Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. MATERIAL AND METHODS: We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. RESULTS: Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycemia were independently associated with a higher mortality. DISCUSSION: We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

CRT implantation after transvenous lead/device extraction (TLE) in a patient with COVID-19: Endocarditis triggered by syndrome coronavirus 2 (SARS-COV-2) infection? A case report.

In the era of coronavirus disease 2019 (COVID-19), the management of cardiac implantable electronic devices infections with concomitant viral infection has not been completely defined yet. In this explorable context, we report the first experience of a Cardiac resynchronization therapy with defibrillator (CRT-D) implantation after transvenous lead extraction for endocarditis in a COVID-19 patient. We describe both the measures and procedures implemented to reduce the cross-infection in the operating room and our clinical practice to improving procedure effectiveness on patient care.

Clinical evaluation of the safety and efficacy of enoxaparin in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), increases thrombotic risk in hospitalised patients. The rate of thrombosis in patients with COVID-19 is unclear. The role of heparin, frequently used in the management of hospitalised patients, also needs to be clarified. In this study, we investigated the efficacy and safety of enoxaparin given at prophylactic or therapeutic dose in hospitalised patients with COVID-19, and evaluated its role in the development of disease in terms of mortality, and incidence of thrombotic and bleeding events. MATERIAL AND METHODS: We included 141 patients with SARS-CoV-2 infection, admitted to five different wards (one intensive care unit, 2 sub-intensive care units, and 2 general infectious disease units) of Cotugno Hospital, a tertiary care hospital in Naples, Italy, between March and May 2020. RESULTS: Over a median time of 17 days (IQR 11-25), enoxaparin was given to 90/141 patients (63.8%) of whom 65 took a prophylactic and 25 a therapeutic dose. We documented 14 episodes of thrombosis (9.9%); almost all were cases of pulmonary embolism. No significant difference in terms of thromboembolic prevention was found between those patients not receiving anticoagulants and those on prophylactic or therapeutic dose of enoxaparin. Five episodes of major bleeding occurred (3.5%); therapeutic dose of enoxaparin was associated with a greater bleeding risk than prophylactic dose (p=0.002). During follow-up, 31 patients (22%) died; these were mostly elderly men with two or more comorbidities at admission. No advantages of enoxaparin, either as prophylaxis or at high doses, in terms of mortality were observed. At multivariate analysis, low estimated glomerular filtration rate, and high total bilirubin and fasting hyperglycaemia were independently associated with a higher mortality. DISCUSSION: We did not observe advantages in terms of either thromboembolic prevention or mortality of enoxaparin, which however was more frequently used in patients with more severe disease. Prophylactic enoxaparin was not seen to be associated with bleeding risk.

Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. MATERIALS AND METHODS: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between 9 March and 1 May 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. RESULTS: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration. CONCLUSIONS: Our data show a high prevalence of hypertension, more likely treated with renin-angiotensin-aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension.

Cardiovascular Comorbidities and Pharmacological Treatments of COVID-19 Patients Not Requiring Hospitalization

Introduction: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. Materials and Methods: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between 9 March and 1 May 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. Results: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ±17 years;193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74;95% CI 1.05 to 13.34;p = 0.04) and hypertension (RR: 1.69;95% CI 1.05 to 2.7;p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43;95% CI 1.01 to 5.8;p = 0.03) was significantly associated with heparin administration. Conclusions: Our data show a high prevalence of hypertension, more likely treated with renin–angiotensin–aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension.

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS.

AIM: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). METHODS: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio RESULTS: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. CONCLUSIONS: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

Effect of Triple Combination Therapy With Lopinavir-Ritonavir, Azithromycin, and Hydroxychloroquine on QT Interval and Arrhythmic Risk in Hospitalized COVID-19 Patients.

INTRODUCTION: No data are provided about the effect of triple combination therapy with Lopinavir/Ritonavir (LPN/RTN), hydroxychloroquine (HQ) and azithromycin (AZT) on corrected QT (QTc) interval and arrhythmic risk, in COVID-19 patients. This study aims to describe the incidence of extreme QTc interval prolongation among COVID-19 patients on this experimental treatment and to identify the clinical features associated with extreme QTc prolongation. MATERIALS AND METHODS: Data of 87 COVID-19 patients, treated with triple combination including LPN/RTN, HQ and AZT, were analyzed. QT interval was obtained by the tangent method and corrected for heart rate using Bazett's formula. Extreme QTc interval prolongation was considered an absolute QTc interval ≥ 500 ms or an increase in QTc intervals of 60 ms or greater (ΔQTc ≥ 60 ms) compared with baseline. RESULTS: Hypertension (66.7%) and diabetes (25.3%) were the most prevalent cardiovascular comorbidities. Twenty patients (23%) showed extreme QTc interval prolongation; no clinical, electrocardiographic or pharmacological characteristics have been associated to extreme QTc prolongation, except the history of ischemic stroke (P= 0,007). One torsade de pointes (TdP) in patient with QTc extreme prolongation (QTc: 560 ms) after 5 days of therapy was recorded. CONCLUSIONS: We observed a high incidence of extreme QTc interval prolongation among COVID-19 patients on triple combination therapy. Since the incidence of malignant arrhythmias seems to be not negligible, a careful electrocardiographic monitoring would be advisable.

Clinical characteristics and prognosis of hospitalized COVID-19 patients with incident sustained tachyarrhythmias: A multicenter observational study.

INTRODUCTION: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID-19. The aim of this study was to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. MATERIALS AND METHODS: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from 15 February to 15 March 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. RESULTS: 414 hospitalized patients with COVID-19 (66.9 ± 15.0 years, 61.1% male) were included in the present study. During a median follow-up of 28 days (IQR: 12-45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new-onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast, incident VT significantly increased the risk of in-hospital mortality (RR: 2.55; P: .003). CONCLUSIONS: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients.