Predictive Value of Echocardiographic Pulmonary to Left Atrial Ratio for In-Hospital Death in Patients with COVID-19.

Background: Echocardiographic Pulmonary to Left Atrial Ratio (ePLAR) represents an accurate and sensitive non-invasive tool to estimate the trans-pulmonary gradient. The prognostic value of ePLAR in hospitalized patients with COVID-19 remains unknown. We aimed to investigate the predictive value of ePLAR on in-hospital mortality in patients with COVID-19. Methods: One hundred consecutive patients admitted to two Italian institutions for COVID-19 undergoing early (<24 h) echocardiographic examination were included; ePLAR was determined from the maximum tricuspid regurgitation continuous wave Doppler velocity (m/s) divided by the transmitral E-wave: septal mitral annular Doppler Tissue Imaging e'-wave ratio (TRVmax/E:e'). The primary outcome measure was in-hospital death. Results: patients who died during hospitalization had at baseline a higher prevalence of tricuspid regurgitation, higher ePLAR, right-side pressures, lower Tricuspid Annular Plane Systolic Excursion (TAPSE)/ systolic Pulmonary Artery Pressure (sPAP) ratio and reduced inferior vena cava collapse than survivors. Patients with ePLAR > 0.28 m/s at baseline showed non-significant but markedly increased in-hospital mortality compared to those having ePLAR ≤ 0.28 m/s (27% vs. 10.8%, p = 0.055). Multivariate Cox regression showed that an ePLAR > 0.28 m/s was independently associated with an increased risk of death (HR 5.07, 95% CI 1.04−24.50, p = 0.043), particularly when associated with increased sPAP (p for interaction = 0.043). Conclusions: A high ePLAR value at baseline predicts in-hospital death in patients with COVID-19, especially in those with elevated pulmonary arterial pressure. These results support an early ePLAR assessment in patients admitted for COVID-19 to identify those at higher risk and potentially guide strategies of diagnosis and care.

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19.

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01-1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05-6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19-10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13-8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

Interaction between thrombin potential and age on early clinical outcome in patients hospitalized for COVID-19.

Patients with Coronavirus Disease-2019 (COVID-19) have haemostatic dysfunction and are at higher risk of thrombotic complications. Although age is a major risk factor for outcome impairment in COVID-19, its impact on coagulative patterns here is still unclear. We investigated the association of Endogenous Thrombin Potential (ETP) with thrombotic and haemorrhagic events according to different ages in patients admitted for COVID-19. A total of 27 patients with COVID-19-related pneumonia, without need for intensive care unit admission or mechanical ventilation at hospital presentation, and 24 controls with non-COVID-19 pneumonia were prospectively included. ETP levels were measured on admission. Patients were evaluated for major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, stroke, transient ischemic attack, venous thromboembolism) and bleeding complications [according to Bleeding Academic Research Consortium (BARC) definition] during in-hospital stay. COVID-19 patients had similar ETP levels compared to controls (AUC 93 ± 24% vs 99 ± 21%, p = 0.339). In the COVID-19 cohort, patients with in-hospital MACE showed lower ETP levels on admission vs those without (AUC 86 ± 14% vs 95 ± 27%, p = 0.041), whereas ETP values were comparable in patients with or without bleeding (AUC 82 ± 16% vs 95 ± 26%, p = 0.337). An interaction between age and ETP levels for both MACE and bleeding complications was observed, where a younger age was associated with an inverse relationship between ETP values and adverse event risk (pint 0.018 for MACE and 0.050 for bleeding). Patients with COVID-19 have similar thrombin potential on admission compared to those with non-COVID-19 pneumonia. In younger COVID-19 patients, lower ETP levels were associated with a higher risk of both MACE and bleeding.

Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study.

INTRODUCTION: A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. AIM: We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. METHODS: In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. RESULTS: Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. CONCLUSION: In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

Clinical outcome with different doses of low-molecular-weight heparin in patients hospitalized for COVID-19.

A pro-thrombotic milieu and a higher risk of thrombotic events were observed in patients with CoronaVirus disease-19 (COVID-19). Accordingly, recent data suggested a beneficial role of low molecular weight heparin (LMWH), but the optimal dosage of this treatment is unknown. We evaluated the association between prophylactic vs. intermediate-to-fully anticoagulant doses of enoxaparin and in-hospital adverse events in patients with COVID-19. We retrospectively included 436 consecutive patients admitted in three Italian hospitals. Outcome according to the use of prophylactic (4000 IU) vs. higher (> 4000 IU) daily dosage of enoxaparin was evaluated. The primary end-point was in-hospital death. Secondary outcome measures were in-hospital cardiovascular death, venous thromboembolism, new-onset acute respiratory distress syndrome (ARDS) and mechanical ventilation. A total of 287 patients (65.8%) were treated with the prophylactic enoxaparin regimen and 149 (34.2%) with a higher dosing regimen. The use of prophylactic enoxaparin dose was associated with a similar incidence of all-cause mortality (25.4% vs. 26.9% with the higher dose; OR at multivariable analysis, including the propensity score: 0.847, 95% CI 0.400-0.1.792; p = 0.664). In the prophylactic dose group, a significantly lower incidence of cardiovascular death (OR 0.165), venous thromboembolism (OR 0.067), new-onset ARDS (OR 0.454) and mechanical intubation (OR 0.150) was observed. In patients hospitalized for COVID-19, the use of a prophylactic dosage of enoxaparin appears to be associated with similar in-hospital overall mortality compared to higher doses. These findings require confirmation in a randomized, controlled study.

Gender differences in acute coronary syndromes patterns during the COVID-19 outbreak.

BACKGROUND: Mortality from acute coronary syndromes (ACS) is strictly related to early management. As female patients usually experience longer delays before diagnosis and treatment, we assessed whether women were more affected by the dramatic drop in hospital admissions for ACS during the Covid-19 pandemic. METHODS: We performed a retrospective analysis of clinical and angiographic characteristics of consecutive patients who were admitted for ACS at 15 hospitals in Northern Italy comparing men and women data. The study period was defined as the time between the first confirmed case of Covid-19 in Italy (February 20, 2020) and March 31, 2020. We compared hospitalization rates between the study period and two control periods: the corresponding period during the previous year (February 20 to March 31, 2019) and the earlier period during the same year (January 1 to February 19, 2020). Incidence rate ratios comparing the study period with each of the control periods were calculated with the use of Poisson regression. RESULTS: Of the 547 patients who were hospitalized for ACS during the study period, only 127 (23%) were females, accounting for a mean of 3.1 admissions per day, while ACS hospitalized males were 420, with a mean of 10.2 admissions per day. There was a significant decrease driven by a similar reduction in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) diagnosis in both sexes compared to the control periods. A trend toward a greater reduction in admitted females was shown in the intra-year control period (46% admission reduction in females vs 37% in males, with females accounting for 26% of ACS, P=0.10) and a significant reduction when compared to the previous year control period (40% admission reduction in females vs 23% in males, with females accounting for 28% of ACS, P=0.03), mainly related to Unstable Angina diagnosis. CONCLUSION: The Covid-19 pandemic period closed the gap between men and women in ACS, with similar rates of reduction of hospitalized STEMI and NSTEMI and a trend toward greater reduction in UA admission among women. Furthermore, many typical differences between males and females regarding ischemic heart disease presentations and vessel distribution were leveled.

Reduction in heart failure hospitalization rate during coronavirus disease 19 pandemic outbreak.

AIMS: The recent coronavirus disease 19 (COVID-19) pandemic outbreak forced the adoption of restraint measures, which modified the hospital admission patterns for several diseases. The aim of the study is to investigate the rate of hospital admissions for heart failure (HF) during the early days of the COVID-19 outbreak in Italy, compared with a corresponding period during the previous year and an earlier period during the same year. METHODS AND RESULTS: We performed a retrospective analysis on HF admissions number at eight hospitals in Italy throughout the study period (21 February to 31 March 2020), compared with an inter-year period (21 February to 31 March 2019) and an intra-year period (1 January to 20 February 2020). The primary outcome was the overall rate of hospital admissions for HF. A total of 505 HF patients were included in this survey: 112 during the case period, 201 during intra-year period, and 192 during inter-year period. The mean admission rate during the case period was 2.80 admissions per day, significantly lower compared with intra-year period (3.94 admissions per day; incidence rate ratio, 0.71; 95% confidence interval [CI], 0.56-0.89; P = 0.0037), or with inter-year (4.92 admissions per day; incidence rate ratio, 0.57; 95% confidence interval, 0.45-0.72; P < 0.001). Patients admitted during study period were less frequently admitted in New York Heart Association (NYHA) Class II compared with inter-year period (P = 0.019). At covariance analysis NYHA class was significantly lower in patients admitted during inter-year control period, compared with patients admitted during case period (P = 0.014). CONCLUSIONS: Admissions for HF were significantly reduced during the lockdown due to the COVID-19 pandemic in Italy.