAMe-TT2R2 score (OR: 1.175, P=.001), high TtTR (>75th percentile, OR: 1.357, P=.017), and number of international normalized ratio checks (OR: 0.998, P=.049). We recorded 113 CVEs (3.1%/y), with a higher rate seen in patients with TtTR >75th percentile compared to those below (log-rank test, P=.006). A multivariable Cox regression analysis showed that SAMe-TT2R2 score (hazard ratio [HR]: 1.331, P<.001), TtTR >75th percentile (HR: 1.505, P=.047), TiTR <70% (HR: 1.931, P=.004), number of international normalized ratio checks (HR: 0.988, P<.001), digoxin (HR: 1.855, P=.008), and proton-pump inhibitors (HR: 0.452, P<.001) were independently associated with CVEs. CONCLUSIONS: High TtTR is associated with poorer long-term quality of VKAs therapy. Patients with TtTR >18days or with high SAMe-TT2R2 score should be considered for treatment with non-vitamin K oral anticoagulants.