Clonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.This work was supported by Fundación “la Caixa” (grant number LCF/PR/HR17/52150007 to VF, and JJF). JJF is supported by a Ramón y Cajal award (RYC2016–20026) from the Spanish Ministerio de Ciencia e Innovación (MICIN)/Agencia Estatal de Investigación (AEI)/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro”. VA’s lab is supported by MICIN/ AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (grant number PID2019-108489RBI00), the Progeria Research Foundation (Award PRF 2019–77), and a donation from Asociación Progeria Alexandra Peraut. LBG is supported by The Progeria Research Foundation. MDD is supported by a predoctoral FPI fellowship from the Spanish MICIN/AEI/10.13039/501100011033 and Fondo Social Europeo “El FSE invierte en tu futuro” (PRE2019-087463), and MA-P is supported by a predoctoral FPU contract from the Ministerio de Educación, Cultura y Deporte (FPU18/02913). The CNIC is supported by the MICIN, the Instituto de Salud Carlos III, the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant number CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S

CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.S

A 3-biomarker 2-point-based risk stratification strategy in acute heart failure

[Abstract] Introduction and Objectives: Most multi-biomarker strategies in acute heart failure (HF) have only measured biomarkers in a single-point time. This study aimed to evaluate the prognostic yielding of NT-proBNP, hsTnT, Cys-C, hs-CRP, GDF15, and GAL-3 in HF patients both at admission and discharge. Methods: We included 830 patients enrolled consecutively in a prospective multicenter registry. Primary outcome was 12-month mortality. The gain in the C-index, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) was calculated after adding each individual biomarker value or their combination on top of the best clinical model developed in this study (C-index 0.752, 0.715–0.789) and also on top of 4 currently used scores (MAGGIC, GWTG-HF, Redin-SCORE, BCN-bioHF). Results: After 12-month, death occurred in 154 (18.5%) cases. On top of the best clinical model, the addition of NT-proBNP, hs-CRP, and GDF-15 above the respective cutoff point at admission and discharge and their delta during compensation improved the C-index to 0.782 (0.747–0.817), IDI by 5% (p < 0.001), and NRI by 57% (p < 0.001) for 12-month mortality. A 4-risk grading categories for 12-month mortality (11.7, 19.2, 26.7, and 39.4%, respectively; p < 0.001) were obtained using combination of these biomarkers. Conclusion: A model including NT-proBNP, hs-CRP, and GDF-15 measured at admission and discharge afforded a mortality risk prediction greater than our clinical model and also better than the most currently used scores. In addition, this 3-biomarker panel defined 4-risk categories for 12-month mortality.Instituto de Salud Carlos III; RD06-0003-0000Instituto de Salud Carlos III; RD12/0042/000

Hyperkalemia in Heart Failure Patients in Spain and Its Impact on Guidelines and Recommendations: ESC-EORP-HFA Heart Failure Long-Term Registry

[Abstract] Introduction and objectives: Hyperkalemia is a growing concern in the treatment of patients with heart failure and reduced ejection fraction because it limits the use of effective drugs. We report estimates of the magnitude of this problem in routine clinical practice in Spain, as well as changes in potassium levels during follow-up and associated factors. Methods: This study included patients with acute (n=881) or chronic (n=3587) heart failure recruited in 28 Spanish hospitals of the European heart failure registry of the European Society of Cardiology and followed up for 1 year. Various outcomes were analyzed, including changes in serum potassium levels and their impact on treatment. Results: Hyperkalemia (K+> 5.4 mEq/L) was identified in 4.3% (95%CI, 3.7%-5.0%) and 8.2% (6.5%-10.2%) of patients with chronic and acute heart failure, respectively, and was responsible for 28.9% of all cases of contraindication to mineralocorticoid receptor antagonist use and for 10.8% of all cases of failure to reach the target dose. Serum potassium levels were not recorded in 291 (10.8%) of the 2693 chronic heart failure patients with reduced ejection fraction. During follow-up, potassium levels increased in 179 of 1431 patients (12.5%, 95%CI, 10.8%-14.3%). This increase was directly related to age, diabetes, and history of stroke and was inversely related to history of hyperkalemia. Conclusions: This study highlights the magnitude of the problem of hyperkalemia in patients with heart failure in everyday clinical practice and the need to improve monitoring of this factor in these patients due to its interference with the possibility of receiving optimal treatment.[Resumen] Introducción y objetivos. La hiperpotasemia es una preocupación creciente en el tratamiento de los pacientes con insuficiencia cardiaca y fracción de eyección reducida, pues limita el uso de fármacos eficaces. Este trabajo ofrece estimaciones de la magnitud de este problema en la práctica clínica habitual en España, los cambios en las concentraciones de potasio en el seguimiento y los factores asociados. Métodos. Pacientes con insuficiencia cardiaca aguda (n = 881) y crónica (n = 3.587) seleccionados en 28 hospitales españoles del registro europeo de insuficiencia cardiaca de la European Society of Cardiology y seguidos 1 año para diferentes desenlaces, incluidos cambios en las cifras de potasio y su impacto en el tratamiento. Resultados. La hiperpotasemia (K+ > 5,4 mEq/l) está presente en el 4,3% (IC95%, 3,7-5,0%) y el 8,2% (6,5-10,2%) de los pacientes con insuficiencia cardiaca crónica y aguda; causa el 28,9% de todos los casos en que se contraindica el uso de antagonistas del receptor de mineralocorticoides y el 10,8% de los que no alcanzan la dosis objetivo. Del total de 2.693 pacientes ambulatorios con fracción de eyección reducida, 291 (10,8%) no tenían registrada medición de potasio. Durante el seguimiento, 179 de 1.431 (12,5%, IC95%, 10,8-14,3%) aumentaron su concentración de potasio, aumento relacionado directamente con la edad, la diabetes mellitus y los antecedentes de ictus e inversamente con los antecedentes de hiperpotasemia. Conclusiones. Este trabajo destaca el problema de la hiperpotasemia en pacientes con insuficiencia cardiaca de la práctica clínica habitual y la necesidad de continuar y mejorar la vigilancia de este factor en estos pacientes por su interferencia en el tratamiento óptimo

Prótesis intracoronarias en la práctica intervencionista actual : resultados clínicos y análisis de predictores a corto y largo plazo / Domingo Andrés Pascual Figal ; Director: Mariano Valdés Chávarri.

Tesis - Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 575.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1782

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.

BACKGROUND Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown. OBJECTIVES The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology. METHODS The study cohort comprised 62 patients with HF and LVEF 2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization. RESULTS CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology. CONCLUSIONS Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.S

Aplicación de una puntuación de riesgo coronario (TIMI Risk Score) en una población no seleccionada de pacientes que consultan por dolor torácico en un servicio de urgencias

Introducción y objetivos. Diferentes algoritmos de estratificación del síndrome coronario agudo (SCA) permiten identificar a los individuos con un mayor riesgo que pueden beneficiarse de tratamientos más agresivos. Se ha demostrado que el TIMI Risk Score (TRS) es útil en pacientes con un riesgo intermedio y alto, pero faltan evidencias acerca de su aplicabilidad clínica en pacientes no seleccionados. El objetivo es comprobar la eficacia del TRS en la estratificación del riesgo en una población con dolor torácico no seleccionada. Pacientes y método. Se incluyó a 1.254 pacientes consecutivos que acudieron a urgencias por dolor torácico no traumático sin ascenso del segmento ST (edad 54 ± 19 años, 57% varones). Se ingresó a 343 (27%) y se dio de alta a 911 (73%). Se registró la aparición de eventos cardíacos a los 6 meses. Resultados. En el grupo dado de alta desde urgencias, 45 (5,3%) pacientes fueron ingresados durante el seguimiento, 9 (1,1%) recibieron tratamiento de revascularización, 5 (0,6%) presentaron un infarto agudo miocárdico (IAM) y 2 (0,2%) fallecieron por causa cardiovascular. Los que obtuvieron una mayor puntuación en el TRS presentaron más riesgo de presentar el evento combinado muerte, infarto o revascularización (riesgo relativo por incremento de unidad = 3,63; intervalo de confianza [IC] del 95%, 2,20-6,00; p < 0,001). En el grupo de ingresados hubo 22 revascularizaciones (6,4%), 4 IAM (1,2%) y 14 muertes de causa cardiovascular (4,1%) durante el seguimiento. El riesgo relativo de evento combinado por cada incremento del TRS fue 1,72 (IC del 95%, 1,32-2,24; p < 0,001). Conclusiones. El TRS es una herramienta eficaz para la estratificación pronóstica de pacientes no seleccionados que consultan por dolor torácico. Permite identificar a los individuos de alto riesgo que se beneficiarían de ingreso hospitalario y tratamiento agresivo precoz. Palabras clave: Dolor torácico. Estratificación pronóstica. TIMI Risk Score. Unidad de dolor torácico. Use of a Coronary Risk Score (the TIMI Risk Score) in a Non-Selected Patient Population Assessed for Chest Pain at an Emergency Department Introduction and objectives. Stratification algorithms for acute coronary syndrome enable the identification of high-risk patients who will benefit from more aggressive treatment. The TIMI Risk Score (TRS) has been shown to be useful in intermediate- and high-risk patients. However, little is known about its value in non-selected patients. Our aim was to assess the efficacy of the TRS for risk stratification in a non-selected population with chest pain. Patients and method. We evaluated 1254 consecutive patients (age, 54 [19] years; 57% male) attending an emergency department for chest pain. Overall, 343 (27%) were admitted and 911 (73%) were discharged. All cardiac events during 6-month follow-up were recorded. Results. Of the 911 discharged patients, 45 (5.3%) were admitted during follow-up: 9 (1.1%) underwent revascularization, 5 (0.6%) had a myocardial infarction (MI), and 2 (0.2%) died from cardiovascular disease. Patients with a high TRS had a significantly higher risk of reaching the composite endpoint of death, MI, or revascularization (relative risk per unit of TRS increase, 3.63; 95% CI, 2.20-6.00; P<.001). Of the patients who were initially admitted, 22 (6.4%) underwent revascularization, 4 (1.2%) had an MI, and 14 died (4.1%) from cardiovascular disease during follow-up. The relative risk of the composite endpoint per unit of TRS increase was 1.72 (95% CI, 1.32-2.24; P<.001). Conclusions. The TIMI risk score is useful for stratifying cardiovascular event risk in non-selected patients with chest pain. The score can identify high-risk patients who will benefit from hospital admission and early aggressive treatment

Cancer Incidence in Heart Transplant Recipients with Previous Neoplasia History

Neoplasm history increases morbidity and mortality after solid organ transplantation and has disqualified patients from transplantation. Studies are needed to identify factors to be considered when deciding on the suitability of a patient with previous tumor for heart transplantation. A retrospective epidemiological study was conducted in heart transplant (HT) recipients (Spanish Post-Heart Transplant Tumor Registry) comparing the epidemiological data, immu-nosuppressive treatments and incidence of post-HT tumors between patients with previous malignant noncardiac tumor and with no previous tumor (NPT). The impact of previous tumor (PT) on overall survival (OS) was also assessed. A total of 4561 patients, 77 PT and 4484 NPT, were evaluated. The NPT group had a higher proportion of men than the PT group (p < 0.001). The incidence of post-HT tumors was 1.8 times greater in the PT group (95% confidence interval [CI] 1.2-2.6; p < 0.001), mainly due to the increased risk in patients with a previous hematologic tumor (rate ratio 2.3, 95% CI 1.3-4.0, p < 0.004). OS during the 10-year posttransplant period was significantly lower in the PT than the NPT group (p = 0.048) but similar when the analysis was conducted after a first post-HT tumor was diagnosed. In conclusion, a history of PT increases the incidence of post-HT tumors and should be taken into account when considering a patient for HT