Insuficiencia cardiaca en octogenarios con fibrilación auricular: incidencia y factores de riesgo / Heart failure in older patients with atrial fibrillation: incidence and risk factors

Introducción y objetivos: La fibrilación auricular (FA) está interconectada con la insuficiencia cardiaca (IC). Sin embargo, los factores que pueden precipitar la aparición de IC en los pacientes con FA están escasamente descritos. Con este estudio, se pretende determinar la incidencia, los predictores y el pronóstico de la IC de nueva aparición en una población de pacientes ancianos con FA sin antecedentes de IC.MétodosPacientes con FA mayores de 80 años, sin antecedente de IC, identificados entre los años 2014 y 2018.ResultadosDurante 3,7 años, se siguió a 5.794 pacientes (edad, 85,2±3,8 años; el 63,2% mujeres). En el 33,3% de los casos (tasa de incidencia, 11,5/100 pacientes-año) apareció IC de novo, mayoritariamente con fracción de eyección del ventrículo izquierdo conservada. A partir de un análisis multivariante, se identificaron 11 factores de riesgo de aparición de la IC independientemente de su subtipo: enfermedad valvular significativa (HR=1,99; IC95%, 1,73-2,28), fracción de eyección del ventrículo izquierdo reducida (HR=1,92; IC95%, 1,68-2,19), enfermedad pulmonar obstructiva crónica (HR=1,59; IC95%, 1,40-1,82), aumento de la aurícula izquierda (HR=1,47; IC95%, 1,33-1,62), enfermedad renal (HR=1,36; IC95%, 1,24-1,49), desnutrición (HR=1,33; IC95%, 1,21-1,46), anemia (HR=1,30; IC95%, 1,17-1,44), FA permanente (HR=1,15; IC95%, 1,03-1,28), diabetes mellitus (HR=1,13; IC95%, 1,01-1,27), por cada año de aumento de la edad (HR=1,04; IC95%, 1,02-1,05) y por cada kg/m2 del índice de masa corporal (HR=1,03; IC95%, 1,02-1,04). La presencia de IC prácticamente duplicó la mortalidad (HR=1,67; IC95%, 1,53-1,81).ConclusionesLa IC de nueva aparición en ancianos con FA fue muy frecuente y prácticamente duplicó la mortalidad. Se identificaron 11 factores de riesgo, lo cual amplía el ámbito de prevención primaria en esta entidad. (AU)

Introduction and objectives: Atrial fibrillation (AF) is linked to heart failure (HF). However, little has been published on the factors that may precipitate the onset of HF in AF patients. We aimed to determine the incidence, predictors, and prognosis of incident HF in older patients with AF with no prior history of HF.MethodsPatients with AF older than 80 years and without prior HF were identified between 2014 and 2018.ResultsA total of 5794 patients (mean age, 85.2±3.8 years; 63.2% women) were followed up for 3.7 years. Incident HF, predominantly with preserved left ventricular ejection fraction, developed in 33.3% (incidence rate, 11.5-100 people-year). Multivariate analysis identified 11 clinical risk factors for incident HF, irrespective of HF subtype: significant valvular heart disease (HR, 1.99; 95%CI, 1.73-2.28), reduced baseline left ventricular ejection fraction (HR, 1.92; 95%CI, 1.68-2.19), chronic pulmonary obstructive disease (HR, 1.59; 95%CI, 1.40-1.82), enlarged left atrium (HR 1.47, 95%CI 1.33-1.62), renal dysfunction (HR 1.36, 95%CI 1.24-1.49), malnutrition (HR, 1.33; 95%CI, 1.21-1.46), anemia (HR, 1.30; 95%CI, 1.17-1.44), permanent AF (HR, 1.15; 95%CI, 1.03-1.28), diabetes mellitus (HR, 1.13; 95%CI, 1.01-1.27), age per year (HR, 1.04; 95%CI, 1.02-1.05), and high body mass index for each kg/m2 (HR, 1.03; 95%CI, 1.02-1.04). The presence of incident HF nearly doubled the mortality risk (HR, 1.67; 95%CI, 1.53-1.81).ConclusionsThe presence of HF in this cohort was relatively frequent and nearly doubled the mortality risk. Eleven risk factors for HF were identified, expanding the scope for primary prevention among elderly patients with AF. (AU)

Nutrition status, obesity and outcomes in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: A paradoxical protective effect of obesity has been previously reported in patients with atrial fibrillation (AF). The aim of this study was to determine the impact of nutritional status and body mass index (BMI) on the prognosis of AF patients. METHODS: We conducted a retrospective population-based cohort study of patients with AF from 2014 to 2017 from a single health area in Spain. The CONUT score was used to assess nutritional status. Cox regression models were used to estimate the association of BMI and CONUT score with mortality. The association with embolism and bleeding was assessed by a competing risk analysis. RESULTS: Among 14 849 AF patients, overweight and obesity were observed in 42.6% and 46.0%, respectively, while malnutrition was observed in 34.3%. During a mean follow-up of 4.4 years, 3335 patients died, 984 patients had a stroke or systemic embolism, and 1317 had a major bleeding event. On univariate analysis, BMI was inversely associated with mortality, embolism, and bleeding; however, this association was lost after adjustment by age, sex, comorbidities, and CONUT score (HR for composite endpoint, 0.98; 95%CI, 0.95-1.01; P=.719). Neither obesity nor overweight were predictors of mortality, embolism, and bleeding events. In contrast, nutritional status-assessed by the CONUT score-was associated with mortality, embolism and bleeding after multivariate analysis (HR for composite endpoint, 1.15; 95%CI, 1.14-1.17; P<.001). CONCLUSIONS: BMI was not an independent predictor of events in patients with AF in contrast to nutritional status, which showed a strong association with mortality, embolism, and bleeding. The study was registered at ClinicalTrials.gov (Identifier: NCT04364516).

Trade-off between the effects of embolic versus bleeding events on mortality in elderly patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: Clinical decision-making on anticoagulation in elderly patients with atrial fibrillation (AF) requires clinicians to consider not only the incidence of embolic and bleeding events, but also the risk of death following these adverse events. We aimed to analyze the trade-off between embolic and bleeding events with respect to mortality in elderly patients with AF. METHODS: The study cohort comprised all patients aged ≥ 75 years from a Spanish health area diagnosed with AF between 2014 and 2017 (n=9365). The risk of death was investigated using Cox proportional hazards models, including embolic and bleeding events as time-dependent binary indicators. RESULTS: During a median follow-up of 4.0 years, both embolic and bleeding events were associated with a higher risk of death (adjusted HR, 2.39; 95%CI, 2.12-2.69; and adjusted HR, 1.79; 95%CI, 1.64-1.96, respectively). The relative risk of death was 33% higher following an embolism than following a bleeding event (rRR, 1.33; 95%CI, 1.15-1.55), although for transient ischemic attack the risk was lower than for bleeding (rRR, 0.79; 95%CI, 0.63-0.99). The risk of death associated with intracranial hemorrhage was similar to that of major embolisms (RR, 1.00; 95%CI, 0.75-1.29). CONCLUSIONS: In elderly AF patients, embolic events appeared to be associated with a higher risk of mortality than extracranial bleeding, except for transient ischemic attacks, which have a better prognosis. For ICH, the mortality risk was similar to that of major embolism.

New Cancer Diagnosis After Bleeding in Anticoagulated Patients With Atrial Fibrillation.

Background Bleeding is frequent in patients with atrial fibrillation (AF) treated with oral anticoagulant therapy, and may be the first manifestation of underlying cancer. We sought to investigate to what extent bleeding represents the unmasking of an occult cancer in patients with AF treated with oral anticoagulants. Methods and Results Using data from CardioCHUVI-AF (Retrospective Observational Registry of Patients With Atrial Fibrillation From Vigo's Health Area), 8753 patients with AF aged ≥75 years with a diagnosis of AF between 2014 and 2017 were analyzed. Of them, 2171 (24.8%) experienced any clinically relevant bleeding, and 479 (5.5%) were diagnosed with cancer during a follow-up of 3 years. Among 2171 patients who experienced bleeding, 198 (9.1%) were subsequently diagnosed with cancer. Patients with bleeding have a 3-fold higher hazard of being subsequently diagnosed with new cancer compared with those without bleeding (4.7 versus 1.4 per 100 patient-years; adjusted hazard ratio [HR], 3.2 [95% CI, 2.6-3.9]). Gastrointestinal bleeding was associated with a 13-fold higher hazard of new gastrointestinal cancer diagnosis (HR, 13.4; 95% CI, 9.1-19.8); genitourinary bleeding was associated with an 18-fold higher hazard of new genitourinary cancer diagnosis (HR, 18.1; 95% CI, 12.5-26.2); and bronchopulmonary bleeding was associated with a 15-fold higher hazard of new bronchopulmonary cancer diagnosis (HR, 15.8; 95% CI, 6.0-41.3). For other bleeding (nongastrointestinal, nongenitourinary, nonbronchopulmonary), the HR for cancer was 2.3 (95% CI, 1.5-3.6). Conclusions In patients with AF treated with oral anticoagulant therapy, any gastrointestinal, genitourinary, or bronchopulmonary bleeding was associated with higher rates of new cancer diagnosis. These bleeding events should prompt investigation for cancers at those sites.

Prevalence and Prognostic Significance of Malnutrition in Patients With Acute Coronary Syndrome.

BACKGROUND: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its prognostic impact in patients with acute coronary syndrome (ACS) is not well known. OBJECTIVES: This study sought to report the prevalence, clinical associations, and prognostic consequences of malnutrition in patients with ACS. METHODS: In this study, the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI) was applied to 5,062 consecutive patients with ACS. The relationships between malnutrition risk and all-cause mortality and major cardiovascular events (MACEs) (cardiovascular mortality, reinfarction, or ischemic stroke) were examined. RESULTS: According to the CONUT score, NRI, and PNI, 11.2%, 39.5%, and 8.9% patients were moderately or severely malnourished, respectively; 71.8% were at least mildly malnourished by at least 1 score. Although worse scores were most strongly related to lower body mass index, between 8.4% and 36.7% of patients with a body mass index of ≥25 kg/m2 were moderately or severely malnourished, depending on the nutritional index used. During a median follow-up of 3.6 years (interquartile range: 1.3 to 5.3 years), 830 (16.4%) patients died, and 1,048 (20.7%) had MACEs. Compared with good nutritional status, malnutrition was associated with significantly increased risk for all-cause death (adjusted hazard ratio for moderate and severe degrees of malnutrition, respectively: 2.02 [95% confidence interval (CI): 1.65 to 2.49] and 3.65 [95% CI: 2.41 to 5.51] for the CONUT score, 1.40 [95% CI: 1.17 to 1.68] and 2.87 [95% CI: 2.17 to 3.79] for the NRI, and 1.71 [95% CI: 1.37 to 2.15] and 1.95 [95% CI: 1.55 to 2.45] for the PNI score; p values <0.001 for all nutritional indexes). Similar results were found for the CONUT score and PNI regarding MACEs. All risk scores improve the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and MACEs. CONCLUSIONS: Malnutrition is common among patients with ACS and is strongly associated with increased mortality and cardiovascular events. Clinical trials are needed to prospectively evaluate the efficacy of nutritional interventions on outcomes in patients with ACS.

Relevance of matrix metalloproteases in non-small cell lung cancer diagnosis.

BACKGROUND: The need for novel biomarkers that could aid in non-small cell lung cancer (NSCLC) detection, together with the relevance of Matrix Metalloproteases (MMPs) -1, -2, -7, -9 and -10 in lung tumorigenesis, prompted us to assess the diagnostic usefulness of these MMPs and the Tissue Inhibitor of Metalloproteinase (TIMP) -1 in NSCLC patients. METHODS: Markers were evaluated in an initial study cohort (19 NSCLC cases and 19 healthy controls). Those that better performed were analyzed in a larger sample including patients with benign lung diseases. Serum MMPs and TIMP-1 were determined by multiplexed immunoassays. Logistic regression was employed for multivariate analysis of biomarker combinations. RESULTS: MMPs and TIMP-1 were elevated in the serum of NSCLC patients compared to healthy controls. MMP-1, -7 and -9 performed at best and were further evaluated in the sample including benign pathologies, corroborating the superiority of MMP-9 in NSCLC discrimination, also at early-stage NSCLC. The optimal diagnostic value was obtained with the model including MMP-9, gender, age and smoking history, that demonstrated an AUC of 0.787, 85.54% sensitivity and 64.89% specificity. CONCLUSION: Our results suggest that MMP-9 is a potential biomarker for NSCLC diagnosis and its combined measurement with other biomarkers could improve NSCLC detection.

Highly Sensitive Marker Panel for Guidance in Lung Cancer Rapid Diagnostic Units.

While evidence for lung cancer screening implementation in Europe is awaited, Rapid Diagnostic Units have been established in many hospitals to accelerate the early diagnosis of lung cancer. We seek to develop an algorithm to detect lung cancer in a symptomatic population attending such unit, based on a sensitive serum marker panel. Serum concentrations of Epidermal Growth Factor, sCD26, Calprotectin, Matrix Metalloproteinases -1, -7, -9, CEA and CYFRA 21.1 were determined in 140 patients with respiratory symptoms (lung cancer and controls with/without benign pathology). Logistic Lasso regression was performed to derive a lung cancer prediction model, and the resulting algorithm was tested in a validation set. A classification rule based on EGF, sCD26, Calprotectin and CEA was established, able to reasonably discriminate lung cancer with 97% sensitivity and 43% specificity in the training set, and 91.7% sensitivity and 45.4% specificity in the validation set. Overall, the panel identified with high sensitivity stage I non-small cell lung cancer (94.7%) and 100% small-cell lung cancers. Our study provides a sensitive 4-marker classification algorithm for lung cancer detection to aid in the management of suspicious lung cancer patients in the context of Rapid Diagnostic Units.

Serum calprotectin, CD26 and EGF to establish a panel for the diagnosis of lung cancer.

Lung cancer is the most lethal neoplasia, and an early diagnosis is the best way for improving survival. Symptomatic patients attending Pulmonary Services could be diagnosed with lung cancer earlier if high-risk individuals are promptly separated from healthy individuals and patients with benign respiratory pathologies. We searched for a convenient non-invasive serum test to define which patients should have more immediate clinical tests. Six cancer-associated molecules (HB-EGF, EGF, EGFR, sCD26, VEGF, and Calprotectin) were investigated in this study. Markers were measured in serum by specific ELISAs, in an unselected population that included 72 lung cancer patients of different histological types and 56 control subjects (healthy individuals and patients with benign pulmonary pathologies). Boosted regression and random forests analysis were conducted for the selection of the best candidate biomarkers. A remarkable discriminatory capacity was observed for EGF, sCD26, and especially for Calprotectin, these three molecules constituting a marker panel boasting a sensitivity of 83% and specificity of 87%, resulting in an associated misclassification rate of 15%. Finally, an algorithm derived by logistic regression and a nomogram allowed generating classification scores in terms of the risk of a patient of suffering lung cancer. In conclusion, we propose a non-invasive test to identify patients at high-risk for lung cancer from a non-selected population attending a Pulmonary Service. The efficacy of this three-marker panel must be tested in a larger population for lung cancer.

Pretreatment levels of the serum biomarkers CEA, CYFRA 21-1, SCC and the soluble EGFR and its ligands EGF, TGF-alpha, HB-EGF in the prediction of outcome in erlotinib treated non-small-cell lung cancer patients.

The aim of this study has been to investigate the potential of serum biomarkers used in clinical practice (CEA, CYFRA 21-1, SCC) together with the serum epidermal growth factor receptor (EGFR) and its associated ligands (EGF, TGF-α, HB-EGF) as outcome predictors of non-small cell lung cancer (NSCLC) patients treated with the TKI erlotinib. The pretreatment levels of these markers were evaluated through immunoassays carried out in 58 patients. The progression-free survival (PFS) and overall survival (OS) were assessed by the Kaplan-Meier method and differences between groups were compared by means of the Log-Rank test. Association of risk factors with survival was evaluated using the univariate and multivariate Cox modelling procedures. Higher CEA (>5 ng/mL) and sEGFR (>56.87 ng/mL) concentrations associated significantly with a higher overall survival. The pre-treatment sEGFR serum levels constituted an independent prognostic factor. The EGFR gene mutational status and the sEGFR level combination was the single to associate significantly with longer progression-free survival periods, in circumstances in which the EGFR gene was mutated and increased protein serum levels were detected. The overall survival as assessed through a Cox analysis revealed similar death hazards with respect to low sEGFR levels combined both with non-mutated EGFR genotypes and low CEA serum levels. Our results suggest that the pre-treatment CEA and sEGFR serum levels may provide a comparable source of information to that supplied by the EGFR gene mutational status with respect to the prognosis of erlotinib treated NSCLC patients. A combined sEGFR and CEA level appraisal could be of considerable value to select patients to undergo EGFR-TKI treatments.

Preoperative serum CA 72.4 as prognostic factor of recurrence and death, especially at TNM stage II, for colorectal cancer.

BACKGROUND: Nowadays, evaluation of colorectal cancer prognosis and decision-making for treatment continues to be based primarily on TNM tumour stage. Administration of adjuvant chemotherapy is especially challenging for stage II patients that can have very different disease-related outcomes. Therefore, more reliable prognostic markers need to be developed to improve the selection of stage II patients at high risk for recurrence. Our purpose is to assess the prognostic value of preoperative serum CA 72.4 to improve the risk stratification of CRC patients. METHODS: Preoperative sera collected from 71 unselected patients between January 1994 and February 1997 was assayed for CA 72.4 and CEA levels. Patients were followed-up for at least 30 months or until relapse. Survival curves were estimated by the Kaplan-Meier method and the prognostic value was determined using Log-Rank test and Cox regression analysis. RESULTS: Preoperative CA 72.4 levels above 7 U/mL correlate with a worse prognosis, with associated recurrence and death percentages exceeding the displayed by CEA. In a multivariate analysis, its combination with CEA proved the most important independent factor predicting survival. Remarkably, at stage II CA 72.4 also discriminates better than CEA those patients that will relapse or die from those with a favourable prognosis; however, CEA has not a negligible effect on survival. CONCLUSIONS: The most outstanding finding of the present work is the correct classification of nearly every patient with bad prognosis (relapse or death) at TNM stage II when CEA and CA 72.4 are used altogether. This could improve the decision-making involved in the treatment of stage II colon cancer. Certainly further large-scale studies must be performed to determine whether CA 72.4 can be effectively used in the clinical setting.

Levels of PEDF in pleural effusions from lung adenocarcinoma and benign disease patients.

Anti-tumor properties assigned to PEDF, beside its role as an inhibitor of angiogenesis, make it a promising candidate in the search of new biomarkers for malignancy. In this study levels of PEDF were investigated in pleural effusions from lung adenocarcinoma and benign inflammatory disease patients. The mean PEDF concentration in the malignant group was slightly superior to that in patients suffering benign diseases (4.59 µ g/mL vs 3.97 µg/mL), although the difference did not reach statistical significance (P 0.166). Pleural effusion PEDF levels were not related to gender, age, smoking habit or pleural effusion size. We also investigated the possible relationship of PEDF levels in pleural effusion regarding clinicopathological features. Correlations were found for monocytes (P 0.010) and polymorphonuclear leukocytes (P 0.023) with PEDF levels in pleural effusion of malignant origin.