Biomarkers in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

Body mass index and outcomes in ischaemic versus non-ischaemic heart failure across the spectrum of ejection fraction.

AIMS: Obesity is related to better prognosis in heart failure with either reduced (HFrEF; left ventricular ejection fraction (LVEF) < 40%) or preserved LVEF (HFpEF; LVEF ≥50%). Whether the obesity paradox exists in patients with heart failure and mid-range LVEF (HFmrEF; LVEF 40-49%) and whether it is independent of heart failure aetiology is unknown. Therefore, we aimed to test the prognostic value of body mass index (BMI) in ischaemic and non-ischaemic heart failure patients across the whole spectrum of LVEF. METHODS: Consecutive ambulatory heart failure patients were enrolled in two tertiary centres in Italy and Spain and classified as HFrEF, HFmrEF or HFpEF, of either ischaemic or non-ischaemic aetiology. Patients were stratified into underweight (BMI < 18.5 kg/m2), normal-weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), mild-obese (BMI 30-34.9 kg/m2), moderate-obese (BMI 35-39.9 kg/m2) and severe-obese (BMI ≥40 kg/m2) and followed up for the end-point of five-year all-cause mortality. RESULTS: We enrolled 5155 patients (age 70 years (60-77); 71% males; LVEF 35% (27-45); 63% HFrEF, 18% HFmrEF, 19% HFpEF). At multivariable analysis, mild obesity was independently associated with a lower risk of all-cause mortality in HFrEF (hazard ratio, 0.78 (95% confidence interval (CI) 0.64-0.95), p = 0.020), HFmrEF (hazard ratio 0.63 (95% CI 0.41-0.96), p = 0.029), and HFpEF (hazard ratio 0.60 (95% CI 0.42-0.88), p = 0.008). Both overweight and mild-to-moderate obesity were associated with better outcome in non-ischaemic heart failure, but not in ischaemic heart failure. CONCLUSIONS: Mild obesity is independently associated with better survival in heart failure across the whole spectrum of LVEF. Prognostic benefit of obesity is maintained only in non-ischaemic heart failure.

Advanced remote care for heart failure in times of COVID-19 using an implantable pulmonary artery pressure sensor: the new normal.

Heart failure (HF) is a major public health problem and a leading cause of hospitalization in western countries. Over the past decades, the goal has been to find the best method for monitoring congestive symptoms to prevent hospitalizations. Addressing this task through regular physician visits, blood tests, and imaging has proven insufficient for optimal control and has not decreased enough HF-related hospitalization rates. In recent years, new devices have been developed for this reason and CardioMEMS is one of the therapeutic monitoring options. CardioMEMS has shown to be effective in preventing and reducing HF hospitalizations in patients both with HF with reduced ejection fraction and HF with preserved ejection fraction. CardioMEMS' versatility has made it a great option for pulmonary artery pressure monitoring, both during the coronavirus disease-19 (COVID-19) pandemic and when the clinic visits have (partially) resumed. CardioMEMS is the remote haemodynamic monitoring system with the most evidence-driven efficacy, and COVID-19 has put it in the spot as a centre-stage technology for HF monitoring. In a few months of the COVID-19 epidemic, CardioMEMS has grown to maturity, making it the new normal for high-quality, high-value remote HF care.

Limitación al flujo aéreo en pacientes con insuficiencia cardíaca: prevalencia y factores asociados / Airflow limitation in patients with heart failure: Prevalence and associated factors

Introducción: La enfermedad pulmonar obstructiva crónica y la insuficiencia cardíaca (IC) son 2 enfermedades con una elevada morbimortalidad. La coexistencia de estas 2 enfermedades se estima que es frecuente, pero ha sido escasamente estudiada. Objetivo: Estudiar la prevalencia de limitación al flujo aéreo en una muestra de pacientes diagnosticados de IC en seguimiento en una unidad de IC y valorar las características y comorbilidades de estos pacientes. Métodos: Se trata de un estudio prospectivo observacional. Se incluyeron de forma consecutiva los pacientes visitados en la Unidad de Insuficiencia Cardíaca del Hospital Universitari Germans Trias i Pujol entre enero del 2014 y junio del 2015. Se realizaron pruebas funcionales respiratorias y se obtuvieron datos clínicos. Resultados: Se incluyeron 118 pacientes en el estudio (edad 67,2 años; DE 12,1; el 77,1% hombres). La prevalencia de limitación al flujo aéreo fue del 36,4%, con un porcentaje de infradiagnóstico del 67,4%. Los pacientes con limitación al flujo aéreo presentaban un aumento de las comorbilidades y de la mortalidad. Conclusión: La prevalencia de limitación al flujo aéreo en pacientes con IC es elevada, con un importante grado de infradiagnóstico. Sería recomendable la realización de una espirometría de cribado en estos pacientes

Background: Chronic obstructive pulmonary disease and heart failure (HF) are 2 diseases with high morbidity and mortality. The coexistence of these two diseases is estimated to be frequent, but has been poorly studied. Aim: To study the prevalence of airflow limitation in a sample of patients diagnosed with HF in follow-up in an HF unit and to assess their characteristics and comorbidities. Methods: This is a prospective observational study. The patients who visited the HF Unit of the Hospital Universitari Germans Trias i Pujol between January 2014 and June 2015 were included consecutively. Respiratory functional tests were performed and clinical data were obtained. Results: 118 patients were included in the study (age 67.2 years, 77.1% men). The prevalence of non-reversible airflow obstruction was 36.4%, with an underdiagnosis percentage of 67.4%. Patients with airflow limitation had an increase in comorbidities, but no worse prognosis. Conclusion: The prevalence of airflow limitation in patients with HF is high, with a significant degree of underdiagnosis. It seems reasonable to recommend performing a screening spirometry in these patients

Elective or emergency heart transplantation: Cost comparison in a single center.

BACKGROUND AND AIMS: Heart transplantation (HT) is the treatment of choice for selected cases of advanced heart failure. There is an increasing rate of emergency HT in our country. The aim of this study was to determine the cost of HT in our hospital according to emergent vs. elective transplantation status. METHODS: The costs of all consecutive HTs performed in our center between January 2010 and May 2015 were analyzed. The cost of elective and emergent HT was compared. RESULTS: HT mean cost at our institution was €62 203 ± 47 976. Elective HT mean cost was €47 540 ± 25 140, whereas emergent HT cost was €102 733 ± 68 050 (emergency status 1, as regional priority, was €66 077 ± 28 067 and emergency status 0, as the highest national priority, was €136 056 ± 77 080; P < 0.001). Increased emergent HT cost was mainly related to a longer admission (32 ± 24 days vs. 69 ± 53 days; P = 0.006; accounting for a cost of €14 517 ± 12 475 vs. €37 846 ± 31 702; P < 0.001) and increased drug-related expenses (€6622 ± 7465 vs. €15,171 ± 15,758; P < 0.02). Elective HT survival rate was 96%, compared to 68% for emergent HT; P = 0.002. CONCLUSIONS: Elective HT showed a high survival rate with a relatively low and less variable cost, leading to a favorable economic balance in today's public health reimbursement system. In contrast, emergent HT showed a higher cost and a lower survival rate. New treatment strategies should be identified for heart failure patients at risk of requiring emergency HT.

Airflow limitation in patients with heart failure: Prevalence and associated factors. / Limitación al flujo aéreo en pacientes con insuficiencia cardíaca: prevalencia y factores asociados.

BACKGROUND: Chronic obstructive pulmonary disease and heart failure (HF) are 2 diseases with high morbidity and mortality. The coexistence of these two diseases is estimated to be frequent, but has been poorly studied. AIM: To study the prevalence of airflow limitation in a sample of patients diagnosed with HF in follow-up in an HF unit and to assess their characteristics and comorbidities. METHODS: This is a prospective observational study. The patients who visited the HF Unit of the Hospital Universitari Germans Trias i Pujol between January 2014 and June 2015 were included consecutively. Respiratory functional tests were performed and clinical data were obtained. RESULTS: 118 patients were included in the study (age 67.2 years, 77.1% men). The prevalence of non-reversible airflow obstruction was 36.4%, with an underdiagnosis percentage of 67.4%. Patients with airflow limitation had an increase in comorbidities, but no worse prognosis. CONCLUSION: The prevalence of airflow limitation in patients with HF is high, with a significant degree of underdiagnosis. It seems reasonable to recommend performing a screening spirometry in these patients.

Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study.

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure. Additionally, 6 healthy animals underwent percutaneous-PADN to compare the pulmonary artery (PA) lesion generated with both approaches. In the surgical-PADN arm, hemodynamic evaluation and cardiac magnetic resonance (CMR) were performed at baseline and at 2 and 3-month follow-up. Histological assessment was carried out at the completion of the protocol. Eighteen pigs (6 following surgical-PADN, 6 sham and 6 percutaneous-PADN) completed the protocol. A complete transmural PA lesion was demonstrated using surgical clamps, whereas only focal damage to adventitial fibers was observed after percutaneous-PADN. In the surgical-PADN arm, the hemodynamic profile did not significantly differ between groups neither at baseline [mean pulmonary artery pressure (mPAP) median values of 32.0 vs. 27.5 mmHg, P = 0.394 and indexed pulmonary vascular resistance (iPVR) 5.9 vs. 4.7 WU m2, P = 0.394 for PADN/sham groups, respectively] nor at any follow-up (mPAP of 35.0 vs. 35.0 mmHg, P = 0.236 and iPVR of 8.3 vs. 6.7 WU m2, P = 0.477 at third month in PADN/sham groups, respectively). Surgical-PADN was not associated with any benefit in RV anatomy or function on CMR/histology. In a large-animal model of chronic postcapillary PH, transmural PADN with surgical clamps was associated with a neutral pulmonary hemodynamic effect.

Predictors of Improvement in Renal Function After Heart Transplant.

OBJECTIVES: Moderate chronic renal insufficiency is often found in patients evaluated for heart transplant. Recovery of cardiac output after heart transplant might lead to improvement of renal function. In this study, our aim was to identify predictors of improvement of renal function after heart transplant. MATERIALS AND METHODS: Our study included a cohort of heart transplant patients treated from 2011 to 2016 whose main outcome was improved renal function, defined as glomerular filtration rate at 6 months after heart transplant of ≥ 10% compared with baseline (before transplant). Univariate and multivariate logistic regression was used to identify independent predictors. RESULTS: Our study included 83 patients, with 29% having improvement in renal function. Multivariate analyses identified baseline glomerular filtration rate (odds ratio of 0.95; 95% confidence interval, 0.93-0.98; P = .005), absence of hypertension (odds ratio of 4.94; 95% confidence interval, 1.37-17.8; P = .015), and elective heart transplant (odds ratio of 13.71; 95% confidence interval, 1.33-141; P = .028) as independent predictors. A scale developed with independent predictors showed good accuracy (area under the curve of 0.76). The probability for improvement in renal function was 7%, 23%, and 58% in patients with low, medium, and high scores, respectively (P < .001). CONCLUSIONS: In patients with heart transplant, baseline glomerular filtration rate, absence of hypertension, and elective heart transplant were independent predictors of improvement in renal function after heart transplant.

Predictors of renal replacement therapy after heart transplantation and its impact on long-term survival.

BACKGROUND: Renal replacement therapy (RRT) after heart transplant (HT) is associated with worse prognosis. We aimed to identify predictors of RRT and the impact of this complication on long-term survival. METHODS: Cohort study of HT patients. Univariate and multivariate competing-risk regression was performed to identify independent predictors of RRT. The cumulative incidence function was plotted for RRT. The Kaplan-Meier method was used to compare long-term survival. RESULTS: We included 103 patients. At multivariate analysis, only the emergency status of HT (short-term mechanical circulatory support as a bridge to transplant), chronic kidney disease, and low oxygen delivery were independent predictors of RRT (subhazard ratio [SHR] 4.11, 95% CI 1.84-9.14; SHR 3.17, 95% CI 1.29-7.77; SHR 2.86, 95% CI 1.14-7.19, respectively). Elective HT patients that required RRT showed a significantly reduced survival comparable to patients with emergency HT and RRT (75% ± 13% vs. 67% ± 16%). The absence of RRT implied an excellent survival in patients with an emergency status of HT and elective HT (100% vs. 93% ± 4%). CONCLUSION: The emergency status of HT, chronic kidney disease, and low oxygen delivery were independent predictors of RRT. The occurrence of RRT increases the risk of death in elective HT as much as in patients with an emergency status.

Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt.

BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR). METHODS AND RESULTS: To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction. CONCLUSIONS: Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation.

Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension.

Beta-3 adrenergic receptor (ß3AR) agonists have been shown to produce vasodilation and prevention of ventricular remodeling in different conditions. Given that these biological functions are critical in pulmonary hypertension (PH), we aimed to demonstrate a beneficial effect of ß3AR agonists in PH. An experimental study in pigs (n = 34) with chronic PH created by pulmonary vein banding was designed to evaluate the acute hemodynamic effect and the long-term effect of ß3AR agonists on hemodynamics, vascular remodeling and RV performance in chronic PH. Ex vivo human experiments were performed to explore the expression of ß3AR mRNA and the vasodilator response of ß3AR agonists in pulmonary arteries. Single intravenous administration of the ß3AR agonist BRL37344 produced a significant acute reduction in PVR, and two-weeks treatment with two different ß3AR selective agonists, intravenous BRL37344 or oral mirabegron, resulted in a significant reduction in PVR (median of -2.0 Wood units/m(2) for BRL37344 vs. +1.5 for vehicle, p = 0.04; and -1.8 Wood units/m(2) for mirabegron vs. +1.6 for vehicle, p = 0.002) associated with a significant improvement in magnetic resonance-measured RV performance. Histological markers of pulmonary vascular proliferation (p27 and Ki67) were significantly attenuated in ß3AR agonists-treated pigs. ß3AR was expressed in human pulmonary arteries and ß3AR agonists produced vasodilatation. ß3AR agonists produced a significant reduction in PVR and improved RV performance in experimental PH, emerging as a potential novel approach for treating patients with chronic PH.

Trabalhadora e mãe: papéis, identidade, consciência política e democracia / Working mother: roles, identity, political consciousness and democracy / Madre trabajadora: papeles, la identidad, la conciencia política y la democracia / La femme travailleuse et mère: les rôles, l'identité, la conscience politique et la démocratie

Diante da complexidade da vida da mulher contemporânea, levantou-se algumas questões sobre os principais conflitos que surgem da conjunção entre trabalho e maternidade. A maior inclusão da mulher no mercado de trabalho - e sua ascensão a cargos antes exclusivamente masculinos - aponta para o reconhecimento de suas competências laborais, mas desconsidera inteiramente a peculiaridade da sua condição em relação ao trabalhador homem, que não vivencia em seu corpo as transformações impostas pela geração de uma família, e não desempenha com a mesma responsabilidade o cuidado com a prole. A partir de uma breve revisão bibliográfica sobre maternidade e trabalho feminino, observou-se a persistência de representações enaltecedoras da maternidade, que pressionam as mulheres para que sejam mães enquanto trabalham - apesar das condições adversas que tornam penosa essa conciliação - e recriminam a escolha por uma destas vivências: a maternidade exclusiva ou o trabalho como prioridade integral, que não inclua o projeto de maternidade. Apontou-se a importância desse debate para o fortalecimento das políticas trabalhistas como proposição objetiva rumo à equidade de gênero na sociedade atual.

Faced to the complexity of contemporary women's life, we raised some questions about the main conflicts of working and motherhood conjunction. The increasing inclusion of women in the market, occupying positions previously exclusive for males, highlights their work skills, but entirely ignores the individuality of women compared to the man, who had not experienced body transformations imposed by the generation of a family, and does not play the same responsibility to the offspring care. Based on a brief literature review about maternity and women's work, we noted the motherhood representation is persistent, demanding women keeping to be mothers even while working - despite the adverse conditions which make those functions painful - and censure the choice for one of those experiences: the maternity exclusively; or primary work and do not include maternity plan. It has been shown the importance of that debate to reinforce the working policies aiming equity of gender in the modern society.

Frente a la complejidad de la vida de la mujer contemporánea, planteamos algunas preguntas sobre los principales conflictos que surgen de la conjunción entre el trabajo y la maternidad. La mayor inclusión de las mujeres en el mercado laboral - y su ascenso a posiciones antes exclusivamente masculinas - puntos clave para el reconocimiento de sus habilidades al trabajo, pero ignora por completo la peculiaridad de su situación en relación al trabajador hombre, que no experimenta las transformaciones corporales impuestas por la formación de una familia y no desarrolla con la misma responsabilidad el cuidado de la prole. A partir de una breve revisión literaria de la maternidad y el trabajo de las mujeres, se ha señalado la persistencia de representaciones consolidadoras de la maternidad al presionarlas a que sean madres mientras trabajadoras - a pesar de las condiciones adversas que hacen dolorosa esta combinación - y la recriminación a la elección de uno de los roles: la maternidad exclusiva; o el trabajo como prioridad integral que no incluya el escenario del ser madre. Este trabajo apunta la importancia sobre este debate para la fortificación de las políticas laborales como proposición objetiva rumbo a la equidad de géneros en la sociedad actual.

Face à la la complexité de la vie des femmes contemporaines, quelques questions se posent sur les principaux conflits qui résultent de la conjonction entre le travail et la maternité. De nos jours, la plus grande inclusion des femmes dans le marché du travail - et leur ascension à des postes auparavant exclusivement masculins - indique la reconnaissance de leurs compétences professionnelles, mais ignore totalement la particularité de leur statut par rapport à l'homme qui travaille, qui ne subit pas dans son corps les transformations imposées pour la génération d'une famille, et ne joue pas avec la même responsabilité de prendre soin de la progéniture. A partir d'une bref analyse de la littérature sur la maternité et le travail des femmes, nous avons constaté la persistance de représentations exaltées de la maternité, qui font pression sur les femmes pour qu'elles soyent mères tout en travaillant - en dépit des conditions défavorables qui rendent pénible cette conciliation - et reprochent la femme qui choisit une de ces expériences: la maternité exclusive; ou le travail comme une priorité complète, qui ne comprend pas la concéption de la maternité. Les auteurs signalent l'importance de ce débat pour le renforcement des politiques de travail en tant que proposition objective envers l'équité des sexes dans la société actuelle.

Pulmonary hypertension is related to peripheral endothelial dysfunction in heart failure with preserved ejection fraction.

BACKGROUND: Pulmonary hypertension (PH) and collagen metabolism abnormalities are prevalent in patients with heart failure with preserved ejection fraction (HFpEF). Peripheral endothelial dysfunction (PED) has been described in HF and in pulmonary arterial hypertension. Our aim is to determine whether PH is associated with PED and impaired collagen metabolism in patients with HFpEF.; METHODS AND RESULTS: Flow-mediated dilation of the brachial artery, matrix metalloproteinase-2 and matrix metalloproteinase-9, tissue metalloproteinase inhibitor 1, and C-terminal propeptide of type I procollagen were determined in 28 patients with HFpEF and 42 hypertensive controls. Patients with systolic pulmonary artery pressure >35 mm Hg on echocardiogram underwent a right heart catheterization. Patients with HFpEF had more severe PED than controls: flow-mediated dilation 1.95% (-0.81 to 4.92) versus 5.02% (3.90 to 10.12), P=0.002. Twenty patients with PH underwent right heart catheterization: mean pulmonary artery pressure 38 (27-52) mm Hg, wedge capillary pressure 18 (16-22) mm Hg, pulmonary vascular resistance 362 (235-603) dyn s cm(-5). There was a significant inverse correlation between flow-mediated dilation and pulmonary vascular resistance in patients with HFpEF and PH (r=-0.679; P=0.002). Patients with HFpEF showed higher matrix metalloproteinase-2 and C-terminal propeptide of type I procollagen values than hypertensive controls. Patients with HFpEF and higher C-terminal propeptide of type I procollagen values also had higher mean pulmonary artery pressure (r=0.553; P=0.014), transpulmonary gradient (r=0.560; P=0.013), and pulmonary vascular resistance (r=0.626; P=0.004). CONCLUSIONS: In patients with HFpEF, there is a significant correlation between PED and pulmonary vascular resistance. Collagen metabolism was more impaired in patients with HFpEF and PH. PED and collagen metabolism assessment could be useful tools to identify patients with HFpEF at risk of developing PH.

Lymphoplasmacytic lymphoma causing light chain cast nephropathy.

Plasma cell dyscrasias are frequently associated with kidney disease through the production of monoclonal immunoglobulin but with a diverse set of pathologic renal patterns. While almost all patients with a renal biopsy showing a cast nephropathy have myeloma, kidney involvement associated with pathological immunoglobulin light chains and lymphoma is rare. To our knowledge, this is the first report of a cast nephropathy associated with lymphoplasmacytic lymphoma. We emphasize the relation between light chain deposition and renal dysfunction in this disease with production of light chains. A therapeutic approach that decreases light chain production appears to be warranted in these patients.