Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.

Estrategias de prevención y tratamiento de la infección por SARS-CoV-2 (Severe Acute Respiratory Coronavirus 2) en pacientes con enfermedad renal crónica: revisión de la literatura / Strategies for prevention and treatment of SARS-CoV-2 infection in patients with chronic kidney disease: Literature review

La COVID-19 ha demostrado ser especialmente agresiva con los pacientes con enfermedad renal crónica (ERC). La menor tasa de respuesta inmunológica y la mayor facilidad para la progresión a formas graves de enfermedad ha propiciado este hecho, que se ha mantenido en la era posvacunal de la pandemia. Paradójicamente, la ERC ha sido excluida de la mayoría de los ensayos clínicos de las principales herramientas terapéuticas desarrolladas frente a SARS-CoV-2. Sin embargo, se ha ido reuniendo experiencia de uso de estos fármacos en distintos estadios de la ERC que avala su uso con garantías de eficacia y seguridad. El objetivo de esta revisión es reunir todas las indicaciones de tratamiento frente a la COVID-19 en los distintos estadios de la enfermedad adaptadas a la ERC en sus distintas fases, incluyendo el tratamiento sustitutivo renal.(AU)

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.(AU)

Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias / Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias

Objetivo: desarrollar un panel de indicadores para monitorizar la actividad de los programas de optimización del uso de antimicrobianos en los servicios de urgencias. Métodos: un grupo multidisciplinar formado por expertos en el manejo de la infección en urgencias y en la implantación de programas de optimización de uso de antimicrobianos (PROA) evaluó una propuesta de indicadores utilizando una metodología Delphi modificada. En una primera ronda, cada uno de los expertos clasificó la relevancia de cada indicador propuesto en 2 dimensiones (repercusión asistencial y facilidad de implantación) y 2 atributos (nivel de priorización y periodicidad de medida). La segunda ronda se realizó a partir del cuestionario modificado de acuerdo con las sugerencias planteadas y nuevos indicadores sugeridos por los participantes. Los expertos efectuaron modificaciones en el orden de priorización y calificaron los nuevos indicadores propuestos de la misma manera que en la primera ronda. Resultados: se propusieron un total de 61 potenciales indicadores divididos en 4 grupos: indicadores de consumo, microbiológicos, de proceso y de resultado. Tras el análisis de las puntuaciones y los comentarios realizados en la primera ronda, 31 indicadores fueron clasificados como de alta prioridad, 25 de prioridad intermedia y 5 de baja prioridad. Además se generaron 19 nuevos indicadores. Tras la segunda ronda, se mantuvieron los 61 indicadores inicialmente propuestos y adicionalmente se incorporaron 18 nuevos: 11 como de alta prioridad, 3 como de intermedia y 4 como de baja prioridad. Conclusiones: los expertos consensuaron un panel de indicadores PROA adaptado a los servicios de urgencias priorizados por nivel de relevancia como un elemento de ayuda para el desarrollo de estos programas, que contribuirá a monitorizar la adecuación del uso de antimicrobianos en estas unidades.(AU)

Objective: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. Methods: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. Results: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. Conclusions: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.(AU)

Factors Associated with SARS-CoV-2 Infection in Fully Vaccinated Nursing Home Residents and Workers.

Persons living or working in nursing homes faced a higher risk of SARS-CoV-2 infections during the pandemic, resulting in heightened morbidity and mortality among older adults despite robust vaccination efforts. This prospective study evaluated the humoral and cellular immunity in fully vaccinated residents and workers from two nursing homes in Madrid, Spain, from 2020 to 2021. Measurements of IgG levels were conducted in August 2020 (pre-vaccination) and June and September 2021 (post-vaccination), alongside assessments of neutralizing antibodies and cellular responses in September 2021 among the most vulnerable individuals. Follow-up extended until February 2022 to identify risk factors for SARS-CoV-2 infection or mortality, involving 267 residents (mean age 87.6 years, 81.3% women) and 302 workers (mean age 50.7 years, 82.1% women). Residents exhibited a significantly higher likelihood of experiencing COVID-19 before June 2021 compared with nursing staff (OR [95% CI], 7.2 [3.0 to 17.2], p < 0.01). Participants with a history of previous COVID-19 infection showed more significant increases in IgG levels in August 2020, June 2021 and September 2021, alongside an increased proportion of neutralizing antibodies in the most vulnerable individuals. However, IgG decay remained the same between June and September 2021 based on the previous COVID-19 status. During the Omicron variant wave, residents and staff showed a similar rate of SARS-CoV-2 infection. Notably, preceding clinical or immunological factors before receiving three vaccination doses did not demonstrate associations with COVID-19 infection or overall mortality in our participant cohort.

[Translated article] Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritisation level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritisation order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analysing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP Indicators adapted to the emergency services prioritised by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

Ten Issues for Updating in Community-Acquired Pneumonia: An Expert Review.

Community-acquired pneumonia represents the third-highest cause of mortality in industrialized countries and the first due to infection. Although guidelines for the approach to this infection model are widely implemented in international health schemes, information continually emerges that generates controversy or requires updating its management. This paper reviews the most important issues in the approach to this process, such as an aetiologic update using new molecular platforms or imaging techniques, including the diagnostic stewardship in different clinical settings. It also reviews both the Intensive Care Unit admission criteria and those of clinical stability to discharge. An update in antibiotic, in oxygen, or steroidal therapy is presented. It also analyzes the management out-of-hospital in CAP requiring hospitalization, the main factors for readmission, and an approach to therapeutic failure or rescue. Finally, the main strategies for prevention and vaccination in both immunocompetent and immunocompromised hosts are reviewed.

Ten Issues to Update in Nosocomial or Hospital-Acquired Pneumonia: An Expert Review.

Nosocomial pneumonia, or hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP) are important health problems worldwide, with both being associated with substantial morbidity and mortality. HAP is currently the main cause of death from nosocomial infection in critically ill patients. Although guidelines for the approach to this infection model are widely implemented in international health systems and clinical teams, information continually emerges that generates debate or requires updating in its management. This scientific manuscript, written by a multidisciplinary team of specialists, reviews the most important issues in the approach to this important infectious respiratory syndrome, and it updates various topics, such as a renewed etiological perspective for updating the use of new molecular platforms or imaging techniques, including the microbiological diagnostic stewardship in different clinical settings and using appropriate rapid techniques on invasive respiratory specimens. It also reviews both Intensive Care Unit admission criteria and those of clinical stability to discharge, as well as those of therapeutic failure and rescue treatment options. An update on antibiotic therapy in the context of bacterial multiresistance, in aerosol inhaled treatment options, oxygen therapy, or ventilatory support, is presented. It also analyzes the out-of-hospital management of nosocomial pneumonia requiring complete antibiotic therapy externally on an outpatient basis, as well as the main factors for readmission and an approach to management in the emergency department. Finally, the main strategies for prevention and prophylactic measures, many of them still controversial, on fragile and vulnerable hosts are reviewed.

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies / Reducción del riesgo de progresión en receptores de trasplantes infectados por SARS-CoV-2 tratados con anticuerpos monoclonales

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural

Los receptores de trasplantes de órganos sólidos (TOS) presentan un alto riesgo de infección por el virus SARS-CoV-2 debido al tratamiento inmunosupresor y múltiples comorbilidades. La COVID-19 puede ser potencialmente mortal en receptores de TOS, con un aumento de la probabilidad de progresión a enfermedad grave. Este trabajo presenta una revisión actualizada del impacto de la COVID-19 en receptores de TOS. En los receptores de TOS no vacunados, la COVID-19 se asocia con una alta tasa de mortalidad, hospitalización, ingreso en la UCI y deterioro del injerto o rechazo. En los pacientes vacunados, incluso con pauta de vacunación completa, se reduce el riesgo de mortalidad, pero el curso de la COVID-19 puede continuar siendo grave en función del tiempo desde el trasplante, el estado neto de inmunosupresión y haber sufrido rechazo o disfunción del injerto. Los receptores de TOS presentan una baja inmunogenicidad a las vacunas de ARNm y respuesta subóptima. El tratamiento con anticuerpos monoclonales (AMC) en receptores de TOS no hospitalizados con alto riesgo de enfermedad grave, se asocia con menores tasas de hospitalización, visitas a urgencias, ingreso en UCI, progresión a enfermedad grave y muerte. Sin embargo, se requieren nuevas vacunas y opciones terapéuticas, teniendo en cuenta la tendencia del virus SARS-CoV-2 a adaptarse y a evadir tanto la inmunidad natural como la inducida por la vacuna (Au)and vaccine-induced immunity (AU)

Expert Consensus: Main Risk Factors for Poor Prognosis in COVID-19 and the Implications for Targeted Measures against SARS-CoV-2.

The clinical evolution of patients infected with the Severe Acute Respiratory Coronavirus type 2 (SARS-CoV-2) depends on the complex interplay between viral and host factors. The evolution to less aggressive but better-transmitted viral variants, and the presence of immune memory responses in a growing number of vaccinated and/or virus-exposed individuals, has caused the pandemic to slowly wane in virulence. However, there are still patients with risk factors or comorbidities that put them at risk of poor outcomes in the event of having the coronavirus infectious disease 2019 (COVID-19). Among the different treatment options for patients with COVID-19, virus-targeted measures include antiviral drugs or monoclonal antibodies that may be provided in the early days of infection. The present expert consensus is based on a review of all the literature published between 1 July 2021 and 15 February 2022 that was carried out to establish the characteristics of patients, in terms of presence of risk factors or comorbidities, that may make them candidates for receiving any of the virus-targeted measures available in order to prevent a fatal outcome, such as severe disease or death. A total of 119 studies were included from the review of the literature and 159 were from the additional independent review carried out by the panelists a posteriori. Conditions found related to strong recommendation of the use of virus-targeted measures in the first days of COVID-19 were age above 80 years, or above 65 years with another risk factor; antineoplastic chemotherapy or active malignancy; HIV infection with CD4+ cell counts < 200/mm3; and treatment with anti-CD20 immunosuppressive drugs. There is also a strong recommendation against using the studied interventions in HIV-infected patients with a CD4+ nadir <200/mm3 or treatment with other immunosuppressants. Indications of therapies against SARS-CoV-2, regardless of vaccination status or history of infection, may still exist for some populations, even after COVID-19 has been declared to no longer be a global health emergency by the WHO.

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department. / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

Temporal Series Analysis of Population Cycle Threshold Counts as a Predictor of Surge in Cases and Hospitalizations during the SARS-CoV-2 Pandemic.

Tools to predict surges in cases and hospitalizations during the COVID-19 pandemic may help guide public health decisions. Low cycle threshold (CT) counts may indicate greater SARS-CoV-2 concentrations in the respiratory tract, and thereby may be used as a surrogate marker of enhanced viral transmission. Several population studies have found an association between the oscillations in the mean CT over time and the evolution of the pandemic. For the first time, we applied temporal series analysis (Granger-type causality) to validate the CT counts as an epidemiological marker of forthcoming pandemic waves using samples and analyzing cases and hospital admissions during the third pandemic wave (October 2020 to May 2021) in Madrid. A total of 22,906 SARS-CoV-2 RT-PCR-positive nasopharyngeal swabs were evaluated; the mean CT value was 27.4 (SD: 2.1) (22.2% below 20 cycles). During this period, 422,110 cases and 36,727 hospital admissions were also recorded. A temporal association was found between the CT counts and the cases of COVID-19 with a lag of 9-10 days (p ≤ 0.01) and hospital admissions by COVID-19 (p < 0.04) with a lag of 2-6 days. According to a validated method to prove associations between variables that change over time, the short-term evolution of average CT counts in the population may forecast the evolution of the COVID-19 pandemic.

Efficacy and safety of oral fosfomycin for asymptomatic bacteriuria in kidney transplant recipients: Results from a Spanish multicenter cohort.

Current guidelines recommend against systematic screening or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of post-transplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR]: 1.1 - 10.5). Most episodes (96.4% [132/137]) were caused by gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended-spectrum ß-lactamase-producing Enterobacterales [20.4%] and carbapenem-resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [95%CI]: 31.9 - 48.9) for the whole cohort and 42.3% (95%CI: 31.2 - 54.0) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR]: 2.42; 95%CI: 1.11 - 5.29; P-value = 0.027) and use of fosfomycin as salvage therapy (OR: 8.31; 95%CI: 1.67 - 41.35; P-value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse event were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.

COVID-19 in donation and transplant

SARS-CoV-2 infection has had a major impact on donation and transplantation. Since the cessation of activity twoyears ago, the international medical community has rapidly generated evidence capable of sustaining and increasing this neccesary activity. This paper analyses the epidemiology and burden of COVID-19 in donation and transplantation, the pathogenesis of the infection and its relationship with graft-mediated transmission, the impact of vaccination on donation and transplantation, the evolution of donation in Spain throughout the pandemic, some lessons learned in SARS-CoV-2 infected donor recipients with positive PCR and the applicability of the main therapeutic tools recently approved for treatment among transplant recipients. (AU)

Biomarkers of stable and decompensated phases of heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a disorder related to patient comorbidities and aging. Whether mitochondrial dysfunction is present during HFpEF decompensation versus the stable phase is largely unknown. The aim of the present study was to identify mitochondrial and cell metabolism blood biomarkers in older patients with acute and stable HFpEF. METHODS: Peripheral blood biomarkers were investigated in a group of eight to 12 patients aged 80-96 years and diagnosed with HFpEF first when they were in decompensated phase and then at least three months later in stable phase. Their data were compared to two control groups with an equal number of participants and sex proportions. One group was age matched and the other included individuals aged between 22 and 44 years. RESULTS: Decompensated patients experienced an increased mitochondrial superoxide production and mitochondrial mass, lower mitochondrial DNA copy number and LDHB expression, and higher lactate level compared to the stable stage. The stable phase was characterized by a sharp reduction in formate level. Multivariate analysis indicated that formate, lactate, and histidine can distinguish both of the HFpEF phases. Many of these parameters, including LDHB, lactate, formate, and mitochondrial mass, followed an age-related pattern, with acute HFpEF at its apex or nadir, suggesting that it represents an exacerbation of an aging-related process. CONCLUSIONS: We identified distinct blood biomarkers of chronic and decompensated HFpEF phases. The data underlined the relationship between HFpEF and aging. These findings could be used to monitor patients and might be therapeutically targeted.