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BACKGROUND: Complications after percutaneous breast biopsy are infrequent but may include hematoma, pseudoaneurysm formation, persistent pain, infection, delayed wound healing, vasovagal reaction, hemothorax, pneumothorax, and neoplastic seeding. The risk factors include tumor factors (size, location, vascularity), procedure-related factors (needle diameter, number of biopsies), and interventionist experience. There has been no previous report of a fatal complication resulting from percutaneous breast biopsy. CASE PRESENTATION: We report a 54-year-old Asian woman with a 3 cm BI-RADS® 4B left breast mass in the lower-inner quadrant who was biopsied by a 16 G needle under ultrasound guidance at a province hospital. She experienced dizziness and near-syncope afterward. The initial evaluation showed evidence of cardiac tamponade with hemodynamic instability. She underwent urgent subxiphoid pericardial window and was transferred to our facility. We brought her directly to the operating room to perform an explorative median sternotomy and found a 0.2 cm hole in the right ventricle. The injured site was successfully repaired without cardiopulmonary bypass. Postoperative echocardiography demonstrated mild right ventricular dysfunction without evidence of septal or valvular injury. She survived with no significant complications. DISCUSSION: This case might be the first report of a life-threatening complication related to percutaneous breast core-needle biopsy. The rapid pericardial release is key to the survival of cardiac tamponade. The patient subsequently required cardiac repair and monitoring to avoid long-term complications. In this report, we suggested a safe biopsy method, complications recognition, and appropriate management of penetrating cardiac injury. CONCLUSION: Penetrating cardiac injury resulting from percutaneous breast biopsy is extremely rare but can occur. A biopsy must be done cautiously, and worst-case management should promptly be considered.
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Neoplasias de la Mama , Lesiones Cardíacas , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/patología , Biopsia con Aguja Gruesa/efectos adversos , Lesiones Cardíacas/etiología , Taponamiento Cardíaco/etiología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/lesiones , Ecocardiografía , Mama/patología , Técnicas de Ventana Pericárdica/efectos adversosRESUMEN
BACKGROUND: Doxorubicin is an important anticancer drug, however, elicits dose-dependently cardiomyopathy. Given its mode of action, i.e. topoisomerase inhibition and DNA damage, we investigated genetic events associated with cardiomyopathy and searched for mechanism-based possibilities to alleviate cardiotoxicity. We treated rats at clinically relevant doses of doxorubicin. Histopathology and transmission electron microscopy (TEM) defined cardiac lesions, and transcriptomics unveiled cardiomyopathy-associated gene regulations. Genomic-footprints revealed critical components of Abl1-p53-signaling, and EMSA-assays evidenced Abl1 DNA-binding activity. Gene reporter assays confirmed Abl1 activity on p53-targets while immunohistochemistry/immunofluorescence microscopy demonstrated Abl1, p53&p73 signaling. RESULTS: Doxorubicin treatment caused dose-dependently toxic cardiomyopathy, and TEM evidenced damaged mitochondria and myofibrillar disarray. Surviving cardiomyocytes repressed Parkin-1 and Bnip3-mediated mitophagy, stimulated dynamin-1-like dependent mitochondrial fission and induced anti-apoptotic Bag1 signaling. Thus, we observed induced mitochondrial biogenesis. Transcriptomics discovered heterogeneity in cellular responses with minimal overlap between treatments, and the data are highly suggestive for distinct cardiomyocyte (sub)populations which differed in their resilience and reparative capacity. Genome-wide footprints revealed Abl1 and p53 enriched binding sites in doxorubicin-regulated genes, and we confirmed Abl1 DNA-binding activity in EMSA-assays. Extraordinarily, Abl1 signaling differed in the heart with highly significant regulations of Abl1, p53 and p73 in atrial cardiomyocytes. Conversely, in ventricular cardiomyocytes, Abl1 solely-modulated p53-signaling that was BAX transcription-independent. Gene reporter assays established Abl1 cofactor activity for the p53-reporter PG13-luc, and ectopic Abl1 expression stimulated p53-mediated apoptosis. CONCLUSIONS: The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity.
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Cardiomiopatías , Doxorrubicina , Miocitos Cardíacos , Proteínas Proto-Oncogénicas c-abl , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteína p53 Supresora de Tumor/metabolismo , Transducción de Señal/efectos de los fármacos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Proteínas Proto-Oncogénicas c-abl/metabolismo , Proteínas Proto-Oncogénicas c-abl/genética , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/efectos de los fármacos , Atrios Cardíacos/patología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Muerte Celular/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.
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Anticoagulantes , Aneurisma Cardíaco , Humanos , Estudios Retrospectivos , Anticoagulantes/uso terapéutico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Aneurisma Cardíaco/tratamiento farmacológico , Aneurisma Cardíaco/epidemiología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/epidemiología , Factores de Riesgo , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Embolia/epidemiología , Embolia/tratamiento farmacológicoRESUMEN
Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.
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Animales Recién Nacidos , Ventrículos Cardíacos , Ramos Subendocárdicos , Regeneración , Animales , Regeneración/fisiología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Ramos Subendocárdicos/fisiopatología , Ramos Subendocárdicos/fisiología , Ramos Subendocárdicos/patología , Proliferación Celular , Hiperplasia/patología , Miocitos Cardíacos/patología , Miocitos Cardíacos/fisiología , Linaje de la Célula , Ratones , Ratones TransgénicosRESUMEN
Pulmonary atresia with intact ventricular septum (PA-IVS) is a rare congenital heart defect characterized by underdeveloped pulmonary valve and right ventricular hypoplasia. Neonates undergoing surgery to open pulmonary valve have a range of post-surgical ventricular recovery: single-ventricle (1v) palliation, one-and-half ventricle (1.5v) palliation, and bi-ventricular (2v) repair. PA-IVS-1.5v typically requires surgical intervention to install cavopulmonary shunt and entails partial right ventricle recovery. NCHi016-A is an iPSC line derived from a 5-year-old female with PA-IVS-1.5v using Sendai Virus reprogramming. This iPSC line shows typical iPSC morphology, has normal karyotype, expresses pluripotency markers, and has potential to differentiate into three germ layers.
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Células Madre Pluripotentes Inducidas , Atresia Pulmonar , Femenino , Atresia Pulmonar/patología , Atresia Pulmonar/cirugía , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Preescolar , Línea Celular , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/cirugía , Diferenciación Celular , Ventrículos Cardíacos/patologíaRESUMEN
BACKGROUND: Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking. METHODS: The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay. RESULTS: A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group (P=0.028), and ΔTWV was 1.2±1.7 cm3 in the placebo group and 0.037±1.9 cm3 in the spironolactone group (P=0.022). Change in LV mass was 3.1±8.4 g in the placebo group and -5.8±8.4 g in the spironolactone group (P=0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of -10.1±36.3 ms in the spironolactone group; P=6.33×10-4). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation. CONCLUSIONS: Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02169089.
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Diabetes Mellitus Tipo 2 , Fibrosis , Antagonistas de Receptores de Mineralocorticoides , Insuficiencia Renal Crónica , Espironolactona , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Método Doble Ciego , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/complicaciones , Espironolactona/uso terapéutico , Progresión de la Enfermedad , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/efectos de los fármacos , Resultado del TratamientoRESUMEN
Background: Individuals suffering from chronic kidney disease (CKD) frequently face a heightened likelihood of experiencing cardiovascular complications, including heart failure and cardiac mortality. Cardiovascular magnetic resonance feature tracking (CMR-FT) is utilized to assess the micro-contraction function of the myocardium. The objective of this research is to explore the relationship between the left ventricular anatomy, myocardial strain, and the clinical outcomes in patients with CKD. Methods: A total of 77 patients with late-stage CKD were enrolled in this retrospective study. They underwent cardiac magnetic resonance imaging and were followed up, with no history of significant cardiac diseases. The patients were divided into two groups: those with a left ventricular global longitudinal strain (LVGLS) ≥ -15.2% (n = 49) and those with LVGLS < -15.2% (n = 28). The clinical endpoints were defined as hospitalization for heart failure or all-cause mortality. Results: Over an average observation period of 22 ± 9 months, 11 (14%) patients passed away and 30 (39%) were admitted to the hospital for heart failure, with eight encountering both incidents. Those with LVGLS ≥ -15.2% had markedly lower rates of event-free survival concerning heart failure admissions and overall mortality than their counterparts (log-rank P = 0.014). Cox multivariable analysis indicated that reduced LVGLS consistently predicted a higher likelihood of combined outcomes of heart failure admissions and total mortality (HR: 3.40, 95% CI [1.35-8.56], P = 0.009), even when factoring in age, diabetes, left atrial diameter, and left ventricular mass index (LVMI). However, the LVMI showed no significant correlation with the risk of heart failure admissions or overall mortality. Conclusion: Compared to patients with LVGLS < -15.2%, CKD patients with LVGLS ≥ -15.2% have an increased risk of heart failure hospitalization and all-cause mortality. The prognostic role of LVMI in assessing CKD patients among the Asian population requires further investigation.
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Insuficiencia Cardíaca , Ventrículos Cardíacos , Insuficiencia Renal Crónica , Humanos , Masculino , Estudios Retrospectivos , Femenino , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/diagnóstico por imagen , Persona de Mediana Edad , Pronóstico , Anciano , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patología , Imagen por Resonancia Magnética , Hospitalización/estadística & datos numéricosRESUMEN
Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kß inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kß expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kß pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.
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Ventrículos Cardíacos , Melatonina , Monocrotalina , Estrés Oxidativo , Ratas Wistar , Transducción de Señal , Receptor Toll-Like 4 , Animales , Melatonina/farmacología , Estrés Oxidativo/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Masculino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/metabolismo , Monocrotalina/toxicidad , Transducción de Señal/efectos de los fármacos , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/patología , FN-kappa B/metabolismo , Inflamación/patología , Inflamación/tratamiento farmacológico , Ratas , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: During pulsed field ablation (PFA), relationships between ablation parameters (contact force [CF], number of burst pulses, impedance decrease, and electrode temperature) and lesion size in beating hearts have not been well validated. METHODS: A 7.5F-catheter with a 3.5-mm ablation electrode and CF sensor (ThermoCool SmartTouch SF-Dual-Energy, Biosense Webster, Inc, Irwindale, CA) was connected to a PFA system (TRUPULSE2, Biosense Webster, Inc). In 11 closed-chest swine, biphasic PFA current was delivered between the ablation electrode and the skin patch at 219 sites in left ventricle and right ventricle using 12, 18, and 24 burst pulses with 4 different levels of CF: (1) low (n=57; CF, 4-15g; median, 10g); (2) moderate (n=60; CF, 16-30g; median, 22.5g); (3) high (n=68; CF, 32-65g; median, 40g); and (4) no electrode contact (n=34), 2 mm away from the endocardium. Swine were euthanized 2 hours after ablation, and lesion size was measured using triphenyl tetrazolium chloride staining. RESULTS: All PFA lesions with electrode-myocardium contact were well demarcated with triphenyl tetrazolium chloride staining, demonstrating (1) pale central zone (contraction band necrosis with minimal coagulation necrosis), (2) dark brown zone (contraction band necrosis with hemorrhage), and (3) hyperstained red zone by triphenyl tetrazolium chloride (unaffected normal myocardium with preserved mitochondrial activity, consistent with reversible zone). Lesion depth increased significantly with increasing CF and the number of PFA burst pulses. An exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlated lesion depth with high accuracy: R=0.809, P<0.0001, ±1.0-mm accuracy in 128 of 163 (79%) lesions, and ±1.5-mm accuracy in 153 of 163 (94%) lesions. Impedance decrease and electrode temperature were poor predictors of lesion size. There were no detectable lesions resulting from ablation without electrode contact. CONCLUSIONS: Acute PFA ventricular lesions demonstrate irreversible and reversible lesion boundaries. Electrode-tissue contact is required for effective lesion formation. Lesion depth increases significantly with increasing CF and PFA burst pulses. A new exponential/logarithmic formula combined with CF and the number of PFA burst pulses correlates lesion depth with high accuracy.
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Ablación por Catéter , Animales , Ablación por Catéter/instrumentación , Ablación por Catéter/métodos , Porcinos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Catéteres Cardíacos , Diseño de Equipo , Miocardio/patología , Modelos Animales , Impedancia Eléctrica , Necrosis , Sus scrofa , Temperatura , Factores de Tiempo , Frecuencia CardíacaRESUMEN
BACKGROUND: Anatomical evidence reveals heterogeneous fat distribution in both atrial and ventricular myocardium that are considered normal, but at the same time arrhythmogenic, and numerous cardiac pathophysiological conditions are associated with myocardial fat deposits. The relationship between fatty infiltration, especially in the epicardial layer and its pathophysiological implication is not completely understood. AIM: The aim of this study was to establish a positive or negative relationship between the ventricular burden and several parameters related to right ventricle (RV) adipose tissue - the RV thickness, RV indexed mass, body mass index (BMI), age, gender. PATIENTS, MATERIALS AND METHODS: Twenty-three patients with documented premature ventricular contractions (PVCs) originating from right ventricular outflow tract based on electrocardiography (ECG) evaluation were hospitalized between January 2018-November 2022 for electrophysiological study and PVCs ablation. Data obtained after collecting the clinical characteristics, ECG, RV measurements from transthoracic echocardiography (TTE), cardiac computed tomography (CT) and magnetic resonance imaging (MRI) were analyzed. RESULTS: A weak positive relationship between the ventricular burden and BMI (r=0.14, p=0.49), tricuspid annular plane systolic excursion (TAPSE) (r=0.07, p=0.7), the RV thickness (r=0.03, p=0.8), epicardial adipose tissue (r=0.13, p=0.55), RV mass indexed (r=0.05, p=0.82) was observed. No clear cut-off of the PVCs burden could be established in terms related to the increase in BMI, RV thickness, epicardial adipose tissue, RV mass indexed. CONCLUSIONS: No significant positive or negative relationship between the ventricular burden and the RV thickness, RV indexed mass were found in individuals with a high PVCs originating from right ventricular outflow tract (RVOT) burden.
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Tejido Adiposo , Ventrículos Cardíacos , Complejos Prematuros Ventriculares , Humanos , Femenino , Complejos Prematuros Ventriculares/fisiopatología , Masculino , Persona de Mediana Edad , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/diagnóstico por imagen , Tejido Adiposo/patología , Adulto , Electrocardiografía/métodos , AncianoRESUMEN
The goal of this study was to evaluate the intensity of autophagy and ubiquitin-dependent proteolysis processes occurring in myocardium of left ventricle (LV) in subsequent stages of pulmonary arterial hypertension (PAH) to determine mechanisms responsible for LV mass loss in a monocrotaline-induced PAH rat model. LV myocardium samples collected from 32 Wistar rats were analyzed in an early PAH group (n = 8), controls time-paired (n = 8), an end-stage PAH group (n = 8), and their controls (n = 8). Samples were subjected to histological analyses with immunofluorescence staining, autophagy assessment by western blotting, and evaluation of ubiquitin-dependent proteolysis in the LV by immunoprecipitation of ubiquitinated proteins. Echocardiographic, hemodynamic, and heart morphometric parameters were assessed regularly throughout the experiment. Considerable morphological and hemodynamic remodeling of the LV was observed over the course of PAH. The end-stage PAH was associated with significantly impaired LV systolic function and a decrease in LV mass. The LC3B-II expression in the LV was significantly higher in the end-stage PAH group compared to the early PAH group (p = 0.040). The measured LC3B-II/LC3B-I ratios in the end-stage PAH group were significantly elevated compared to the controls (p = 0.039). Immunofluorescence staining showed a significant increase in the abundance of LC3 puncta in the end-stage PAH group compared to the matched controls. There were no statistically significant differences in the levels of expression of all ubiquitinated proteins when comparing both PAH groups and matched controls. Autophagy may be considered as the mechanism behind the LV mass loss at the end stage of PAH.
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Autofagia , Ventrículos Cardíacos , Proteolisis , Hipertensión Arterial Pulmonar , Ratas Wistar , Ubiquitina , Animales , Ubiquitina/metabolismo , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Ratas , Masculino , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/patología , Modelos Animales de Enfermedad , Miocardio/metabolismo , Miocardio/patología , Ecocardiografía , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Remodelación VentricularRESUMEN
BACKGROUND: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). METHODS: Transmission electron microscopy was used to analyze mitochondria within 0-3.5 µm and 3.5-7 µm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. RESULTS: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. CONCLUSION: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.
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Mitocondrias Cardíacas , Humanos , Masculino , Femenino , Proyectos Piloto , Persona de Mediana Edad , Anciano , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/ultraestructura , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/metabolismo , Cardiopatías/metabolismo , Cardiopatías/patología , Microscopía Electrónica de Transmisión , Adulto , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/ultraestructura , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Fibrilación Atrial/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Miocardio/ultraestructuraRESUMEN
An 80-year-old man presented to the cardiology outpatient clinic due to shortness of breath. His past medical history included alcohol intake, hypertension, inferior wall myocardial infarction (five years ago), an ischemic stroke, and permanent atrial fibrillation (diagnosed three years before the current examination). A physical exam revealed a decreased intensity of S1 and S2, irregular rate and rhythm, and no murmurs nor friction rub. X-rays, Computed Tomography, and echocardiography exhibited pericardial calcification, involving mostly the inferior wall and protruding into the left ventricle. A diagnosis of constrictive pericarditis due to pericardial calcification was established and considered idiopathic. Even when it may be related to ischemic heart disease, post-infarction pericarditis could explain how the calcification extended to adjacent territory perfused by the circumflex coronary artery. Combined imaging studies were crucial not only for identifying calcium deposits in the pericardium but also in assessing a patient inherently prone to co-existing and exacerbating conditions. Even though pericardiectomy allows for removal of the clinical manifestations of congestive pericarditis in the most symptomatic patients with pericardial calcification, among patients like ours, with tolerable symptoms, cardiologists should discuss the therapeutic options considering the patient's choices, potentially including a rehabilitation plan as part of non-pharmacological management.
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Calcinosis , Ecocardiografía , Pericarditis Constrictiva , Pericardio , Tomografía Computarizada por Rayos X , Humanos , Masculino , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Anciano de 80 o más Años , Pericardio/patología , Pericardio/diagnóstico por imagen , Ecocardiografía/métodos , Pericarditis Constrictiva/diagnóstico por imagen , Pericarditis Constrictiva/patología , Tomografía Computarizada por Rayos X/métodos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/diagnóstico por imagenRESUMEN
Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.
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Endostatinas , Disfunción Ventricular Derecha , Remodelación Ventricular , Animales , Endostatinas/metabolismo , Humanos , Masculino , Femenino , Disfunción Ventricular Derecha/metabolismo , Disfunción Ventricular Derecha/fisiopatología , Ratas , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/patología , Ratas Sprague-Dawley , Colágeno Tipo XVIII/metabolismo , Colágeno Tipo XVIII/genética , Persona de Mediana Edad , Adulto , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/patología , Progresión de la Enfermedad , Modelos Animales de Enfermedad , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patologíaRESUMEN
Ebstein anomaly is a rare congenital heart defect, accounting for less than 1% of cardiac malformations and occurring in approximately 1 out of 210,000 live births. It is characterized by an abnormality of the tricuspid valve, where the valve is positioned lower than normal in the right ventricle. Although primarily a tricuspid valve defect, the right ventricle itself is often structurally abnormal and weakened (myopathic).
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Anomalía de Ebstein , Válvula Tricúspide , Anomalía de Ebstein/diagnóstico por imagen , Anomalía de Ebstein/terapia , Anomalía de Ebstein/fisiopatología , Humanos , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/anomalías , Válvula Tricúspide/fisiopatología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patologíaRESUMEN
Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.
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Desdiferenciación Celular , Paro Cardíaco , Miocitos Cardíacos , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/patología , Paro Cardíaco/metabolismo , Paro Cardíaco/patología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Biomarcadores/metabolismo , Anciano , Troponina T/metabolismo , Células Madre/metabolismo , Células Madre/citología , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patologíaRESUMEN
Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.
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Displasia Ventricular Derecha Arritmogénica , Ventrículos Cardíacos , Humanos , Displasia Ventricular Derecha Arritmogénica/diagnóstico por imagen , Displasia Ventricular Derecha Arritmogénica/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Pronóstico , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patología , Imagen por Resonancia Cinemagnética/métodos , Imagen por Resonancia Magnética , Función Ventricular Derecha/fisiologíaRESUMEN
Purpose To perform a systematic review and meta-analysis to assess the effect of enzyme replacement therapy on cardiac MRI parameters in patients with Fabry disease. Materials and Methods A systematic literature search was conducted from January 1, 2000, through January 1, 2024, in PubMed, ClinicalTrials.gov, Embase, and Cochrane Library databases. Study outcomes were changes in the following parameters: (a) left ventricular wall mass (LVM), measured in grams; (b) LVM indexed to body mass index, measured in grams per meters squared; (c) maximum left ventricular wall thickness (MLVWT), measured in millimeters; (d) late gadolinium enhancement (LGE) extent, measured in percentage of LVM; and (e) native T1 mapping, measured in milliseconds. A random-effects meta-analysis of the pooled mean differences between baseline and follow-up parameters was conducted. The study protocol was registered in PROSPERO (CRD42022336223). Results The final analysis included 11 studies of a total of 445 patients with Fabry disease (mean age ± SD, 41 years ± 11; 277 male, 168 female). Between baseline and follow-up cardiac MRI, the following did not change: T1 mapping (mean difference, 6 msec [95% CI: -2, 15]; two studies, 70 patients, I2 = 88%) and LVM indexed (mean difference, -1 g/m2 [95% CI: -6, 3]; four studies, 290 patients, I2 = 81%). The following measures minimally decreased: LVM (mean difference, -18 g [95% CI: -33, -3]; seven studies, 107 patients, I2 = 96%) and MLVWT (mean difference, -1 mm [95% CI: -2, -0.02]; six studies, 151 patients, I2 = 90%). LGE extent increased (mean difference, 1% [95% CI: 1, 1]; three studies, 114 patients, I2 = 85%). Conclusion In patients with Fabry disease, enzyme replacement therapy was associated with stabilization of LVM, MLVWT, and T1 mapping values, whereas LGE extent mildly increased. Keywords: Fabry Disease, Enzyme Replacement Therapy (ERT), Cardiac MRI, Late Gadolinium Enhancement (LGE) Supplemental material is available for this article. © RSNA, 2024.
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Terapia de Reemplazo Enzimático , Enfermedad de Fabry , Imagen por Resonancia Magnética , Enfermedad de Fabry/tratamiento farmacológico , Enfermedad de Fabry/diagnóstico por imagen , Enfermedad de Fabry/patología , Humanos , Terapia de Reemplazo Enzimático/métodos , Imagen por Resonancia Magnética/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patologíaRESUMEN
AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.
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Diabetes Mellitus Tipo 2 , Estado Prediabético , Remodelación Ventricular , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Estado Prediabético/fisiopatología , Masculino , Femenino , Adulto , Adulto Joven , Edad de Inicio , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/patología , Adolescente , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/fisiopatología , Factores de Riesgo , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/fisiopatología , Glucemia/metabolismo , Glucemia/análisis , Índice de Masa Corporal , Triglicéridos/sangreRESUMEN
Aging is a risk factor for cardiovascular disease, the leading cause of death worldwide. Cardiac fibrosis is a harmful result of repeated myocardial infarction that increases risk of morbidity and future injury. Interestingly, both rates and outcomes of cardiac fibrosis differ between young and aged individuals, as well as men and women. Here, for the first time, we identify and isolate matrix-bound extracellular vesicles from the left ventricles (LVs) of young or aged males and females in both human and murine models. These LV vesicles (LVVs) show differences in morphology and content between these four cohorts in both humans and mice. LVV effects on fibrosis were also investigated in vitro, and aged male LVVs were pro-fibrotic while other LVVs were anti-fibrotic. From these LVVs, we could identify therapeutic miRNAs to promote anti-fibrotic effects. Four miRNAs were identified and together, but not individually, demonstrated significant cardioprotective effects when transfected. This suggests that miRNA synergy can regulate cell response, not just individual miRNAs, and also indicates that biological agent-associated therapeutic effects may be recapitulated using non-immunologically active agents. Furthermore, that chronic changes in LVV miRNA content may be a major factor in sex- and age-dependent differences in clinical outcomes of cardiac fibrosis.