Role of vericiguat in management of patients with heart failure with reduced ejection fraction after worsening episode.

Worsening heart failure (HF) is a vulnerable period in which the patient has a markedly high risk of death or HF hospitalization (up to 10% and 30%, respectively, within the first weeks after episode). The prognosis of HF patients can be improved through a comprehensive approach that considers the different neurohormonal systems, with the early introduction and optimization of the quadruple therapy with sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, and inhibitors. Despite that, there is a residual risk that is not targeted with these therapies. Currently, it is recognized that the cyclic guanosine monophosphate deficiency has a negative direct impact on the pathogenesis of HF, and vericiguat, an oral stimulator of soluble guanylate cyclase, can restore this pathway. The effect of vericiguat has been explored in the VICTORIA study, the largest chronic HF clinical trial that has mainly focused on patients with recent worsening HF, evidencing a significant 10% risk reduction of the primary composite endpoint of cardiovascular death or HF hospitalization (number needed to treat 24), after adding vericiguat to standard therapy. This benefit was independent of background HF therapy. Therefore, optimization of treatment should be performed as earlier as possible, particularly within vulnerable periods, considering also the use of vericiguat.

Machine learning for the development of diagnostic models of decompensated heart failure or exacerbation of chronic obstructive pulmonary disease.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are two chronic diseases with the greatest adverse impact on the general population, and early detection of their decompensation is an important objective. However, very few diagnostic models have achieved adequate diagnostic performance. The aim of this trial was to develop diagnostic models of decompensated heart failure or COPD exacerbation with machine learning techniques based on physiological parameters. A total of 135 patients hospitalized for decompensated heart failure and/or COPD exacerbation were recruited. Each patient underwent three evaluations: one in the decompensated phase (during hospital admission) and two more consecutively in the compensated phase (at home, 30 days after discharge). In each evaluation, heart rate (HR) and oxygen saturation (Ox) were recorded continuously (with a pulse oximeter) during a period of walking for 6 min, followed by a recovery period of 4 min. To develop the diagnostic models, predictive characteristics related to HR and Ox were initially selected through classification algorithms. Potential predictors included age, sex and baseline disease (heart failure or COPD). Next, diagnostic classification models (compensated vs. decompensated phase) were developed through different machine learning techniques. The diagnostic performance of the developed models was evaluated according to sensitivity (S), specificity (E) and accuracy (A). Data from 22 patients with decompensated heart failure, 25 with COPD exacerbation and 13 with both decompensated pathologies were included in the analyses. Of the 96 characteristics of HR and Ox initially evaluated, 19 were selected. Age, sex and baseline disease did not provide greater discriminative power to the models. The techniques with S and E values above 80% were the logistic regression (S: 80.83%; E: 86.25%; A: 83.61%) and support vector machine (S: 81.67%; E: 85%; A: 82.78%) techniques. The diagnostic models developed achieved good diagnostic performance for decompensated HF or COPD exacerbation. To our knowledge, this study is the first to report diagnostic models of decompensation potentially applicable to both COPD and HF patients. However, these results are preliminary and warrant further investigation to be confirmed.

Nosocomial COVID-19: A Nationwide Spanish Study.

INTRODUCTION: SARS-CoV-2 is a highly contagious virus, and despite professionals' best efforts, nosocomial COVID-19 (NC) infections have been reported. This work aimed to describe differences in symptoms and outcomes between patients with NC and community-acquired COVID-19 (CAC) and to identify risk factors for severe outcomes among NC patients. METHODS: This is a nationwide, retrospective, multicenter, observational study that analyzed patients hospitalized with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from March 1, 2020, to April 30, 2021. NC was defined as patients admitted for non-COVID-19 diseases with a positive SARS-CoV-2 test on the fifth day of hospitalization or later. The primary outcome was 30-day in-hospital mortality (IHM). The secondary outcome was other COVID-19-related complications. A multivariable logistic regression analysis was performed. RESULTS: Of the 23,219 patients hospitalized with COVID-19, 1,104 (4.8%) were NC. Compared to CAC patients, NC patients were older (median 76 vs. 69 years; p < 0.001), had more comorbidities (median Charlson Comorbidity Index 5 vs. 3; p < 0.001), were less symptomatic (p < 0.001), and had normal chest X-rays more frequently (30.8% vs. 12.5%, p < 0.001). After adjusting for sex, age, dependence, COVID-19 wave, and comorbidities, NC was associated with lower risk of moderate/severe acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR]: 0.72; 95% confidence interval [CI]: 0.59-0.87; p < 0.001) and higher risk of acute heart failure (aOR: 1.40; 1.12-1.72; p = 0.003), sepsis (aOR: 1.73; 1.33-2.54; p < 0.001), and readmission (aOR: 1.35; 1.03-1.83; p = 0.028). NC was associated with a higher case fatality rate (39.1% vs. 19.2%) in all age groups. IHM was significantly higher among NC patients (aOR: 2.07; 1.81-2.68; p < 0.001). Risk factors for increased IHM in NC patients were age, moderate/severe dependence, malignancy, dyspnea, moderate/severe ARDS, multiple organ dysfunction syndrome, and shock; odynophagia was associated with lower IHM. CONCLUSIONS: NC is associated with greater mortality and complications compared to CAC. Hospital strategies to prevent NC must be strengthened.

The "FIFTY SHADOWS" of the RALES Trial: Lessons about the Potential Risk of Dietary Potassium Supplementation in Patients with Chronic Kidney Disease.

Hyperkalaemia (HK) is one of the most common electrolyte disorders and a frequent reason for nephrological consultations. High serum potassium (K+) levels are associated with elevated morbidity and mortality, mainly due to life-threatening arrhythmias. In the majority of cases, HK is associated with chronic kidney disease (CKD), or with the use of renin-angiotensin-aldosterone system inhibitors (RAASis) and/or mineral corticoid antagonists (MRAs). These drugs represent the mainstays of treatment in CKD, HF, diabetes, hypertension, and even glomerular diseases, in consideration of their beneficial effect on hard outcomes related to cardiovascular events and CKD progression. However, experiences in relation to the Randomised Aldactone Evaluation Study (RALES) cast a long shadow that extends to the present day, since the increased risk for HK remains a major concern. In this article, we summarise the physiology of K+ homeostasis, and we review the effects of dietary K+ on blood pressure and cardiovascular risk in the general population and in patients with early CKD, who are often not aware of this disease. We conclude with a note of caution regarding the recent publication of the SSaSS trial and the use of salt substitutes, particularly in patients with a limited capacity to increase K+ secretion in response to an exogenous load, particularly in the context of "occult" CKD, HF, and in patients taking RAASis and/or MRAs.

Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry.

Uncontrolled inflammation following COVID-19 infection is an important characteristic of the most seriously ill patients. The present study aims to describe the clusters of inflammation in COVID-19 and to analyze their prognostic role. This is a retrospective observational study including 15,691 patients with a high degree of inflammation. They were included in the Spanish SEMI-COVID-19 registry from March 1, 2020 to May 1, 2021. The primary outcome was in-hospital mortality. Hierarchical cluster analysis identified 7 clusters. C1 is characterized by lymphopenia, C2 by elevated ferritin, and C3 by elevated LDH. C4 is characterized by lymphopenia plus elevated CRP and LDH and frequently also ferritin. C5 is defined by elevated CRP, and C6 by elevated ferritin and D-dimer, and frequently also elevated CRP and LDH. Finally, C7 is characterized by an elevated D-dimer. The clusters with the highest in-hospital mortality were C4, C6, and C7 (17.4% vs. 18% vs. 15.6% vs. 36.8% vs. 17.5% vs. 39.3% vs. 26.4%). Inflammation clusters were found as independent factors for in-hospital mortality. In detail and, having cluster C1 as reference, the model revealed a worse prognosis for all other clusters: C2 (OR = 1.30, p = 0.001), C3 (OR = 1.14, p = 0.178), C4 (OR = 2.28, p < 0.001), C5 (OR = 1.07, p = 0.479), C6 (OR = 2.29, p < 0.001), and C7 (OR = 1.28, p = 0.001). We identified 7 groups based on the presence of lymphopenia, elevated CRP, LDH, ferritin, and D-dimer at the time of hospital admission for COVID-19. Clusters C4 (lymphopenia + LDH + CRP), C6 (ferritin + D-dimer), and C7 (D-dimer) had the worst prognosis in terms of in-hospital mortality.

Impact of the iCODEX tool in routine clinical practice in Spain.

INTRODUCTION: The prognosis of COPD patients can be calculated using multidimensional indexes that improve the predictive capacity of the individual variables. The CODEX index can be calculated using iCODEX, a digital support tool available on the web and in an app. The aim of this study was to evaluate how the usefulness and applicability of iCODEX and its recommendations in routine clinical practice are perceived by specialists in internal medicine, pneumology, and primary care. METHODS: A cross-sectional study was conducted from November 2019 to February 2020 with the participation of specialists in internal medicine, primary care, and pneumology. All respondents completed a survey consisting of 104 questions on their perception of the iCODEX tool. RESULTS: Overall, 335 physicians responded. Of these, 95.2% had no difficulty accessing the tool and 83.1% were quite or very satisfied with it. Regarding the applicability and implementation of iCODEX recommendations in routine clinical practice, respondents reported that the recommendations were generally applicable: most questions obtained a median score of ≥ 4 out of 5. The recommendations with the greatest expected clinical benefit are listed. CONCLUSIONS: Our study shows that the iCODEX tool is easy for participating specialists to use and identifies the recommendations that have the greatest clinical impact in areas such as lung obstruction, severe exacerbations, exercise, smoking, and patient follow-up.

Clinical Features and Risk Factors for Mortality Among Long-term Care Facility Residents Hospitalized Due to COVID-19 in Spain.

BACKGROUND: COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents. METHODS: This is a cross-sectional analysis within a retrospective cohort of hospitalized patients ≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis. RESULTS: Of 6 189 patients ≥75 years, 1 185 (19.1%) were LTCF residents and 4 548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs 82.1 years), mostly female (61.6% vs 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p < .001). Mortality risk factors in LTCF residents were severe functional dependence (adjusted odds ratios [aOR]: 1.79; 95% confidence interval [CI]: 1.13-2.83; p = .012), dyspnea (1.66; 1.16-2.39; p = .004), SatO2 < 94% (1.73; 1.27-2.37; p = .001), temperature ≥ 37.8°C (1.62; 1.11-2.38; p = .013); qSOFA index ≥ 2 (1.62; 1.11-2.38; p = .013), bilateral infiltrates (1.98; 1.24-2.98; p < .001), and high C-reactive protein (1.005; 1.003-1.007; p < .001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR: 0.74, 95%CI: 0.62-0.87; p < .001). CONCLUSION: Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.

Does admission acetylsalicylic acid uptake in hospitalized COVID-19 patients have a protective role? Data from the Spanish SEMI-COVID-19 Registry.

Acetylsalicylic acid (ASA) is widely used in the treatment and prevention of cardiovascular disorders. Our objective is to evaluate its possible protective role, not only in mortality but also in other aspects such as inflammation, symptomatic thrombosis, and intensive care unit (ICU) admission in hospitalized COVID-19 patients. We realized an observational retrospective cohort study of 20,641 patients with COVID-19 pneumonia collected and followed-up from Mar 1st, 2020 to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Propensity score matching (PSM) was performed to determine whether treatment with ASA affected outcomes in COVID-19 patients. On hospital admission, 3291 (15.9%) patients were receiving ASA. After PSM, 3291 patients exposed to ASA and 2885 not-exposed patients were analyzed. In-hospital mortality was higher in the ASA group (30.4 vs. 16.9%, p < 0.001) in the global sample. After PSM, no differences were found between groups (30.4 vs. 30.3%, p = 0.938). There were no differences in inflammation, symptomatic thrombosis, or ICU admission. In conclusion, ASA intake is not associated with in-hospital mortality or any other health outcome evaluated after applying PSM analysis in a real-world large sample of hospitalized COVID-19 patients.

Aspiration pneumonia: A renewed perspective and practical approach.

Aspiration pneumonia (AP) is a sub-type of community-acquired pneumonia (CAP) still poorly recognized especially in the absence of an aspiration event. A further difficulty is the differentiation between AP and aspiration pneumonitis. From a clinical perspective, AP is becoming increasingly relevant as a potential cause of severe and life-threatening respiratory infection among frail and very old patients, particularly among those with CAP requiring inpatient care. Moreover, AP is frequently underdiagnosed and a clear-cut definition of this pathological entity is lacking. There are different factors that increase the risk for aspiration, but other common factors influencing oral colonization such as malnutrition, smoking, poor oral hygiene or dry mouth, are also important in the pathogenesis of AP and should be considered. While there is no doubt in the diagnosis of AP in cases of a recent witnessed aspiration of oropharyngeal or gastric content, we here proposed a definition of AP that also includes silent unobserved aspirations. For this reason, the presence of one or more risk factors of oropharyngeal aspiration is required together with one or more risk factors for oral bacterial colonization. This proposed definition based on expert opinion not only unifies the diagnostic criteria of AP, but also provides the possibility to devise easily applicable strategies to prevent oral colonization.

Severe loss of mechanical efficiency in COVID-19 patients.

BACKGROUND: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). METHODS: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2 peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. RESULTS: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2 peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2 , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2 peak and DE and between the peak power output and DE (P < 0.001). CONCLUSIONS: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation.

Autoimmune Diseases and COVID-19 as Risk Factors for Poor Outcomes: Data on 13,940 Hospitalized Patients from the Spanish Nationwide SEMI-COVID-19 Registry.

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects.

Prior Treatment with Statins is Associated with Improved Outcomes of Patients with COVID-19: Data from the SEMI-COVID-19 Registry.

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry.

AIM: To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). METHODS: Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. RESULTS: As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). CONCLUSIONS: Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality.