RESUMEN
AIMS: This study aimed to identify the impact of increased epicardial adipose tissue (EAT) and its regional distribution on cardiac function in patients with diastolic dysfunction. METHODS AND RESULTS: Sixty-eight patients with exertional dyspnoea (New York Heart Association ≥II), preserved ejection fraction (≥50%), and diastolic dysfunction (E/e' ≥ 8) underwent rest and stress right heart catheterization, transthoracic echocardiography, and cardiovascular magnetic resonance (CMR). EAT volumes were depicted from CMR short-axis stacks. First, the impact of increased EAT above the median was investigated. Second, the association of ventricular and atrial EAT with myocardial deformation at rest and during exercise stress was analysed in a multivariable regression analysis. Patients with high EAT had higher HFA-PEFF and H2FPEFF scores as well as N-terminal prohormone of brain natriuretic peptide levels (all P < 0.048). They were diagnosed with manifest heart failure with preserved ejection fraction (HFpEF) more frequently (low EAT: 37% vs. high EAT: 64%; P = 0.029) and had signs of adverse remodelling indicated by higher T1 times (P < 0.001). No differences in biventricular volumetry and left ventricular mass (all P > 0.074) were observed. Patients with high EAT had impaired atrial strain at rest and during exercise stress, and impaired ventricular strain during exercise stress. Regionally increased EAT was independently associated with functional impairment of the adjacent chambers. CONCLUSIONS: Patients with diastolic dysfunction and increased EAT show more pronounced signs of diastolic functional failure and adverse structural remodelling. Despite similar morphological characteristics, patients with high EAT show significant cardiac functional impairment, in particular in the atria. Our results indicate that regionally increased EAT directly induces atrial functional failure, which represents a distinct pathophysiological feature in HFpEF.
Asunto(s)
Tejido Adiposo , Diástole , Imagen por Resonancia Cinemagnética , Pericardio , Volumen Sistólico , Humanos , Masculino , Femenino , Pericardio/diagnóstico por imagen , Pericardio/fisiopatología , Tejido Adiposo/fisiopatología , Tejido Adiposo/diagnóstico por imagen , Imagen por Resonancia Cinemagnética/métodos , Volumen Sistólico/fisiología , Persona de Mediana Edad , Anciano , Función Ventricular Izquierda/fisiología , Ecocardiografía , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/diagnóstico , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Estudios de Seguimiento , Cateterismo Cardíaco , Tejido Adiposo EpicárdicoAsunto(s)
Insuficiencia Cardíaca Diastólica , Defectos del Tabique Interatrial , Hipertensión Arterial Pulmonar , Humanos , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/diagnóstico , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/fisiopatología , Defectos del Tabique Interatrial/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/diagnóstico , Femenino , Persona de Mediana EdadRESUMEN
La insuficiencia cardíaca con fracción de eyección preservada (ICFEp) y reducida presentan marcadas diferencias. Mientras que la última tiene un algoritmo diagnóstico y terapéutico desde hace años, con guías y fármacos que mejoran su pronóstico, la ICFEp no solo presenta dificultades para llegar al diagnóstico, sino que tampoco hay fármacos que hayan demostrado disminuir la mortalidad. En esta revisión se hace un abordaje amplio de la ICFEp, comenzando por definirla y distinguirla de la disfunción diastólica. Se describe el gold standard para su diagnóstico invasivo y se analizan los scores no invasivos recientemente desarrollados que estiman la probabilidad de tener la enfermedad. A través del análisis de las comorbilidades frecuentemente asociadas, se describen los mecanismos fisiopatológicos implicados. Asimismo, se detallan los fenotipos propuestos para agrupar pacientes y diseñar ensayos clínicos con fármacos que prueben disminuir la mortalidad. Por último, se reseñan las medidas terapéuticas no farmacológicas y farmacológicas recomendadas.
Heart failure with preserved and reduced ejection fraction have significant differences. While the latter has had a diagnostic and therapeutic algorithm for years, with guidelines and drugs that improve its prognosis, heart failure with preserved ejection fraction (HFpEF) not only presents difficulties in reaching a diagnosis, but also there are no drugs that have been proven to be effective in reducing mortality. In this review, a broad approach to HFpEF is made, beginning by defining it and distinguishing it from diastolic dysfunction. The gold standard for its invasive diagnosis is described and recently developed non-invasive scores that estimate the probability of having the disease are analyzed. Through the analysis of the frequently associated comorbidities, the pathophysiological mechanisms involved are described. Likewise, the phenotypes proposed to group patients and design clinical trials with drugs that try to reduce mortality are detailed. Finally, the recommended non-pharmacological and pharmacological therapeutic measures are outlined.
A insuficiência cardíaca com fração de ejeção preservada (ICFEp) e reduzida apresentam diferenças marcantes. Enquanto esta última conta com um algoritmo diagnóstico e terapêutico há anos, com diretrizes e medicamentos que melhoram seu prognóstico, a ICFEp não só apresenta dificuldades no diagnóstico, mas nenhum há medicamentos que tenham demonstrado reduzir a mortalidade. Nesta revisão, é feita uma abordagem ampla da ICFEp, começando por defini-la e distinguindo-a da disfunção diastólica. O padrão ouro para seu diagnóstico invasivo é descrito e são analisados os escores não invasivos recentemente desenvolvidos que estimam a probabilidade de ter a doença. Através da análise de comorbidades frequentemente associadas, são descritos os mecanismos fisiopatológicos envolvidos. Da mesma forma, são detalhados os fenótipos propostos para agrupar pacientes e desenhar ensaios clínicos com medicamentos que podem ser mostradas para reduzir a mortalidade. Por fim, são delineadas as medidas terapêuticas não farmacológicas e farmacológicas recomendadas.
Asunto(s)
Humanos , Insuficiencia Cardíaca Diastólica/fisiopatología , Factores de Riesgo , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/terapiaRESUMEN
BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.
Asunto(s)
Angioplastia Coronaria con Balón , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca Sistólica , Factores de Edad , Anciano , Angioplastia Coronaria con Balón/métodos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Angiografía Coronaria/métodos , Angiografía Coronaria/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Femenino , Francia/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/etiología , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Volumen SistólicoRESUMEN
The objective is to define the clinical echocardiographic characteristics and cardiovascular outcome in patients with acute heart failure (HF) with versus without diabetes mellitus (DM). Demographic, clinical, laboratory, and echocardiographic data were collected in Olmsted County adults hospitalized for acute HF between 2005 and 2008. Analyses were performed for mortality and acute HF hospitalization outcomes stratified by diabetic status, systolic function, and diastolic function. There were 912 subjects who met inclusion criteria, and mean age was 79 (SD 13.1) years with 53% women. Prevalence of DM was 42% in the study population, and those with DM had worse diastolic function and increased mortality and HF rehospitalization. Among those with DM and acute HF, reduced left ventricular ejection fraction and worse diastolic function conferred increased HF rehospitalization (p = 0.010 and p = 0.022, respectively). In conclusion, DM is common in those hospitalized for acute HF and is associated with worse long-term clinical outcomes. The subgroup of DM with acute HF and left ventricular systolic dysfunction or diastolic dysfunction had worse HF rehospitalization outcomes.
Asunto(s)
Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Mortalidad , Volumen Sistólico , Disfunción Ventricular Izquierda/fisiopatología , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca Diastólica/epidemiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/epidemiología , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , MasculinoRESUMEN
AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.
Asunto(s)
Insuficiencia Cardíaca Diastólica , Insuficiencia Cardíaca Sistólica , Diálisis Renal , Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Anciano , Brasil/epidemiología , Ecocardiografía Doppler/métodos , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/epidemiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/epidemiología , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).
Asunto(s)
Insuficiencia Cardíaca Diastólica , Ubiquinona/análogos & derivados , Anciano , Método Doble Ciego , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Diastólica/terapia , Humanos , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Estudios Prospectivos , Volumen Sistólico/efectos de los fármacos , Ubiquinona/farmacología , Ubiquinona/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.
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Inductores de la Angiogénesis/uso terapéutico , Vasos Coronarios/efectos de los fármacos , Terapia Genética , Insuficiencia Cardíaca Diastólica/terapia , Insuficiencia Cardíaca Sistólica/terapia , Microvasos/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Vacunas/uso terapéutico , Inductores de la Angiogénesis/efectos adversos , Animales , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/fisiopatología , Terapia Genética/efectos adversos , Insuficiencia Cardíaca Diastólica/genética , Insuficiencia Cardíaca Diastólica/metabolismo , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/genética , Insuficiencia Cardíaca Sistólica/metabolismo , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Microcirculación/efectos de los fármacos , Microvasos/metabolismo , Microvasos/fisiopatología , ARN no Traducido/genética , ARN no Traducido/metabolismo , Recuperación de la Función , Vacunas/efectos adversos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Heart failure with preserved ejection fraction (HFpEF) is a complex disease associated with multiple co-morbidities, where impaired cardiac mechanics are often the end effect. At the cellular level, cardiac mechanics can be pharmacologically manipulated by altering calcium signalling and the sarcomere. However, the link between cellular level modulations and whole organ pump function is incompletely understood. Our goal is to develop and use a multi-scale computational cardiac mechanics model of the obese ZSF1 HFpEF rat to identify important biomechanical mechanisms that underpin impaired cardiac function and to predict how whole-heart mechanical function can be recovered through altering cellular calcium dynamics and/or cellular contraction. The rat heart was modelled using a 3D biventricular biomechanics model. Biomechanics were described by 16 parameters, corresponding to intracellular calcium transient, sarcomere dynamics, cardiac tissue and hemodynamics properties. The model simulated left ventricular (LV) pressure-volume loops that were described by 14 scalar features. We trained a Gaussian process emulator to map the 16 input parameters to each of the 14 outputs. A global sensitivity analysis was performed, and identified calcium dynamics and thin and thick filament kinetics as key determinants of the organ scale pump function. We employed Bayesian history matching to build a model of the ZSF1 rat heart. Next, we recovered the LV function, described by ejection fraction, peak pressure, maximum rate of pressure rise and isovolumetric relaxation time constant. We found that by manipulating calcium, thin and thick filament properties we can recover 34%, 28% and 24% of the LV function in the ZSF1 rat heart, respectively, and 39% if we manipulate all of them together. We demonstrated how a combination of biophysically based models and their derived emulators can be used to identify potential pharmacological targets. We predicted that cardiac function can be best recovered in ZSF1 rats by desensitising the myofilament and reducing the affinity to intracellular calcium concentration and overall prolonging the sarcomere staying in the active force generating state.
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Calcio/metabolismo , Insuficiencia Cardíaca Diastólica , Sarcómeros/metabolismo , Función Ventricular Izquierda/fisiología , Animales , Teorema de Bayes , Biología Computacional , Insuficiencia Cardíaca Diastólica/metabolismo , Insuficiencia Cardíaca Diastólica/fisiopatología , Hemodinámica/fisiología , Modelos Cardiovasculares , Obesidad , RatasRESUMEN
[Figure: see text].
Asunto(s)
Presión Sanguínea/fisiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Frecuencia Cardíaca/fisiología , Pierna/irrigación sanguínea , Microvasos/fisiopatología , Músculo Esquelético/fisiopatología , Anciano , Femenino , Humanos , Masculino , Flujo Sanguíneo Regional/fisiología , Volumen Sistólico/fisiologíaRESUMEN
Rheumatoid arthritis (RA) carries a twofold increased incidence of heart failure with preserved ejection fraction, accompanied by diastolic dysfunction, which can lead to death. The causes of diastolic dysfunction are unknown, and there are currently no well-characterized animal models for studying these mechanisms. Current medications for RA do not have marked beneficial cardio-protective effects. K/BxN F1 progeny and KRN control mice were analyzed over time for arthritis development, monitoring left ventricular diastolic and systolic function using echocardiography. Excised hearts were analyzed by flow cytometry, qPCR, and histology. In pharmacological experiments, K/BxN F1 mice were treated with human recombinant AnxA1 (hrAnxA1, 1 µg/mouse) or vehicle daily. K/BxN F1 mice exhibited fully developed arthritis with normal cardiac function at 4 wk; however, by week 8, all mice displayed left ventricular diastolic dysfunction with preserved ejection fraction. This dysfunction was associated with cardiac hypertrophy, myocardial inflammation and fibrosis, and inflammatory markers. Daily treatment of K/BxN F1 mice with hrAnxA1 from weeks 4 to 8 halted progression of the diastolic dysfunction. The treatment reduced cardiac transcripts of proinflammatory cytokines and profibrotic markers. At the cellular level, hrAnxA1 decreased activated T cells and increased MHC IIlow macrophage infiltration in K/BxN F1 hearts. Similar effects were obtained when hrAnxA1 was administered from week 8 to week 15. We describe an animal model of inflammatory arthritis that recapitulates the cardiomyopathy of RA. Treatment with hrAnxA1 after disease onset corrected the diastolic dysfunction through modulation of both fibroblast and inflammatory cell phenotype within the heart.
Asunto(s)
Anexina A1/metabolismo , Artritis Reumatoide/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Animales , Anexina A1/farmacología , Anexina A1/fisiología , Artritis Reumatoide/complicaciones , Cardiomiopatías/patología , Diástole , Modelos Animales de Enfermedad , Corazón/fisiopatología , Cardiopatías/patología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/fisiopatología , Ventrículos Cardíacos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Miocardio/patología , Volumen Sistólico/efectos de los fármacos , Disfunción Ventricular Izquierda/etiología , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with sex-specific pathophysiology. Estrogen deficiency is believed to be responsible for the development of HFpEF in women. However, estrogen deficiency does not seem to be completely responsible for the differences in HFpEF prevalence between sexes. While diabetes mellitus (DM) frequently coexists with HFpEF in women and is associated with worse outcomes, the changes in myocardial contractility among women with HFpEF and the DM phenotype is yet unknown. Therefore, we aimed to investigate sex-related differences in left ventricular (LV) contractility dysfunction in HFpEF comorbid with DM. METHODS: A total of 224 patients who underwent cardiac cine MRI were included in this study. Sex-specific differences in LV structure and function in the context of DM were determined. LV systolic strains (global longitudinal strain [GLS], circumferential strain [GCS] and radial strain [GRS]) were measured using cine MRI. The determinants of impaired myocardial strain for women and men were assessed. RESULTS: The prevalence of DM did not differ between sexes (p > 0.05). Despite a similar LV ejection fraction, women with DM demonstrated a greater LV mass index than women without DM (p = 0.023). The prevalence of LV geometry patterns by sex did not differ in the non-DM subgroup, but there was a trend toward a more abnormal LV geometry in women with DM (p = 0.072). The magnitudes of systolic strains were similar between sexes in the non-DM group (p > 0.05). Nevertheless, in the DM subgroup, there was significant impairment in women in systolic strains compared with men (p < 0.05). In the multivariable analysis, DM was associated with impaired systolic strains in women (GLS [ß = 0.26; p = 0.007], GCS [ß = 0.31; p < 0.001], and GRS [ß = -0.24; p = 0.016]), whereas obesity and coronary artery disease were associated with impaired systolic strains in men (p < 0.05). CONCLUSIONS: Women with DM demonstrated greater LV contractile dysfunction, which indicates that women with HFpEF comorbid with DM have a high-risk phenotype of cardiac failure that may require more aggressive and personalized medical treatment.
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Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca Diastólica/epidemiología , Contracción Miocárdica , Disfunción Ventricular Izquierda/epidemiología , Función Ventricular Izquierda , Anciano , China/epidemiología , Comorbilidad , Diabetes Mellitus/diagnóstico , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico por imagen , Insuficiencia Cardíaca Diastólica/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Medición de Riesgo , Factores de Riesgo , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.
Asunto(s)
Tolerancia al Ejercicio , Insuficiencia Cardíaca Diastólica/fisiopatología , Envejecimiento/fisiología , Animales , HumanosRESUMEN
Preclinical diastolic dysfunction (PDD) results in impaired cardiorenal response to volume load (VL) which may contribute to the progression to clinical heart failure with preserved ejection fraction (HFpEF). The objective was to evaluate if phosphodiesterase V inhibition (PDEVI) alone or combination PDEVI plus B-type natriuretic peptide (BNP) administration will correct the impaired cardiorenal response to VL in PDD. A randomized double-blinded placebo-controlled cross-over study was conducted in 20 subjects with PDD, defined as left ventricular ejection fraction (LVEF) >50% with moderate or severe diastolic dysfunction by Doppler echocardiography and without HF diagnosis or symptoms. Effects of PDEVI with oral tadalafil alone and tadalafil plus subcutaneous (SC) BNP, administered prior to acute volume loading, were assessed. Tadalafil alone did not result in improvement in cardiac response to VL, as measured by LVEF, LV end diastolic volume, left atrial volume (LAV), or right ventricular systolic pressure (RVSP). Tadalafil plus SC BNP resulted in improved cardiac response to VL, with increased LVEF (4.1 vs. 1.8%, p = 0.08) and heart rate (4.3 vs. 1.6 bpm, p = 0.08), and reductions in both LAV (-4.3 ± 10.4 vs. 2.8 ± 6.6 ml, p = 0.03) and RVSP (-4.0 ± 3.0 vs. 2.1 ± 6.0 mmHg, p < 0.01) versus tadalafil alone. Plasma and urinary cyclic guanosine monophosphate (cGMP) excretion levels were higher (11.3 ± 12.3 vs. 1.7 ± 3.8 pmol/ml, 1851.0 ± 1386.4 vs. 173.4 ± 517.9 pmol/min, p < 0.01) with tadalafil plus SC BNP versus tadalafil alone. There was no improvement in renal response as measured by GFR, renal plasma flow, sodium excretion, and urine flow with tadalafil plus SC BNP compared to tadalafil alone. In subjects with PDD, tadalafil alone resulted in no improvement in cardiac adaptation, while tadalafil and SC BNP resulted in enhanced cardiac adaptation to VL. TRIAL REGISTRATION: ClinicalTrials.gov NCT01544998.
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Insuficiencia Cardíaca Diastólica/tratamiento farmacológico , Péptido Natriurético Encefálico/uso terapéutico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Tadalafilo/uso terapéutico , Anciano , Anciano de 80 o más Años , GMP Cíclico/sangre , GMP Cíclico/orina , Combinación de Medicamentos , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca Diastólica/fisiopatología , Humanos , Masculino , Contracción Miocárdica , Péptido Natriurético Encefálico/administración & dosificación , Péptido Natriurético Encefálico/efectos adversos , Péptido Natriurético Encefálico/farmacocinética , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Inhibidores de Fosfodiesterasa 5/efectos adversos , Inhibidores de Fosfodiesterasa 5/farmacocinética , Eliminación Renal , Tadalafilo/administración & dosificación , Tadalafilo/efectos adversos , Tadalafilo/farmacocinéticaAsunto(s)
Disnea/diagnóstico por imagen , Prueba de Esfuerzo/métodos , Ejercicio Físico/fisiología , Insuficiencia Cardíaca Diastólica/diagnóstico por imagen , Anciano , Disnea/etiología , Disnea/fisiopatología , Electrocardiografía/métodos , Insuficiencia Cardíaca Diastólica/complicaciones , Insuficiencia Cardíaca Diastólica/fisiopatología , Humanos , Masculino , Consumo de Oxígeno/fisiologíaRESUMEN
BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.
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Insuficiencia Cardíaca Diastólica/sangre , Admisión del Paciente , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/mortalidad , Insuficiencia Cardíaca Diastólica/fisiopatología , Humanos , Japón , Masculino , Concentración Osmolar , Readmisión del Paciente , Pronóstico , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). BACKGROUND: Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. METHODS: Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. RESULTS: Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). CONCLUSIONS: AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.
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Fibrilación Atrial/fisiopatología , Tolerancia al Ejercicio , Insuficiencia Cardíaca Diastólica/fisiopatología , Hemodinámica , Insuficiencia de la Válvula Tricúspide/fisiopatología , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico , Cateterismo Cardíaco , Estudios de Casos y Controles , Enfermedad Crónica , Prueba de Esfuerzo , Femenino , Estado Funcional , Insuficiencia Cardíaca Diastólica/diagnóstico , Insuficiencia Cardíaca Diastólica/etiología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Insuficiencia de la Válvula Tricúspide/diagnóstico , Insuficiencia de la Válvula Tricúspide/etiologíaRESUMEN
OBJECTIVE: To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM). BACKGROUND: Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized. METHODS: In this single-centre, observational, cross-sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme-linked immunosorbent sandwich assay (ELISA). RESULTS: After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern. CONCLUSIONS: Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM.
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Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Restrictiva/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Activación Neutrófila , Anciano , Biomarcadores/metabolismo , Cardiomiopatía Dilatada/diagnóstico por imagen , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Cardiomiopatía Restrictiva/diagnóstico por imagen , Cardiomiopatía Restrictiva/etiología , Cardiomiopatía Restrictiva/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/fisiopatología , Ecocardiografía , Femenino , Insuficiencia Cardíaca Diastólica/diagnóstico por imagen , Insuficiencia Cardíaca Diastólica/etiología , Insuficiencia Cardíaca Diastólica/metabolismo , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/diagnóstico por imagen , Insuficiencia Cardíaca Sistólica/etiología , Insuficiencia Cardíaca Sistólica/metabolismo , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Masculino , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Peroxidasa/metabolismo , Resistina/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
BACKGROUND: Evidence of diastolic dysfunction (DD) required for the diagnosis of heart failure with preserved ejection fraction (HFpEF) is elusive in atrial fibrillation (AF). Left ventricular (LV) and left atrial (LA) speckle-tracking echocardiography (STE) may provide rhythm independent indications of DD. We aimed to find common LV/LA myocardial mechanics parameters to demonstrate DD, using STE in patients with AF. METHODS: 176 echocardiographic assessments of patients were studied retrospectively by STE. 109 patients with history of AF were divided in three groups: sinus with normal diastolic function (n = 32, ND), sinus with DD (n = 35, DD) and patients with AF during echocardiography (n = 42). These assessments were compared to 67 normal controls. Demographic, clinical, echocardiographic and myocardial mechanic characteristics were obtained. RESULTS: The patients with DD in sinus rhythm and patients with AF were similar in age, mostly women, and had cardiovascular risk factors as well as higher dyspnea prevalence compared to either controls or patients with ND. In the AF group, LV ejection fraction (LVEF) (p = 0.008), global longitudinal strain and LA emptying were lower (p < 0.001), whereas LA volumes were larger (p < 0.001) compared to the other groups. In a multivariable analysis of patients in sinus rhythm, LA minimal volume indexed to body surface area (Vmin-I) was found to be the single significant factor associated with DD (AUC 83%). In all study patients, Vmin-I correlated with dyspnea (AUC 80%) and pulmonary hypertension (AUC 90%). CONCLUSIONS: Vmin-I may be used to identify DD and assist in the diagnosis of HFpEF in patients with AF.