RESUMEN
The cross-sectional study enrolled 231 patients with heart failure (n = 115; 60.87% were men; mean age, 74.34 ± 12.70 years) and heart transplantation (n = 116; 72.41% were men; mean age, 56.85 ± 11.87 years) who self-reported their technology usage, physical activity, and source of motivation for exercise. Patients with heart failure were significantly older ( P = .0001) than patients with heart transplantation. Physical activity levels in patients with heart failure decreased as the New York Heart Association classification increased. Patients with heart failure reported significantly lower physical activity than patients with heart transplantation ( P = .0008). Smartphones were the most widely used electronic device to access the Internet in both groups. Patients with heart transplantation seemed to use more than one device to access the Internet. In both groups, patients reporting more technology usage also reported higher levels of physical activity. Patients who accessed the Internet daily reported lower levels of physical activity. Whereas patients with heart failure identified encouragement by family members as a source of motivation for exercise, patients with heart transplantation reported that they were likely to exercise if motivated by their healthcare provider. Patients with heart failure and heart transplantation have unique technological and motivational needs that need consideration for mobile health-driven interventions.
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Insuficiencia Cardíaca , Trasplante de Corazón , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto , Femenino , Motivación , Estudios Transversales , Ejercicio FísicoRESUMEN
The study aimed to study the influence of musculoskeletal pain on kinesiophobia in patients with heart failure. This cross-sectional study recruited 107 heart failure patients aged 73.18±12.68 years (57% men) from an outpatient setting. Participants self-reported pain using the Musculoskeletal System Assessment Inventory and the Cornell Musculoskeletal Discomfort Questionnaire. Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia-11. About 62% reported musculoskeletal pain, with knees (16.8%) and lower back (12.%) being the most painful locations. About 31% reported moderate levels and 24% indicated high levels of kinesiophobia. There were positive and significant associations between the indicators of pain and kinesiophobia. Results showed an adequate structural equation model fit to the data with musculoskeletal pain factors explaining 22.09% of the variance in kinesiophobia. Assessment of kinesiophobia in patients with heart failure with musculoskeletal pain is essential to improve self-care and overall quality of life.
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Insuficiencia Cardíaca , Dolor Musculoesquelético , Masculino , Humanos , Anciano , Femenino , Miedo , Kinesiofobia , Calidad de Vida , Estudios Transversales , Dimensión del Dolor , Insuficiencia Cardíaca/complicacionesRESUMEN
OBJECTIVE: To determine whether physical activity enjoyment mediated the association between motivation and physical activity in patients with heart failure. DESIGN AND SETTING: A cross-sectional study at the cardiology clinic in the university hospital in Valencia, Spain. SUBJECTS: A total of 134 patients with heart failure. MAIN MEASUREMENTS: Physical activity was assessed with the International Physical Activity Questionnaire, motivation was assessed with the Exercise Motivation Index and Physical Activity Enjoyment was assessed with the Physical Activity Enjoyment Scale. ANALYSIS: Mediation analysis using Hayes' PROCESS macro (Model 4) for SPSS. RESULTS: The mean age of the sample was 70 ± 14 years, 47 patients were female (35%), and 87 patients were in New York Heart Association I/II (67%). A positive relationship was found between exercise motivation and physical activity (t = 4.57, p < .01) and physical activity enjoyment (t = 11.52, p < .01). Physical activity enjoyment was found to positively affect physical activity (t = 3.50, p < .01). After controlling for physical activity enjoyment, the effect of exercise motivation on physical activity changed from a significant to non-significant (t = 1.33, p = .89), indicating that enjoyment completely mediated the relationship between motivation and physical activity. Overall, 25% of the variation in physical activity was explained by the mediation model. CONCLUSIONS: Physical activity enjoyment mediates the relationship between exercise motivation and physical activity in patients with heart failure. This means that even highly motivated heart failure patients may not be physically active if they do not enjoy the physical activity.
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Insuficiencia Cardíaca , Motivación , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ejercicio Físico , Femenino , Humanos , Masculino , Análisis de Mediación , Persona de Mediana Edad , PlacerRESUMEN
BACKGROUND: Macitentan is a dual endothelin receptor antagonist indicated for the long-term treatment of pulmonary arterial hypertension (PAH). We evaluated the change over time in REVEAL risk score in incident and prevalent patients receiving macitentan for the first time. METHODS: Retrospective, observational study including adult patients with idiopathic/heritable PAH or PAH associated with connective tissue disorders or congenital heart disease treated with macitentan for ≥6-month follow-up in Spain. The REVEAL risk score and risk strata were computed at the start of macitentan and after ≥6-month in patients with ≥7 out of 12 valid REVEAL components. RESULTS: Overall, 81 patients (57 for the REVEAL score) were analysed, 77.8% women. The mean age was 57.2 years and 50.6% of patients had idiopathic/heritable PAH. Prevalent patients were 59.3 and 40.7% were incident. Main therapies for PAH included macitentan monotherapy (42.0%) and macitentan in combination with phosphodiesterase type 5 inhibitor (44.4%). With a median time of macitentan treatment of 10.5 months, the mean REVEAL score was 8.7 points at baseline and was 7.2 points after ≥6-month follow-up. The mean change (95% CI) in REVEAL risk score was - 1.4 (- 2.0, - 0.9) points (p < 0.0001), being - 1.8 (- 3.0, - 0.7) points (p = 0.0040) and - 1.2 (- 1.8, - 0.5) points (p = 0.0010), in incident and prevalent patients, respectively. The reduction was also significant by risk stratum (36.8% of patients in the high-very high risk strata at baseline versus 14.0% after ≥6-month, p < 0.05) and therapy group. The REVEAL components that significantly improved were WHO functional class (FC) (63.9% FC III at macitentan initiation and 23.6% after ≥6-month, p < 0.0001), 6-min walk test (mean change: 41.8 m, p < 0.01), brain natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) (mean change of - 157.6 pg/mL and - 530.0 pg/mL, respectively, p < 0.05 both), and pulmonary vascular resistance (PVR) (mean change: - 3.4 WU, p < 0.01). CONCLUSIONS: In this study, treatment with macitentan improved the REVEAL risk strata and score in both incident and prevalent PAH patients, and in all patients regardless of the therapy strategy. Macitentan significantly improved some of REVEAL components including WHO FC, BNP/NT-proBNP, PVR, and 6-min walk test after at least 6-month follow-up.
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Antagonistas de los Receptores de Endotelina/uso terapéutico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Resistencia Vascular/efectos de los fármacos , Prueba de PasoRESUMEN
To explore if genic expression of ß(1)- or ß(2)-adrenoceptors (ARs) exhibits a common regulatory pattern with G protein-coupled receptor kinase (GRK) 2, GRK3, or GRK5 expression, we determined messenger RNA levels for these genes in different tissues from human and animal models of cardiovascular disease. We measured genic expression by qRT polymerase chain reaction in the left and right ventricles or peripheral blood mononuclear cells from healthy (n = 21), hypertensive (n = 20), heart failure (n = 24), and heart transplanted patients (n = 17) or in left ventricle, peripheral blood mononuclear cells, and kidney from spontaneously hypertensive rats or L-N-methyl-arginine-induced hypertensive rats and their respective controls (n = 4-5). In diseased versus healthy subjects and rats, parallel changes in messenger RNA levels of GRK2 and ß(2)-AR or GRK5 and ß(1)-AR were observed in each territory. Therefore, without excluding other regulatory mechanisms, the parallelism observed suggests a common regulatory pattern for the ß(1)-AR/GRK5 and ß(2)-AR/GRK2 genes, which is independent of cellular type or pathology. This highlights the need to focus not only on GRKs but also on ß(1)- or ß(2)-AR changes to completely understand the involvement of ß-AR/GRK pathways in cardiovascular diseases.
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Quinasa 2 del Receptor Acoplado a Proteína-G/metabolismo , Quinasa 5 del Receptor Acoplado a Proteína-G/metabolismo , Cardiopatías/metabolismo , Hipertensión/metabolismo , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Animales , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Quinasa 2 del Receptor Acoplado a Proteína-G/genética , Quinasa 5 del Receptor Acoplado a Proteína-G/genética , Regulación de la Expresión Génica , Cardiopatías/genética , Humanos , Hipertensión/inducido químicamente , Hipertensión/genética , NG-Nitroarginina Metil Éster , Especificidad de Órganos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genéticaRESUMEN
The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women.
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Trasplante de Corazón/mortalidad , Sistema de Registros , Obtención de Tejidos y Órganos/métodos , Receptores de Trasplantes , Adolescente , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , España/epidemiología , Tasa de Supervivencia/tendencias , Adulto JovenRESUMEN
Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug-induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy.
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Frecuencia de los Genes , Genotipo , Inmunosupresores/metabolismo , Inmunosupresores/farmacocinética , Inactivación Metabólica/genética , Población Blanca/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Sistema Enzimático del Citocromo P-450/genética , Glucuronosiltransferasa/genética , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metiltransferasas/genética , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Proteína Adaptadora de Señalización NOD2/genética , Transportadores de Anión Orgánico/genética , Polimorfismo de Nucleótido Simple/genética , España , Donantes de Tejidos , Receptores de Trasplantes , UDP Glucuronosiltransferasa 1A9RESUMEN
AIMS: After heart transplantation (HTx), increments in physical activity (PA) are strongly recommended. However, participation rates in exercise-based cardiac rehabilitation and engagement in PA are insufficient in many patients. Hence, this study aimed to explore the central factors and the interconnections among distinct types of motivation to exercise, PA, sedentary time, psychosomatic, diet, and activity limitation characteristics in post-HTx patients. METHODS AND RESULTS: This is a cross-sectional study involving 133 post-HTx patients (79 men, mean age 57 ± 13 years, mean time from transplantation 55 ± 42 months) recruited from an outpatient clinic in Spain. The patients were asked to fill in questionnaires measuring self-reported PA, motivation to exercise, kinesiophobia, musculoskeletal pain, quality of sleep, depression, functional capacity, frailty, sarcopenia risk, and diet quality. Two network structures were estimated: one network including PA and one network including sedentary time as nodes. The relative importance of each node in the network structures was determined using centrality analyses. According to the strength centrality index, functional capacity and identified regulation (subtypes of motivation to exercise) are the two most central nodes of the network (strength: z-score = 1.35-1.51). Strong and direct connections emerged between frailty and PA and between sarcopenia risk and sedentary time. CONCLUSION: Functional capacity and autonomous motivation to exercise are the most promising targets of interventions to improve PA levels and sedentary time in post-HTx patients. Furthermore, frailty and sarcopenia risk were found to mediate the effects of several other factors on PA and sedentary time.
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Fragilidad , Trasplante de Corazón , Sarcopenia , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Estudios Transversales , Ejercicio Físico/psicologíaRESUMEN
AIMS: Patients with heart failure (HF) can exhibit kinesiophobia, an excessive, debilitating, and irrational fear of movement. This study aimed to enhance the understanding of kinesiophobia in patients with HF by analysing associations with the following variables: musculoskeletal pain, quality of life, quality of sleep, functional capacity, disability, frailty, sex, and age. METHODS AND RESULTS: In this cross-sectional study, 107 participants were included, with ages ranging from 28 to 97 years (57% men, mean age 73.18 ± 12.68 years). Multiple regression analyses were performed with all variables, including polynomial regressions for variables with a non-linear relationship. Kinesiophobia was significantly correlated (P < 0.01) with musculoskeletal pain, quality of life, quality of sleep, functional capacity, disability, and being at risk of frailty, while age and sex were not statistically significant. Frailty disability and musculoskeletal pain intensity were variables linearly associated with kinesiophobia, while quality of sleep and disability had a non-linear relationship with kinesiophobia. CONCLUSION: Kinesiophobia needs to be evaluated and better understood in patients with HF to improve physical activity and exercise adherence. This study found that musculoskeletal pain intensity, quality of sleep, disability, and frailty risk have a significant association with kinesiophobia in patients with HF. Our results suggest multi-dimensional associations of kinesiophobia in patients with HF, which require further examination and understanding.
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Fragilidad , Insuficiencia Cardíaca , Dolor Musculoesquelético , Trastornos Fóbicos , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Trastornos Fóbicos/diagnóstico , Kinesiofobia , Calidad de Vida , Estudios Transversales , Insuficiencia Cardíaca/complicacionesRESUMEN
AIMS: Iron deficiency (ID) is associated with an impaired cardiac function and remodelling in heart failure (HF). Treatment with ferric carboxymaltose (FCM) has been showed recently to improve biventricular systolic function and ventricular strain parameters in patients with HF with reduced ejection fraction and ID, but there is no evidence on the benefit of FCM on the left atrium (LA). In this study, we aimed to evaluate the effect of FCM on LA longitudinal strain (LA-LS). METHODS AND RESULTS: This is a post hoc subanalysis of a double-blind, placebo-controlled, randomized clinical trial that enrolled 53 ambulatory patients with HF, left ventricular ejection fraction (LVEF) < 50%, and ID [Myocardial-IRON trial (NCT03398681)], treated with FCM or placebo. Cardiac magnetic resonance-featured tracking (CMR-FT) strain changes were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. The median age of the sample was 68 years (interquartile range: 64-76), and 20 (69%) were men. Mean ± standard deviation of LVEF was 39 ± 11%, and most (97%) were in stable New York Heart Association class II. At baseline, mean LA-LS was -8.9 ± 3.5%. At 30 days, and compared with placebo, LA-LS significantly improved in those allocated to FCM treatment arm (LA-LS = -12.0 ± 0.5 and -8.5 ± 0.6, respectively; - ∆ 3.55%, P < 0.001). CONCLUSIONS: In patients with stable HF, LVEF < 50%, and ID, treatment with FCM was associated with short-term improvements in LA-LS assessed by CMR-FT. Future works should assess the potential benefit of iron repletion on LA function.
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Compuestos Férricos , Insuficiencia Cardíaca , Deficiencias de Hierro , Maltosa/análogos & derivados , Masculino , Humanos , Anciano , Femenino , Volumen Sistólico , Función Ventricular Izquierda , Atrios CardíacosRESUMEN
INTRODUCTION AND OBJECTIVES: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. METHODS: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. RESULTS: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients' clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). CONCLUSIONS: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations.
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Insuficiencia Cardíaca , Trasplante de Corazón , Piridazinas , Humanos , Simendán/uso terapéutico , Cardiotónicos/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/cirugía , Hidrazonas/uso terapéutico , Piridazinas/uso terapéuticoRESUMEN
We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.
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Inhibidores de la Calcineurina , Rechazo de Injerto/etiología , Trasplante de Corazón , Inmunosupresores/uso terapéutico , Anciano , Proliferación Celular/efectos de los fármacos , Everolimus , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Sirolimus/análogos & derivados , Sirolimus/uso terapéutico , España/epidemiología , Tasa de SupervivenciaRESUMEN
OBJECTIVES: The aim of the study was to combine clinical results from the European Cohort of the REVERSE study and costs associated with the addition of cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular dysfunction and markers of cardiac dyssynchrony in Spain. METHODS: A Markov model was developed with CRT + OMT (CRT-ON) versus OMT only (CRT-OFF) based on a retrospective cost-effectiveness analysis. Raw data was derived from literature and expert opinion, reflecting clinical and economic consequences of patient's management in Spain. Time horizon was 10 years. Both costs (euro 2010) and effects were discounted at 3 percent per annum. RESULTS: CRT-ON showed higher total costs than CRT-OFF; however, CRT reduced the length of hospitalization in ICU by 94 percent (0.006 versus 0.091 days) and general ward in by 34 percent (0.705 versus 1.076 days). Surviving CRT-ON patients (88.2 percent versus 77.5 percent) remained in better functional class longer, and they achieved an improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years (QALYs). CRT-ON proved to be cost-effective after 6 years, except for the 7th year due to battery depletion. At 10 years, the results were 18,431 per LYG and 21,500 per QALY gained. Probabilistic sensitivity analysis showed CRT-ON was cost-effective in 75.4 percent of the cases at 10 years. CONCLUSIONS: The use of CRT added to OMT represents an efficient use of resources in patients suffering from heart failure in NYHA functional classes I and II.
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Terapia de Resincronización Cardíaca/economía , Insuficiencia Cardíaca/terapia , Análisis Costo-Beneficio , Europa (Continente) , Insuficiencia Cardíaca/clasificación , Humanos , Cadenas de Markov , Estudios Retrospectivos , España , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty-four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non-diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3-phophate dehydrogenase up-regulation in both ICM and DCM, and alpha-crystallin B down-regulation in both ICM and DCM. Heat shock 70 protein 1 was up-regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression.
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Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/fisiopatología , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Proteoma/análisis , Adulto , Western Blotting , Regulación hacia Abajo , Electroforesis en Gel Bidimensional , Femenino , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/genética , Gliceraldehído 3-Fosfato Deshidrogenasa (NADP+)/metabolismo , Proteínas del Choque Térmico HSP72/genética , Proteínas del Choque Térmico HSP72/metabolismo , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Espectrometría de Masas , Microscopía Fluorescente , Persona de Mediana Edad , Proteómica , Regulación hacia Arriba , Cadena B de alfa-Cristalina/genética , Cadena B de alfa-Cristalina/metabolismoRESUMEN
Downregulation of ß(1)- adrenergic receptors (ß(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α(1A), α(1B), α(1D), ß(1), ß(2), and ß(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the α(1A)-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) ß(1)-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC.
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Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Quinasas de Receptores Acoplados a Proteína-G/genética , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Isquemia Miocárdica/complicaciones , Miocardio/química , Receptores Adrenérgicos/análisis , Adulto , Análisis de Varianza , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/genética , Cardiomiopatías/fisiopatología , Cardiomiopatía Dilatada/tratamiento farmacológico , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/fisiopatología , Femenino , Genotipo , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Fenotipo , ARN Mensajero/análisis , Receptores Adrenérgicos/genética , España , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial ß-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale. METHODS: We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples. RESULTS: In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in ß-agonist-treated patients (vs ß-blockers: P < .05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P < .05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings. CONCLUSIONS: Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.
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Quinasas de Receptores Acoplados a Proteína-G/genética , Insuficiencia Cardíaca/enzimología , Miocardio/enzimología , Regulación hacia Abajo , Femenino , Quinasa 2 del Receptor Acoplado a Proteína-G/genética , Quinasa 5 del Receptor Acoplado a Proteína-G/genética , Quinasas de Receptores Acoplados a Proteína-G/química , Quinasas de Receptores Acoplados a Proteína-G/metabolismo , Regulación Enzimológica de la Expresión Génica , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Corazón Auxiliar , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Sistema de Registros , Índice de Severidad de la Enfermedad , EspañaRESUMEN
BACKGROUND: Congenital heart diseases (CHDs) have high infant mortality in their severe forms. When adulthood is reached, a heart transplant (HTx) may be required. Spanish adult population transplanted for CHD was analyzed and compared with the most frequent causes of HTx and between different subgroups of CHD. MATERIALS AND METHODS: A total of 6048 patients (HTx 1984-2009) were included. Pediatric transplants (<15 yr), combined transplants, reHTx, and HTx for heart diseases other than idiopathic dilated cardiomyopathy (IDCM) and ischemic heart disease (IHD) were excluded. Total patients included: 3166 (IHD = 1888; IDCM = 1223; CHD = 55). Subgroups were studied as follows: (1) single ventricle with pulmonary stenosis (n = 18), (2) single ventricle with tricuspid atresia and Glenn/Fontan surgery (n = 10), (3) congenitally corrected transposition of the great vessels (TGV) or with switch atrial surgery (n = 10), and (4) CHD with right ventricle overload (n = 17). RESULTS: Survival probability was different between groups (p = 0.0001). Post hoc analysis showed some differences between groups (CHD vs. IHD, p = 0.05; CHD vs. IDCM, p = 0.5; IHD vs. IDCM, p = 0.0001). Early mortality was different between CHD subgroups (group 1 = 19%, group 2 = 40%, group 3 = 0%, group 4 = 29%; p < 0.001); however, overall mortality did not show differences between subgroups (p = 0.5). CONCLUSIONS: The percentage of Spanish adult HTx patients for CHD is low (1%). The survival curve is better than for other HTx causes (IHD). Nevertheless, early mortality was higher, particularly in some subgroups (Fontan).
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Cardiopatías Congénitas/mortalidad , Trasplante de Corazón/mortalidad , Adulto , Femenino , Estudios de Seguimiento , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Sistema de Registros , Tasa de SupervivenciaRESUMEN
BACKGROUND: From clinical experience, kinesiophobia represents a barrier to being physically active after a heart transplantation (HTx), but studies in this field are lacking. Identifying the factors associated with kinesiophobia is essential to determine preventive interventions to avoid negative consequences for health. AIMS: To study the influence of disability, physical, and behavioural variables on kinesiophobia in patients with an HTx. METHODS: A total of 117 patients with an HTx [51 women; mean age 56 (SD 12.1) years] were recruited at an outpatient clinic. These patients were asked to fill in questionnaires measuring kinesiophobia, self-reported physical activity (PA), exercise self-efficacy, motivation for PA, and disability. A multiple regression analysis was conducted to examine the statistical prediction of kinesiophobia as a dependent variable, with the questionnaires, gender and education as independent variables. RESULTS: The independent variables explained 70% of the variance in kinesiophobia. The prediction model was significant (F = 32.1, P < 0.001). The time from transplantation (standardised coefficient, beta; -0.17), the total exercise self-efficacy (-0.16), extrinsic motivation (-0.23), and the disability total score (0.63) were significant predictors of kinesiophobia, while the independent variables of gender, education, intrinsic motivation, and the PA total score were not significant. CONCLUSIONS: This study highlights that a short time from transplantation, low self-efficacy, low extrinsic motivation, and a high level of disability explained high levels of kinesiophobia in patients after an HTx. These results suggest that an increased awareness of the biopsychosocial health perspective is essential in order to maximising patient outcomes after an HTx.
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Personas con Discapacidad , Trasplante de Corazón , Ejercicio Físico , Miedo , Femenino , Humanos , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The aim of this study was to explore the readiness for physical activity (PA) and its related factors in patients with heart failure. This cross-sectional study included 163 patients with heart failure (mean age 66 ± 16, 50% female). The ability to safely engage in PA was assessed with the PA Readiness Questionnaire (PAR-Q). Psychological readiness was measured using two questionnaires, namely: Exercise Self-efficacy Scale and the Motivation for PA and Exercise/Working Out. A multivariate analysis of covariance was conducted to test the effect of background variables on readiness for PA. 64% (n = 105) of patients reported not being able to safely engage in PA, 80% (n = 129) reported low self-efficacy, and 45% (n = 74) were extrinsically motivated indicating external factors drove their motivation. Factors that positively influenced the PA readiness included lower age (p < 0.01), being male (p < 0.01), being married (p < 0.01), having higher education (p < 0.01), being in NYHA-class I compared with II (p < 0.01), less time since diagnosis (p < 0.01), lower BMI (p = 0.02), and not suffering from COPD (p = 0.02). Prior to recommending exercise, assessment of safety to engage in PA along with self-efficacy and motivation in patients with heart failure is essential.
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Ejercicio Físico , Insuficiencia Cardíaca , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Ejercicio Físico/psicología , Autoeficacia , Motivación , Encuestas y CuestionariosRESUMEN
The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61-105.69) vs. 35.33 ng/mL (IQR, 19.18-64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.