Cyclosporine A in hospitalized COVID-19 pneumonia patients to prevent the development of interstitial lung disease: a pilot randomized clinical trial.

Post-COVID-19 interstitial lung disease (ILD) is a new entity that frequently causes pulmonary fibrosis and can become chronic. We performed a single-center parallel-group open-label pilot randomized clinical trial to investigate the efficacy and safety of cyclosporine A (CsA) in the development of ILD in the medium term among patients hospitalized with COVID-19 pneumonia. Patients were randomized 1:1 to receive CsA plus standard of care or standard of care alone. The primary composite outcome was the percentage of patients without ILD 3 months after diagnosis of pneumonia and not requiring invasive mechanical ventilation (IMV) (response without requiring IMV). The key secondary composite outcomes were the percentage of patients who achieve a response requiring IMV or irrespective of the need for IMV, and adverse events. A total of 33 patients received at least one dose of CsA plus standard of care (n = 17) or standard of care alone (n = 16). No differences were found between the groups in the percentage of patients who achieved a response without requiring IMV or a response requiring IMV. A higher percentage of patients achieved a response irrespective of the need for IMV in the CsA plus standard of care group although the RR was almost significant 2.833 (95% CI, 0.908-8.840; p = 0.057). No differences were found between the groups for adverse events. In hospitalized patients with COVID-19 pneumonia, we were unable to demonstrate that CsA achieved a significant effect in preventing the development of ILD. (EU Clinical Trials Register; EudraCT Number: 2020-002123-11; registration date: 08/05/2020).

Clinical Characteristics and Prognostic Impact of Short Physical Performance Battery in Hospitalized Patients with Acute Heart Failure-Results of the PROFUND-IC Registry.

BACKGROUND: Most patients diagnosed with heart failure (HF) are older adults with multiple comorbidities. Multipathological patients constitute a population with common characteristics: greater clinical complexity and vulnerability, frailty, mortality, functional deterioration, polypharmacy, and poorer health-related quality of life with more dependency. OBJECTIVES: To evaluate the clinical characteristics of hospitalized patients with acute heart failure and to determine the prognosis of patients with acute heart failure according to the Short Physical Performance Battery (SPPB) scale. METHODS: Observational, prospective, and multicenter cohort study conducted from September 2020 to May 2022 in patients with acute heart failure as the main diagnosis and NT-ProBNP > 300 pg. The cohort included patients admitted to internal medicine departments in 18 hospitals in Spain. Epidemiological variables, comorbidities, cardiovascular risk factors, cardiovascular history, analytical parameters, and treatment during admission and discharge of the patients were collected. Level of frailty was assessed by the SPPB scale, and dependence, through the Barthel index. A descriptive analysis of all the variables was carried out, expressed as frequencies and percentages. A bivariate analysis of the SPPB was performed based on the score obtained (SPPB ≤ 5 and SPPB > 5). For the overall analysis of mortality, HF mortality, and readmission of patients at 30 days, 6 months, and 1 year, Kaplan-Meier survival curves were used, in which the survival experience among patients with an SPPB > 5 and SPPB ≤ 5 was compared. RESULTS: A total of 482 patients were divided into two groups according to the SPPB with a cut-off point of an SPPB < 5. In the sample, 349 patients (77.7%) had an SPPB ≤ 5 and 100 patients (22.30%) had an SPPB > 5. Females (61%) predominated in the group with an SPPB ≤ 5 and males (61%) in those with an SPPB > 5. The mean age was higher in patients with an SPPB ≤ 5 (85.63 years). Anemia was more frequent in patients with an SPPB ≤ 5 (39.5%) than in patients with an SPPB ≥ 5 (29%). This was also seen with osteoarthritis (32.7%, p = 0.000), diabetes (49.6%, p = 0.001), and dyslipidemia (69.6%, p = 0.011). Patients with an SPPB score > 5 had a Barthel index < 60 in only 4% (n = 4) of cases; the remainder of the patients (96%, n = 96) had a Barthel index > 60. Patients with an SPPB > 5 showed a higher probability of survival at 30 days (p = 0.029), 6 months (p = 0.031), and 1 year (p = 0.007) with (OR = 7.07; 95%CI (1.60-29.80); OR: 3.9; 95%CI (1.30-11.60); OR: 6.01; 95%CI (1.90-18.30)), respectively. No statistically significant differences were obtained in the probability of readmission at 30 days, 6 months, and 1 year (p > 0.05). CONCLUSIONS: Patients admitted with acute heart failure showed a high frequency of frailty as assessed by the SPPB. Patients with an SPPB ≤ 5 had greater comorbidities and greater functional limitations than patients with an SPPB > 5. Patients with heart failure and a Barthel index > 60 frequently presented an SPPB < 5. In daily clinical practice, priority should be given to performing the SPPB in patients with a Barthel index > 60 to assess frailty. Patients with an SPPB ≤ 5 had a higher risk of mortality at 30 days, 6 months, and 1 year than patients with an SPPB ≤ 5. The SPPB is a valid tool for identifying frailty in acute heart failure patients and predicting 30-day, 6-month, and 1-year mortality.

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure: a retrospective cohort study of the RICA registry.

BACKGROUND: Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure (HF) and reduced ejection fraction. The PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and deaths. Real-life studies in the elderly population are scarce. The aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors (ACEI) in elderly patients who initiate this treatment during hospitalization for acute HF. METHODS: We conducted a retrospective cohort study using the Spanish acute heart failure registry (RICA) comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitril-valsartan during hospitalization for acute HF versus those treated with ACEI. RESULTS: One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included, with a median age of 82 years and high rate of comorbidity. Of these, 107 were treated with sacubitril-valsartan and 92 with ACEI. The adjusted OR for readmission for HF at 3 months was 0.906 (95% CI: 0.241-3.404) and for the combined variable readmission for HF or death at 3 months was 0.696 (95% CI: 0.224-2.167). The adjusted OR for HF readmission at one year was 0.696 (95% CI: 0.224 -2.167). and for the combined variable HF readmission or death at one year 0.724 (95% CI: 0.325-1.612). CONCLUSION: Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI, which did not reach statistical significance either at 3 months or 1 year of follow-up.

Prognostic Significance of Lung and Cava Vein Ultrasound in Elderly Patients Admitted for Acute Heart Failure: PROFUND-IC Registry Analysis.

Introduction: Heart failure is an extremely prevalent disease in the elderly population of the world. Most patients present signs and symptoms of decompensation of the disease due to worsening congestion. This congestion has been clinically assessed through clinical signs and symptoms and complementary imaging tests, such as chest radiography. Recently, pulmonary and inferior vena cava ultrasound has been shown to be useful in assessing congestion but its prognostic significance in elderly patients has been less well evaluated. Objectives: This study aims to compare the clinical and radiological characteristics and predictive values for mortality in patients admitted for heart failure through the determination of B lines by lung ultrasound and the degree of collapsibility of the inferior vena cava (IVC). Secondarily, the study aims to assess the prediction of 30-day mortality based on the diameter of the IVC by means of the ROC curve. Methods: This is an observational cohort study based on data collected in the PROFUND-IC study, a nationwide multicentric registry of patients admitted with decompensated heart failure. Data were collected from these patients between October 2020 and April 2022. Results: A total of 482 patients were entered into the PROFUND-IC registry between October 2020 and April 2022. Bedside clinical ultrasound was performed during admission in 301 patients (64.3%). The number of patients with more than 6 B-lines on lung ultrasound amounted to 194 (66%). Statistically significant differences in 30-day mortality (22.1% vs. 9.2%; p = 0.01) were found in these patients. The sum of patients with IVC collapsibility of less than 50% amounted to 195 (67%). Regarding prognostic value, collapsibility data were significant for the number of admissions in the last year (12.5% vs. 5.5%; p = 0.04), in-hospital mortality (10.1% vs. 3.3%, p = 0.04) and 30-day mortality (22.6% vs. 8.1%; p < 0.01), but not for readmissions. Regarding the prognostic value of IVC diameter for 30-day mortality, the area under the ROC curve (AUC) was 0.73, with a p < 0.01. The curve cut-off point with the highest sensitivity (70%) and specificity (70.3%) was for an IVC value of 22.5 mm. In the logistic regression analysis, we observed that the variable most associated with patient survival at 30 days was the presence of a collapsible inferior vena cava, with more than 50% OR 0.359 (CI 0.139−0.926; p = 0.034). Conclusions: The subgroups of patients analyzed with more than six B lines per field and IVC collapsibility less than or equal to 50%, as measured by clinical ultrasound, had higher 30-day mortality rates than patients who did not fall into these subgroups. IVC diameter may be a good independent predictor of 30-day mortality in patients with decompensated heart failure. Comparing both ultrasound variables, it seems that in our population, the assessment of the inferior vena cava may be more associated with short-term prognosis than the pulmonary congestion variables assessed by B lines.

Cancer Impacts Prognosis on Mortality in Patients with Acute Heart Failure: Analysis of the EPICTER Study.

INTRODUCTION: Heart failure (HF) and cancer are currently the leading causes of death worldwide, with an increasing incidence with age. Little is known about the treatment received and the prognosis of patients with acute HF and a prior cancer diagnosis. OBJECTIVE: to determine the clinical characteristics, palliative treatment received, and prognostic impact of patients with acute HF and a history of solid tumor. METHODS: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for acute HF in 74 Spanish hospitals. Patients were classified into two groups according to whether they met criteria for acute HF with and without solid cancer, and the groups were subsequently compared. A multivariable logistic regression analysis was conducted, using the forward stepwise method. A Kaplan-Meier survival analysis was performed to evaluate the impact of solid tumor on prognosis in patients with acute HF. RESULTS: A total of 3127 patients were included, of which 394 patients (13%) had a prior diagnosis of some type of solid cancer. Patients with a history of cancer presented a greater frequency of weight loss at admission: 18% vs. 12% (p = 0.030). In the cancer group, functional impairment was noted more frequently: 43% vs. 35%, p = 0.039). Patients with a history of solid cancer more frequently presented with acute HF with preserved ejection fraction (65% vs. 58%, p = 0.048) than reduced or mildly reduced. In-hospital and 6-month follow-up mortality was 31% (110/357) in patients with solid cancer vs. 26% (637/2466), p = 0.046. CONCLUSION: Our investigation demonstrates that in-hospital mortality and mortality during 6-month follow-up in patients with acute HF were higher in those subjects with a history of concomitant solid tumor cancer diagnosis.

Epidemiology of heart failure with preserved ejection fraction: Results from the RICA Registry. / Epidemiología de la insuficiencia cardiaca con fracción de eyección preservada: resultados del Registro RICA.

INTRODUCTION AND OBJECTIVES: There is great interest in better characterizing patients with heart failure (HF) with preserved ejection fraction (HF-PEF). The objective of this study is to determine the prevalence, progression over time and to describe the clinical and epidemiological characteristics of patients with HF-PEF. METHODS: From the National Registry of Heart Failure (RICA, prospective multicentre cohort study) we analysed patients consecutively admitted for HF in Internal Medicine wards over a period of 11 years (2008-2018). RESULTS: 4752 patients were included, 2957 (62.2%) with preserved ejection fraction. This prevalence remained constant from 2008 to 2019. Compared to patients with HF and reduced ejection fraction (HF-REF) patients with HF-PEF are older, more are female, there is a higher prevalence of hypertensive and valvular aetiology, they have a profile of different comorbidities and worse functional status. A high proportion of patients receive disease-modifying treatment for IC-REF (renin-angiotensin-aldosterone system inhibitors and beta-blockers). The overall mortality after one-year follow-up was 24% and 30% in the HF-PEF and the HF-REF, respectively. In the multivariate analysis, the risk of death was higher in patients with HF-REF compared to HF-PEF (OR: 1.84; 95% CI: [1.43-2.36]). The length of hospital stay was also lower in the HF-PEF patients but there were no differences in re-hospitalizations. CONCLUSIONS: Sixty percent of patients in the RICA registry have preserved ejection fraction. These patients have a higher comorbidity burden and a worse functional status, but lower mortality compared with HF-REF patients.

Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia.

BACKGROUND: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250 mg of prednisone daily and use of equivalent doses greater than or equal to 250 mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250 mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250 mg prednisone daily) versus patients with glucocorticoids doses <250 mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250 mg have a more favorable evolution (less mortality and less admission to ICU).

INTRODUCCIÓN: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides. MÉTODOS: Estudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250 mg de prednisona y dosis diarias equivalentes mayores o iguales a 250 mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante. RESULTADOS: De los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30­1,66]), tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11­1,08]) y tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus pacientes con dosis de glucocorticoides < 250 mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10­0,88]). CONCLUSIÓN: Los resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250 mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI).

[Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia]. / Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2.

INTRODUCTION: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU).

De novo acute heart failure: Clinical features and one-year mortality in the Spanish nationwide Registry of Acute Heart Failure. / Insuficiencia cardiaca aguda de novo: características clínicas y mortalidad al año en el Registro Español de Insuficiencia Cardiaca Aguda.

INTRODUCTION AND OBJECTIVES: Acute heart failure (AHF), can occur as decompensated chronic heart failure (HF) or as a first episode, "new onset". The aim of this study was to analyse the clinical characteristics and prognosis at one-year in a cohort of patients with new onset AHF. METHODS: Prospective observational study of 3,550 patients with AHF. We compared patients with new onset HF with the others. Restricting the analysis to new onset AHF patients, we analysed the clinical characteristics, readmissions, mortality and impact of left ventricular ejection fraction on the prognosis. RESULTS: A total of 1,105 (31%) patients fulfil the criteria for new onset AHF. These patients versus the rest, were younger, had a higher aetiology of hypertension and preserved left ventricular ejection fraction, less global comorbidity and better baseline overall functional status. After one year, mortality in new onset HF was less than chronic decompensated HF (15 vs. 27%; p<.001; respectively). Multivariate analysis showed a correlation between mortality and higher global comorbidity (hazard ratio. -HR- 1.11), renal failure (HR 1.73), higher prescription of antialdosteronics and antiaggregant (HR 2.13; 1.8; respectively). Left ventricular ejection fraction was unrelated to mortality. CONCLUSIONS: New onset AHF shows a clinical profile and prognosis different to that of chronic decompensated HF. Higher comorbidity, renal function and treatment post-discharge predict a higher risk of mortality.

Digoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study.

BACKGROUND: The value of digoxin in heart failure (HF) remains controversial, particularly in patients with preserved ejection fraction (HFpEF). This study evaluated the 1-year risk of events after digoxin treatment for acute heart failure (AHF) in patients >70 years old with HFpEF. METHODS: 1833 patients were included in this analysis (mean age, 82 years). The main endpoints were all-cause death and the composite of death and/or HF re-admission within 1 year. Cox regression analysis was used to evaluate the association between digoxin treatment and prognosis. RESULTS: 401 patients received digoxin treatment; of these, 86% had atrial fibrillation. The mean baseline heart rate was 86 ±â€¯22 bpm. At the 1-year follow-up, 375 patients (20.5%) died and 684 (37.3%) presented composite endpoints. Patients treated with digoxin showed higher rates of death (3.21 vs. 2.44 per 10 person-years, p = .019) and composite endpoint (6.72 vs. 5.18 per 10 person-years, p = .003). After multivariate adjustment, digoxin treatment remained associated with increased risks of death (HR = 1.46, 95% CI: 1.16-1.85, p = .001) and the composite endpoint (HR = 1.35, 95% CI: 1.13-1.61, p = .001). A distinctive prognostic effect of digoxin was found across the heart rate continuum; the risks for both endpoints were higher at lower heart rates and neutral at higher heart rates (p of the interactions = 0.007 and 0.03, respectively). CONCLUSIONS: In older patients with HFpEF discharged after AHF, digoxin treatment was associated with increased mortality and/or re-admission, particularly in patients with lower heart rates.

Inflammatory responses associated with acute coronary syndrome up-regulate IRAK-M and induce endotoxin tolerance in circulating monocytes.

Acute coronary syndrome (ACS) groups different cardiac diseases whose development is associated with inflammation. Here we have analyzed the levels of inflammatory cytokines and of members of the TLR/IRAK pathway including IRAK-M in monocytes from ACS patients classified as either UA (unstable angina), STEMI (ST-elevation myocardial infarction) or NSTEMI (non-ST-elevation myocardial infarction). Circulating monocytes from all patients, but not from healthy individuals, showed high levels of pro-inflammatory cytokines, TNF-alpha and IL-6, as well as of IRAK-M and IL-10. TLR4 was also up-regulated, but IRAK-1, IRAK-4 and MyD88 levels were similar in patients and controls. Further, we investigated the consequences of cytokines/IRAK-M expression on the innate immune response to endotoxin. Ex vivo responses to LPS were markedly attenuated in patient monocytes compared to controls. Control monocytes cultured for 6 h in supplemented medium (10% serum from ACS patients) expressed IRAK-M, and LPS stimulation failed to induce TNF-alpha and IL-6 in these cultures. Pre-incubation of the serum with a blocking anti-TNF-alpha antibody reduced this endotoxin tolerance effect, suggesting that TNF-alpha controls this phenomenon, at least partially. We show for the first time that inflammatory responses associated with ACS induce an unresponsiveness state to endotoxin challenge in circulating monocytes, which correlates with expression of IRAK-M, TLR4 and IL-10. The magnitude of this response varies according to the clinical condition (UA, STEMI or NSTEMI), and is regulated by TNF-alpha.