Manejo de los pacientes con insuficiencia cardiaca atendidos en la consulta de cardiología : Estudio IC-BERG

To determine the perception and management of heart failure with reduced ejection fraction (HFrEF) by clinical cardiologists and to establish a consensus with recommendations. We employed the modified Delphi method among a panel of 150 experts who answered a questionnaire that included three blocks: definition and perception of patients with «stable» HFrEF (15 statements), management of patients with «stable» HFrEF (51 statements) and recommendations for optimising the management and follow-up (9 statements). The level of agreement was assessed with a Likert 9-point scale. A consensus of agreement was reached on 49 statements, a consensus of disagreement was reached on 16, and 10 statements remained undetermined. There was consensus regarding the definition of «stable» HF (82%), that HFrEF had a silent nature that could increase the mortality risk for mildly symptomatic patients (96%) and that the drug treatment should be optimised, regardless of whether a patient with HFrEF remains stable in the same functional class (98.7%). In contrast, there was a consensus of disagreement regarding the notion that treatment with an angiotensin receptor-neprilysin inhibitor is justified only when the functional class worsens (90.7%). Our current understanding of «stable» HF is insufficient, and the treatment needs to be optimised, even for apparently stable patients, to decrease the risk of disease progression

Valor pronóstico de un nuevo modelo de evaluación clínica de pacientes ambulatorios con insuficiencia cardiaca

[Resumen] Introducción y objetivos. Estudiar el valor pronóstico de un modelo de 5 ítems clínicos basado en las recomendaciones IC-BERG para la evaluación en consulta de pacientes ambulatorios con insuficiencia cardiaca (IC). Métodos. Estudio observacional basado en la cohorte histórica de pacientes con IC remitidos a una consulta monográfica entre 2010 y 2019. Se evaluó la presencia de 5 ítems clínicos de riesgo: NYHA III-IV, signos de congestión, ingreso por descompensación en el último año, dosis diaria de furosemida ≥ 40 mg o equivalente y NT-proBNP ≥ 1.000 pg/ml. Se estudió la incidencia de desenlaces clínicos adversos mediante el método de Kaplan-Meier y la regresión de Cox. Resultados. Se estudiaron 1.909 pacientes, que presentaban una media de 2,29 ítems de riesgo. El análisis de Kaplan-Meier mostró una tendencia incremental entre un mayor número de ítems de riesgo y el desenlace combinado muerte o ingreso por IC, la mortalidad global y la mortalidad cardiovascular (p < 0,001). Las hazard ratio ajustadas para el desenlace muerte o ingreso por IC, estimadas por regresión multivariante de Cox, fueron de 1,47 (IC95%, 1-2,15), 2,03 (IC95%, 1,41-2,92), 2,98 (IC95%, 2,08-4,28), 5,07 (IC95%, 3,51-7,32) y 7,73 (IC95%, 5,21-11,45) para pacientes con 1, 2, 3, 4 o 5 ítems de riesgo, respectivamente. El peso proporcional de las causas cardiovasculares de muerte, y en especial la IC, fue mayor en los pacientes con mayor número de ítems de riesgo. Conclusiones. Este estudio apoya el valor pronóstico de un modelo de evaluación clínica para pacientes ambulatorios con IC basado en las recomendaciones IC-BERG.[Abstract] Introduction and objectives. To assess the prognostic value of a 5-item clinical model based in the IC-BERG recommendations to evaluate ambulatory patients with heart failure (HF) in the clinic. Methods. Observational study based on the historical cohort of patients with HF referred to a specific facility since 2010 to 2019. The presence of 5 clinical ítems was evaluated: NYHA III-IV class, signs of congestion, admission due to decompensation in the previous year, daily dose ≥ 40 mg furosemide or equivalent, and NT-proBNP ≥ 1,000 pg/ml. The incidence of adverse clinical events was assessed by means of the Kaplan-Meier method and multivariable Cox's regression. Results. We studied 1909 patients, whose mean number of clinical ítems indicating risk was 2.29. Kaplan-Meier survival analysis showed an incremental trend between an increasing number of clinical ítems of risk and the combined event death or admission due to HF, overall mortality, and cardiovascular mortality (P < .001). Adjusted hazard-ratio for the combined end-point death or admission due to HF, as estimated by means of multivariable Cox's regression, were 1.47 (95%CI, 1–2.15), 2.03 (95%CI, 1.41–2.92), 2.98 (95%CI, 2.08–4.28), 5.07 (95%C,: 3.51–7.32), and 7.73 (95%CI, 5.21–11.45) for patients who showed 1, 2, 3, 4, or 5 clinical ítems indicating risk, respectively. The proportional weight of cardiovascular causes of risk, especially refractory HF, was higher in patients with a higher number of clinical ítems of risk. Conclusions. This study supports the prognostic value of a 5-item clinical model based on IC-BERG recommendations in ambulatory patients with HF

Markers of inflammation and multiple complex stenoses (pancoronary plaque vulnerability) in patients with non-ST segment elevation acute coronary syndromes

Objective: To assess the relation between markers of inflammation and the presence of multiple vulnerable plaques in patients with non-ST segment elevation acute coronary syndromes. Design: Prospective cohort study of 55 patients with non-ST segment elevation acute coronary syndromes and angiographically documented coronary disease. Blood samples were obtained at study entry for the assessment of high sensitivity C reactive protein (CRP), neopterin, and neutrophil count. Coronary stenoses were assessed by quantitative computerised angiography and classified as “complex” (irregular borders, ulceration, or filling defects) or “smooth” (absence of complex features). Extent of disease was also assessed by a validated angiographic score. Results: Neutrophil count (r  =  0.36, p  =  0.007), CRP concentration (r  =  0.33, p  =  0.02), and neopterin concentration (r  =  0.45, p < 0.001) correlated with the number of complex stenoses. Patients with multiple (three or more) complex stenoses, but not patients with multiple smooth lesions, had a higher neutrophil count (5.9 (1.4) × 10(9)/l v 4.8 (1.4) × 10(9)/l, p  =  0.02), CRP concentration (log transformed) (1.08 (0.63) v 0.6 (0.6), p  =  0.03), and neopterin concentration (log transformed) (0.94 (0.18) v 0.79 (0.15), p  =  0.002). Multiple regression analysis showed that neopterin concentration (B  =  4.8, 95% confidence interval (CI) 1.9 to 7.7, p  =  0.002) and extent of coronary artery disease (B  =  0.6, 95% CI 0.03 to 1.2, p  =  0.04) were independently associated with the number of complex stenoses. Conclusions: Acute inflammatory markers such as high neutrophil count, CRP concentration, and neopterin concentration correlate with the presence of multiple angiographically complex coronary stenoses. Neopterin concentration was a stronger predictor of multiple complex plaques than were neutrophil count and CRP concentration. These findings suggest that a relation exists between inflammation and pancoronary plaque vulnerability

LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells

Cromosomes; Marcadors pronòsticsCromosomas; Marcadores de pronósticoChromosomes; Prognostic markersOxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) FIS/FEDER (PI12/01250; CP08/00223; PI16/00253; and CB16/12/00449), MINECO (SAF2013-48849-C2-1-R) to SP, BFU2015-68354 to THS, Breast Cancer Research Foundation (BCRF-17-008) to JA, AGL2014-52395-C2-2-R to DA, Worldwide Cancer Research, Red Temática de Investigación Cooperativa en Cáncer (RD012/0036/005), Fundación Científica de la Asociación Española contra el Cáncer, and Fundació La Marató TV3. THS was supported by institutional funding (MINECO) through the Centres of Excellence Severo Ochoa award and the CERCA Programme of the Catalan Government, and SS-B, by a Fundació La Caixa fellowship. We thank La Caixa Foundation and Cellex Foundation for provide research facilities and equipment. GV has received funding from the MINECO (a “Juan de la Cierva Incorporation” fellowship; IJCI-2014-20723). SP was a recipient of a Miguel Servet contract (ISCIII/FIS), and AI, JPC-C, LP-G, and GS-B are supported by contracts from Worldwide Cancer Research, Fundació La Marató TV3, Fundació FERO, and a FI Fellowship from the Generalitat de Catalunya, respectively