Sex and Gender-related Disparities in Clinical Characteristics and Outcomes in Heart Transplantation.

PURPOSE OF REVIEW: Limited research has been conducted on sex disparities in heart transplant (HT). The aim of this review is to analyse the available evidence on the influence of sex and gender-related determinants in the entire HT process, as well as to identify areas for further investigation. RECENT FINDINGS: Although women make up half of the population affected by heart failure and related mortality, they account for less than a third of HT recipients. Reasons for this inequality include differences in disease course, psychosocial factors, concerns about allosensitisation, and selection or referral bias in female patients. Women are more often listed for HT due to non-ischaemic cardiomyopathy and have a lower burden of cardiovascular risk factors. Although long-term prognosis appears to be similar for both sexes, there are significant disparities in post-HT morbidity and causes of mortality (noting a higher incidence of rejection in women and of malignancy and cardiac allograft vasculopathy in men). Additional research is required to gain a better understanding of the reasons behind gender disparities in eligibility and outcomes following HT. This would enable the fair allocation of resources and enhance patient care.

Incidence and Prognosis of Colorectal Cancer After Heart Transplantation: Data From the Spanish Post-Heart Transplant Tumor Registry.

In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.

Low-precision feature selection on microarray data: an information theoretic approach.

The number of interconnected devices, such as personal wearables, cars, and smart-homes, surrounding us every day has recently increased. The Internet of Things devices monitor many processes, and have the capacity of using machine learning models for pattern recognition, and even making decisions, with the added advantage of diminishing network congestion by allowing computations near to the data sources. The main restriction is the low computation capacity of these devices. Thus, machine learning algorithms capable of maintaining accuracy while using mechanisms that exploit certain characteristics, such as low-precision versions, are needed. In this paper, low-precision mutual information-based feature selection algorithms are employed over DNA microarray datasets, showing that 16-bit and some times even 8-bit representations of these algorithms can be used without significant variations in the final classification results achieved. Graphical Abstract Graphical abstract.

Serum potassium dynamics during acute heart failure hospitalization.

BACKGROUND: Available information about prognostic implications of potassium levels alteration in the setting of acute heart failure (AHF) is scarce. OBJECTIVES: We aim to describe the prevalence of dyskalemia (hypo or hyperkalemia), its dynamic changes during AHF-hospitalization, and its long-term clinical impact after hospitalization. METHODS: We analyzed 1779 patients hospitalized with AHF who were included in the REDINSCOR II registry. Patients were classified in three groups, according to potassium levels both on admission and discharge: hypokalemia (potassium < 3.5 mEq/L), normokalemia (potassium = 3.5-5.0 mEq/L and, hyperkalemia (potassium > 5 mEq/L). RESULTS: The prevalence of hypokalemia and hyperkalemia on admission was 8.2 and 4.6%, respectively, and 6.4 and 2.7% at discharge. Hyperkalemia on admission was associated with higher in-hospital mortality (OR = 2.32 [95% CI: 1.04-5.21] p = 0.045). Among patients with hypokalemia on admission, 79% had normalized potassium levels at discharge. In the case of patients with hyperkalemia on admission, 89% normalized kalemia before discharge. In multivariate Cox regression, dyskalemia was associated with higher 12-month mortality, (HR = 1.48 [95% CI, 1.12-1.96], p = 0.005). Among all patterns of dyskalemia persistent hypokalemia (HR = 3.17 [95% CI: 1.71-5.88]; p < 0.001), and transient hyperkalemia (HR = 1.75 [95% CI: 1.07-2.86]; p = 0.023) were related to reduced 12-month survival. CONCLUSIONS: Potassium levels alterations are frequent and show a dynamic behavior during AHF admission. Hyperkalemia on admission is an independent predictor of higher in-hospital mortality. Furthermore, persistent hypokalemia and transient hyperkalemia on admission are independent predictors of 12-month mortality.

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.

Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure.

BACKGROUND: Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization. METHODS: Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0-9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST. RESULTS: Median UNa after FST in the 65 patients included was 113 (97-122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P=0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P<0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months. CONCLUSIONS: Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.

Sistema renina-angiotensina-aldosterona y COVID19. Implicaciones clínicas / The renin-angiotensin-aldosterone system and COVID-19. Clinical implications

La pandemia ocasionada por la rápida expansión del SARS-CoV-2 ha producido la mayor crisis sanitaria de la época moderna. La estrecha relación del virus con la enzima de conversión de la angiotensina ha suscitado un torrente de especulaciones por el posible papel del sistema renina-angiotensina-aldosterona (SRAA) en la regulation de la infection. La alerta generada ha cuestionado el empleo de fármacos inhibidores del SRAA, tanto los inhibidores de la enzima de conversión de la angiotensina como los antagonistas del receptor de la angiotensina II. está situación ha motivado la publication de varios estudios que no han encontrado asociación entre el uso de inhibidores del SRAA y una mayor susceptibilidad a la infección o a una peor evolution clínica. En está revisión se abordan los aspectos más relevantes de la interacción del SARS-CoV-2 con el SRAA y las implicaciones clínicas en torno al uso de inhibidores del SRAA durante la pandemia

The pandemic caused by the rapid spread of the SARS-CoV-2 virus has produced the greatest health crisis of modern times. The close relationship between the virus and angiotensin-II converting enzyme has provoked a torrent of speculation about the possible role of the renin-angiotensin-aldosterone system (RAAS) in mediating infection. The subsequent alarm has raised questions about the use of RAAS inhibitors, such as angiotensin-converting enzyme inhibitors and angiotensin-II receptor blockers. The result has been the publication of several studies that have failed to find an association between the use of RAAS inhibitors and greater susceptibility to infección or a worse clínical outlook. This review considers the most significant aspects of the interaction between SARS-CoV-2 and the RAAS and the clínical implications of using RAAS inhibitors during the pandemic

The development of chronic diuretic resistance can be predicted during a heart-failure hospitalization. Results from the REDIHF registry.

INTRODUCTION: Diuretic resistance (DR) is a common condition during a heart failure (HF) hospitalization, and is related to worse prognosis. Although the risk factors for DR during a HF hospitalization are widely described, we do not know whether the risk of chronic DR could be predicted during admission. MATERIAL AND METHODS: We conducted a multicenter, prospective observational study between July 2017 and July 2019. All patients admitted for acute HF with intravenous diuretic treatment and at least one criterion of congestion on admission were invited to participate. Patients on renal replacement therapy, under intravenous diuretic treatment for >72 hours before screening and those who were unable to sign the informed consent were excluded. We monitored decongestion (physical exam, hemoconcentration, NTproBNP change and lung ultrasound) and DR (diuresis and weight loss per unit of 40mg furosemide and fractional excretion of sodium) on the fifth day of admission. Chronic DR was evaluate two months after hospitalization and was defined as persistent signs of congestion despite ≥80 mg furosemide per day. We compared variables from the hospitalization between patients with and without chronic DR. A multivariate logistic regression analysis was conducted to find predictors of chronic DR. RESULTS: A total of 105 patients were included in the study. Mean age was 74.5±12.0 years, 64.8% were male and mean LVEF was 46±17%. In the two months follow-up, five patients have died and one patient has had a heart transplant. Of the 99 remaining patients, 21 patients (21.2%) had chronic DR. The dose of furosemide before admission and the decrease in NT-proBNP ≤30% during admission were predictors of chronic DR in the multivariate analysis. CONCLUSIONS: We can predict during a HF hospitalization which patients will develop chronic DR. The dose of furosemide before admission and the change in NT-proBNP are independent predictors of chronic DR.

Spanish Heart Transplant Registry. 31th Official Report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: The present report describes the clinical characteristics and outcomes of heart transplants in Spain and updates the data to 2019. METHODS: We describe the clinical characteristics and outcomes of heart transplants performed in Spain in 2019, as well as trends in this procedure from 2010 to 2018. RESULTS: In 2019, 300 transplants were performed (8794 since 1984; 2745 between 2010 and 2019). Compared with previous years, the most notable findings were the decreasing rate of urgent transplants (38%), and the consolidation of the type of circulatory support prior to transplant, with an almost complete disappearance of counterpulsation balloon (0.7%), stabilization in the use of extracorporeal membrane oxygenation (9.6%), and an increase in the use of ventricular assist devices (29.0%). Survival from 2016 to 2018 was similar to that from 2013 to 2015 (P=.34). Survival in both these periods was better than that from 2010 to 2012 (P=.002 and P=.01, respectively). CONCLUSIONS: Heart transplant activity has remained stable during the last few years, as have outcomes (in terms of survival). There has been a trend to a lower rate of urgent transplants and to a higher use of ventricular assist devices prior to transplant.

Evaluation of a nurse-led intervention program in heart failure: A randomized trial / Evaluación de un programa de intervención de enfermería en insuficiencia cardiaca: un ensayo aleatorizado

Background and objective: Several trials have evaluated the effect of disease management programs in heart failure (HF) with diverse results. The aim of this study was to develop a simple nurse-led clinic intervention program for patients with HF and assess whether this intervention positively affects the prognosis of patients, their care costs and perceived quality of life (QoL). Methods: Between 2011 and 2013, 127 patients with reduced ejection fraction were prospectively randomly allocated (1:2) to standard care or intervention program. Primary composite endpoint was all-cause mortality and hospital readmissions. Secondary endpoints were all-cause mortality, all-cause hospital readmissions, readmissions for HF, time to first readmission and QoL improvements assessed by "Minnesota Living with Heart Failure Questionnaire" (MLHFQ). An intention-to-treat analysis was performed. Results: After a median follow-up of 2-years, no differences were found in the primary composite endpoint. Likewise, there were no differences between groups in the predefined secondary endpoints of mortality and readmissions from any cause. However, in the intervention group, readmissions for HF were significantly reduced (35% vs. 18%; p=0.04) and QoL significantly improved (MLHFQ±SD: 2.29±14 vs. 10.9±14.75; p=0.04). Conclusions: In patients with HF, the use of a nurse-led intervention program significantly improves perceived QoL and reduce HF hospital readmissions

Introducción y objetivos: Se han publicado múltiples ensayos sobre programas de gestión de enfermedades en la insuficiencia cardiaca (IC) con resultados muy heterogéneos. El objetivo de este estudio fue desarrollar un sencillo programa de intervención clínica dirigido por enfermería en pacientes con IC y evaluar si dicha intervención afecta positivamente sobre el pronóstico de los pacientes, sus costes de atención y la calidad de vida percibida. Métodos: Entre 2011 y 2013, 127 pacientes con fracción de eyección reducida fueron aleatorizados (1:2) a manejo estándar o al programa de intervención. El objetivo primario compuesto fue mortalidad y reingresos hospitalarios por cualquier causa. Los criterios de valoración secundarios fueron mortalidad por cualquier causa, reingresos hospitalarios por cualquier causa, reingresos hospitalarios por IC, tiempo hasta el primer ingreso y mejoría de la calidad de vida evaluado por el Minnesota Living with Heart Failure Questionnaire (MLHFQ). Resultados: Tras un seguimiento medio de 2 años, no se encontraron diferencias en el criterio de valoración compuesto primario. Igualmente, no hubo diferencias en la mortalidad o los reingresos por cualquier causa. Sin embargo, en el grupo de intervención, los reingresos por IC se redujeron (35 vs. 18%; p=0,04) y la calidad de vida percibida mejoró de forma significativa (MLHFQ±DE: 2,29±14 vs. 10,9±14,75; p=0,04). Conclusiones: En los pacientes con IC, el empleo de un programa de intervención dirigido por enfermería mejora significativamente la calidad de vida percibida y reduce los reingresos hospitalarios por IC

A Review of Microarray Datasets: Where to Find Them and Specific Characteristics.

The advent of DNA microarray datasets has stimulated a new line of research both in bioinformatics and in machine learning. This type of data is used to collect information from tissue and cell samples regarding gene expression differences that could be useful for disease diagnosis or for distinguishing specific types of tumor. Microarray data classification is a difficult challenge for machine learning researchers due to its high number of features and the small sample sizes. This chapter is devoted to reviewing the microarray databases most frequently used in the literature. We also make the interested reader aware of the problematic of data characteristics in this domain, such as the imbalance of the data, their complexity, and the so-called dataset shift.

Feature Selection Applied to Microarray Data.

A typical characteristic of microarray data is that it has a very high number of features (in the order of thousands) while the number of examples is usually less than 100. In the context of microarray classification, this poses a challenge for machine learning methods, which can suffer overfitting and thus degradation in their performance. A common solution is to apply a dimensionality reduction technique before classification, to reduce the number of features. This chapter will be focused on one of the most famous dimensionality reduction techniques: feature selection. We will see how feature selection can help improve the classification accuracy in several microarray data scenarios.

Evaluation of a nurse-led intervention program in heart failure: A randomized trial.

BACKGROUND AND OBJECTIVE: Several trials have evaluated the effect of disease management programs in heart failure (HF) with diverse results. The aim of this study was to develop a simple nurse-led clinic intervention program for patients with HF and assess whether this intervention positively affects the prognosis of patients, their care costs and perceived quality of life (QoL). METHODS: Between 2011 and 2013, 127 patients with reduced ejection fraction were prospectively randomly allocated (1:2) to standard care or intervention program. Primary composite endpoint was all-cause mortality and hospital readmissions. Secondary endpoints were all-cause mortality, all-cause hospital readmissions, readmissions for HF, time to first readmission and QoL improvements assessed by "Minnesota Living with Heart Failure Questionnaire" (MLHFQ). An intention-to-treat analysis was performed. RESULTS: After a median follow-up of 2-years, no differences were found in the primary composite endpoint. Likewise, there were no differences between groups in the predefined secondary endpoints of mortality and readmissions from any cause. However, in the intervention group, readmissions for HF were significantly reduced (35% vs. 18%; p=0.04) and QoL significantly improved (MLHFQ±SD: 2.29±14 vs. 10.9±14.75; p=0.04). CONCLUSIONS: In patients with HF, the use of a nurse-led intervention program significantly improves perceived QoL and reduce HF hospital readmissions.

Hipocratismo digital en la enfermedad veno-oclusiva pulmonar / Digital clubbing in pulmonary veno-occlusive disease

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Area strain from 3D speckle-tracking echocardiography as an independent predictor of early symptoms or ventricular dysfunction in asymptomatic severe mitral regurgitation with preserved ejection fraction.

The indication for surgery in asymptomatic severe mitral regurgitation (SMR) with preserved left ventricular ejection fraction (LVEF) is controversial. We sought to study 3D myocardial mechanics in this population and test 3D-speckle tracking (3DST) parameters as possible predictors of events. 45 asymptomatic patients with SMR and LVEF >60 % and 20 control individuals without cardiac disease underwent 3DST echocardiography. MR group additionally underwent further clinical monitoring. Dyspnea, LVEF under 60 %, or admissions for heart failure were considered as events. When compared with control group, MR group showed lower percentage of global 3D strain, (35.4 ± 9.1 vs. 43.9 ± 10.6; p = 0.003), lower radial strain, lower area change rate and higher end-diastolic volume. In a follow-up time of 23.2 ± 14.5 months we found 15 events (33.3 %). When comparing the remaining patients with this new-onset HF group we found significant differences in longitudinal strain (-17.9 ± 3.3 vs. -15.8 ± 2.1; p = 0.036), area strain (AS) (-48.6 ± 4.6 vs. -43.7 ± 6.2; p = 0.006), circumferential strain (-35.8 ± 4.7 vs. -31.8 ± 6.1; p = 0.034), 3D LVEF (67.1 ± 4.6 vs. 63.0 ± 7.4; p = 0.034) and E/E' index (13.5 ± 3.9 vs. 19.3 ± 9.5; p = 0.006). In multivariate Cox regression AS alone was the only independent predictor. A cutoff value of AS greater than -41.6 % reached a hazard ratio of 4.41 (p = 0.004) for prediction of events. In asymptomatic patients with SMR and preserved ejection fraction, 3DST derived AS is a promising tool for predicting the development of heart failure. This finding may be useful for guiding the selection of patients for early mitral valve repair/replacement surgery even if they are asymptomatic.

Inoperable chronic thromboembolic pulmonary hypertension treated with riociguat: A case study.

A 51-year-old woman presented with a one-year history of progressive dyspnea, WHO functional class III-IV and exercise-related syncope. Transthoracic echocardiography and computed tomography pulmonary angiography were performed, leading to a diagnosis of pulmonary arterial hypertension. She was referred to our pulmonary hypertension unit, where a complete study was performed, including ventilation/perfusion scan, which was consistent with chronic thromboembolic pulmonary hypertension. Risk factors for this condition were excluded and therapeutic options were evaluated. Imaging studies showed distal pulmonary disease so pulmonary endarterectomy was rejected. Further therapeutic options were evaluated and the patient was subsequently enrolled in an open-label uncontrolled trial with riociguat. After one year of treatment, significant improvement in functional class, 6-minute walk test and NT-proBNP were seen, without significant secondary effects.