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AIMS/HYPOTHESIS: Hyper-reflective crystalline deposits found in retinal lesions have been suggested to predict the progression of diabetic retinopathy, but the nature of these structures remains unknown. METHODS: Scanning electron microscopy and immunohistochemistry were used to identify cholesterol crystals (CCs) in human donor, pig and mouse tissue. The effects of CCs were analysed in bovine retinal endothelial cells in vitro and in db/db mice in vivo using quantitative RT-PCR, bulk RNA sequencing, and cell death and permeability assays. Cholesterol homeostasis was determined using 2H2O and 2H7-cholesterol. RESULTS: We identified hyper-reflective crystalline deposits in human diabetic retina as CCs. Similarly, CCs were found in the retina of a diabetic mouse model and a high-cholesterol diet-fed pig model. Cell culture studies demonstrated that treatment of retinal cells with CCs can recapitulate all major pathogenic mechanisms leading to diabetic retinopathy, including inflammation, cell death and breakdown of the blood-retinal barrier. Fibrates, statins and α-cyclodextrin effectively dissolved CCs present in in vitro models of diabetic retinopathy, and prevented CC-induced endothelial pathology. Treatment of a diabetic mouse model with α-cyclodextrin reduced cholesterol levels and CC formation in the retina, and prevented diabetic retinopathy. CONCLUSIONS/INTERPRETATION: We established that cholesterol accumulation and CC formation are a unifying pathogenic mechanism in the development of diabetic retinopathy.
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Diabetes Mellitus Experimental , Retinopatía Diabética , alfa-Ciclodextrinas , Animales , Bovinos , Ratones , Humanos , Porcinos , Retinopatía Diabética/metabolismo , alfa-Ciclodextrinas/efectos adversos , alfa-Ciclodextrinas/metabolismo , Células Endoteliales/metabolismo , Diabetes Mellitus Experimental/metabolismo , Retina/metabolismo , Modelos Animales de Enfermedad , Colesterol/metabolismoRESUMEN
Left ventricular non-compaction cardiomyopathy (LVNC) is a rare and unclassified cardiomyopathy that carries the potential to cause heart failure, arrhythmias, and embolic events within adults. The diagnosis of this cardiomyopathy can be based off a variety of echocardiographic, cardiac magnetic resonance (CMR), and computed tomography (CT) imaging criteria; none of which have been standardized to establish a firm diagnosis. This is further complicated by the observation from prior studies that LVNC may present as different forms of cardiomyopathy, each with its own subset of nuances that may change treatment strategies. Management of such cardiomyopathy has been debated in terms of anticoagulation, electrophysiologic studies to prevent arrhythmia, as well as heart failure prevention. Not enough data exists in regard to establishing firm guidelines for management. The following article aims to provide a comprehensive review in regard to the etiologies, pathogenesis, diagnostic criteria, management, and treatment of LVNC.
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Cardiomiopatías , Insuficiencia Cardíaca , No Compactación Aislada del Miocardio Ventricular , Adulto , Arritmias Cardíacas , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Ecocardiografía , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , No Compactación Aislada del Miocardio Ventricular/diagnóstico , No Compactación Aislada del Miocardio Ventricular/terapiaRESUMEN
Anthracycline is a mainstay in treatment of many cancers including lymphoma and breast cancer among many others. However, anthracycline treatment can be cardiotoxic. Although anthracycline-induced cardiotoxicity is dose dependent, it can also occur early at the onset of treatment and even up to several years following completion of treatment. This review article focuses on the understanding of mechanisms of anthracycline-induced cardiotoxicity, the treatments, and recommended follow-up and preventive approaches.
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Antraciclinas , Neoplasias de la Mama , Antraciclinas/efectos adversos , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Femenino , Humanos , Incidencia , Factores de RiesgoRESUMEN
ABSTRACT: Calcific aortic valve disease is a common heart disease that contributes to increased cardiovascular morbidity and mortality. There is a lack of effective pharmaceutical therapy because its mechanisms are not yet fully known. Ginkgo biloba extract (EGB761) is reported to alleviate vascular calcification. However, whether EGB761 protects against aortic valve calcification, a disease whose pathogenesis shares many similarities with vascular calcification, and potential molecular mechanisms remain unknown. In this study, porcine aortic valve interstitial cell (pAVIC) calcification was induced by warfarin with or without the presence of EGB761. Immunostaining was performed to establish and characterize the pAVIC phenotype. Calcium deposition and calcium content were examined by Alizarin Red S staining and an intracellular calcium content assay. Alkaline phosphatase activity was detected by the p-nitrophenyl phosphate method. The expression levels of bone morphogenetic protein-2 (BMP2), Runt-related transcription factor 2 (Runx2), homeobox protein MSX-2, and phosphorylated (p)-Smad1/5 were detected by reverse transcription-quantitative polymerase chain reaction (PCR) and Western blot analysis. Consistent with these in vitro data, we also confirmed the suppression of in vivo calcification by EGB761 in the warfarin-induced C57/Bl6 mice. The results indicated that both pAVICs and aortic valves tissue of mice stimulated with warfarin showed increased calcium deposition and expression of osteogenic markers (alkaline phosphatase, BMP2, homeobox protein MSX-2, and Runx2) and promoted p-Smad1/5 translocation from the cytoplasm to the nucleus. The addition of EGB761 significantly inhibited p-Smad1/5 translocation from the cytoplasm to the nucleus, thus suppressing calcification. In conclusion, EGB761 could ameliorate warfarin-induced aortic valve calcification through the inhibition of the BMP2-medicated Smad1/5/Runx2 signaling pathway.
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Válvula Aórtica/efectos de los fármacos , Proteína Morfogenética Ósea 2/metabolismo , Calcinosis/prevención & control , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Enfermedades de las Válvulas Cardíacas/prevención & control , Extractos Vegetales/farmacología , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Transporte Activo de Núcleo Celular , Animales , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Calcinosis/inducido químicamente , Calcinosis/metabolismo , Calcinosis/patología , Calcio/metabolismo , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Modelos Animales de Enfermedad , Ginkgo biloba , Enfermedades de las Válvulas Cardíacas/inducido químicamente , Enfermedades de las Válvulas Cardíacas/metabolismo , Enfermedades de las Válvulas Cardíacas/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Masculino , Ratones Endogámicos C57BL , Osteogénesis/efectos de los fármacos , Fosforilación , Transducción de Señal , Sus scrofa , WarfarinaRESUMEN
OBJECTIVE: Carotid revascularization procedures, carotid artery stenting (CAS) and carotid endarterectomy (CEA), are among the most common vascular interventions performed in the United States, with significant resource utilization. Whereas multiple studies have reported outcomes after these procedures, data regarding 30-day readmission rates after these interventions remain scant. METHODS: The U.S. Nationwide Readmission Database (2010-2014) was queried to identify all patients ≥18 years who were readmitted within 30 days after a hospital discharge for CEA or CAS. RESULTS: Among 476,260 patients included, 13.5% underwent CAS and 86.5% underwent CEA. The combined 30-day readmission rate for all carotid revascularization procedures was 9.2% (10.6% after CAS and 9.0% after CEA). After 1:3 propensity matching, CAS was associated with higher risk of readmission compared with CEA (10.4% vs 9.4%). Neurologic complications and cardiac conditions were the two most common causes of readmission after both CAS (29.7% and 23.7%, respectively) and CEA (28.2% and 21.7%, respectively). The 30-day readmission rates were higher in CAS patients across all age groups as well as in those with a low or high baseline burden of comorbidities. CONCLUSIONS: In this large nationwide study, CAS was associated with higher 30-day readmission rates compared with CEA irrespective of age or baseline burden of comorbidities. Neurologic or cardiac adverse events were responsible for >50% of readmissions after CAS and CEA.
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Estenosis Carotídea/terapia , Endarterectomía Carotidea , Readmisión del Paciente/tendencias , Stents , Anciano , Anciano de 80 o más Años , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: Selection of an appropriate antithrombotic regimen in patients requiring oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) still remains a challenge. An ideal 9-2regimen should balance the risk of bleeding against ischemic benefit. METHODS: A comprehensive literature search for studies comparing triple antithrombotic therapy (TAT) vs double antithrombotic therapy (DAT) in patients requiring OAC undergoing PCI was performed in clinicalTrials.gov, PubMed, Web of Science, EBSCO Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from inception to May 1st, 2019. A meta-analysis was performed using random-effects model to calculate risk ratio (RR) and 95% confidence interval (CI). RESULTS: Fifteen studies were eligible and included 13 967 patients, of which 7349 received TAT and 6618 received DAT. Compared with DAT, TAT was associated with lower risk of myocardial infarction (RR, 0.82; 95%CI, 0.69-0.98; P = .03) and stent thrombosis (RR, 0.66; 95%CI, 0.46-0.96; P = .03). There was no difference in risk of trial defined major adverse cardiac events, all-cause mortality, and stroke between two groups. Compared with DAT, TAT was associated with higher risk of trial defined major bleeding (RR, 1.67; 95%CI, 1.38-2.01; P < .00001), including thrombolysis in myocardial infarction major bleeding (RR, 1.81; 95%CI, 1.47-2.24; P < .00001) but no significant difference in risk of intracranial bleeding. CONCLUSION: In patients requiring OAC undergoing PCI, TAT was associated with a lower risk of myocardial infarction but with a significantly higher risk of major bleeding when compared with DAT.
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Anticoagulantes/administración & dosificación , Enfermedad de la Arteria Coronaria/terapia , Fibrinolíticos/administración & dosificación , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Trombosis/prevención & control , Anciano , Anticoagulantes/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Terapia Antiplaquetaria Doble , Femenino , Fibrinolíticos/efectos adversos , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Inhibidores de Agregación Plaquetaria/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Stents , Trombosis/diagnóstico , Trombosis/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: PET/CTA was used to evaluate the effect of cholesterol crystal emboli (CCE) on muscle injury. Cholesterol crystals (CCs) released during plaque rupture travel downstream and lodge in muscle triggering inflammation and tissue injury. METHODS: Thigh muscles in three groups of rabbits (n = 22) were studied after intra-arterial injection of CCs, Group I (n = 10); polystyrene microspheres, Group II (n = 5); or normal saline, Group III (n = 7). After 48 hours, muscle inflammation and injury were measured by fluorodeoxy-glucose uptake using PET/CTA, serum tissue factor (TF), and creatinine phosphokinase (CPK). Macrophages were stained with RAM11 and CCs with Bodipy. RESULTS: SUVmax of thigh muscles was greater for Group I vs Group II and III (0.40 ± 0.16 vs 0.21 ± 0.11, P = .038 and 0.23 ± 0.06, P = .036). CPK levels rose significantly in Group I vs Group II and III (6.7 ± 6.0 vs 0.6 ± 0.4, P = .007 and 0.9 ± 0.4 mg·dL-1, P = .023). No arterial thrombosis was detected by CTA or histology of embolized arteries and TF did not rise significantly. There were extensive macrophage infiltrates surrounding muscle necrosis in Group I only. CONCLUSIONS: Cholesterol crystal emboli triggered muscle inflammation and necrosis with an intact circulation. PET/CTA may help in the early detection of inflammation caused by CCs.
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Arterias/diagnóstico por imagen , Colesterol/química , Placa Aterosclerótica/diagnóstico por imagen , Trombosis/diagnóstico por imagen , Animales , Arterias/metabolismo , Biomarcadores/sangre , Angiografía por Tomografía Computarizada , Cristalización , Fluorodesoxiglucosa F18 , Inflamación/diagnóstico por imagen , Inyecciones Intraarteriales , Microesferas , Músculo Esquelético/lesiones , Miositis/diagnóstico por imagen , Necrosis , Placa Aterosclerótica/química , Poliestirenos , Tomografía de Emisión de Positrones , Conejos , Trombosis/metabolismoRESUMEN
Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1ß (IL-1ß) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1ß or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.
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Arteritis , Colesterol , Células Espumosas , Humanos , Lipoproteínas HDL , Placa AteroscleróticaRESUMEN
Persistent inflammation and mechanical injury associated with cholesterol crystal accretion within atherosclerotic plaques typically precedes plaque disruption (rupture and/or erosion) and thrombosis--often the terminal events of atherosclerotic cardiovascular disease. To elucidate the mechanisms of these events, the atherosclerotic rabbit model provides a unique and powerful tool that facilitates studies of atherogenesis starting with plaque buildup to eventual disruption. Examination of human coronary arteries obtained from patients who died with myocardial infarction demonstrates evidence of cholesterol crystals perforating the plaque cap and intimal surface of the arterial wall that can lead to rupture. These observations were made possible by omitting ethanol, an avid lipid solvent, from the tissue processing steps. Importantly, the atherosclerotic rabbit model exhibits a similar pathology of cholesterol crystals perforating the intimal surface as seen in ruptured human plaques. Local and systemic inflammatory responses in the model are also similar to those observed in humans. The strong parallel between the rabbit and human pathology validates the atherosclerotic rabbit model as a predictor of human pathophysiology of atherosclerosis. Thus, the atherosclerotic rabbit model can be used with confidence to evaluate diagnostic imaging and efficacy of novel anti-atherosclerotic therapy.
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Aterosclerosis/fisiopatología , Enfermedad de la Arteria Coronaria/fisiopatología , Modelos Animales de Enfermedad , Placa Aterosclerótica/patología , Trombosis/patología , Animales , Aterosclerosis/etiología , Aterosclerosis/patología , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/patología , Humanos , Inflamación/patología , Infarto del Miocardio/patología , Conejos , Rotura Espontánea/etiología , Rotura Espontánea/patología , Rotura Espontánea/fisiopatología , Túnica Íntima/patologíaRESUMEN
The inflammatory nature of atherosclerosis is well established but the agent(s) that incite inflammation in the artery wall remain largely unknown. Germ-free animals are susceptible to atherosclerosis, suggesting that endogenous substances initiate the inflammation. Mature atherosclerotic lesions contain macroscopic deposits of cholesterol crystals in the necrotic core, but their appearance late in atherogenesis had been thought to disqualify them as primary inflammatory stimuli. However, using a new microscopic technique, we revealed that minute cholesterol crystals are present in early diet-induced atherosclerotic lesions and that their appearance in mice coincides with the first appearance of inflammatory cells. Other crystalline substances can induce inflammation by stimulating the caspase-1-activating NLRP3 (NALP3 or cryopyrin) inflammasome, which results in cleavage and secretion of interleukin (IL)-1 family cytokines. Here we show that cholesterol crystals activate the NLRP3 inflammasome in phagocytes in vitro in a process that involves phagolysosomal damage. Similarly, when injected intraperitoneally, cholesterol crystals induce acute inflammation, which is impaired in mice deficient in components of the NLRP3 inflammasome, cathepsin B, cathepsin L or IL-1 molecules. Moreover, when mice deficient in low-density lipoprotein receptor (LDLR) were bone-marrow transplanted with NLRP3-deficient, ASC (also known as PYCARD)-deficient or IL-1alpha/beta-deficient bone marrow and fed on a high-cholesterol diet, they had markedly decreased early atherosclerosis and inflammasome-dependent IL-18 levels. Minimally modified LDL can lead to cholesterol crystallization concomitant with NLRP3 inflammasome priming and activation in macrophages. Although there is the possibility that oxidized LDL activates the NLRP3 inflammasome in vivo, our results demonstrate that crystalline cholesterol acts as an endogenous danger signal and its deposition in arteries or elsewhere is an early cause rather than a late consequence of inflammation. These findings provide new insights into the pathogenesis of atherosclerosis and indicate new potential molecular targets for the therapy of this disease.
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Aterosclerosis/metabolismo , Aterosclerosis/patología , Proteínas Portadoras/metabolismo , Colesterol/química , Colesterol/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis , Aterosclerosis/inducido químicamente , Trasplante de Médula Ósea , Proteínas Adaptadoras de Señalización CARD , Proteínas Portadoras/genética , Catepsina B/metabolismo , Catepsina L/metabolismo , Colesterol/farmacología , Cristalización , Proteínas del Citoesqueleto/deficiencia , Dieta Aterogénica , Femenino , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Interleucina-1/deficiencia , Interleucina-18/metabolismo , Lisosomas/efectos de los fármacos , Lisosomas/patología , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Cavidad Peritoneal/patología , Fagocitos/efectos de los fármacos , Fagocitos/patología , Fagocitos/fisiología , Receptores de LDL/deficiencia , Factores de TiempoRESUMEN
PURPOSE: The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. METHODS: Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. RESULTS: The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. CONCLUSIONS: Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.
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Receptores de Hialuranos/efectos de los fármacos , Nanopartículas/química , Placa Aterosclerótica/patología , Animales , Línea Celular , Ácido Hialurónico/metabolismo , Magnetismo , Masculino , Placa Aterosclerótica/diagnóstico , ARN Interferente Pequeño/genética , Conejos , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
This is the case of a 31-year-old man with no significant past medical history who presented to the emergency department experiencing persistent fevers, chills, and malaise for the past 2-3 weeks. During this period, he had multiple urgent care visits for possible left-sided otitis media which was treated with short a course of Augmentin. While on antibiotics his symptoms would improve, but they would reappear once he had finished treatment. The patient also had significant dental carries with a chronic right molar infection. At the emergency department, blood cultures grew two out of two Gemella morbillorum. Transthoracic echocardiography showed a 1 cm x 0.5 cm mobile density on the left coronary cusp of the aortic valve with moderate-severe aortic insufficiency. The patient was started on empiric IV vancomycin. Further workup revealed that the source of infection was dental carries. While proceeding with a transesophageal echocardiogram, the patient went into flash pulmonary edema requiring ICU admission. Imaging revealed an elongated 1.7 cm x 0.6 cm vegetation attached to the base of the left coronary cusp on the left ventricular outflow tract side with severe aortic regurgitation and a small 0.8 cm x 0.8 cm vegetation on the atrial side of the anterior mitral leaflet at A2 associated with mitral leaflet perforation with severe mitral regurgitation. Oral surgery removed the infected teeth. Cardiothoracic surgery performed open heart valve replacement which revealed a completely destroyed aortic valve, droplet vegetation, and destruction of the mitral valve leading to mechanical valve replacement. The patient received a two-week course of gentamycin while in the ICU with meropenem. Once sensitivities were back, he was switched to IV penicillin therapy for a total of six weeks.
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Pulmonary hypertension (PH) is a known chronic condition that can lead to increased morbidity and mortality. Patients who develop PH due to thromboembolic disease are catalogued as chronic thromboembolic pulmonary hypertension (CTEPH). Anticoagulation remains a topic of interest in these patients. PUBMED, EMBASE and COCHRANE databases were searched by two investigators until December 2023. Information was analyzed for all-cause mortality, venous thromboembolism and major bleeding. We included a total of 10 studies in this meta-analysis. Our pooled analysis demonstrated that DOACs were non-inferior in all-cause mortality [OR 0.88, 95 % CI (0.48, 1.61)], venous thromboembolism [OR 1.00, 95 % CI (0.50, 1.98)] and major bleeding [OR 0.78, 95 % CI (0.43, 1.40)] when compared to VKAs. In conclusion, our meta-analysis supports the use of DOACs in patients with CTEPH. Further randomized trials are still needed to confirm our results in terms of safety and mortality.
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Anticoagulantes , Hipertensión Pulmonar , Embolia Pulmonar , Vitamina K , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Vitamina K/antagonistas & inhibidores , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/complicaciones , Embolia Pulmonar/mortalidad , Administración Oral , Enfermedad Crónica , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Resultado del Tratamiento , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/administración & dosificaciónRESUMEN
Background: Inflammation is pivotal to the progression of atherosclerosis. Cholesterol crystals (CCs) that grow and enlarge within the plaque core can cause plaque rupture and trigger inflammation as they deposit into the atherosclerotic bed. Thus, agents that affect CC formation, expansion, and morphology may reduce cardiovascular (CV) risk independent of lipid-lowering and anti-inflammatory therapy. Objective: Because colchicine is highly concentrated in leukocytes that can enter the atherosclerotic plaque core, we tested its effect on the formation and growth of CCs in bench experiments to determine whether it may have direct effects on CCs, independent of its known anti-inflammatory actions. Method: Different dosages of colchicine mixed with cholesterol (0.05-5â mg/ml/g of cholesterol) were used to influence the formation CCs and volume expansion in vitro. These were compared to control samples with cholesterol in ddH2O without colchicine. In an ex vivo study, fresh atherosclerotic human plaques were incubated with and without colchicine in a water bath at 37°C for 48â h to assess the impact of colchicine on CC morphology. Scanning electron microscopy (SEM) was utilized to analyze CC morphology in samples from the various treatment groups. Results: The addition of colchicine to cholesterol caused a substantial dose-dependent reduction in volume (p < 0.05). Pairwise comparisons of volume reduction, showed a significant reduction in volume at 5â mg/ml/g when compared to control (p < 0.02) but the calculated Cohen's d effect size was large for five of the six pairwise comparisons. By SEM, CCs from both in vitro and ex vivo samples treated with colchicine had evidence of dissolution and changes in their morphology as evidenced by the loss of their sharp edges. In contrast, CCs in untreated specimens retained their typical geometric structure. Conclusions: Colchicine can reduce CC formation and expansion and alter CC morphology. These previously unappreciated effects of colchicine may contribute to its clinical benefit in patients with CV disease independent of its anti-inflammatory effects.
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Tricuspid valve infective endocarditis (TVIE), often associated with vegetation in people who inject drugs, has introduced a less invasive option for vegetation removal: transcatheter vacuum-assisted mass extraction (TVME). This technique is emerging as an alternative to standard surgical debridement (SD) and valve repair. However, the comparative effectiveness of TVME versus SD in treating TVIE has yet to be investigated. A comprehensive systematic literature search was performed on PubMed, Embase, and Cochrane to identify all relevant studies comparing TVME with SD in patients with TVIE. The search covered studies from inception up to August 15, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random-effects model to calculate risk ratios (RRs), mean differences, and 95% confidence intervals (CIs). Five studies included a total of 431 patients (244 in the TVME arm and 187 in the SD arm). In-hospital mortality (p = 0.72), procedural mortality (p = 0.77), 30-day mortality (p = 0.25), and 1-year mortality (p = 0.44) insignificantly favored SD over TVME. Overall mortality across the 5 studies insignificantly favored TVME over SD (RR = 0.66, 95% CI 0.31 to 1.39, p = 0.27, I2 = 57%). When addressing heterogeneity by excluding 1 study, no statistical significance in the difference between the 2 arms regarding overall mortality was observed (RR 0.99, 95% CI 0.60 to 1.63, p = 0.97, I2 = 0%). This meta-analysis of the 5 observational studies found no significant difference in overall mortality between TVME and SD for the treatment of TVIE. However, prospective randomized controlled trials are necessary to further understand and compare the outcomes of these 2 approaches.
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Endocarditis , Válvula Tricúspide , Humanos , Válvula Tricúspide/cirugía , Desbridamiento , Estudios Prospectivos , Resultado del Tratamiento , Endocarditis/complicaciones , Estudios Observacionales como AsuntoRESUMEN
Key Clinical Message: Middle-aged male athletes, with or without underlying coronary artery disease, exhibiting exercise induced blood pressure (BP) variability and diabetes can have an increased risk of developing atrial fibrillation (AF). Assessment in athletes should include long-term arrhythmia monitoring. In addition, it is important to exert patients beyond their calculated target heart rate (HR) during an exercise stress test to detect exercise-induced AF. We suggest this strategy be specifically used for athletes with complaints of intermittent palpitation and chest pain. Referral to an electrophysiologist for a possible ablation procedure should be considered for the management of AF in athletes in whom the use of beta-blockers may limit exercise tolerance. Bleeding risk with the use of oral anticoagulation needs to be adequately evaluated in athletes with AF who engage in high-intensity exercise or activities. Abstract: The report highlights the case of a 54-year-old Caucasian male (height 5.11', BMI 29.8) who presented with complaints of chest pain, mild coronary artery disease, palpitation, dizziness, and labile BP with high-intensity biking exercise. Diagnostic tests (exercise stress test, cardiac catheterization, Holter monitor, and Bardy patch) using standard procedure were unsuccessful at detecting the problem. In a repeat exercise stress test, the patient was exerted beyond the calculated HRmax (up to 117%) when the patient's heart rhythm flipped from sinus rhythm to AF. The patient was referred to a cardiac electrophysiologist and an ablation procedure was performed to prevent exercise-induced AF with high-intensity exercise. Young adults, with or without early coronary artery disease, performing high-intensity endurance exercises may be at risk of developing exercise-induced AF. This phenomenon is prevalent and well documented in the skiing population and patients with variance in BP during exercise. Endurance athletes tend to have a lower resting HR. As such, the use of standard rate-control medications in patients with exercise-induced AF may not be appropriate. Referral to a cardiac electrophysiologist and ablation procedures should be considered in this population for management and symptom control. If tolerated, especially in young adults with complaints of palpitation and chest pain, patients should be exerted beyond their calculated HRmax during an exercise stress test to diagnose an underlying condition of exercise-induced AF.
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The foramen ovale serves as an opening between the right and left atria at the site of the fossa ovalis in the fetus during uterine life. During fetal life, it makes it possible for venous blood from the maternal placenta with oxygen and nutrients to bypass the immature fetal lung and get transported to the left side of the heart and onto the systemic circulation. This hole from the right to the left atrium is usually occluded at the time of birth or shortly after birth, due to increased pressures in the left-sided cardiac cavities associated with normal breathing during delivery or shortly afterwards. If the foramen ovale remains open and fails to fuse beyond the first year of life, it is known as a patent foramen ovale (PFO). PFO occurs when, during fetal life, the septum primum and secundum, which develop and overlap normally, fail to fuse at birth. This results in the persistence of communication between the right and left atria. Paradoxical embolism from the right to the left side of the heart can occur through a PFO, causing a cryptogenic stroke or embolic stroke of an undetermined source in an otherwise healthy adult. There was a debate on the long-term benefits of closure. However, data from the randomized evaluation of the recurrent stroke comparing PFO closure to established current standard of care treatment (RESPECT) trial and two randomized trials (patent foramen ovale closure or anticoagulants versus antiplatelet therapy to prevent stroke recurrence (CLOSE) and reduction by dutasteride of prostate cancer events (REDUCE)) have clarified that there is a benefit to closure. In this case report, we describe a patient who presented with cryptogenic stroke, the investigations, imaging modalities for diagnosis of PFO, and procedure for closure. We also describe long-term outcomes and management following closure.
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This abstract presents the case of a 37-year-old female with no significant past medical history who presented to the emergency department with a unique and challenging clinical scenario. The patient complained of chest pain, dyspnea, and a productive cough associated with stabbing chest pain that improved with leaning forward for the past week. Despite an initial diagnosis of community-acquired pneumonia, the patient's condition deteriorated rapidly, leading to septic shock. Blood cultures ultimately revealed Streptococcus pneumoniae as the causative organism. Subsequent imaging and diagnostic procedures demonstrated a complex clinical course, including loculated pleural and pericardial effusions. The patient's condition necessitated multiple interventions, including pericardiocentesis, chest tube placement, and intracavitary lytic therapies, in addition to intubation for acute respiratory failure. The case further evolved with the development of a pericardial abscess, successfully managed with surgical drainage and a partial pericardiectomy. The patient eventually showed significant clinical improvement and was discharged on a targeted antibiotic regimen. This case highlights the importance of vigilance in identifying rare complications of pneumonia and the need for prompt, multidisciplinary management to ensure the best possible outcome for the patient. Long-term follow-up was recommended to assess the patient's recovery. This case underscores the complexities and challenges of managing uncommon presentations of infectious diseases and emphasizes the value of a comprehensive, multidisciplinary approach in such cases.
RESUMEN
Because of its anatomic and procedural complexities, bicuspid aortic valve (BAV) has been excluded from previous trials investigating transcatheter aortic valve replacement (TAVR). We aimed to compare the clinical outcomes of TAVR in BAV and tricuspid aortic valve patients. We searched the databases systematically from inception until March 2023 for studies that reported the outcomes of TAVR in BAV and tricuspid aortic valve patients. The primary focus was all-cause mortality at 1 year. Additional outcomes included outcomes at 30-day follow-up. Secondary and subgroup analyses were performed on propensity-matched patients, patients at low surgical risk, and based on the type of transcatheter valve type. We included 30 studies with a total of 193,274 patients who underwent TAVR, of which 14,353 patients had BAV stenosis. The rate of 1-year mortality was lower in the BAV group compared with the tricuspid group with the results reaching statistical significance (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.75 to 0.98, p = 0.02). The rate of 30-day stroke, however, was higher in patients with BAV who underwent TAVR (OR 1.24, 95% CI 1.08 to 1.43, p <0.05). Other 30-day clinical outcomes were similar between the 2 groups. Similar outcomes were observed in secondary analysis of matched populations with less mortality and higher rate of stroke in patients with BAV (OR 0.84, 95% CI 0.72 to 0.96, p = 0.01, and OR 1.38, 95% CI 1.09 to 1.75, p <0.05, respectively). Comparing the outcomes for self-expandable and balloon-expandable valves resulted in similar results. Subgroup analysis of low-surgical-risk patients similarly showed lower 1-year mortality in patients with BAV (OR 0.67, 95% CI 0.50 to 0.91, p = 0.01), without difference in 30-day stroke between the 2 groups (OR 1.24, 95% CI 0.83 to 1.88, p = 0.30). In conclusion, this report indicates that TAVR is safe and feasible in patients with BAV, including patients at low surgical risk. The higher rate of 30-day stroke, however, warrants caution when pursuing TAVR in this population. More studies, specifically randomized trials, are still warranted to further assess the safety and the long-term outcomes in this group.
Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Estenosis de la Válvula Tricúspide , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/complicaciones , Válvula Aórtica/cirugía , Estenosis de la Válvula Tricúspide/cirugía , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones , Accidente Cerebrovascular/etiologíaRESUMEN
Atrial fibrillation (AF) is a common complication in patients who underwent transcatheter aortic valve implantation. Some of these patients have preexisting AF as well. The management of these patients is complex, especially after the procedure, when there is a sudden change in hemodynamics. There are no established guidelines about the management of the patients who underwent transcatheter aortic valve replacement with preexisting or new-onset AF. This review article discusses the management of these patients with rate and rhythm control strategies with medications. This article also highlights the role of newer oral anticoagulation medications and left atrial occlusion devices to prevent stroke after the procedure. We will also discuss new advances in the care of this patient population to prevent the occurrence of AF after transcatheter aortic valve implantation. In conclusion, this article is a synopsis of both pharmacologic and device interventions for the management of AF in patients who underwent transcatheter aortic valve replacement.