Impact of RAAS Inhibitors on Clinical Outcome and Mortality in Patients With STEMI During the COVID-19 Era: A Multicenter Observational Study

Conflicting results are available regarding the influence of ACEi/ARBs on the risk of COVID-19 infection, while less is known about their impact on the clinical outcome of patients with STEMI diagnosed with COVID-19. Our aim was to evaluate the impact of ACEi/ARBs therapy on in-hospital mortality and clinical outcomes of patients with STEMI during the COVID-19 pandemic. We retrospectively analyzed consecutive patients with STEMI hospitalized from February 20 to May 10, 2020 in four Hospitals in Lombardy. SARS-COV-2 diagnosis was performed by nasopharyngeal swab test. Procedural outcome, respiratory complications, and in-hospital mortality were reported. Univariate and multivariate analyses were performed by logistic regressions. Our population was represented by 182 patients with STEMI, 76.9% of which were males, and mean age was 67 ± 12.5. Hypertension was reported in 53.3%, and 29.1% was treated with ACEi/ARBs. COVID-19 diagnosis was confirmed in 17.1% of the patients. In-hospital mortality (13.2%) was significantly higher in patients with COVID-19 (31 vs. 10%, p = 0.003), even if ejection fraction [OR 0.93 (95% CI) 0.87–0.99;p = 0.03] and respiratory complications [OR 9.39 (95% CI) 1.91–45.9;p = 0.006] were the only two independent predictors. The incidence of COVID-19 infection was not influenced by ACEi/ARBs (16.5 in naïve vs. 18.8%) whose presence on admission did not correlate with respiratory complications or mortality both in the case of discontinuation and maintenance. In conclusion, in a high-risk population, such as that of patients with STEMI, the potential benefit of ACEi/ARB discontinuation in patients with COVID-19 is overcome by its detrimental effect. Intensive care, additional preventive respiratory investigations, regardless of swab test result, should be suggested for all patients admitted for STEMI during the pandemic.

Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score.

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19. Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus. Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); and high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis. Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry.

BACKGROUND: Obesity has been described as a protective factor in cardiovascular and other diseases being expressed as 'obesity paradox'. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI). METHODS: We retrospectively collected data up to May 31st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m2; n = 1110, 25-30 kg/m2; n = 1464, and >30 kg/m2; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed. RESULTS: The rate of respiratory insufficiency was more recorded in BMI 25-30 kg/m2 as compared to BMI < 25 kg/m2 (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m2 than BMI < 25 kg/m2, respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m2 and BMI > 30 kg/m2 did not impact the mortality rate (HR 1.15, 95% CI: 0.889-1.508; p = 0.27) (HR 1.15, 95% CI: 0.893-1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m2 is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538-1.004; p = 0.05). CONCLUSIONS: HOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.

Platelet and Endothelial Activation as Potential Mechanisms Behind the Thrombotic Complications of COVID-19 Patients.

The authors hypothesized that the cytokine storm described in COVID-19 patients may lead to consistent cell-based tissue factor (TF)-mediated activation of coagulation, procoagulant microvesicles (MVs) release, and massive platelet activation. COVID-19 patients have higher levels of TF+ platelets, TF+ granulocytes, and TF+ MVs than healthy subjects and coronary artery disease patients. Plasma MV-associated thrombin generation is present in prophylactic anticoagulated patients. A sustained platelet activation in terms of P-selectin expression and platelet-leukocyte aggregate formation, and altered nitric oxide/prostacyclin synthesis are also observed. COVID-19 plasma, added to the blood of healthy subjects, induces platelet activation similar to that observed in vivo. This effect was blunted by pre-incubation with tocilizumab, aspirin, or a P2Y12 inhibitor.

Prognostic Impact of Hyponatremia and Hypernatremia in COVID-19 Pneumonia. A HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry Analysis.

Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1th through April 31th, 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa <135 mmol/L), eunatremic (SNa 135-145 mmol/L), or hypernatremic (SNa >145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52-77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291.

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.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Clinical profile and prognosis in patients on oral anticoagulation before admission for COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) shows high morbidity and mortality, particularly in patients with concomitant cardiovascular diseases. Some of these patients are under oral anticoagulation (OAC) at admission, but to date, there are no data on the clinical profile, prognosis and risk factors of such patients during hospitalization for COVID-19. DESIGN: Subanalysis of the international 'real-world' HOPE COVID-19 registry. All patients with prior OAC at hospital admission for COVID-19 were suitable for the study. All-cause mortality was the primary endpoint. RESULTS: From 1002 patients included, 110 (60.9% male, median age of 81.5 [IQR 75-87] years, median Short-Form Charlson Comorbidity Index [CCI] of 1 [IQR 1-3]) were on OAC at admission, mainly for atrial fibrillation and venous thromboembolism. After propensity score matching, 67.9% of these patients died during hospitalization, which translated into a significantly higher mortality risk compared to patients without prior OAC (HR 1.53, 95% CI 1.08-2.16). After multivariate Cox regression analysis, respiratory insufficiency during hospitalization (HR 6.02, 95% CI 2.18-16.62), systemic inflammatory response syndrome (SIRS) during hospitalization (HR 2.29, 95% CI 1.34-3.91) and the Short-Form CCI (HR 1.24, 95% CI 1.03-1.49) were the main risk factors for mortality in patients on prior OAC. CONCLUSIONS: Compared to patients without prior OAC, COVID-19 patients on OAC therapy at hospital admission showed lower survival and higher mortality risk. In these patients on OAC therapy, the prevalence of several comorbidities is high. Respiratory insufficiency and SIRS during hospitalization, as well as higher comorbidity, pointed out those anticoagulated patients with increased mortality risk.

Impact of renal function on admission in COVID-19 patients: an analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its international aggressive extension, with a significant morbidity and mortality, the impact of renal function on its prognosis is uncertain. METHODS: Analysis from the international HOPE-Registry (NCT04334291). The objective was to evaluate the association between kidney failure severity on admission with the mortality of patients with SARS-CoV-2 infection. Patients were categorized in 3 groups according to the estimated glomerular filtration rate on admission (eGFR > 60 mL/min/1.73 m2, eGFR 30-60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2). RESULTS: 758 patients were included: mean age was 66 ± 18 years, and 58.6% of patient were male. Only 8.5% of patients had a history of chronic kidney disease (CKD); however, 30% of patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m2). These patients received less frequently pharmacological treatment with hydroxychloroquine or antivirals and had a greater number of complications such as sepsis (11.9% vs 26.4% vs 40.8%, p < 0.001) and respiratory failure (35.4% vs 72.2% vs 62.0%, p < 0.001) as well as a higher in-hospital mortality rate (eGFR > 60 vs eGFR 30-60 vs and eGFR < 30, 18.4% vs 56.5% vs 65.5%, p < 0.001). In multivariate analysis: age, hypertension, renal function, 02 saturation < 92% and lactate dehydrogenase elevation on admission independently predicted all-cause mortality. CONCLUSIONS: Renal failure on admission in patients with SARS-CoV-2 infection is frequent and is associated with a greater number of complications and in-hospital mortality. Our data comes from a multicenter registry and therefore does not allow to have a precise mortality risk assessment. More studies are needed to confirm these findings.