Low-cost, open-source device for simultaneously subjecting rodents to different circadian cycles of light, food, and temperature.

Exposure of experimental rodents to controlled cycles of light, food, and temperature is important when investigating alterations in circadian cycles that profoundly influence health and disease. However, applying such stimuli simultaneously is difficult in practice. We aimed to design, build, test, and open-source describe a simple device that subjects a conventional mouse cage to independent cycles of physiologically relevant environmental variables. The device is based on a box enclosing the rodent cage to modify the light, feeding, and temperature environments. The device provides temperature-controlled air conditioning (heating or cooling) by a Peltier module and includes programmable feeding and illumination. All functions are set by a user-friendly front panel for independent cycle programming. Bench testing with a model simulating the CO2 production of mice in the cage showed: a) suitable air renewal (by measuring actual ambient CO2), b) controlled realistic illumination at the mouse enclosure (measured by a photometer), c) stable temperature control, and d) correct cycling of light, feeding, and temperature. The cost of all the supplies (retail purchased by e-commerce) was <300 US$. Detailed technical information is open-source provided, allowing for any user to reliably reproduce or modify the device. This approach can considerably facilitate circadian research since using one of the described low-cost devices for any mouse group with a given light-food-temperature paradigm allows for all the experiments to be performed simultaneously, thereby requiring no changes in the light/temperature of a general-use laboratory.

Factors associated with disease progression in patients with atrial fibrillation and heart failure anticoagulated with rivaroxaban.

BACKGROUND: Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended. HYPOTHESIS: This study was aimed to explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain. METHODS: Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2 DS2 -VASc was 4.1 ± 1.5, HAS-BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow-up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment. CONCLUSIONS: Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow-up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population.

Lung cancer multi-omics digital human avatars for integrating precision medicine into clinical practice: the LANTERN study.

BACKGROUND: The current management of lung cancer patients has reached a high level of complexity. Indeed, besides the traditional clinical variables (e.g., age, sex, TNM stage), new omics data have recently been introduced in clinical practice, thereby making more complex the decision-making process. With the advent of Artificial intelligence (AI) techniques, various omics datasets may be used to create more accurate predictive models paving the way for a better care in lung cancer patients. METHODS: The LANTERN study is a multi-center observational clinical trial involving a multidisciplinary consortium of five institutions from different European countries. The aim of this trial is to develop accurate several predictive models for lung cancer patients, through the creation of Digital Human Avatars (DHA), defined as digital representations of patients using various omics-based variables and integrating well-established clinical factors with genomic data, quantitative imaging data etc. A total of 600 lung cancer patients will be prospectively enrolled by the recruiting centers and multi-omics data will be collected. Data will then be modelled and parameterized in an experimental context of cutting-edge big data analysis. All data variables will be recorded according to a shared common ontology based on variable-specific domains in order to enhance their direct actionability. An exploratory analysis will then initiate the biomarker identification process. The second phase of the project will focus on creating multiple multivariate models trained though advanced machine learning (ML) and AI techniques for the specific areas of interest. Finally, the developed models will be validated in order to test their robustness, transferability and generalizability, leading to the development of the DHA. All the potential clinical and scientific stakeholders will be involved in the DHA development process. The main goals aim of LANTERN project are: i) To develop predictive models for lung cancer diagnosis and histological characterization; (ii) to set up personalized predictive models for individual-specific treatments; iii) to enable feedback data loops for preventive healthcare strategies and quality of life management. DISCUSSION: The LANTERN project will develop a predictive platform based on integration of multi-omics data. This will enhance the generation of important and valuable information assets, in order to identify new biomarkers that can be used for early detection, improved tumor diagnosis and personalization of treatment protocols. ETHICS COMMITTEE APPROVAL NUMBER: 5420 - 0002485/23 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore Ethics Committee. TRIAL REGISTRATION: clinicaltrial.gov - NCT05802771.

Subclinical congestion assessed by lung ultrasound in ST segment elevation myocardial infarction.

OBJECTIVE: We evaluated the prognostic value of subclinical congestion assessed by lung ultrasound (LUS) in patients admitted for ST segment elevation myocardial infarction (STEMI). METHODS: This was a multicentre study that prospectively enrolled 312 patients admitted for STEMI without signs of heart failure (HF) at admission. LUS was performed during the first 24 hours after revascularisation and classified patients as having either wet lung (three or more B-lines in at least one lung field) or dry lung. The primary endpoint was a composite of acute HF, cardiogenic shock or death during hospitalisation. The secondary endpoint was a composite of readmission for HF or new acute coronary syndrome or death during 30-day follow-up. Zwolle score was calculated in all patients to assess predictive improvement by adding the result of the LUS to this score. RESULTS: 14 patients (31.1%) in the wet lung group presented the primary endpoint vs 7 (2.6%) in the dry lung group (adjusted RR 6.0, 95% CI 2.3 to 16.2, p=0.007). The secondary endpoint occurred in five patients (11.6%) in the wet lung group and in three (1.2%) in the dry lung group (adjusted HR 5.4, 95% CI 1.0 to 28.7, p=0.049). Addition of LUS improved the ability of the Zwolle score to predict the follow-up composite endpoint (net reclassification improvement 0.99). LUS showed a very high negative predictive value in predicting in-hospital and follow-up endpoints (97.4% and 98.9%, respectively). CONCLUSION: Early subclinical pulmonary congestion identified by LUS in patients with Killip I STEMI at hospital admission is associated with adverse outcomes during hospitalisation and 30-day follow-up.

Resultados de la radioterapia en los carcinomas de orofaringe / Results of radiotherapy in oropharyngeal carcinomas

Objetivo Presentar los resultados del tratamiento con radioterapia en pacientes con carcinomas de orofaringe. Material y métodos Estudio retrospectivo de una cohorte de 359 pacientes tratados con radioterapia, incluyendo quimio- y bio-radioterapia, durante el periodo 2000-2019. Se dispuso de información del estatus del virus del papiloma humano (VPH) para 202 pacientes, de los que un 26,2% resultaron VPH-positivos. Resultados La supervivencia libre de recidiva local a los 5 años fue del 73,5% (IC 95%: 68,8-78,2%). Las variables que se relacionaron con el control local de la enfermedad en un estudio multivariante fueron la categoría de extensión local del tumor y el estatus VPH. La supervivencia libre de recidiva local a los 5 años para los pacientes con tumores cT1 fue del 90,0%, para los cT2 del 88,0%, para los cT3 del 70,6% y para los cT4 del 42,3%. La supervivencia libre de recidiva local a los 5 años para los tumores VPH-negativos fue del 67,2% y para los VPH-positivos del 93,3%. La supervivencia específica a los 5 años fue del 64,4% (IC 95%: 59,1-69,7%). Las variables que se relacionaron con la supervivencia específica en un estudio multivariante fueron el estado general del paciente, la extensión local y regional del tumor, y el estatus VPH. Conclusiones La supervivencia libre de recidiva local a los 5 años de los pacientes con carcinomas de orofaringe tratados con radioterapia fue del 73,5%. Las variables que se relacionaron con el control local fueron la extensión local del tumor y el estatus VPH. (AU)

Objective To present the results of radiotherapy treatment in patients with oropharyngeal carcinomas. Material and methodsRetrospective study of a cohort of 359 patients treated with radiotherapy, including chemo- and bio-radiotherapy, during the period 2000-2019. Information on human papillomavirus (HPV) status was available for 202 patients, of whom 26.2% were HPV-positive. Results Five-year local recurrence-free survival was 73.5% (95% CI: 68.8-78.2%). The variables that were related to local disease control in a multivariate study were the local tumor extension category and the HPV status. Five-year local recurrence-free survival for patients with cT1 tumors was 90.0%, for cT2 88.0%, for cT3 70.6%, and for cT4 42.3%. Five-year local recurrence-free survival for HPV-negative tumors was 67.2% and for HPV-positive tumors 93.3%. Five-year specific-disease survival was 64.4% (95% CI: 59.1-69.7%). Variables that were related to specific survival in a multivariate study were the patient's general condition, local and regional extent of the tumor, and HPV status. Conclusions Five-year local recurrence-free survival of patients with oropharyngeal carcinomas treated with radiotherapy was 73.5%. Variables that were related to local control were local tumor extension and HPV status. (AU)

Results of radiotherapy in oropharyngeal carcinomas.

OBJECTIVE: To present the results of radiotherapy treatment in patients with oropharyngeal carcinomas. MATERIAL AND METHODS: Retrospective study of a cohort of 359 patients treated with radiotherapy, including chemo- and bio-radiotherapy, during the period 2000-2019. Information on human papillomavirus (HPV) status was available for 202 patients, of whom 26.2% were HPV-positive. RESULTS: Five-year local recurrence-free survival was 73.5% (95% CI: 68.8%-78.2%). The variables that were related to local disease control in a multivariate study were the local tumor extension category and the HPV status. Five-year local recurrence-free survival for patients with cT1 tumors was 90.0%, for cT2 88.0%, for cT3 70.6%, and for cT4 42.3%. Five-year local recurrence-free survival for HPV-negative tumors was 67.2% and for HPV-positive tumors 93.3%. Five-year specific-disease survival was 64.4% (95% CI: 59.1%-69.7%). Variables that were related to specific survival in a multivariate study were the patient's general condition, local and regional extent of the tumor, and HPV status. CONCLUSIONS: Five-year local recurrence-free survival of patients with oropharyngeal carcinomas treated with radiotherapy was 73.5%. Variables that were related to local control were local tumor extension and HPV status.

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Background and objective: Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. Methods: We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Results: Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Conclusions: Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Characteristics of Patients with Heart Failure and Advanced Chronic Kidney Disease (Stages 4-5) Not Undergoing Renal Replacement Therapy (ERCA-IC Study).

BACKGROUND: Despite the frequent coexistence of heart failure (HF) in patients with advanced chronic kidney disease (CKD), it has been understudied, and little is known about its prevalence and prognostic relevance. METHODS: A retrospective study of 217 patients with advanced CKD (stages 4 and 5) who did not undergo renal replacement therapy (RRT). The patients were followed up for two years. The primary outcome was all-cause death or the need for RRT. RESULTS: Forty percent of patients had a history of HF. The mean age was 78.2 ± 8.8 years and the mean eGFR was 18.4 ± 5.5 mL/min/1.73 m2. The presence of previous HF identified a subgroup of high-risk patients with a high prevalence of cardiovascular comorbidities and was significantly associated with the composite endpoint of all-cause hospitalization or need for RRT (66.7% vs. 53.1%, HR 95% CI 1.62 (1.04-2.52), p = 0.034). No differences were found in the need for RRT (27.6% vs. 32.2%, p = 0.46). Nineteen patients without HF at baseline developed HF during the follow-up and all-cause death was numerically higher (36.8 vs. 19.8%, p = 0.1). CONCLUSIONS: Patients with advanced CKD have a high prevalence of HF. The presence of previous HF identified a high-risk population with a worse prognosis that required close follow-up.

Drug-drug interactions in an intensive care unit and comparison of updates in two databases.

OBJECTIVE: Critically ill patients are at increased risk of drug-drug interactions  but their prevalence and clinical relevance remains unclear. The prevalence of  potential drug-drug interactions in an intensive care unit according to  Micromedex Drug-Reax® and Lexi-Interact® databases was studied and the  concordance between the two databases was assessed. In addition, drug-drug  interactions detected in 2013 were compared with those identified in 2018 to  determine updates between these years. METHOD: Between January and June 2013, 152 critical care patients were  prospectively included. Cardiac patients were excluded. Demographic and  clinical data together with the drugs administered on the first calendar day of  intensive care unit admission were recorded. Potential drug-drug interactions  were searched in both Drug-Reax® and Lexi-Interact ® and their prevalence,  level of severity and evidence were compared considering the same sample in  2013 and 2018. RESULTS: In 2013, 1,025 potential drug-drug interactions were identified, corresponding to 438 unique pairs. Lexi-Interact® identified more  interactions (92.8%) than Drug-Reax® (34.0%). The percentage of agreement between databases was 27.4%. The number of interactions  included in both databases increased after the five years but their level of  evidence   decreased. The most common potential drug-drug interactions involved sedatives and analgesics, intentionally prescribed concomitantly. Only two potential drug-drug interactions were classified as contraindicated by both  databases. None of the potential drug-drug interactions identified had a  noticeable clinical impact. Neither did they imply a prescription change. CONCLUSIONS: This study shows that the prevalence of potential drugdrug interactions in the intensive care unit is high, although their clinical relevance is generally low. Our data also show a lack of concordance between Drug-Reax® and Lexi-Interact®, as well as their  updates.

OBJETIVO: Los pacientes críticos presentan un mayor riesgo de interacciones farmacológicas, aunque su prevalencia y relevancia clínica siguen  sin estar claras. En el presente estudio se analizó la prevalencia de  interacciones farmacológicas potenciales en una unidad de cuidados intensivos  mediante las bases de datos Micromedex Drug-Reax® y Lexi-Interact® y se  evaluó la concordancia entre ambas bases de datos. También se compararon  las interacciones farmacológicas detectadas en 2013 con las identificadas en  2018 para evaluar las actualizaciones realizadas durante este periodo de  tiempo. Método: Entre enero y junio de 2013 se incluyeron de forma prospectiva 152  pacientes críticos. Los pacientes cardiacos fueron excluidos. Se registraron los  datos demográficos y clínicos junto con los fármacos administrados durante el  primer día de ingreso en la unidad de cuidados intensivos. Las interacciones se  buscaron tanto en Micromedex Drug-Reax® como en Lexi-Interact® y se  comparó su prevalencia, el nivel de severidad y la evidencia considerando la  misma muestra en 2013 y 2018. Resultados: En 2013 se identificaron 1.025 interacciones farmacológicas potenciales, correspondientes a 438 pares únicos. Lexi- Interact® identificó más interacciones (92,8%) que Drug-Reax® (34,0%). El  porcentaje de concordancia entre las dos bases de datos fue del 27,4%. El  número de interacciones incluidas en ambas bases de datos aumentó durante  los cinco años, pero su nivel de evidencia disminuyó. Las interacciones  farmacológicas potenciales más comunes incluyeron sedantes y analgésicos,  rescritos intencionadamente de forma concomitante. Sólo dos interacciones farmacológicas potenciales fueron clasificadas como contraindicadas por ambas  bases de datos. Ninguna de las interacciones identificadas tuvo un impacto clínico notable ni supuso un cambio de prescripción. CONCLUSIONES: ste estudio muestra que la prevalencia de interacciones farmacológicas potenciales en las unidades de cuidados intensivos es alta,  aunque su relevancia clínica es generalmente baja. Nuestros datos también  muestran la falta de concordancia entre Drug-Reax® y Lexi- Interact®, así  como sus actualizaciones.

Interacciones farmacológicas en una unidadde cuidados intensivos y comparación de lasactualizaciones de dos bases de datos / Drug-drug interactions in an intensive care unit and comparison of updates in two databases

Objetivo: Los pacientes críticos presentan un mayor riesgo de interacciones farmacológicas, aunque su prevalencia y relevancia clínica siguen sinestar claras. En el presente estudio se analizó la prevalencia de interaccionesfarmacológicas potenciales en una unidad de cuidados intensivos mediantelas bases de datos Micromedex Drug-Reax® y Lexi-Interact® y se evaluó laconcordancia entre ambas bases de datos. También se compararon las interacciones farmacológicas detectadas en 2013 con las identificadas en 2018para evaluar las actualizaciones realizadas durante este periodo de tiempo.Método: Entre enero y junio de 2013 se incluyeron de forma prospectiva 152 pacientes críticos. Los pacientes cardiacos fueron excluidos. Seregistraron los datos demográficos y clínicos junto con los fármacos administrados durante el primer día de ingreso en la unidad de cuidados intensivos. Las interacciones se buscaron tanto en Micromedex Drug-Reax®como en Lexi-Interact® y se comparó su prevalencia, el nivel de severidady la evidencia considerando la misma muestra en 2013 y 2018.Resultados: En 2013 se identificaron 1.025 interacciones farmacológicas potenciales, correspondientes a 438 pares únicos. Lexi-Interact® identificó más interacciones (92,8%) que Drug-Reax® (34,0%). El porcentajede concordancia entre las dos bases de datos fue del 27,4%. El número deinteracciones incluidas en ambas bases de datos aumentó durante los cinco años, pero su nivel de evidencia disminuyó. Las interacciones farmacológicas potenciales más comunes incluyeron sedantes y analgésicos, prescritos intencionadamente de forma concomitante. Sólo dos interaccionesfarmacológicas potenciales fueron clasificadas como contraindicadas porambas bases de datos. Ninguna de las interacciones identificadas tuvo unimpacto clínico notable ni supuso un cambio de prescripción. (AU)

Objective: Critically ill patients are at increased risk of drug-druginteractions but their prevalence and clinical relevance remains unclear.The prevalence of potential drug-drug interactions in an intensive careunit according to Micromedex Drug-Reax® and Lexi-Interact® databaseswas studied and the concordance between the two databases wasassessed. In addition, drug-drug interactions detected in 2013 werecompared with those identified in 2018 to determine updates betweenthese years.Method: Between January and June 2013, 152 critical care patientswere prospectively included. Cardiac patients were excluded. Demographic and clinical data together with the drugs administered on the firstcalendar day of intensive care unit admission were recorded. Potentialdrug-drug interactions were searched in both Drug-Reax® and Lexi-Interact® and their prevalence, level of severity and evidence were comparedconsidering the same sample in 2013 and 2018.Results: In 2013, 1,025 potential drug-drug interactions were identified,corresponding to 438 unique pairs. Lexi-Interact® identified more interactions (92.8%) than Drug-Reax® (34.0%). The percentage of agreementbetween databases was 27.4%. The number of interactions included inboth databases increased after the five years but their level of evidence decreased. The most common potential drug-drug interactions involvedsedatives and analgesics, intentionally prescribed concomitantly. Onlytwo potential drug-drug interactions were classified as contraindicated byboth databases. None of the potential drug-drug interactions identifiedhad a noticeable clinical impact. Neither did they imply a prescriptionchange. (AU)

An intensive, structured, mobile devices-based healthcare intervention to optimize the lipid-lowering therapy improves lipid control after an acute coronary syndrome.

Aims: Despite the evidence, lipid-lowering treatment (LLT) in secondary prevention remains insufficient, and a low percentage of patients achieve the recommended LDL cholesterol (LDLc) levels by the guidelines. We aimed to evaluate the efficacy of an intensive, mobile devices-based healthcare lipid-lowering intervention after hospital discharge in patients hospitalized for acute coronary syndrome (ACS). Methods and results: Ambiespective register in which a mobile devices-based healthcare intervention including periodic follow-up, serial lipid level controls, and optimization of lipid-lowering therapy, if appropriate, was assessed in terms of serum lipid-level control at 12 weeks after discharge. A total of 497 patients, of which 462 (93%) correctly adhered to the optimization protocol, were included in the analysis. At the end of the optimization period, 327 (70.7%) patients had LDLc levels ≤ 70 mg/dL. 40% of patients in the LDLc ≤ 70 mg/dL group were upgraded to very-high intensity lipid-lowering ability therapy vs. 60.7% in the LDLc > 70 mg/dL group, p < 0.001. Overall, 38.5% of patients had at least a change in their LLT. Side effects were relatively infrequent (10.7%). At 1-year follow-up, LDLc levels were measured by the primary care physician in 342 (68.8%) of the whole cohort of 497 patients. In this group, 71.1% of patients had LDLc levels ≤ 70 mg/dL. Conclusion: An intensive, structured, mobile devices-based healthcare intervention after an ACS is associated with more than 70% of patients reaching the LDLc levels recommended by the clinical guidelines. In patients with LDLc measured at 1-year follow-up, 71.1% had LDLc levels ≤ 70 mg/dL.

Individualizing the treatment of patients with heart failure with reduced ejection fraction: a journey from hospitalization to long-term outpatient care.

INTRODUCTION: Despite the relevant advances achieved thanks to the traditional step-by-step therapeutic approach, heart failure with reduced ejection fraction (HFrEF) remains associated with considerable morbidity and mortality. The pathogenesis of HFrEF is complex, with the implication of various neurohormonal systems, including activation of deleterious pathways (i.e. renin-angiotensin-aldosterone, sympathetic, and sodium-glucose cotransporter-2 [SGLT2] systems) and the inhibition of protective pathways (i.e. natriuretic peptides and the guanylate cyclase system). Therefore, the burden of HF can only be reduced through a comprehensive approach that involves all evidence-based use of available HF drugs targeting the neurohormonal systems involved. AREAS COVERED: We performed a critical analysis of evidence from recent clinical trials and assessed the effects of HF therapies on hemodynamics and renal function. EXPERT OPINION: HF therapy must be adapted to the clinical profile (i.e. congestion, blood pressure, heart rate, renal function, and electrolytes). Consequently, blood pressure is reduced by beta blockers, renin-angiotensin-aldosterone system inhibitors, sacubitril/valsartan, and, minimally, by SGLT2 inhibitors and vericiguat; heart rate decreases with beta blockers and ivabradine; and renal function is impaired and potassium are levels increased with renin-angiotensin-aldosterone system inhibitors and sacubitril/valsartan. Practical recommendations on how to individualize HF therapy according to patient profile are provided.

Quality of Life in Older Patients after a Heart Failure Hospitalization: Results from the SENECOR Study.

Background: Information about health-related quality of life (HRQoL) in heart failure (HF) in older adults is scarce. Methods: We aimed to describe the HRQoL of the SENECOR study cohort, a single-center, randomized trial comparing the effects of multidisciplinary intervention by a geriatrician and a cardiologist (intervention group) to that of a cardiologist alone (control group) in older patients with a recent HF hospitalization. Results: HRQoL was assessed by the short version of the disease-specific Kansas Cardiomyopathy Questionnaire (KCCQ-12) in 141 patients at baseline and was impaired (KCCQ-12 < 75) in almost half of the cohort. Women comprised 50% of the population, the mean age was 82.2 years, and two-thirds of patients had preserved ejection fraction. Comorbidities were highly prevalent. Patients with impaired HRQoL had a worse NYHA functional class, a lower NT-proBNP, a lower Barthel index, and a higher Clinical Frailty Scale. One-year all-cause mortality was 22.7%, significantly lower in the group with good-to-excellent HRQoL (14.5% vs. 30.6%; hazard ratio 0.28; 95% confidence interval 0.10−0.78; p = 0.014). In the group with better HRQoL, all-cause hospitalization was lower, and there was a trend towards lower HF hospitalization. Conclusions: The KCCQ-12 questionnaire can provide inexpensive prognostic information even in older patients with HF. (Funded by grant Primitivo de la Vega, Fundación MAPFRE. ClinicalTrials number, NCT03555318).

Socioeconomic Status and Prognosis of Patients With ST-Elevation Myocardial Infarction Managed by the Emergency-Intervention "Codi IAM" Network.

Background: Despite the spread of ST-elevation myocardial infarction (STEMI) emergency intervention networks, inequalities in healthcare access still have a negative impact on cardiovascular prognosis. The Family Income Ratio of Barcelona (FIRB) is a socioeconomic status (SES) indicator that is annually calculated. Our aim was to evaluate whether SES had an effect on mortality and complications in patients managed by the "Codi IAM" network in Barcelona. Methods: This is a cohort study with 3,322 consecutive patients with STEMI treated in Barcelona from 2010 to 2016. Collected data include treatment delays, clinical and risk factor characteristics, and SES. The patients were assigned to three SES groups according to FIRB score. A logistic regression analysis was conducted to estimate the adjusted effect of SES on 30-day mortality, 30-day composite cardiovascular end point, and 1-year mortality. Results: The mean age of the patients was 65 ± 13% years, 25% were women, and 21% had diabetes mellitus. Patients with low SES were younger, more often hypertensive, diabetic, dyslipidemic (p < 0.003), had longer reperfusion delays (p < 0.03) compared to participants with higher SES. Low SES was not independently associated with 30-day mortality (OR: 0.95;9 5% CI: 0.7-1.3), 30-day cardiovascular composite end point (OR: 1.03; 95% CI: 0.84-1.26), or 1-year all-cause mortality (HR: 1.09; 95% CI: 0.76-1.56). Conclusion: Although the low-SES patients with STEMI in Barcelona city were younger, had worse clinical profiles, and had longer revascularization delays, their 30-day and 1-year outcomes were comparable to those of the higher-SES patients.

Short-Term Mortality in Patients with Heart Failure at the End-of-Life Stages: Hades Study.

Background: Information regarding short-term vital prognosis in patients with heart failure at advanced stages of the disease is scarce. Objective: To develop a three-month mortality predictive model for patients with advanced heart failure. Methods: Prospective observational study carried out in primary care and a convalescence community facility. Heart failure patients either New York Heart Association (NYHA) III with at least two HF hospitalizations during the previous six months or NYHA IV with/without previous recent hospitalization were included in the study. Multivariable predictive models using Cox regression were performed. Results: Of 271 patients included, 55 (20.3%) died during the first three months of follow-up. Mean age was 84.2 years (SD 8.3) and 59.8% were women. Predictive model including NT-proBNP had a C-index of 0.78 (95% CI 0.71; 0.85) and identified male gender, low body mass index, high potassium and NT-proBNP levels, and moderate-to-severe dependence for daily living activities (Barthel index < 40) as risk factors of mortality. In the model without NT-proBNP, C index was 0.72 (95% CI 0.64; 0.79) and, in addition to gender, body mass index, low Barthel index, and severe reductions in glomerular filtration rate showed the highest predictive hazard ratios for short-term mortality. Conclusions: In addition to age, male gender, potassium levels, low body mass index, and low glomerular filtration, dependence for activities of daily living add strong power to predict mortality at three months in patients with advanced heart failure.

Prognostic Utility of a New Risk Stratification Protocol for Secondary Prevention in Patients Attending Cardiac Rehabilitation.

Several risk scores have been used to predict risk after an acute coronary syndrome (ACS), but none of these risk scores include functional class. The aim was to assess the predictive value of risk stratification (RS), including functional class, and how cardiac rehabilitation (CR) changed RS. Two hundred and thirty-eight patients with ACS from an ambispective observational registry were stratified as low (L) and no-low (NL) risk and classified according to exercise compliance; low risk and exercise (L-E), low risk and control (no exercise) (L-C), no-low risk and exercise (NL-E), and no-low risk and control (NL-C). The primary endpoint was cardiac rehospitalization. Multivariable analysis was performed to identify variables independently associated with the primary endpoint. The L group included 56.7% of patients. The primary endpoint was higher in the NL group (18.4% vs. 4.4%, p < 0.001). After adjustment for age, sex, diabetes, and exercise in multivariable analysis, HR (95% CI) was 3.83 (1.51−9.68) for cardiac rehospitalization. For RS and exercise, the prognosis varied: the L-E group had a cardiac rehospitalization rate of 2.5% compared to 26.1% in the NL-C group (p < 0.001). Completing exercise training was associated with reclassification to low-risk, associated with a better outcome. This easy-to-calculate risk score offers robust prognostic information. No-exercise groups were independently associated with the worst outcomes. Exercise-based CR program changed RS, improving classification and prognosis.

Randomized Controlled Trial Comparing a Multidisciplinary Intervention by a Geriatrician and a Cardiologist to Usual Care after a Heart Failure Hospitalization in Older Patients: The SENECOR Study.

BACKGROUND: The prognosis of older patients after a heart failure (HF) hospitalization is poor. METHODS: In this randomized trial, we consecutively assigned 150 patients 75 years old or older with a recent heart failure hospitalization to follow-up by a cardiologist (control) or follow-up by a cardiologist and a geriatrician (intervention). The primary outcome was all-cause hospitalization at a one-year follow-up. RESULTS: All-cause hospitalization occurred in 47 of 75 patients (62.7%) in the intervention group and in 58 of 75 patients (77.3%) in the control group (hazard ratio, 0.67; 95% confidence interval, 0.46 to 0.99; p = 0.046). The number of patients with at least one HF hospitalization was similar in both groups (34.7% in the intervention group vs. 40% in the control group, p = 0.5). There were a total of 236 hospitalizations during the study period. The main reasons for hospitalization were heart failure (38.1%) and infection (14.8%). Mortality was 24.7%. Heart failure was the leading cause of mortality (54.1% of all deaths), without differences between groups. CONCLUSIONS: A follow-up by a cardiologist and geriatrician in older patients after an HF hospitalization was superior to a cardiologist's follow-up in reducing all-cause hospitalization in older patients. (Funded by Beca Primitivo de la Vega, Fundación MAPFRE. CLINICALTRIALS: gov number, NCT03555318).

Dose of furosemide before admission predicts diuretic efficiency and long-term prognosis in acute heart failure.

AIMS: The outpatient diuretic dose is a marker of diuretic resistance and prognosis in chronic heart failure (HF). Still, the impact of the preadmission dose on diuretic efficiency (DE) and prognosis in acute HF is not fully known. METHODS AND RESULTS: We conducted an observational and prospective study. All patients admitted for acute HF treated with intravenous diuretic and at least one criterion of congestion on admission were evaluated. Decongestion [physical examination, hemoconcentration, N-terminal pro-brain natriuretic peptide (NT-proBNP) change, and lung ultrasound], DE (weight loss and urine output per unit of 40 mg furosemide), and urinary sodium were monitored on the fifth day of admission. DE was dichotomized into high-low based on the median value. A multivariate Cox regression analysis was conducted to find predictors of HF readmission or mortality. A total of 105 patients were included between July 2017 and July 2019. Mean age was 74.5 ± 12.0 years, 64.8% were male, 33.3% had de novo HF, and mean left ventricular ejection fraction was 46 ± 17%. Median follow-up was 26 [15-35] months. Low DE based on weight loss was associated with a higher previous dose of furosemide (odds ratio [OR] 1.01 [1.00-1.02]), thiazide treatment before admission (OR 9.37 [2.19-40.14]), and lower diastolic blood pressure (OR 0.95 [0.91-0.98]) in the multivariate regression model. Only previous dose of furosemide (OR 1.01 [1.00-1.02]) and haemoglobin at admission (OR 0.76 [0.58-0.99]) were associated with low DE based on urine output in the multivariate analysis. The correlation between the previous dose of furosemide and DE based on weight loss was poor (r = -0.12; P = 0.209) and with DE based on urine output was weak to moderate (r = -0.33; P < 0.001). Low DE based on weight loss and urine output was associated with lesser decongestion measured by NT-proBNP (P = 0.011; P = 0.007), hemoconcentration (P = 0.006; P = 0.044), and lung ultrasound (P = 0.034; P = 0.029), but not by physical examination (P = 0.506; P = 0.560). Survival and event-free survival in acute decompensated HF (ADHF) were lower than in de novo HF; a preadmission dose of furosemide > 80 mg in ADHF identified patients with particularly poor prognosis (log-rank < 0.001). In ADHF, the preadmission dose of furosemide (hazard ratio [HR] 1.34 [1.08-1.67] per 40 mg) and NT-proBNP at admission (HR 1.03 [1.01-1.06] per 1000 pg/mL) were independently associated with mortality or HF readmission in the multivariate Cox regression analysis. CONCLUSIONS: The outpatient dose of furosemide before acute HF admission predicts DE and must be taken into account when deciding on the initial diuretic dose. In ADHF, the outpatient dose of furosemide can predict long-term prognosis better than DE during hospitalization.