RESUMEN
INTRODUCTION: We have previously reported that genetically positive patients have a more profound early decrease in provocable left ventricular outflow tract gradient compared to genetically negative patients utilizing mavacamten in the first 12 weeks of therapy. METHODS AND RESULTS: In this current analysis, we found that genetically positive patients have less favorable remodeling as measured by left ventricular wall thickness regression when evaluated long-term as compared to genetically negative patients, despite an overall better early response to mavacamten. The majority of genetically positive patients were maintained on only 2.5 mg of mavacamten due to early robust response. CONCLUSION: We hypothesize that this lower dosing attenuated the long-term benefit of mavacamten in genetically positive patients. We believe that the long-term benefit of mavacamten on positive cardiac remodeling is dose-dependent and not solely related to the magnitude of left ventricular outflow gradient decrease.
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Remodelación Ventricular , Humanos , Remodelación Ventricular/efectos de los fármacos , Remodelación Ventricular/genética , Masculino , Femenino , Estudios de Seguimiento , Persona de Mediana Edad , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Resultado del Tratamiento , Factores de Tiempo , Bencilaminas , Uracilo/análogos & derivadosRESUMEN
BACKGROUND: Supraventricular extra beats (SVEB) are frequently observed in athletes but data on significance, prognostic role and correlation with cardiac remodeling are contrasting. It is uncertain whether SVEB may indicate the development of more complex arrhythmias and the need for closer monitoring is undetermined. The aim was to assess the prevalence and clinical significance of BESV in Olympic athletes of different sporting disciplines, evaluating potential correlations with cardiac remodeling and clinical features. METHODS: We enrolled athletes who participated at 2012-2022 Olympic Games, submitted to physical examination, blood tests, echocardiography and exercise tests, categorized into power, skills, endurance and mixed disciplines. RESULTS: We studied 1492 elite athletes: 56% male individuals, mean age 25.8â±â5.1âyears; 29.5% practiced power, 12.3% skills, 21% endurance and 37.2% mixed disciplines. At exercise-stress tests, 6.2% had SVEB, mostly single beats. SVEB were not influenced by anthropometrics or blood test results. They were more common in male individuals (77.4 vs. 54.6%, Pâ<â0.0001) and older athletes (27.1â±â5.7 vs. 25.7â±â5.1, Pâ=â0.01). In male athletes with SVEB, higher left atrial volumes were observed (24.2â±â7.3 vs. 22.2â±â7.1âml/m2, Pâ=â0.03). No differences were found in terms of sporting discipline: despite larger left atrial dimensions in aerobic disciplines, SVEB rates were similar in different sporting disciplines (6.1% endurance, 6.3% mixed, 5.2% power and 8.7% skills; Pâ=â0.435). CONCLUSION: SVEB were more common in older, male athletes and associated with higher left atrial volume (especially in male individuals) regardless of sport practiced. Athletes with greater left atrial volume and SVEB are supposed to have higher risk, in middle age, of developing more complex arrhythmias.
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Atletas , Humanos , Masculino , Adulto , Atletas/estadística & datos numéricos , Adulto Joven , Femenino , Prevalencia , Deportes/fisiología , Deportes/estadística & datos numéricos , Remodelación Ventricular , Complejos Atriales Prematuros/fisiopatología , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/epidemiología , Factores de Riesgo , Ecocardiografía , Frecuencia Cardíaca , Prueba de Esfuerzo , Estudios Transversales , Resistencia Física/fisiologíaRESUMEN
Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.
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Arritmias Cardíacas , Modelos Animales de Enfermedad , Arteria Pulmonar , Animales , Ratas , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Remodelación Ventricular/fisiología , Masculino , Hipertensión Pulmonar/fisiopatologíaRESUMEN
BACKGROUND: Although the "obesity paradox" is comprehensively elucidated in heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), the role of body composition in left ventricular (LV) remodeling, LV reverse remodeling (LVRR), and clinical outcomes is still unclear for HF with mildly reduced ejection fraction (HFmrEF). METHODS: Our study is a single-centre, prospective, and echocardiography-based study. Consecutive HFmrEF patients, defined as HF patients with a left ventricular ejection fraction (LVEF) between 40 and 49%, between January 2016 to December 2021 were included. Echocardiography was re-examined at 3-, 6-, and 12-month follow-up to assess the LVRR dynamically. Body mass index (BMI), fat mass, fat-free mass, percent body fat (PBF), CUN-BAE index, and lean mass index (LMI) were adopted as anthropometric parameters in our study to assess body composition. The primary outcome was LVRR, defined as: (1) a reduction higher than 10% in LV end-diastolic diameter index (LVEDDI), or a LVEDDI < 33 mm/m2, (2) an absolute increase of LVEF higher than 10 points compared with baseline echocardiogram, or a follow-up LVEF ≥50%. The secondary outcome was a composite of re-hospitalization for HF or cardiovascular death. RESULTS: A total of 240 HFmrEF patients were enrolled in our formal analysis. After 1-year follow-up based on echocardiography, 113 (47.1%) patients developed LVRR. Patients with LVRR had higher fat mass (21.7 kg vs. 19.3 kg, P = 0.034) and PBF (28.7% vs. 26.6%, P = 0.047) compared with those without. The negative correlation between anthropometric parameters and baseline LVEDDI was significant (all P < 0.05). HFmrEF patients with higher BMI, fat mass, PBF, CUN-BAE index, and LMI had more pronounced and persistent increase of LVEF and decline in LV mass index (LVMI). Univariable Cox regression analysis revealed that higher BMI (HR 1.042, 95% CI 1.002-1.083, P = 0.037) and fat mass (HR 1.019, 95% CI 1.002-1.036, P = 0.026) were each significantly associated with higher cumulative incidence of LVRR for HFmrEF patients, while this relationship vanished in the adjusted model. Mediation analysis indicated that the association between BMI and fat mass with LVRR was fully mediated by baseline LV dilation. Furthermore, higher fat mass (aHR 0.957, 95% CI 0.917-0.999, P = 0.049) and PBF (aHR 0.963, 95% CI 0.924-0.976, P = 0.043) was independently associated with lower risk of adverse clinical events. CONCLUSIONS: Body composition played an important role in the LVRR and clinical outcomes for HFmrEF. For HFmrEF patients, BMI and fat mass was positively associated with the cumulative incidence of LVRR, while higher fat mass and PBF predicted lower risk of adverse clinical events but not LMI.
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Composición Corporal , Insuficiencia Cardíaca , Obesidad , Volumen Sistólico , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Obesidad/fisiopatología , Obesidad/diagnóstico , Estudios Prospectivos , Factores de Tiempo , Factores de Riesgo , Adiposidad , Medición de Riesgo , Índice de Masa Corporal , Pronóstico , EcocardiografíaRESUMEN
BACKGROUND: In acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into circulation and contribute to inflammation and adverse cardiac remodelling. We aimed to investigate gut leakage markers and their associations with inflammation, infarct size and cardiac function. METHODS: We examined 61 ST-elevation myocardial infarction (STEMI) patients who developed acute HF within 48 hours of successful percutaneous coronary intervention (PCI). Serial blood samples were taken to measure lipopolysaccharide (LPS), LPS-binding protein (LBP), soluble cluster of differentiation 14 (sCD14) and intestinal fatty acid binding protein (I-FABP). Cumulative areas under the curve (AUCs) from baseline to day 5 were calculated. Serial echocardiography was performed to assess left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and wall motion score index (WMSI). Single-photon emission CT (SPECT) was performed at 6 weeks to determine infarct size and LVEF. RESULTS: I-FABPAUC correlated positively with infarct size (rs=0.45, p=0.002), GLS (rs=0.32, p=0.035) and WMSI (rs=0.45, p=0.002) and negatively with LVEF measured by SPECT (rs=-0.40, p=0.007) and echocardiography (rs=-0.33, p=0.021) at 6 weeks. LPSAUC, LBPAUC and sCD14AUC did not correlate to any cardiac function marker or infarct size. Patients, who at 6 weeks had above median GLS and WMSI, and below-median LVEF measured by SPECT, were more likely to have above median I-FABPAUC during admission (adjusted OR (aOR) 5.22, 95% CI 1.21 to 22.44; aOR 5.05, 95% CI 1.25 to 20.43; aOR 5.67, 95% CI 1.42 to 22.59, respectively). The same was observed for patients in the lowest quartile of LVEF measured by echocardiography (aOR 9.99, 95% CI 1.79 to 55.83) and three upper quartiles of infarct size (aOR 20.34, 95% CI 1.56 to 264.65). CONCLUSIONS: In primary PCI-treated STEMI patients with acute HF, I-FABP, a marker of intestinal epithelial damage, was associated with larger infarct size and worse cardiac function after 6 weeks.
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Biomarcadores , Proteínas de Unión a Ácidos Grasos , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Función Ventricular Izquierda , Humanos , Masculino , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Función Ventricular Izquierda/fisiología , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/sangre , Volumen Sistólico/fisiología , Tomografía Computarizada de Emisión de Fotón Único , Proteínas Portadoras/sangre , Ecocardiografía/métodos , Proteínas de Fase Aguda , Glicoproteínas de Membrana/sangre , Factores de Tiempo , Receptores de Lipopolisacáridos/sangre , Enfermedad Aguda , Estudios Prospectivos , Lipopolisacáridos , Remodelación Ventricular/fisiologíaRESUMEN
Histone deacetylase 6 (HDAC6) belongs to the class IIb group of the histone deacetylase family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of HDAC6 in cardiac remodelling post-infarction. Experimental myocardial infarction (MI) was created in HDAC6-deficient (HDAC6-/-) mice and wild-type (HADC6+/+) by left coronary artery ligation. At days 0 and 14 post-MI, we evaluated cardiac function, morphology and molecular endpoints of repair and remodelling. At day 14 after surgery, the ischemic myocardium had increased levels of HADC6 gene and protein of post-MI mice compared to the non-ischemic myocardium of control mice. As compared with HDAC6-/--MI mice, HADC6 deletion markedly improved infarct size and cardiac fibrosis as well as impaired left ventricular ejection fraction and left ventricular fraction shortening. At the molecular levels, HDAC6-/- resulted in a significant reduction in the levels of the transforming growth factor-beta 1 (TGF-ß1), phosphor-Smad-2/3, collagen I and collagen III proteins and/or in the ischemic cardiac tissues. All of these beneficial effects were reproduced by a pharmacological inhibition of HADC6 in vivo. In vitro, hypoxic stress increased the expressions of HADC6 and collagen I and III gene; these alterations were significantly prevented by the HADC6 silencing and TubA loading. These findings indicated that HADC6 deficiency resists ischemic injury by a reduction of TGF-ß1/Smad2/3 signalling activation, leading to decreased extracellular matrix production, which reduces cardiac fibrosis and dysfunction, providing a potential molecular target in the treatment of patients with MI.
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Fibrosis , Histona Desacetilasa 6 , Infarto del Miocardio , Transducción de Señal , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Remodelación Ventricular , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/genética , Factor de Crecimiento Transformador beta1/metabolismo , Proteína Smad2/metabolismo , Ratones , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Miocardio/metabolismo , Miocardio/patología , Ratones Noqueados , Masculino , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFß inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.
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Dioxoles , Fibrosis , Infarto del Miocardio , Piridinas , Ingeniería de Tejidos , Animales , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Infarto del Miocardio/metabolismo , Infarto del Miocardio/genética , Ratones , Humanos , Piridinas/farmacología , Piridinas/uso terapéutico , Ingeniería de Tejidos/métodos , Dioxoles/farmacología , Dioxoles/uso terapéutico , Miocardio/patología , Miocardio/metabolismo , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Benzamidas/farmacología , Benzamidas/uso terapéutico , Modelos Animales de Enfermedad , Transducción de Señal , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Remodelación Ventricular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Corazón/fisiopatología , Corazón/efectos de los fármacos , AmidasRESUMEN
BACKGROUND AND AIM: Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients' prognoses. METHODS AND RESULTS: Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62-2.26 vs. HR: 1.75, 95% CI: 1.43-2.16, P < 0.001). CONCLUSIONS: RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality. TRIAL REGISTRATION: NCT03727828, 21 Oct 2018.
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Colesterol , Insuficiencia Cardíaca , Hipertensión , Hipertrofia Ventricular Izquierda , Triglicéridos , Humanos , Hipertrofia Ventricular Izquierda/sangre , Masculino , Femenino , Hipertensión/complicaciones , Hipertensión/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Colesterol/sangre , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Pronóstico , Triglicéridos/sangre , Remodelación Ventricular , Curva ROC , Modelos de Riesgos Proporcionales , HDL-Colesterol/sangre , Factores de RiesgoAsunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Válvula Pulmonar , Función Ventricular Derecha , Remodelación Ventricular , Humanos , Válvula Pulmonar/cirugía , Válvula Pulmonar/fisiopatología , Válvula Pulmonar/diagnóstico por imagen , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Resultado del Tratamiento , Insuficiencia de la Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/fisiopatología , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/etiología , Recuperación de la Función , Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/cirugía , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
Background: Heterogenous deposition and homeostasis roles of physiologic and ectopic adipose tissues underscore the impact of fat compartmentalization on cardiometabolic risk. We aimed to characterize the distribution of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and liver fat on magnetic resonance imaging (MRI), and evaluate their associations with anthropometric indices and adverse cardiac remodeling. Methods: In this cross-sectional observational study, 149 Asian adults (57.0 ± 12.8 years; 65% males) with at least one cardiometabolic risk factor underwent multiparametric fat and cardiovascular MRI. Anthropometric indices included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and bioimpedance body fat mass (BFM). Associations between fat depots and anthropometric measures as well as cardiac remodeling features were examined as a single cohort and stratified by type 2 diabetes mellitus (T2DM) status. Results: VAT and SAT had opposing associations with liver fat and EAT. Therefore the VAT/SAT ratio was explored as an integrated marker of visceral adiposity. VAT/SAT was positively associated with EAT (ß=0.35, P<0.001) and liver fat (ß=0.32, P=0.003) independent of confounders. Of the anthropometric measurements assessed, only WHR was independently associated with VAT/SAT (ß=0.17, P=0.021). Individuals with T2DM had higher VAT and lower SAT compared to those without T2DM, translating to a significantly higher VAT/SAT ratio. EAT volume was independently associated with adverse features of cardiac remodeling: increased left ventricular (LV) mass (ß=0.24, P=0.005), larger myocyte volume (ß=0.26, P=0.001), increased myocardial fibrosis (ß=0.19, P=0.023), higher concentricity (ß=0.18, P=0.035), and elevated wall stress (ß=-0.18, P=0.023). Conclusion: Multiparametric MRI revealed abdominal VAT and SAT have differential associations with anthropometric indices and ectopic fats in a single cohort of Asians at risk of cardiometabolic disease. People with T2DM have expanded VAT and diminished SAT, endorsing the VAT/SAT ratio beyond usual anthropometric measurements as a marker for multiorgan visceral fat composition. Among the fat depots examined, EAT is uniquely associated with adverse cardiac remodeling, suggesting its distinctive cardiometabolic properties and implications.
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Adiposidad , Grasa Intraabdominal , Pericardio , Remodelación Ventricular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adiposidad/fisiología , Pericardio/diagnóstico por imagen , Pericardio/patología , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Anciano , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Pueblo Asiatico , Hígado/diagnóstico por imagen , Hígado/patología , Antropometría , Imagen por Resonancia Magnética , Adulto , Grasa Abdominal/diagnóstico por imagen , Grasa Abdominal/patologíaRESUMEN
INTRODUCTION: Several biomarkers are characteristically elevated in patients with acute heart failure (AHF). Our hypothesis was they could predict early changes in left ventricular (LV) characteristics in acute coronary syndrome (ACS) patients. The objective of this study was two-fold: a) compare circulating concentrations of NT-pro BNP, CA-125, ST2, galectin-3 and pro-adrenomedullin among 4 groups of individuals (healthy controls; patients with ACS without AHF; patients with ACS and AHF and patients admitted for AHF); and b) evaluate whether these biomarkers predict adverse LV remodeling and ejection fraction changes in ACS. METHODS: 6 biomarkers (NT-pro BNP, CA-125, ST2, galectin-3, pro-adrenomedullin and C-reactive) were measured within the first 48 h of admission. Echocardiograms were performed during admission and at 3 months. Variables associated with LV end-diastolic volume (EDV) and ejection fraction (LVEF) change were assessed by multivariate linear regression. RESULTS: We analyzed 51 patients with ACS, 16 with AHF and, 20 healthy controls. NT-pro BNP and ST2 concentrations were elevated at similar values in patients admitted for AHF and ACS complicated with HF but CA-125 concentrations were higher in AHF patients. NT-pro BNP concentrations were positively correlated with CA-125 (rho = 0.58; p < 0.001), ST2 (rho = 0.58; p < 0.001) and galectin-3 (rho = 0.37; p < 0.001) Median change (median days was 83 days after) in EDV and LVEF was 5 %. CA-125 concentrations were positively associated to LV EDV change (ß-coefficient 1.56) and negatively with LVEF trend (ß-coefficient = -0.86). No other biomarker predicted changes in EDV or LVEF. CONCLUSIONS: CA-125 correlates with early LV remodeling and LVEF deterioration in ACS patients.
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Síndrome Coronario Agudo , Biomarcadores , Insuficiencia Cardíaca , Remodelación Ventricular , Humanos , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/fisiopatología , Biomarcadores/sangre , Femenino , Masculino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Anciano , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Volumen Sistólico , Estudios de Casos y Controles , Péptido Natriurético Encefálico/sangre , Galectinas/sangre , Antígeno Ca-125/sangre , Proteína 1 Similar al Receptor de Interleucina-1RESUMEN
BACKGROUND: Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. METHODS AND RESULTS: 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non-gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P<0.05). Kaplan-Meier survival analyses suggested significant differences for SIQPS in all 5 cohorts, for EIQPS and EIQGS in 4 cohorts, and for end-systolic and end-diastolic SIQGS in 3 cohorts (all P<0.05). Multivariate Cox analysis showed that abnormal SI and EI remained statistically significant predictors for MACE after adjusting for total perfusion deficit, LVEF, and other confounding factors. CONCLUSIONS: For patients diagnosed or suspected of coronary artery disease with preserved or supra-normal LVEF, resting sphericity indexes by myocardial perfusion imaging displayed incremental long-term prognostic value. Among these indicators, SIQPS is particularly promising across different perfusion or preserved functional conditions.
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Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Volumen Sistólico/fisiología , Imagen de Perfusión Miocárdica/métodos , Estudios Retrospectivos , Pronóstico , Anciano , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/fisiología , Valor Predictivo de las Pruebas , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
BACKGROUND: High cognitive reserve (CR) has been related to lower dementia risk, but its association with heart disease (HD) is unknown. We aimed to explore the relation of CR to HD and cardiac structure and function. METHODS AND RESULTS: Within the UK Biobank, 349 907 HD-free participants were followed up. A composite CR indicator involving education/occupation attainment/television viewing time/confiding frequency/social connection frequency/variety of leisure activities was generated, and further categorized into low/moderate/high levels. Incident HD, including coronary HD, cardiac arrhythmia, and heart failure, was ascertained on the basis of medical records. During the follow-up, a subsample (n=31 182) underwent cardiac magnetic resonance imaging to assess ventricular structure and function. Data were analyzed using Cox regression, Laplace regression, and linear regression. Compared with low CR, the hazard ratio and 95% CI of any HD for high CR was 0.78 (0.75-0.80) (including 0.68 [0.66-0.71] for coronary HD, 0.91 [0.87-0.95] for cardiac arrhythmia, and 0.63 [0.58-0.68] for heart failure). Furthermore, high CR was associated with delayed HD onset by 1.59 (95% CI, 1.37-1.82) years compared with low CR. In cardiac magnetic resonance imaging data analysis, compared with low CR, high CR was associated with larger left ventricular end-diastolic volume (ß, 0.13 [95% CI, 0.09-0.17]), left ventricular end-systolic volume (ß, 0.05 [95% CI, 0.01-0.10]), left ventricular stroke volume (ß, 0.16 [95% CI, 0.12-0.21]), and left ventricular ejection fraction (ß, 0.08 [95% CI, 0.03-0.13]). CONCLUSIONS: High CR is associated with favorable HD health. Our findings suggest that the beneficial effect of CR is not limited to dementia but also HD.
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Reserva Cognitiva , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Longitudinales , Reserva Cognitiva/fisiología , Reino Unido/epidemiología , Función Ventricular Izquierda/fisiología , Cardiopatías/fisiopatología , Cardiopatías/epidemiología , Cardiopatías/diagnóstico , Volumen Sistólico/fisiología , Imagen por Resonancia Magnética , Incidencia , Adulto , Factores de Riesgo , Medición de Riesgo , Remodelación Ventricular/fisiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/diagnósticoRESUMEN
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterised by multiple risk factors touching various organs outside the heart. Using a murine HFpEF model, we studied cardiac reverse remodelling (RR) after stopping the causing metabolic-hypertensive stress (MHS; Angiotensin II [AngII] and a high-fat diet [HFD]) after 28 days and introducing voluntary exercise (VE) for four more weeks. We measured the effects of MHS and RR on the plasma and myocardial microRNA (miR) profile (miRNome) to characterise better cardiac and non-cardiac responses to HFpEF-inducing risk factors and their reversibility. AngII alone, the HFD or the MHS caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in females. Only AngII and the MHS, but not HFD, did in males. After RR, CH, LV concentric remodelling and atrial enlargement were normalised. Among the 25 most abundant circulating miRs, 10 were modulated by MHS. Plasma miRNomes from AngII, HFD or MHS mice shared 31 common significantly modulated miRs (24 upregulated and 7 downregulated), suggesting that the response of organs producing the bulk of those circulating miRs was similar even for seemingly different stress. In the LV, 19 out of 25 most expressed miRs were modulated. RR restored normality for the plasma miRNome but not for the LV miRNome, which remained mostly unchanged. Our results suggest that abnormalities persist in the myocardium of the HFpEF mice and that the normalisation of circulatory markers may be falsely reassuring after recovery.
Asunto(s)
Modelos Animales de Enfermedad , Insuficiencia Cardíaca , MicroARNs , Miocardio , Volumen Sistólico , Remodelación Ventricular , Animales , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/metabolismo , Ratones , MicroARNs/genética , MicroARNs/sangre , MicroARNs/metabolismo , Masculino , Miocardio/metabolismo , Miocardio/patología , Femenino , Angiotensina II/sangre , Angiotensina II/metabolismo , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversosRESUMEN
Recent clinical studies have reported that heart failure with preserved ejection fraction (HFpEF) can be divided into two phenotypes based on the range of ejection fraction (EF), namely HFpEF with higher EF and HFpEF with lower EF. These phenotypes exhibit distinct left ventricle (LV) remodelling patterns and dynamics. However, the influence of LV remodelling on various LV functional indices and the underlying mechanics for these two phenotypes are not well understood. To address these issues, this study employs a coupled finite element analysis (FEA) framework to analyse the impact of various ventricular remodelling patterns, specifically concentric remodelling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH), with and without LV wall thickening on LV functional indices. Further, the geometries with a moderate level of remodelling from each pattern are subjected to fibre stiffening and contractile impairment to examine their effect in replicating the different features of HFpEF. The results show that with severe CR, LV could exhibit the characteristics of HFpEF with higher EF, as observed in recent clinical studies. Controlled fibre stiffening can simultaneously increase the end-diastolic pressure (EDP) and reduce the peak longitudinal strain (ell) without significant reduction in EF, facilitating the moderate CR geometries to fit into this phenotype. Similarly, fibre stiffening can assist the CH and 'EH with wall thickening' cases to replicate HFpEF with lower EF. These findings suggest that potential treatment for these two phenotypes should target the bio-origins of their distinct ventricular remodelling patterns and the extent of myocardial stiffening.
Asunto(s)
Insuficiencia Cardíaca , Modelos Cardiovasculares , Remodelación Ventricular , Remodelación Ventricular/fisiología , Humanos , Insuficiencia Cardíaca/fisiopatología , Fenotipo , Volumen Sistólico/fisiología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Simulación por ComputadorRESUMEN
Infiltration of monocyte-derived macrophages plays a crucial role in cardiac remodeling and dysfunction. The serum and glucocorticoid-inducible protein kinase 3 (SGK3) is a downstream factor of PI3K signaling, regulating various biological processes via an AKT-independent signaling pathway. SGK3 has been implicated in cardiac remodeling. However, the contribution of macrophagic SGK3 to hypertensive cardiac remodeling remains unclear. A cardiac remodeling model was established by angiotensin II (Ang II) infusion in SGK3-Lyz2-CRE (f/f, +) and wild-type mice to assess the function of macrophagic SGK3. Additionally, a co-culture system of SGK3-deficient or wild-type macrophages and neonatal rat cardiomyocytes (CMs) or neonatal rat fibroblasts (CFs) was established to evaluate the effects of SGK3 and the underlying mechanisms. SGK3 levels were significantly elevated in both peripheral blood mononuclear cells and serum from patients with heart failure. Macrophage SGK3 deficiency attenuated Ang II-induced macrophage infiltration, myocardial hypertrophy, myocardial fibrosis, and mitochondrial oxidative stress. RNA sequencing suggested Ndufa13 as the candidate gene in the effect of SGK3 on Ang II-induced cardiac remolding. Downregulation of Ndufa13 in CMs and CFs prevented the suppression of cardiac remodeling caused by SGK3 deficiency in macrophages. Mechanistically, the absence of SGK3 led to a reduction in IL-1ß secretion by inhibiting the NLRP3/Caspase-1/IL-1ß pathway in macrophages, consequently suppressing upregulated Ndufa13 expression and mitochondrial oxidative stress in CMs and CFs. This study provides new evidence that SGK3 is a potent contributor to the pathogenesis of hypertensive cardiac remodeling, and targeting SGK3 in macrophages may serve as a potential therapy for cardiac remodeling.
Asunto(s)
Angiotensina II , Macrófagos , Miocitos Cardíacos , Estrés Oxidativo , Proteínas Serina-Treonina Quinasas , Remodelación Ventricular , Animales , Angiotensina II/farmacología , Macrófagos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ratones , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas , Humanos , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Transducción de Señal , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Cardiomegalia/metabolismo , Cardiomegalia/patología , Cardiomegalia/inducido químicamente , Cardiomegalia/genética , Ratones Noqueados , Células CultivadasRESUMEN
Reverse remodeling, the overarching concept behind myocardial recovery, describes the process in which the maladaptive cardiac structural and functional alterations are reversed by removing the underlying etiology or by therapy. This review addresses different imaging modalities and biomarkers as possible predictors for reverse remodeling in patients with chronic heart failure. Although echocardiography remains the imaging modality of choice in daily practice, the presence and amount of fibrosis on cardiac magnetic resonance is a better predictor and inversely correlated with the likelihood for reverse remodeling. A decrease in NT-proBNP levels and serum soluble ST3 during follow-up is associated with better clinical and structural outcomes. The role of troponins and galectine-3 is less clear. There is a promising role for microRNAs in the future, although more research is necessary. Accurate predictors of reverse remodeling could help identify patients with an increased likelihood for reverse remodeling and, in turn, improve patient-tailored medicine.
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Biomarcadores , Insuficiencia Cardíaca , Valor Predictivo de las Pruebas , Recuperación de la Función , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Biomarcadores/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Fibrosis , Miocardio/patología , Miocardio/metabolismo , Enfermedad Crónica , Imagen por Resonancia Magnética , Resultado del Tratamiento , EcocardiografíaRESUMEN
Psychological processes have a crucial role in the recovery from acute myocardial infarction (AMI), yet the underlying mechanisms of these effects remain elusive. Here we demonstrate the impact of the reward system, a brain network associated with motivation and positive expectations, on the clinical outcomes of AMI in mice. Chemogenetic activation of dopaminergic neurons in the reward system improved the remodeling processes and vascularization after AMI, leading to enhanced cardiac performance compared to controls. These effects were mediated through several physiological mechanisms, including alterations in immune activity and reduced adrenergic input to the liver. We further demonstrate an anatomical connection between the reward system and the liver, functionally manifested by altered transcription of complement component 3, which in turn affects vascularization and recovery from AMI. These findings establish a causal connection between a motivational brain network and recovery from AMI, introducing potential therapeutic avenues for intervention.
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Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Infarto del Miocardio , Recuperación de la Función , Recompensa , Animales , Infarto del Miocardio/psicología , Infarto del Miocardio/fisiopatología , Masculino , Recuperación de la Función/fisiología , Neuronas Dopaminérgicas/metabolismo , Hígado , Remodelación Ventricular/fisiología , Neovascularización Fisiológica , Motivación , Ratones , Miocardio/patología , Miocardio/metabolismo , Clozapina/análogos & derivadosRESUMEN
BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.
Asunto(s)
Acetilcisteína , Hipertensión , NADPH Oxidasas , Estrés Oxidativo , Ratas Endogámicas SHR , Remodelación Ventricular , Animales , Masculino , Estrés Oxidativo/efectos de los fármacos , Acetilcisteína/farmacología , Remodelación Ventricular/efectos de los fármacos , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , NADPH Oxidasas/metabolismo , NADPH Oxidasas/genética , Ratas , Antioxidantes/farmacología , Condicionamiento Físico Animal , Modelos Animales de Enfermedad , NADPH Oxidasa 2/metabolismo , NADPH Oxidasa 2/genética , NADPH Oxidasa 4/metabolismo , NADPH Oxidasa 4/genética , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Miocardio/metabolismo , Miocardio/patología , Peróxidos Lipídicos/metabolismo , Función Ventricular Izquierda/efectos de los fármacos , Suplementos Dietéticos , Hipertrofia Ventricular Izquierda/fisiopatología , Hipertrofia Ventricular Izquierda/prevención & control , Hipertrofia Ventricular Izquierda/metabolismoRESUMEN
BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.