RESUMEN
BACKGROUND: Little is known about the underlying factors contributing to unfavourable clinical outcomes in patients with diabetes mellitus (DM) complicated by new-onset acute myocardial infarction (AMI). The aim of this study was to investigate the impact of DM on the pathophysiologic features and prognosis of patients with new-onset AMI following successful revascularization by utilizing cardiac magnetic resonance (CMR). METHODS: Consecutive patients diagnosed with new-onset AMI between June 2022 and January 2024 were included. All patients underwent culprit vessel revascularization upon admission and CMR imaging 3-7 days later. The primary clinical endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), for which the average follow-up was 10 months. RESULTS: A total of 72 patients were divided into a DM group (n = 23) and a non-DM group (n = 49). Multivariate logistic regression analysis revealed that DM was an independent risk factor for the occurrence of microvascular obstruction. Multivariate linear regression analysis found that DM was the influencing factor of global radial strain (B = -4.107, t = -2.328, p = 0.023), while fasting blood glucose influenced infarct segment myocardial radial strain (B = -0.622, t = -2.032, p = 0.046). DM independently contributed to the risk of MACCEs following successful revascularization in patients with AMI (p < 0.05). CONCLUSION: Comprehensive phenotypic characterization of myocardial injury and microcirculatory status could enable reliable identification of high-risk MACCEs in DM patients with new-onset AMI following successful revascularization.
Asunto(s)
Infarto del Miocardio , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Pronóstico , Anciano , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Revascularización Miocárdica/estadística & datos numéricos , Factores de Riesgo , Imagen por Resonancia Magnética , Imagen por Resonancia Cinemagnética/métodosRESUMEN
BACKGROUND: While left ventricular ejection fraction (LVEF) is the primary variable utilized for prognosis following myocardial infarction (MI), it is relatively indiscriminate for survival in patients with mildly reduced (> 40%) or preserved LVEF (> 50%). Improving risk stratification in patients with mildly reduced or preserved LVEF remains an unmet need, and could be achieved by using a combination approach using prognostically validated measures of left-ventricular (LV) size, geometry, and function. AIMS: The aim of this study was to compare the prognostic utility of a Combined Echo-Score for predicting all-cause (ACM) and cardiac mortality (CM) following MI to LVEF alone, including the sub-groups with LVEF > 40% and LVEF > 50%. METHODS: Retrospective data on 3094 consecutive patients with MI from 2013 to 2021 who had inpatient echocardiography were included, including both patients with ST-elevation MI (n = 869 [28.1%]) and non-ST-elevation MI (n = 2225 [71.9%]). Echo-Score consisted of LVEF < 40% (2 points) or LVEF < 50% (1 point), and 1 point each for left atrial volume index > 34 mL/m2, septal E/e' > 15, abnormal LV mass-index, tricuspid regurgitation velocity > 2.8 m/s, and abnormal LV end-systolic volume-index. Simple addition was used to derive a score out of 7. RESULTS: At a median follow-up of 4.5 years there were 445 deaths (130 cardiac deaths). On Cox proportional-hazards multivariable analysis incorporating significant clinical and echocardiographic predictors, Echo-Score was an independent predictor of both ACM (HR 1.34, p < .001) and CM (HR 1.59, p < .001). Inter-model comparisons of model ð2, Harrel's C and Somer's D, and Receiver operating curves confirmed the superior prognostic value of Echo-Score for both endpoints compared to LVEF. In the subgroups with LVEF > 40% and LVEF > 50%, Echo-Score was similarly superior to LVEF for predicting ACM and CM. CONCLUSIONS: An Echo-Score composed of prognostically validated LV parameters is superior to LVEF alone for predicting survival in patients with MI, including the subgroups with mildly reduced and preserved LVEF. This could lead to improved patient risk stratification, better-targeted therapies, and potentially more efficient use of device therapies. Further studies should be considered to define the benefit of further investigation and treatment in high-risk subgroups.
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Ecocardiografía , Ventrículos Cardíacos , Infarto del Miocardio , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Estudios Retrospectivos , Medición de Riesgo/métodos , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/mortalidad , Infarto del Miocardio/diagnóstico por imagen , Persona de Mediana Edad , Pronóstico , Función Ventricular Izquierda/fisiología , Anciano , Volumen Sistólico/fisiología , Tasa de Supervivencia , Valor Predictivo de las PruebasRESUMEN
Background: Acute myocardial infarction (AMI) is a critical cardiovascular disease with high morbidity and mortality. Identifying practical parameters for predicting long-term mortality is crucial in this patient group. The percentage of mean arterial pressure (%MAP) is a useful parameter used to assess peripheral artery disease. It can be easily calculated from ankle pulse volume recording. Previous studies have shown that %MAP is a useful predictor of all-cause mortality in specific populations, but its relationship with mortality in AMI patients is unclear. Methods: In this observational cohort study, 191 AMI patients were enrolled between November 2003 and September 2004. Ankle-brachial index (ABI) and %MAP were measured using an ABI-form device. All-cause and cardiovascular mortality data were collected from a national registry until December 2018. Cox proportional hazards model and Kaplan-Meier survival plot were used to analyze the association between %MAP and long-term mortality in AMI patients. Results: The median follow-up to mortality was 65 months. There were 130 overall and 36 cardiovascular deaths. High %MAP was associated with increased overall mortality after multivariable analysis (HR = 1.062; 95% CI: 1.017-1.109; p =0.006). However, high % MAP was only associated with cardiovascular mortality in the univariable analysis but became insignificant after the multivariable analysis. Conclusions: In conclusion, this study is the first to evaluate the usefulness of %MAP in predicting long-term mortality in AMI patients. Our study shows that %MAP might be an independent predictor of long-term overall mortality in AMI patients and has better predictive power than ABI.
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Índice Tobillo Braquial , Presión Arterial , Infarto del Miocardio , Humanos , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estimación de Kaplan-Meier , Enfermedad Arterial Periférica/mortalidad , Enfermedad Arterial Periférica/fisiopatología , Factores de Riesgo , Pronóstico , Modelos de Riesgos Proporcionales , Estudios de CohortesRESUMEN
Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Simulación por Computador , Infarto del Miocardio , Humanos , Infarto del Miocardio/terapia , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Arritmias Cardíacas/terapia , Arritmias Cardíacas/fisiopatología , Modelos Cardiovasculares , Enfermedad Crónica , Masculino , Ramos Subendocárdicos/fisiopatología , Electrocardiografía , Enfermedad Aguda , Femenino , Persona de Mediana EdadRESUMEN
BACKGROUND: The aim of this study was to investigate the clinical implication of incidentally induced atrial fibrillation (AF) during programmed electrical stimulation (PES) in patients with left ventricular systolic dysfunction (≤40%) after an acute myocardial infarction (MI). METHODS: In this study, we included 231 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with left ventricular ejection fraction ≤40% and no prior history of AF. These patients underwent PES 6 weeks post-MI as part of the study protocol. Patients all received an implantable cardiac monitor (ICM) 3-21 days post-MI and were continuously monitored for cardiac arrhythmias for 2 years. Induction of AF was unwanted but reported if this incidentally occurred. RESULTS: A total of 61 patients (26%) developed AF within 2 years of follow-up, in which n = 10 (29%) had incidental AF during PES at baseline. The overall risk of AF was not significantly increased in patients with incidental AF (n = 34) during PES compared to patients without incidental AF (n = 197) (HR 1.6 [0.9-3.0], p = 0.14). The risk of bradyarrhythmia (HR = 0.2 [0.0-1.2], p = 0.07), ventricular arrhythmias (HR = 0.7 [0.1-5.8], p = 0.77), and major cardiovascular events (MACE) (HR 0.5 [0.2-1.7], p = 0.28) was not significantly different in patients with versus without incidental AF. CONCLUSIONS: Incidentally induced AF during PES in post-MI patients with reduced LVEF was not significantly associated with a higher risk of long-term atrial fibrillation, other cardiac arrhythmias, or major cardiac events. TRIAL REGISTRATION: NCT00145119.
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Fibrilación Atrial , Infarto del Miocardio , Disfunción Ventricular Izquierda , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Electrocardiografía Ambulatoria/métodos , Estudios de Seguimiento , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/complicacionesRESUMEN
BACKGROUND: The relationship between ankle blood pressure (BP) and cardiovascular disease remains unclear. We examined the relationships between known and new ankle BP indices and major cardiovascular outcomes in people with and without type 2 diabetes. METHODS: We used data from 3 large trials with measurements of ankle systolic BP (SBP), ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). The primary outcome was a composite of cardiovascular mortality, myocardial infarction, hospitalization for heart failure, or stroke. Secondary outcomes included death from cardiovascular causes, total (fatal and non-fatal) myocardial infarction, hospitalization for heart failure, and total stroke. RESULTS: Among 42,929 participants (age 65.6 years, females 31.3%, type 2 diabetes 50.1%, 53 countries), the primary outcome occurred in 7230 (16.8%) participants during 5 years of follow-up (19.4% in people with diabetes, 14.3% in those without diabetes). The incidence of the outcome increased with lower ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, multivariable-adjusted hazard ratios (HRs, 95% CI) of the outcome for each lower fourth were 1.05 (0.98-1.12), 1.17 (1.08-1.25), and 1.54 (1.54-1.65) for ankle SBP; HR 1.06 (0.99-1.14), 1.26 (1.17-1.35), and 1.48 (1.38-1.58) for ABI; and HR 1.02 (0.95-1.10), 1.15 (1.07-1.23), and 1.48 (1.38-1.58) for APPD. The largest effect size was noted for ankle SBP (HRs 1.05 [0.90-1.21], 1.21 [1.05-1.40], and 1.93 [1.68-2.22]), and APPD (HRs 1.08 [0.93-1.26], 1.30 [1.12-1.50], and 1.97 [1.72-2.25]) with respect to hospitalization for heart failure, while only a marginal association was observed for stroke. The relationships were similar in people with and without diabetes (all p for interaction > 0.05). CONCLUSIONS: Inverse and independent associations were observed between ankle BP and cardiovascular events, similarly in people with and without type 2 diabetes. The largest associations were observed for heart failure and the smallest for stroke. Including ankle BP indices in routine clinical assessments may help to identify people at highest risk of cardiovascular outcomes.
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Índice Tobillo Braquial , Presión Sanguínea , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Masculino , Anciano , Persona de Mediana Edad , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Factores de Riesgo , Incidencia , Medición de Riesgo , Valor Predictivo de las Pruebas , Factores de Tiempo , Pronóstico , Hospitalización , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/epidemiologíaRESUMEN
PURPOSE: Following acute myocardial infarction (AMI), patients with diabetes mellitus (DM) have a poorer prognosis than those without DM. This study aimed to investigate the benefit of cardiac rehabilitation on cardiorespiratory fitness in patients with AMI, examining whether this effect varied depending on DM and glycated hemoglobin (HbA1c) levels. METHODS: Data were collected from the medical records of 324 patients diagnosed with AMI who were subsequently referred to participate in a supervised exercise-based cardiac rehabilitation program. Cardiorespiratory fitness was assessed using cardiopulmonary exercise testing before and at 3 and 6 mo after the start of cardiac rehabilitation. Linear mixed models were used to evaluate changes in cardiorespiratory fitness between patients with and without DM during the follow-up period. RESULTS: In total, 106 patients (33%) had DM. Both patients with and without DM showed a significant improvement in cardiorespiratory fitness from baseline to the 6-mo follow-up. However, the improvement was significantly lower in patients with DM than in those without DM (1.9 ± 1.5 vs. 3.7 ± 3.2 mL/kg/min, P < .001). Among patients with DM, those with HbA1c levels < 7% showed a greater improvement in cardiorespiratory fitness than those with HbA1c ≥ 7% (2.7 ± 1.5 vs. 1.1 ± 1.8 mL/kg/min, P < .001) during the follow-up period. CONCLUSIONS: Improvements in cardiorespiratory fitness following cardiac rehabilitation were significantly lower in patients with AMI and DM. The response to cardiac rehabilitation in patients is influenced by HbA1c levels. These findings suggest potential implications for individualizing cardiac rehabilitation programming and ensuring optimal glycemic control in patients with AMI and DM.
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Rehabilitación Cardiaca , Capacidad Cardiovascular , Diabetes Mellitus , Hemoglobina Glucada , Infarto del Miocardio , Humanos , Masculino , Hemoglobina Glucada/análisis , Femenino , Infarto del Miocardio/rehabilitación , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/sangre , Capacidad Cardiovascular/fisiología , Persona de Mediana Edad , Rehabilitación Cardiaca/métodos , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/sangre , Anciano , Terapia por Ejercicio/métodos , Prueba de Esfuerzo/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long-term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction. METHODS AND RESULTS: A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long-term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%-49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow-up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group (P<0.001). In the mrEF group, age>65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high-risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high-risk mrEF group was comparable with the rEF group, while it was lower in the low-risk mrEF group than in the pEF group. CONCLUSIONS: Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high-risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.
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Infarto del Miocardio , Sistema de Registros , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Volumen Sistólico/fisiología , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Medición de Riesgo/métodos , Pronóstico , Factores de Riesgo , Factores de Tiempo , Incidencia , Causas de Muerte , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/epidemiología , Japón/epidemiologíaRESUMEN
BACKGROUND: To investigate the association between serum osmolality and deteriorating renal function in patients with acute myocardial infarction (AMI). METHODS: Three thousand eight hundred eighty-five AMI patients from the Medical Information Mart for Intensive Care IV were enrolled for this study. The primary outcome was deteriorating renal function. Secondary outcomes included the new-onset of acute kidney injury (AKI) and progress of AKI. < 293.2725 mmol/L was defined as low serum osmolality, and ≥ 293.2725 mmol/L as high serum osmolality based on upper quartile. Univariate and multivariate logistic regression models were used to explore the associations between serum osmolality and the development of deteriorating renal function, the new-onset of AKI and progress of AKI among AMI patients. Subgroup analysis was also conducted. RESULTS: One thousand three hundred ninety-three AMI patients developed deteriorating renal function. After adjusting all confounding factors, high serum osmolality was associated with increased risk of deteriorating renal function [odds ratio (OR) = 1.47, 95% confidence interval (CI): 1.22-1.78], new-onset of AKI (OR = 1.31, 95% CI: 1.01-1.69), and progress of AKI risk (OR = 1.26, 95% CI: 1.01-1.59) among AMI patients. In addition, when the stratified analysis was performed for age, AMI type, cardiogenic shock, and estimated glomerular filtration rate (eGFR), high serum osmolality was risk factor for the risk of deteriorating renal function among patients aged 65 years or older, without cardiogenic shock, and with an eGFR ≥ 60 mL/min/1.73m2. CONCLUSION: Higher serum osmolality increased the risk of deteriorating renal function among AMI patients.
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Lesión Renal Aguda , Bases de Datos Factuales , Riñón , Infarto del Miocardio , Humanos , Masculino , Femenino , Concentración Osmolar , Anciano , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Factores de Riesgo , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Medición de Riesgo , Riñón/fisiopatología , Pronóstico , Factores de Tiempo , Progresión de la Enfermedad , Estudios Retrospectivos , Tasa de Filtración Glomerular , Anciano de 80 o más Años , Biomarcadores/sangreRESUMEN
ABSTRACT: The role of intravenous immunoglobulin in protecting the diabetic heart from ischemia/reperfusion (I/R) injury is unclear. Hearts isolated from adult diabetic and nondiabetic Wistar rats (n = 8 per group) were treated with intravenous immunoglobulin (IVIG) either 2 hours before euthanasia, before ischemia, or at reperfusion. Hemodynamic data were acquired using the Isoheart software version 1.524-S. Ischemia/reperfusion (I/R) injury was evaluated by 2,3,5-triphenyltetrazolium chloride staining and troponin T levels. The levels of apoptosis markers, caspases-3/8, antioxidant enzymes, superoxide dismutase and catalase, glucose transporters, GLUT-1 and GLUT-4, phosphorylated ERK1/2, and phosphorylated eNOS were estimated by Western blotting. Proinflammatory and anti-inflammatory cytokine levels were evaluated using enzyme-linked immunosorbent assays. Intravenous immunoglobulin administration abolished the effects of I/R injury in hearts subjected to hyperglycemia when infused at reperfusion, before ischemia, or at reperfusion in 4-week diabetic rat hearts and only at reperfusion in 6-week diabetic rat hearts. IVIG infusion resulted in a significant (P < 0.05) recovery of cardiac hemodynamics and decreased infarct size. IVIG also reduced the levels of troponin T, apoptotic enzymes, and proinflammatory cytokines. IVIG significantly (P < 0.05) increased the levels of anti-inflammatory cytokines, antioxidant enzymes, GLUT-4, and phosphorylated eNOS. Intravenous immunoglobulin protected the hearts from I/R injury if infused at reperfusion in the presence of hyperglycemia, in 4- and 6-week diabetic rat hearts, and when infused before ischemia in 4-week diabetic rat hearts. IVIG exerts its cardioprotective effects associated with the upregulated phosphorylated eNOS/GLUT-4 pathway.
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Diabetes Mellitus Experimental , Transportador de Glucosa de Tipo 4 , Daño por Reperfusión Miocárdica , Óxido Nítrico Sintasa de Tipo III , Ratas Wistar , Transducción de Señal , Animales , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Inmunoglobulinas Intravenosas/farmacología , Apoptosis/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Miocardio/enzimología , Infarto del Miocardio/patología , Infarto del Miocardio/metabolismo , Infarto del Miocardio/prevención & control , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Ratas , Estrés Oxidativo/efectos de los fármacos , Citocinas/metabolismo , Preparación de Corazón Aislado , Mediadores de Inflamación/metabolismoRESUMEN
BACKGROUND: Myocardial bridging is a cardiac anomaly where a segment of epicardial coronary arteries runs through the myocardium and can rarely cause MI. Takotsubo syndrome is a stress-induced cardiomyopathy that can mimic MI. Catecholamine surge during stress can contribute to Takotsubo syndrome, but whether this surge can trigger an inconspicuous myocardial bridging to manifest symptomatically remains unclear, and alternately, whether a myocardial bridge might cause worsening of Takotsubo syndrome is also a matter that needs further research. CASE PRESENTATION: We report the case of a patient who initially presented with features of acute exacerbation of bronchiectasis and subsequently developed symptoms and ECG features suggestive of acute myocardial infarction. Echocardiography revealed features of takotsubo syndrome, and complete myocardial bridging was revealed via coronary angiography. The patient was managed conservatively with pharmacological treatment, and after a few days, echocardiographic features were reversed. As such, the diagnosis shifted toward Takotsubo syndrome with myocardial stunning due to co-existent myocardial bridging. CONCLUSION: We report a rare case of a patient with acute bronchiectasis exacerbation with features suggestive of acute myocardial infarction who had findings of Takotsubo syndrome and complete myocardial bridging. In the beginning, it was difficult to determine whether the symptoms arose due to acute MI resulting from myocardial bridging or were solely due to takotsubo syndrome because of stress from bronchiectasis. Although myocardial bridging is often overlooked as an etiology for acute MI, this case highlights the importance of expanding the differential diagnosis to myocardial bridging in the work-up for the cause of acute MI and how Takotsubo syndrome can mimic acute MI and pose a diagnostic challenge.
Asunto(s)
Angiografía Coronaria , Puente Miocárdico , Infarto del Miocardio , Valor Predictivo de las Pruebas , Cardiomiopatía de Takotsubo , Humanos , Cardiomiopatía de Takotsubo/fisiopatología , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/diagnóstico por imagen , Cardiomiopatía de Takotsubo/terapia , Cardiomiopatía de Takotsubo/etiología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/etiología , Diagnóstico Diferencial , Puente Miocárdico/complicaciones , Puente Miocárdico/diagnóstico por imagen , Puente Miocárdico/diagnóstico , Puente Miocárdico/fisiopatología , Aturdimiento Miocárdico/diagnóstico , Aturdimiento Miocárdico/etiología , Aturdimiento Miocárdico/fisiopatología , Femenino , Resultado del Tratamiento , Electrocardiografía , Anciano , MasculinoRESUMEN
Minipigs are widely used in biomedical research for translational studies. However, information about pain elicited by experimental procedures is lacking. Non-invasive methods as quantitative sensory testing and conditioned pain modulation are particularly attractive. Our overarching aim was to explore and refine these methods for assessing post-operative pain in minipigs after myocardial infarction. As first step, we aimed at defining mechanical and thermal thresholds in healthy adults Göttingen Minipigs, evaluating their reliability, and testing their modifications after the application of a conditioning stimulus. Thresholds were assessed at different body sites before and after a painful conditioning stimulus (CS) (cuffed tourniquet) and sham CS (uncuffed tourniquet) in eleven animals. Thresholds' reliability was assessed using interclass correlation coefficient (ICC). The effect of the CS was assessed calculating absolute change, percentage change of the thresholds and standard error of measurement. Baseline mechanical thresholds (Newton) were: left hindlimb 81 [73; 81]; left forearm 81 [72.1; 81]; right forearm 81 [76; 81]; left chest 80.5 [68; 81]; right chest 81 [76.5; 81]; left neck 81 [70.3; 81]; right neck 74.8 [62.3; 80.5]. Reliability of mechanical thresholds was good at right chest (ICC = 0.835) and moderate at left chest (ICC = 0.591), left hindlimb (ICC = 0.606) and left neck (ICC = 0.518). Thermal thresholds showed poor reliability in all the tested sites. A modulatory effect was present at right chest, but it was seen when both a painful CS and a sham CS was applied. Minipigs tendentially showed a pro-nociceptive profile (i.e. conditioning pain facilitation). The measured thresholds are a reference for future trials in this species. Mechanical thresholds showed to be more reliable and, therefore, more useful, than thermal ones. The pain facilitation might be explained by the phenomenon of stress induced hyperalgesia, but this finding needs to be further investigated with a stricter paradigm.
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Umbral del Dolor , Porcinos Enanos , Animales , Porcinos , Umbral del Dolor/fisiología , Masculino , Femenino , Reproducibilidad de los Resultados , Dimensión del Dolor/métodos , Dolor Postoperatorio/fisiopatología , Infarto del Miocardio/fisiopatologíaRESUMEN
BACKGROUND: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell-derived exosome nebulization therapy (SCENT). METHODS: Stem cell-derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging. RESULTS: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC-Cd36fl/- conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall. CONCLUSIONS: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC-Cd36fl/- mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.
Asunto(s)
Exosomas , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Infarto del Miocardio/fisiopatología , Exosomas/metabolismo , Ratones , Administración por Inhalación , Modelos Animales de Enfermedad , Porcinos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Masculino , Función Ventricular Izquierda , Humanos , Miocardio/metabolismo , Miocardio/patología , Células Madre/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genéticaRESUMEN
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.
Asunto(s)
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
Injectable extracellular matrix (iECM) is a versatile biological material with beneficial properties such as good degradability, promotion of cell survival, immunomodulation, and facilitation of vascular formation. However, intravenous injection of iECM faces challenges like a short retention time in vivo and low concentration at the lesion site. To address these issues, we prepared a composite hydrogel composed of sodium alginate and iECM and administered it via intrapericardial injection, forming a structure akin to cardiac patches within the pericardium. Compared with intramyocardial injection, intrapericardial injection avoids direct myocardial injury and ectopic tumor formation, offering less invasiveness and better biocompatibility. This study demonstrates that the sodium alginate/infusible extracellular matrix (SA/iECM) composite hydrogel can effectively prolong the local retention time of iECM in the heart, enhance electrical conduction between cardiomyocytes, promote angiogenesis at ischemic myocardial sites, inhibit apoptosis in the infarcted region, mitigate left ventricular remodeling postmyocardial infarction (MI), and improve cardiac function after infarction. Precise coordination of cardiomyocyte contraction and relaxation depends on the rhythmic occurrence of calcium-dependent action potentials. Cardiac dysfunction is partially attributed to the disruption of the excitation-contraction coupling (ECC) mechanism, which is associated with prolonged intracellular Ca2+ transients and alterations in contraction and relaxation Ca2+ levels. Our results show that the SA/iECM composite hydrogel improves electrical conduction, as evidenced by increased Cx43 expression and enhanced intercellular electrical connectivity. This research establishes that intrapericardial injection of a SA/iECM composite hydrogel is a safe and effective treatment modality, providing a theoretical basis for the use of biomaterials in MI therapy.
Asunto(s)
Alginatos , Matriz Extracelular , Hidrogeles , Infarto del Miocardio , Neovascularización Fisiológica , Pericardio , Alginatos/química , Alginatos/farmacología , Animales , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Hidrogeles/química , Hidrogeles/farmacología , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Pericardio/efectos de los fármacos , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Masculino , Ratas , AngiogénesisRESUMEN
The analysis of cardiac wall mechanics is of importance for understanding coronary heart diseases (CHD). The inhalation of ultrafine particles could deteriorate CHD. The aim of the study is to investigate the effects of cardiac wall mechanics on rats of myocardial infarction (MI) after long-term inhalation of ultrafine Zn particles. Cardiac wall stresses and strains were computed, based on echocardiographic and hemodynamic measurements. It was found that MI resulted in the significantly elevated stresses and the reduced strains. The short-term inhalation of ultrafine Zn particles decreased stresses and increased strains in MI rats, but the long-term inhalation had the opposite effects. Hence, the short-term inhalation of ultrafine Zn particles could alleviate the MI-induced LV dysfunction while the long-term inhalation impaired it.
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Infarto del Miocardio , Estrés Mecánico , Zinc , Infarto del Miocardio/fisiopatología , Animales , Zinc/administración & dosificación , Zinc/farmacología , Ratas , Masculino , Factores de Tiempo , Administración por Inhalación , Tamaño de la Partícula , Ratas Sprague-Dawley , Fenómenos Biomecánicos , Corazón/efectos de los fármacos , Corazón/fisiopatología , Hemodinámica/efectos de los fármacosRESUMEN
Increased platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in acute myocardial infarction (AMI), which indicate accelerated thrombus formation and inflammatory response, potentially have prognostic implications. Given that cardiovascular disease and renal function exacerbate each other, an elevated PLR and NLR at admission for AMI may worsen renal function after AMI. However, only a few clinical studies have addressed this issue. Therefore, this study aimed to examine the effects of PLR and NLR at AMI onset on renal function. This retrospective study analyzed data from 234 patients hospitalized for AMI. First, correlations between various parameters (age; sex; body mass index; hemoglobin level, albumin level, B-type natriuretic peptide level, C-reactive protein level, creatinine (Cr) level, blood urea nitrogen (BUN) level, PLR, and NLR at admission; contrast medium usage; and maximum creatine kinase) and Cr and BUN levels at discharge were examined using single and multiple regression analyses. Then, correlations between these parameters and the change in Cr (ΔCr) and BUN levels (ΔBUN) were investigated using single and multiple regression analysis, followed by structural equation modeling (SEM). Multiple regression analysis revealed significant positive correlations between PLR at admission and Cr level at discharge (ßâ =â 0.135, Pâ =â .021), PLR at admission and BUN level at discharge (ßâ =â 0.218, Pâ =â .006), PLR at admission and ΔCr (ßâ =â 0.244, Pâ =â .019), and PLR at admission and ΔBUN (ßâ =â 0.312, Pâ =â .003). SEM results revealed significant positive correlations between PLR at admission and ΔCr (ßâ =â 0.260, Pâ =â .008) and PLR at admission and ΔBUN (ßâ =â 0.292, Pâ =â .003). Conversely, NLR demonstrated a minimal association with renal function at discharge compared to PLR. This study suggests that increased PLR at admission in AMI significantly affects and exacerbates renal function but does not increase NLR at admission. PLR is one of the predictors of renal dysfunction after AMI.
Asunto(s)
Linfocitos , Infarto del Miocardio , Humanos , Masculino , Estudios Retrospectivos , Femenino , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Persona de Mediana Edad , Anciano , Recuento de Linfocitos , Plaquetas , Recuento de Plaquetas , Riñón/fisiopatología , Creatinina/sangre , Neutrófilos , Nitrógeno de la Urea Sanguínea , PronósticoRESUMEN
BACKGROUND: Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling. METHODS: ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats: 10, 20, and 40 mg/kg; H9c2 cells: 1, 10, and 100 µmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot. RESULTS: ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury. CONCLUSION: ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.
Asunto(s)
Proteínas Quinasas Activadas por AMP , Homólogo de la Proteína 1 Relacionada con la Autofagia , Autofagia , Chalconas , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Ratas Sprague-Dawley , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Masculino , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Línea Celular , Chalconas/farmacología , Modelos Animales de Enfermedad , Fibrosis , Infarto del Miocardio/patología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/enzimología , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-ß-mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.