RESUMEN
Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (n = 16) were placed on a high-fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68Ga-DOTATATE, 18F-NaF, and 18F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal-corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (r = .813, p = .008) and macrophage/smooth muscle cell (SMC) ratio (r = .813, p = .026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r = .883, p = .004) and %stenosis (r = .901, p = .002), similar to IVUS. 68Ga-DOTATATE correlated with intimal macrophage infiltration (r = .861, p = .003) and macrophage/SMC ratio (r = .831, p = .021), 18F-NaF with SMC infiltration (r = -.842, p = .018), and 18F-FDG correlated with macrophage/SMC ratio (r = .787, p = .036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease.
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Aterosclerosis , Espectroscopía Dieléctrica , Animales , Conejos , Espectroscopía Dieléctrica/métodos , Masculino , Aterosclerosis/patología , Aterosclerosis/diagnóstico por imagen , Aorta Abdominal/patología , Aorta Abdominal/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Tomografía de Emisión de Positrones/métodos , Fenotipo , Modelos Animales de Enfermedad , Macrófagos/patología , Macrófagos/metabolismoRESUMEN
An 81-year-old male with a history of coronary artery disease, hypertension, paroxysmal atrial fibrillation and chronic kidney disease presents with asymptomatic bradycardia. Examination was notable for an early diastolic heart sound. 12-lead electrocardiogram revealed sinus bradycardia with a markedly prolonged PR interval and second-degree atrioventricular block, type I Mobitz. We review the differential diagnosis of early diastolic heart sounds and present a case of Wenckebach associated with a variable early diastolic sound on physical exam.
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Fibrilación Atrial , Bloqueo Atrioventricular , Ruidos Cardíacos , Anciano de 80 o más Años , Humanos , Masculino , Fibrilación Atrial/diagnóstico , Bloqueo Atrioventricular/diagnóstico , Bradicardia , Electrocardiografía , Atrios CardíacosRESUMEN
PURPOSE OF REVIEW: Adult congenital heart disease patients with systemic right ventricle comprise a distinctly clinically challenging group of patients with increased morbidity and mortality. This article aims to review the different subgroups, most common complications and different treatment strategies. RECENT FINDINGS: Most commons long-term complications include heart failure and arrhythmias. Heart failure medical therapy treatments include several new agents, which show promise in systemic right ventricle patients. In addition, interventional therapies to mitigate atrioventricular valve regurgitation, baffle/conduit stenosis are discussed. Furthermore, several electrophysiological approaches to manage tachyarrhythmias as well as bradycardias are discussed. There is ongoing excitement on the new medical as well as interventional therapies that could provide benefit in additional to standard goal-directed medical therapy. SUMMARY: There is an array of medications as well as interventions aimed to treat patients with systemic right ventricle with limited benefits. A multidisciplinary approach with a prudent combination of such therapies to maximize benefit is imperative. This article reviews the data supporting such therapies.
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Cardiopatías Congénitas , Insuficiencia Cardíaca , Adulto , Arritmias Cardíacas , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/terapia , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos , HumanosRESUMEN
Extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) in the setting of pulmonary arterial hypertension (PAH) is an increasingly recognized disease entity. LMCA compression has been associated with angina, arrhythmia, heart failure, and sudden cardiac death in patients with PAH. Recent studies suggest that at least 6% of patients with PAH have significant LMCA compression. Screening for LMCA compression can be achieved with computed coronary tomography angiography, with a particular emphasis on assessment of PA size and any associated downward displacement and reduced takeoff angle of the LMCA. Indeed, evidence of a dilated PA (>40 mm), a reduced LMCA takeoff angle (<60°), and/or LMCA stenosis on CCTA imaging should prompt further diagnostic evaluation. Coronary angiography in conjunction with intravascular imaging has proven effective in diagnosing LMCA compression and guiding subsequent treatment. While optimal medical therapy and surgical correction remain in the clinician's arsenal, percutaneous coronary intervention has emerged as an effective treatment for LMCA compression. Given the prevalence of LMCA compression, its associated morbidity, and mortality, and the wide array of successful treatment strategies, maintaining a high degree of suspicion for this condition, and understanding the potential treatment strategies is critical.
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Angioplastia Coronaria con Balón , Estenosis Coronaria , Hipertensión Pulmonar , Angiografía Coronaria , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Arteria Pulmonar/diagnóstico por imagen , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both. CASE PRESENTATION: A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated. CONCLUSIONS: This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.
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COVID-19 , Procedimiento de Fontan , Gangrena , Trombolisis Mecánica , Complicaciones Posoperatorias , Tromboflebitis , Atresia Tricúspide , Warfarina/uso terapéutico , Amputación Quirúrgica/métodos , Aleteo Atrial/tratamiento farmacológico , Aleteo Atrial/etiología , COVID-19/sangre , COVID-19/complicaciones , COVID-19/terapia , Procedimiento de Fontan/efectos adversos , Procedimiento de Fontan/métodos , Gangrena/etiología , Gangrena/cirugía , Cardiopatías Congénitas/cirugía , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/patología , Extremidad Inferior/cirugía , Masculino , Trombolisis Mecánica/efectos adversos , Trombolisis Mecánica/métodos , Persona de Mediana Edad , Flebografía/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/cirugía , Síndrome del Seno Enfermo/diagnóstico , Síndrome del Seno Enfermo/etiología , Tromboflebitis/diagnóstico , Tromboflebitis/etiología , Tromboflebitis/cirugía , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Atresia Tricúspide/etiología , Atresia Tricúspide/cirugíaRESUMEN
WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning. Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels. The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention. In this review, we first will focus on the constituents of the pathway and their regulation and the different signaling routes. Subsequently, the role of WNT signaling in cardiovascular development is addressed, followed by a detailed discussion of its involvement in vascular and cardiac disease. After highlighting the crosstalk between WNT, transforming growth factor-ß and angiotensin II signaling, and the emerging role of WNT signaling in the regulation of stem cells, we provide an overview of drugs targeting the pathway at different levels. From the combined studies we conclude that, despite the sometimes conflicting experimental data, a general picture is emerging that excessive stimulation of WNT signaling adversely affects cardiovascular pathology. The rapidly increasing collection of drugs interfering at different levels of WNT signaling will allow the evaluation of therapeutic interventions in the pathway in relevant animal models of cardiovascular diseases and eventually in patients in the near future, translating the outcomes of the many preclinical studies into a clinically relevant context.
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Enfermedades Cardiovasculares/metabolismo , Vía de Señalización Wnt/fisiología , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Humanos , Terapia Molecular Dirigida , Vía de Señalización Wnt/efectos de los fármacosRESUMEN
Congenital heart disease patients, specifically with unbalanced atrioventricular septal defects and common atrioventricular valves requiring single ventricle palliation, have substantial morbidity and mortality. Atrioventricular valve regurgitation (AVVR) is associated with poor outcomes in single ventricle patients, and many of them require surgical treatment of AVVR in their lifetimes. We describe a unique case of transcatheter edge-to-edge valve repair using the MitraClip system (Abbott, Chicago, IL) in a single ventricle patient with severe common AVVR.
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Procedimientos Quirúrgicos Cardíacos , Ventrículo Derecho con Doble Salida/cirugía , Defectos de los Tabiques Cardíacos/complicaciones , Defectos de los Tabiques Cardíacos/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Válvulas Cardíacas/cirugía , Síndrome de Heterotaxia/cirugía , Adulto , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Ventrículo Derecho con Doble Salida/diagnóstico por imagen , Ventrículo Derecho con Doble Salida/fisiopatología , Defectos de los Tabiques Cardíacos/fisiopatología , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/etiología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Válvulas Cardíacas/diagnóstico por imagen , Válvulas Cardíacas/fisiopatología , Síndrome de Heterotaxia/diagnóstico por imagen , Síndrome de Heterotaxia/fisiopatología , Humanos , Masculino , Recuperación de la Función , Resultado del TratamientoRESUMEN
Survival of patients with congenital heart disease has significantly improved over the last 2 decades, confronting interventionalists, surgeons, anesthesiologists, cardiologists, and intensivists with often unfamiliar complex pathophysiology in the perioperative setting. Aside from cardiac catheterization, echocardiography has become the main imaging modality in the hospitalized adult with congenital heart disease. The great variety of congenital lesions and their prior surgical management challenges practitioners to generate optimal imaging, reporting, and interpretation of these complex anatomic structures. Standardization of echocardiographic studies can not only provide significant benefits in the surveillance of these patients, but also facilitate understanding of pathophysiologic mechanism and assist clinical management in the perioperative setting. Knowledge in obtaining and interpreting uniform imaging protocols is essential for the perioperative clinician. In this publication, the authors review current international consensus recommendations on echocardiographic imaging of adults with congenital heart disease and describe the fundamental components by specific lesion. The authors will emphasize key aspects pertinent to the clinical management when imaging these patients in the perioperative setting. The goal of this review is to familiarize the perioperative physician on how to structure and standardize echocardiographic image acquisition of congenital heart disease anatomy for optimal clinical management.
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Cardiopatías Congénitas , Adulto , Anestesiólogos , Cateterismo Cardíaco , Consenso , Ecocardiografía , Ecocardiografía Transesofágica , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , HumanosRESUMEN
OBJECTIVES: We sought to delineate the risk factors for infective endocarditis (IE) in patients undergoing transcatheter pulmonary valve replacement (TCPVR). BACKGROUND: Despite the therapeutic benefits of TCPVR for treatment of dysfunctional right ventricular outflow tracts, IE is a major complication of the approach. Specific hemodynamic gradients and patient immune status as predisposing factors for IE are largely unexplored. METHODS: We performed a retrospective review of patients who had undergone TCPVR at UCLA between October 2010 and October 2017. Cases of IE were diagnosed based on the modified Duke criteria. RESULTS: Two hundred and thirty-five cases of TCPVR were performed with a mean follow-up of 2.6 years (range 0.0-8.0 years). Sixteen distinct IE events developed in 13 patients (Melody™ n = 12, SAPIEN n = 1), with a median time from implant to IE of 3.3 years (range 2.0-7.2 years). Univariate Cox regression showed that immunocompromised status was significantly associated with the development of IE hazard ratios (HR 5.43 [1.80-16.4], p = .003). Kaplan-Meier curves show that the 5-year freedom from IE among immunocompetent patients was 87% (95% CI 78-96%) versus 64% (95% CI 39-89%) among immunocompromised patients (log-rank p = .02). Postimplant right ventricular systolic pressure was higher among immunocompromised patients (p = .03). The risk of IE post-TCPVR in immunocompromised patients with residual pulmonary stenosis was 43%. CONCLUSIONS: Among the risk factors examined in this study, immunocompromised status was the most significant predictor of IE development post-TCPVR. Patients with the lowest risk of IE are those with competent immune systems, without a history of IE, and with minimal residual pulmonary valve gradients post-TCPVR.
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Cateterismo Cardíaco/efectos adversos , Endocarditis/etiología , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Insuficiencia de la Válvula Pulmonar/cirugía , Estenosis de la Válvula Pulmonar/cirugía , Válvula Pulmonar/cirugía , Adolescente , Adulto , Cateterismo Cardíaco/instrumentación , Toma de Decisiones Clínicas , Endocarditis/diagnóstico , Endocarditis/inmunología , Femenino , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/inmunología , Cardiopatías Congénitas/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Hemodinámica , Humanos , Huésped Inmunocomprometido , Masculino , Supervivencia sin Progresión , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/inmunología , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/fisiopatología , Insuficiencia de la Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/inmunología , Insuficiencia de la Válvula Pulmonar/fisiopatología , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/inmunología , Estenosis de la Válvula Pulmonar/fisiopatología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Chronic pulmonary regurgitation (PR) following surgical correction in Tetralogy of Fallot (TOF) leads to right ventricular (RV) dysfunction, arrhythmias and sudden cardiac death (SCD). Pulmonary valve replacement (PVR) decreases PR and improves RV function, but data regarding QRS duration reduction remain scarce. METHODS: All adult TOF patients undergoing transcatheter PVR or surgical PVR from 2010 to 2016 were included. Clinical characteristics and QRS duration were measured and compared to post-intervention QRS duration using an institutional software and manually verified. Significantly wide QRS was defined as QRS >140â¯ms. RESULTS: Of 133 PVR patients, 85 had TOF and 27 (21.1%) had QRSâ¯>â¯140â¯ms (14 transcatheter, 13 surgical) and were included in this analysis. A 6â¯ms decrease in QRS duration was seen at 3-year follow-up (168.0⯱â¯3.5â¯ms vs. 161.8⯱â¯3.5â¯ms, pâ¯=â¯.04). There was a significant decrease in the median RV size (defined as RV/LV diameter ratio) pre-intervention to 3-year post-intervention: (0.96 vs 0.89, pâ¯=â¯.03). The median PR decreased significantly from moderate-severe to mild post-intervention (pâ¯<â¯.0001). CONCLUSIONS: Replacement of the pulmonary valve in high risk TOF patients reduces QRS duration at 3â¯years. Further study is needed to assess whether this QRS duration reduction may identify patients at lower risk of ventricular arrhythmias.
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Arritmias Cardíacas/prevención & control , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Pulmonar/etiología , Insuficiencia de la Válvula Pulmonar/cirugía , Válvula Pulmonar/cirugía , Tetralogía de Fallot/cirugía , Adolescente , Adulto , Muerte Súbita Cardíaca/etiología , Electrocardiografía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Disfunción Ventricular Derecha/etiologíaRESUMEN
OBJECTIVES: To provide a comparison of the outcome of infective endocarditis (IE) in patients undergoing transcatheter pulmonary valve replacement (TPVR) versus surgical pulmonary valve replacement (SPVR). BACKGROUND: Although TPVR is thought to be associated with a higher risk of IE than SPVR, there is paucity of data to support this. METHODS: Patients who underwent TPVR or SPVR at UCLA between October 2010 and September 2016 were included and retrospectively analyzed. RESULTS: Three hundred forty-two patients underwent PVR at UCLA including 134 SPVR and 208 TPVR. Patients undergoing TPVR were more likely to have had a history of endocarditis than those undergoing SPVR (5.3% vs. 0.7%, P = 0.03) and a right ventricle to pulmonary artery (RV to PA) conduit (37% vs. 17%, P = 0.0001). Two SPVR and seven TPVR patients developed IE with a 4-year freedom from endocarditis of 94.0% in the SPVR versus 84% in the TPVR group (P = 0.13). In patients who underwent TPVR and developed endocarditis, the mean gradient across the RVOT prior to intervention was higher (28.1 ± 4.5 vs. 17.4 ± 0.6 mmHg, P = 0.02) and were more likely to have a conduit (71% vs. 36%, P = 0.049). CONCLUSIONS: In this study, patients undergoing TPVR were not at a higher risk of IE than patients undergoing SPVR. TPVR patients were more likely to have had a prior history of IE and RV-PA conduit. The patients at highest risk were those with stenotic RV to PA conduits who were treated with TPVR.
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Cateterismo Cardíaco/efectos adversos , Endocarditis/epidemiología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Válvula Pulmonar/cirugía , Adolescente , Adulto , Cateterismo Cardíaco/instrumentación , Cateterismo Cardíaco/métodos , Niño , Endocarditis/diagnóstico , Endocarditis/terapia , Femenino , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/métodos , Humanos , Incidencia , Los Angeles/epidemiología , Masculino , Válvula Pulmonar/diagnóstico por imagen , Válvula Pulmonar/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: We evaluated the clinical outcomes of elderly patients who underwent orbital atherectomy for the treatment of severe coronary artery calcification (CAC) prior to stenting. BACKGROUND: Percutaneous coronary intervention (PCI) of severe CAC is associated with worse clinical outcomes including death, myocardial infarction (MI), and target vessel revascularization (TVR). The elderly represents a high-risk group of patients, often have more comorbid conditions, and have worse outcomes after PCI compared to younger patients. Clinical trials and a large multicenter registry have demonstrated the safety and efficacy of orbital atherectomy for the treatment of severe CAC. Clinical outcomes of elderly patients who undergo orbital atherectomy are unknown. METHODS: Of the 458 patients, 229 were ≥75 years old (elderly) and 229 were <75 years old (younger). The primary endpoint was rate of 30-day major adverse cardiac and cerebrovascular events (MACCE), comprised of cardiac death, MI, TVR, and stroke. RESULTS: The primary endpoint was similar in the elderly and younger groups (2.2% vs. 2.2%, P = 1), as were the individual endpoints of death (2.2% vs. 0.4%, P = 0.1), MI (0.9% vs. 1.3%, P = 0.65), TVR (0% vs. 0%, P = 1), and stroke (0% vs. 0.4%, P = 0.32). The rates of angiographic complications and stent thrombosis were similarly low in both groups. CONCLUSIONS: The elderly represented a sizeable number of patients who underwent orbital atherectomy. It is a safe and effective treatment strategy for elderly patients with severe CAC as the clinical outcomes were similar to their younger counterparts. A randomized trial should further clarify the role of orbital atherectomy in these patients.
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Aterectomía Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Calcificación Vascular/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
RATIONALE: During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown. OBJECTIVE: Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature. METHODS AND RESULTS: As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors. CONCLUSION: Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.
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Diferenciación Celular/genética , Vasos Coronarios/crecimiento & desarrollo , Desarrollo Embrionario/genética , Corazón/crecimiento & desarrollo , Animales , Linaje de la Célula/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Vasos Coronarios/embriología , Vasos Coronarios/metabolismo , Embrión de Mamíferos , Transición Epitelial-Mesenquimal/genética , Ratones , Ratones NoqueadosRESUMEN
BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.
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Procedimiento de Fontan , Cardiopatías Congénitas , Hepatopatías , Adulto , Humanos , Masculino , Femenino , Estudios Retrospectivos , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Hepatopatías/genética , Hepatopatías/cirugía , Fibrosis , Perfilación de la Expresión Génica , ARN , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/cirugíaRESUMEN
Background: Distinguishing quiescent from rupture-prone atherosclerotic lesions has significant translational and clinical implications. Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies.We evaluated invasive 6-point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Methods: Male New Zealand White rabbits (n=16) were placed on a high-fat diet for 4 or 8 weeks, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in vivo micro-PET imaging of the abdominal aorta with 68 Ga-DOTATATE, 18 F-NaF, and 18 F-FDG, followed by invasive interrogation via IVUS and EIS. Background signal corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histological analyses. Analyses were performed blindly. Results: Phase delay correlated with anatomic markers of plaque burden, namely intima/media ratio (r=0.883 at 1 kHz, P =0.004) and %stenosis (r=0.901 at 0.25 kHz, P =0.002), similar to IVUS. Moreover, impedance was associated with markers of plaque activity including macrophage infiltration (r=0.813 at 10 kHz, P =0.008) and macrophage/smooth muscle cell (SMC) ratio (r=0.813 at 25 kHz, P =0.026). 68 Ga-DOTATATE correlated with intimal macrophage infiltration (r=0.861, P =0.003) and macrophage/SMC ratio (r=0.831, P =0.021), 18 F-NaF with SMC infiltration (r=-0.842, P =0.018), and 18 F-FDG correlated with macrophage/SMC ratio (r=0.787, P =0.036). Conclusions: EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non-invasive imaging approaches to capture. These findings indicate the potential of invasive EIS as a comprehensive modality for evaluation of human coronary artery disease. HIGHLIGHTS: Electrochemical impedance spectroscopy (EIS) characterizes both anatomic features - via phase delay; and inflammatory activity - via impedance profiles, of underlying atherosclerosis.EIS can serve as an integrated, comprehensive metric for atherosclerosis evaluation by capturing morphological and compositional plaque characteristics that otherwise require multiple imaging modalities to obtain.Translation of these findings from animal models to human coronary artery disease may provide an additional strategy to help guide clinical management.
RESUMEN
INTRODUCTION: Fontan patients have variable exercise capacity. Contemporary understanding as to which factors predict high tolerance is limited. METHODS: Records from the Ahmanson/University of California, Los Angeles Adult Congenital Heart Disease Center were reviewed for adult Fontan patients who underwent CPET. Patients were considered "high performers" if their maximum oxygen uptake (VO2 max/kg)-predicted was greater than 80%. Cross-sectional clinical, hemodynamic, and liver biopsy data was gathered. High-performers were compared to control patients across these parameters via associations and regression. RESULTS: A total of 195 adult patients were included; 27 patients were considered "high performers". They had lower body mass indices (BMI, p < 0.001), mean Fontan pressures (p = 0.026), and cardiac outputs (p = 0.013). High performers also had higher activity levels (p < 0.001), serum albumin levels (p = 0.003), non-invasive and invasive systemic arterial oxygen saturations (p < 0.001 and p = 0.004), lower New York Heart Association (NYHA) heart failure class (p = 0.002), and were younger at Fontan completion (p = 0.011). High performers had less severe liver fibrosis (p = 0.015). Simple regression found Fontan pressure, non-invasive O2 saturation, albumin level, activity level, age at Fontan surgery, NYHA class, and BMI to predict significant changes in VO2 max/kg %-predicted. These associations persisted in multiple regression for non-invasive O2 saturation, NYHA class II, activity level, and BMI. CONCLUSIONS: Thin Fontan patients who exercise more had better exercise capacity, Fontan hemodynamic profiles, and less liver fibrosis.
Asunto(s)
Procedimiento de Fontan , Cardiopatías Congénitas , Humanos , Adulto , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/cirugía , Consumo de Oxígeno , Tolerancia al Ejercicio , Estudios Transversales , Oxígeno , Cirrosis Hepática , Prueba de EsfuerzoRESUMEN
Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death. Results: Patients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development. Conclusions: Patients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.
RESUMEN
BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital heart defect and is associated with a number of cardiac pathologies including coarctation of the aorta (CoA), aortic dilation, aortic stenosis, and premature coronary artery disease (CAD). Furthermore, BAV has been associated with left dominant coronary artery anatomy but there is still much debate regarding this association. To date, no study has investigated the association between coronary artery dominance and cardiac pathologies in patients with BAV. METHODS: A total of 45 patients with BAV who underwent coronary computed tomography angiography (CTA) and/or cardiac catheterization at a single center were included. Coronary artery dominance, presence of CAD, CoA, and aortic dilation was determined from coronary CTA and/or cardiac catheterization reports. Incidence of aortic valve stenosis and aortic valve regurgitation was determined from echo reports. RESULTS: Of the 45 patients with BAV, 80% (36) had right dominant coronary artery circulations. Patients with BAV with left dominant circulations had a significantly (p = 0.04) higher incidence of CoA compared to patients with right dominant circulations (44% vs. 14%). There was no significant difference when comparing the incidences of aortic dilation, aortic valve stenosis, aortic valve regurgitation and CAD in right and left dominant patients. CONCLUSIONS: Our study found a predominance of right dominant coronary artery circulation in patients with BAV, similar to the general population. Interestingly, left dominance was significantly associated with CoA in patients with BAV. This observation highlights the importance of further studies regarding how coronary artery dominance can be associated with other cardiovascular pathologies in patients with BAV.
Asunto(s)
Coartación Aórtica , Enfermedades de la Aorta , Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Enfermedades de las Válvulas Cardíacas , Humanos , Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/epidemiología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/epidemiología , Vasos Coronarios/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/epidemiología , Estudios RetrospectivosRESUMEN
Background: Congenital heart defects (CHDs) palliated with Fontan surgery often result in a functional single ventricle that is either a morphologically right or left ventricle, and much less commonly undefined. Given this departure from normal physiology, especially for systemic right ventricle Fontan patients, our study sought to compare cardiopulmonary exercise test (CPET) results of adult patients with single right ventricle (SRV) and single left ventricle (SLV) morphology. Methods: Of 237 Fontan patients from the Ahmanson/UCLA Adult Congenital Heart Disease Center database, 135 patients met the inclusion criteria and were split into 2 groups: SRV (n = 44) and SLV (n = 91). Data were collected on baseline demographics, cardiac history, and CPET results. The 2 groups were compared using unpaired t-test, Mann-Whitney, or Chi-square test. Results: Regarding baseline demographics, SRV patients underwent CPET at a slightly younger age than the SLV group (26.5 ± 6.2 vs 29.6 ± 8.5 years, P = .03). There were no significant differences in CPET parameters (including peak heart rate, oxygen saturation, and maximum VO2/kg) between the SRV and SLV groups. When evaluated subsequent CPET at 3 to 4 years, there was no difference in CPET peak heart rate, peak oxygen saturation, and maximum VO2/kg between the 2 groups. Conclusions: This single-center retrospective analysis suggests that dominant single ventricle morphology may not be associated with an appreciable difference in exercise performance in adult survivors with a Fontan palliation.