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Acute coronary syndromes (ACS) may complicate the clinical course of patients with Coronavirus Disease 2019 (COVID-19). It is still unclear whether this condition is a direct consequence of the primary disease. However, several mechanisms including direct cellular damage, endothelial dysfunction, in-situ thrombosis, systemic inflammatory response, and oxygen supply-demand imbalance have been described in patients with COVID-19. The onset of a pro-thrombotic state may also be facilitated by the endothelial dysfunction secondary to the systemic inflammatory response and to the direct viral cell damage. Moreover, dysfunctional endothelial cells may enhance vasospasm and platelet aggregation.The combination of these factors promotes atherosclerotic plaque instability, thrombosis and, consequently, type 1 myocardial infarction.Furthermore, severe hypoxia due to extensive pulmonary involvement, in association with other conditions described in COVID-19 such as sepsis, tachyarrhythmias, anemia, hypotension, and shock, may lead to mismatch between oxygen supply and demand, and cause type 2 myocardial infarction.A deeper understanding of the potential pathophysiological mechanisms underlying ACS in patients with COVID-19 could help the therapeutic management of these very high-risk patients.
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Background/Introduction: The bactericidal/permeability-increasing fold-containing family-B-member-4 (BPIFB4) serves as a biomarker of healthy aging [1,2] and displays prognostic relevance in vascular pathology [3–5]. We recently described a drop in plasma BPIFB4 level in patients with severe COVID-19 compared to low-grade disease patients [6]. Purpose: As COVID-19 is associated with autoimmune features, we developed the methods for determination of Anti-BPIFB4 IgG (autoAbs) and then characterized their neutralizing activity in COVID-19 patients. Methods: A sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs against BPIFB4 in 60 hospitalized COVID-19 patients and in 30 healthy volunteers. Compared to the healthy controls, the optical density (OD) level of autoAbs in COVID-19 showed considerable variability distributing over a range between 0.13 and 0.85. We thus divided the patients into two groups, one with OD >0,29 and the other one with a OD >0,29, where 0,29 represents the OD mean value of autoAbs against BPIFB4 in physiological conditions. Results: Since patients with higher OD are mainly those who spend in average a higher number of days in hospital, we stratified the patients according to the Length of Stay (LoS) in hospital (Figure 1), and found a trend towards a positive correlation between AutoAbs OD level and length of hospitalization within COVID-19 patients.When present, autoAbs exclusively target the WT-BPIFB4 autoantigens and neglect the recognition of the Longevity-associated-variant-(LAV) of the BPIFB4 gene known for its therapeutic efficacy in cardiomyopathy, atherosclerosis (4), diabetes (6) and platelets' reactivity.As expected, the pre-treatment of human PrP with the recombinant rhLAV-BPIFB4 reduces platelets' aggregation in response to ADP and collagen in COVID-19 patients in vitro.On the other hand, at functional level, the well established LAV-BPIFB4-regulated M2 macrophage polarization (4,7), is neutralized in presence of anti-BPIFB4 autoAbs-enriched plasma. Conclusion: We conclude that a significant proportion of hospitalized COVID-19 patients displays BPIFB4-AutoAbs which are positively correlated with the Length of Stay (LoS) in hospital. In future, it will be of utmost importance to clarify if the 4 missense SNPs which distinguish LAV-BPIFB4 gene from its WT-counterpart, are instrumental to prevent the self-tolerance brake-down and the potential development of specific antibodies against endogenous cardiovascular protectors. Funding Acknowledgement: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Cariplo Foundation (n.2016-0874) to AAP and CV;Ministry of Health (RF-2016-02364864) to AAP and CVFigure 1
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Background: Despite several pharmacological advances, the morbidity and mortality in heart failure (HF) remain high, posing a problem for both patients and the National Health System. The natural history of this disease alternates phases of stability and phases of exacerbation, with a progressive decline in the patient's functional capacity and quality of life;this has led to the development of remote monitoring systems. These devices are emerging as an important tool for the effective HF management, even during the COVID-19 pandemic. Methods: We enrolled 6 patients with end-stage HF, who received the combined CardioMEMS / Levosimendan strategy to reduce the number of hospitalizations and optimize both tailored adjustment of home therapy and infusions of Levosimendan. Specifically, CardioMEMS is a wireless sensor that can be implanted in the pulmonary artery, where it detects cardiac filling pressures, an objective measure of the patient's hemodynamic congestion;these pressures increase two weeks before the onset of symptomatic congestion. Results: The 6 patients (72.25±4.60 years;33.33% female) who received the device did not have any complications related to the procedure. Patients were monitored daily by CardioMEMS;if the cardiologist detected a tendency for pulmonary artery diastolic pressure (PAPd) to rise, patients were contacted for home therapeutic changes. If no further changes were possible, the patient was hospitalized for the infusion of Levosimendan. In particular, following the implantation of CardioMEMS, a significant reduction in HF unscheduled hospital admissions was recorded (hospitalizations / month: pre-CardioMEMS 0.657±0.303 vs post-CardioMEMS 0.029±0.021, p 0.0313) (Figure 1). In addition, lower pulmonary arterial pressures were recorded at 6-months FU on CardioMEMS monitoring (pre vs post: PAPs: 51.25±2.56 vs 42.75±2.46 mmHg, p 0.0168;PAPd: 26.25±0.85 vs 20.25±0.85 mmHg, p 0.0034), a reduction in the echocardiographic E/e' ratio (20.86±1.77 vs 14.13±2.02, p 0.0057), an improvement in the quality of life (EQ5D 75.17±2.06 vs 108.60±8.70, p 0.0078) and a reduction in IL-6 levels (p 0.0211). Conclusions: In this study we present the first experience of serial infusions of Levosimendan guided by CardioMEMS. Our results support the usefulness of this device in remote management of the HF patient, especially during this pandemic.
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Aims: Pulmonary involvement in Coronavirus 19 disease (COVID-19) may affect right ventricular (RV) function and pulmonary pressures resulting in further deterioration of patient clinical status. However, the prognostic value of echocardiographic parameters including tricuspid annular plane systolic excursion (TAPSE), systolic pulmonary artery pressure (PASP), and TAPSE/PASP ratio has been poorly investigated in this clinical setting. Methods and results: This is a multicentre Italian study including patients admitted for severe COVID-19 in seven Italian Hospitals. Transthoracic echocardiography (TTE) was performed within 48 h from admission in all cases. In-hospital mortality and pulmonary embolism (PE) were identified as the primary and secondary outcome measures, respectively. Of 1401 patients with severe COVID-19, 227 (16.1%) subjects underwent TTE within 48 h from admission and were included in this study. The mean age was 68±13 years and 62.6% of patients were male. Intensive care unit (ICU) admission was reported in 73 patients (32.2%);ICU patients showed lower left ventricular ejection fraction (LVEF), lower TAPSE, and higher LV end systolic volume and PASP values than non-ICU patients. Also, ICU patients showed higher incidence of acute respiratory distress syndrome (82.2% vs. 30.5%;P<0.001), acute cardiac injury (46.6% vs. 22.7%;P<0.001), acute heart failure (34.2% vs. 9.1%;P<0.001), and death (63.9% vs. 14.3%;P<0.001) compared with non-ICU patients. By stratifying the study population into tertiles according to TAPSE, PASP, and TAPSE/PASP values, patients in the lower TAPSE and TAPSE/PASP ratio tertiles, and those in the higher PASP tertile, showed a significantly higher incidence of death during the hospitalization. At univariable logistic regression analysis, TAPSE, PASP, and TAPSE/PASP were significantly associated with a higher risk of death and PE, both in patients admitted or not to ICU. After propensity score weighting adjustment for multiple baseline potential confounders and further multivariable adjustment for LVEF value, the regression analysis showed that TAPSE, PASP and TAPSE/PASP were independently associated with risk of death (TAPSE: OR: 0.85, CI: 0.74-0.97, P=0.017;PASP: OR: 1.08, CI: 1.03-1.13, P=0.002;TAPSE/PASP: OR: 0.02, CI: 0.02 × 10-1-0.20, P<0.001) and with the risk of PE (TAPSE: OR: 0.70, CI: 0.60-0.82, P<0.001;PASP: OR: 1.10, CI: 1.05-1.14, P<0.001;TAPSE/PASP: OR: 0.02 × 10-1, CI: 0.01 × 10-2- 0.04, P<0.001) during the hospitalization. The risk death according to TAPSE, PASP, and TAPSE/PASP ratio tertiles was estimated considering discharge alive as competing risk (Figure). The lowest TAPSE and TAPSE/PASP tertiles, and the highest PASP tertile, were significantly associated with poorer survival during the hosptialization (P<0.001). Conclusions: Echocardiographic evidence of RV systolic dysfunction, increased PASP and a poor RV-arterial coupling assessed by TAPSE/PAPS ratio may help to identify COVID-19 patients at higher risk of mortality and PE during the hospitalization.
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Background: A high prevalence of cardiovascular risk factors including age, male sex, hypertension, diabetes, and tobacco use, has been reported in patients with Coronavirus disease 2019 (COVID-19) who experienced adverse outcome. The aim of this study: was to investigate the relationship between cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Methods: MEDLINE, Cochrane, Web of Sciences, and SCOPUS were searched for retrospective or prospective observational studies reporting data on cardiovascular risk factors and in-hospital mortality in patients with COVID-19. Univariable and multivariable age-adjusted analyses were conducted to evaluate the association between cardiovascular risk factors and the occurrence of in-hospital death. Results: The analysis included 45 studies enrolling 18,300 patients. The pooled estimate of in-hospital mortality was 12% (95% CI: 9-15%). The univariable meta-regression analysis showed a significant association between age (coefficient: 1.06;95% CI:1.04-1.09;p<0.001), diabetes (coefficient: 1.04;95% CI: 1.02-1.07;p<0.001) and hypertension (coefficient: 1.01;95% CI:1.01-1.03;p=0.013) with in-hospital death. Male sex and smoking did not significantly affect mortality. At multivariable age-adjusted meta-regression analysis, diabetes was significantly associated with in-hospital mortality (coefficient: 1.02;95% CI: 1.01-1.05;p=0.043);conversely, hypertension was no longer significant after adjustment for age (coefficient: 1.00;95% CI: 0.99-1.01;p=0.820). A significant association between age and in-hospital mortality was confirmed in all multivariable models. Conclusions: This meta-analysis suggests that older age and diabetes are associated with higher risk of in-hospital mortality in patients infected by SARS-CoV-2. Conversely, male sex, hypertension, and smoking did not independently correlate with fatal outcome.