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OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.
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BACKGROUND: While fast track clinical pathways have been demonstrated to reduce resource utilization in patients undergoing cardiac surgery, it remains unclear as to whether they adversely affect post-operative outcomes. The purpose of this study was to determine the impact of fast tracking on post-operative outcomes following cardiac surgery. METHODS: In a retrospective study, all patients undergoing first-time, on-pump, non-emergent coronary artery bypass grafting, valve, or coronary artery bypass grafting + valve at a single centre between 2010 and 2017 were included. Patients were considered to have been fast tracked if they were extubated and transferred from intensive care to a step-down unit on the same day as their procedure. The risk-adjusted effect of fast tracking on a 30-day composite of all-cause mortality, stroke, renal failure, infection, atrial fibrillation, and readmission to hospital was determined. Furthermore, propensity score matching was used to match fasting track patients in a 1-to-1 manner with their nearest "neighbor" in the control group and subsequently compared in terms of 30-day post-operative outcomes. RESULTS: 3252 patients formed the final study population (fast track: n = 245; control: n = 3007). Patients who were fast tracked experienced reduced time to initial extubation (4.3 vs. 5.6 h, p < 0.0001) and lower median initial intensive care unit length of stay (7.8 vs. 20.4 h, p < 0.0001). Fast tracked patients experienced lower 30-day rates of the composite outcome (42.4% vs. 51.5%, p = 0.008). However, following propensity score matching, fast tracked patients experienced similar 30-day rates of the composite outcome as the control group (42.4% vs. 44.5%, p = 0.72). After risk adjustment using multivariable regression modeling, fast tracking was predictive of an improved 30-day composite outcome (OR 0.75, 95% CI 0.57-0.98, p = 0.03). CONCLUSION: Fast track clinical pathways was associated with reduced intensive care unit, overall length of stay and similar 30-day post-operative outcomes. These results suggest that fast tracking appropriate patients may reduce resource utilization, while maintaining patient safety.
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Procedimientos Quirúrgicos Cardíacos , Extubación Traqueal , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente de Arteria Coronaria , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios RetrospectivosRESUMEN
The Ascyrus Medical Dissection Stent (AMDS) has proved to promote false lumen closure at the distal anastomosis in type A dissection repairs. During the past 20 years, open techniques have developed into endovascular repairs. We report a case of thoracic endovascular aortic repair (TEVAR) landed inside an AMDS. A 63-year-old man with hypertension presented with type A aortic dissection. After initial repair with AMDS, he returned for TEVAR to fix residual type B dissection. A proper seal was created between the AMDS and TEVAR stents, demonstrating a successful off-label use of the AMDS stent.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Masculino , Humanos , Persona de Mediana Edad , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , Diseño de Prótesis , Resultado del Tratamiento , Factores de Tiempo , Stents , Estudios RetrospectivosRESUMEN
In an effort to further improve surgical outcomes in patients with acute type A aortic dissection (ATAD), the Canadian Thoracic Aortic Collaborative (CTAC), with the support of the Canadian Society of Cardiac Surgeons (CSCS), endeavoured to develop quality indicators (QIs) for the management of patients with ATAD. After 2 successive consultations with the CTAC membership, 11 QIs were selected and separated into 5 broad categories: preoperative (time from presentation to diagnosis, time from presentation to the operating room), intraoperative (use of hypothermic circulatory arrest and antegrade cerebral perfusion), 30-day outcomes (30-day rates of all-cause mortality, 30-day rates of new postoperative stroke), 1-year outcomes (1-year rates of follow-up imaging, 1-year rates of all-cause mortality, and 1-year rates of surgical reintervention), and institutional (institutional surgical volumes, individual surgical volumes, and presence of institutional aortic disease teams). The purpose of this article is to describe the process by which QIs for the management of ATAD were developed and the feasibility by which they may be collected using existing clinical and administrative data sources. Furthermore, we demonstrate how they may be used to evaluate success following surgery for repair of ATAD and ultimately improve clinical outcomes.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Cardiología , Manejo de la Enfermedad , Indicadores de Calidad de la Atención de Salud/tendencias , Sociedades Médicas , Procedimientos Quirúrgicos Vasculares/normas , Enfermedad Aguda , Aorta Torácica/cirugía , Canadá , Estudios de Seguimiento , Humanos , Estudios RetrospectivosRESUMEN
Background: The New Brunswick Heart Centre (NBHC) entered a contractual partnership with Integrated Health Solutions (IHS) to help address increasing wait times in the province of New Brunswick. Methods: Team leaders were identified from each of the target areas, including surgeons, anesthesiologists, nurses (operating room, intensive care unit [ICU] and postoperative ward), access coordinators and administrators. The methodology used was based on Lean principles and involved exercises by stakeholders aimed at identifying opportunities for improvement. A weekly dashboard was created to monitor and facilitate improvement efforts. No additional hospital beds or operating room theatres were added during the study period. Results: After 2 years, the annual number of cardiac surgical interventions increased from 788 to 873, representing a 10.8% increase in capacity. The best median wait time for patients decreased from 52 to 35 days (35% reduction). The best 90th percentile wait time decreased from 126 to 98 days (22% reduction). The overall increase in capacity could be explained in part by the significant increase in fast tracking from the ICU to the ward (> 2-fold) or bypassing the ICU altogether (4-fold increase reaching 13%). Despite these successes, challenges persist as the number of OR cancellations remained around 7.5% of all cases, mainly because of limited ICU resources. Conclusion: The NBHC-IHS partnership on this project has resulted in excellent engagement by stakeholders and promoted team cohesiveness. Furthermore, it has allowed significant reorganization and realignment of efforts to limit wait times and maximize overall capacity.
Contexte: Le New-Brunswick Heart Centre (NBHC) a conclu une entente contractuelle avec Integrated Health Solutions (IHS) pour remédier aux temps d'attente de plus en plus longs au Nouveau-Brunswick. Méthodes: Des chefs d'équipe ont été identifiés pour chaque domaine cible, notamment la chirurgie, l'anesthésie, les soins infirmiers (en salle d'opération, aux soins intensifs et en soins postopératoires), la coordination des soins et la direction. La méthodologie utilisée se fondait sur l'approche Lean et comprenait des exercices visant à relever les possibilités d'amélioration. Un tableau de bord hebdomadaire a été créé pour suivre et faciliter les mesures d'amélioration. On n'a ajouté aucun lit d'hôpital et aucune salle d'opération pendant la période étudiée. Résultats: Après 2 ans, le nombre de chirurgies cardiaques par année est passé de 788 à 873, une augmentation de 10,8 % de la capacité. Le temps d'attente médian pour les patients est tombé de 52 à 35 jours (réduction de 35 %). Le temps d'attente au 90e centile est passé de 126 à 98 jours (réduction de 22 %). L'augmentation générale de la capacité peut s'expliquer en partie par la réduction significative du temps passé aux soins intensifs avant l'admission en soins généraux (> 2 fois) ou par l'élimination complète du passage aux soins intensifs (augmentation de 400 %; 13 % des cas). Malgré ces réussites, des défis demeurent puisque le taux d'annulation des interventions est resté autour de 7,5 % des cas, surtout en raison des ressources limitées aux soins intensifs. Conclusion: Le partenariat NBHCIHS sur ce projet a permis de mobiliser efficacement les participants et a favorisé la cohésion au sein de l'équipe. Il a en outre permis une importante réorganisation des ressources pour réduire les temps d'attente et augmenter la capacité générale.
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Procedimientos Quirúrgicos Cardíacos/estadística & datos numéricos , Prestación Integrada de Atención de Salud/organización & administración , Humanos , Nuevo Brunswick , Factores de Tiempo , Listas de EsperaAsunto(s)
Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular/efectos adversos , Endofuga/clasificación , Procedimientos Endovasculares/efectos adversos , Terminología como Asunto , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Prótesis Vascular , Implantación de Prótesis Vascular/instrumentación , Enfermedad Crónica , Consenso , Endofuga/diagnóstico por imagen , Endofuga/etiología , Procedimientos Endovasculares/instrumentación , Humanos , Medición de Riesgo , Factores de Riesgo , Stents , Resultado del TratamientoRESUMEN
BACKGROUND: Hybrid aortic arch surgery has evolved to include several technical variations, with most including an off-label use of a conventional thoracic endograft. We describe the early clinical outcomes of the Thoraflex Hybrid graft (Vascutek, Glasgow, Scotland) specifically designed for the treatment of complex arch and proximal descending aortic disease. METHODS: Between January 2014 and April 2017, 40 consecutive patients (66 ± 14 years of age, 45% women) underwent hybrid aortic arch and frozen elephant trunk repair with the multibranched Thoraflex Hybrid graft at 9 Canadian centers. Surgical indications included transverse arch or proximal descending aortic aneurysm in 100%, acute dissection in 10%, chronic dissection in 43%, and acute aortic rupture in 1 patient. Antegrade cerebral perfusion and moderate hypothermia (24.3 ± 1.8°C) were employed in all cases. RESULTS: All 40 device implants were successful. The 30-day or in-hospital mortality was 5%. Stroke and transient neurological deficits occurred in 5% and 3% of patients, respectively. Two (5%) patients experienced transient spinal cord ischemia-there were no instances of permanent paraplegia. Mean follow-up was 550 ± 328 days and late complications included type A aortic dissection in 1 patient, type B dissection in 2 patients, and further distal endografting in 2 patients. Survival at 30 days, 1 year, and 2 years was 95%, 95%, and 90%, respectively. CONCLUSIONS: Hybrid aortic arch and frozen elephant trunk repair with the Thoraflex Hybrid graft appears to be associated with good clinical outcomes, despite being early in the learning curve with this graft. Further investigation with this device is warranted to establish its role within the variations of hybrid arch repair.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Implantación de Prótesis Vascular , Prótesis Vascular , Procedimientos Endovasculares , Stents , Anciano , Anciano de 80 o más Años , Disección Aórtica/mortalidad , Aneurisma de la Aorta Torácica/mortalidad , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Long-term quality of life following open surgical valve replacement is an increasingly important outcome to patients and their caregivers. This study examines non-institutionalized survival and rehospitalization within our surgical aortic valve replacement (AVR) and mitral valve replacement (MVR) populations. METHODS: A retrospective single-centre study of all consecutive open surgical valve replacements between 1995 and 2014 was undertaken. Clinical data were linked to provincial administrative data for 3219 patients who underwent AVR, MVR or double (aortic and mitral) valve replacement with or without concomitant coronary artery bypass grafting (CABG). Non-institutionalized survival and cumulative incidence of rehospitalization was examined up to 15 years. RESULTS: Follow-up was complete for 96.9% of the 2146 patients who underwent AVR ± CABG (66.7% of the overall cohort), 878 who underwent MVR ± CABG (27.3%) and 195 who underwent double (aortic and mitral) valve replacement ± CABG (6.0%) with a median follow-up time of 5.6 years. Overall non-institutionalized survival was 35.4% at 15 years, and the cumulative incidence of rehospitalization was 34.4%, 63.2% and 87.0% at 1, 5 and 15 years, respectively, without significant differences between valve procedure cohorts. Both non-institutionalized survival and cumulative incidence of rehospitalization improved in more recent eras, despite increasing age and comorbidities. CONCLUSIONS: Non-institutionalized survival and rehospitalization data for up to 15 years suggest good functional outcomes long after surgical AVR and/or MVR. Continued improvements are seen in these metrics over the past 2 decades. This provides a unique insight into the quality of life after surgical valve replacement in the ageing demographics with valvular heart disease.
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Válvula Aórtica , Procedimientos Quirúrgicos Cardíacos , Enfermedades de las Válvulas Cardíacas/mortalidad , Enfermedades de las Válvulas Cardíacas/cirugía , Válvula Mitral , Anciano , Anciano de 80 o más Años , Puente de Arteria Coronaria , Femenino , Prótesis Valvulares Cardíacas , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Calidad de Vida , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Surgery confers the best chance of survival following acute Type A dissection (ATAD), yet perioperative mortality remains high. Although perioperative risk factors for mortality have been described, information on the actual causes of death is sparse. In this study, we aimed to characterize the inciting events causing death during surgical repair of ATAD. METHODS: Nine centers participated in the study. We included all patients who died following surgical repair for ATAD between January 2007 and December 2013. An aortic surgeon at each site determined the primary cause of death from seven predetermined categories: cardiac, stroke, hemorrhage, other organ ischemia (peripheral, renal, or visceral), multiorgan failure, sepsis, or other causes. Additional characteristics and variables were analyzed to delineate potential modifiable factors for mortality. RESULTS: Of the 692 surgeries for ATAD, there were 123 deaths (17.8% mortality rate). Mean age at death was 66 years. Events contributing to death were: cardiac (25%), stroke (22%), hemorrhage (21%), multiorgan failure (12%), other organ ischemia (11%), sepsis (4%), and other causes (5%). Neurologic injury at presentation was a predictor of stroke as the inciting cause of death (p = 0.04). Peripheral, renal, or visceral ischemia at presentation was highly predictive of death due to these presenting ischemic conditions (p = 0.004). We found no associations between cardiogenic shock, tamponade, or cardiopulmonary bypass duration and cardiac death. CONCLUSION: Operative mortality for ATAD remains high in Canada. Nearly 70% of deaths arise from cardiac failure, stroke, or hemorrhage. Therefore, novel surgical, hybrid, and endovascular strategies should target these three areas.
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Transcatheter aortic valve implantation (TAVI) has emerged as an alternative technique to treating aortic stenosis in patients with high surgical risk. We present a case of a successful transfemoral TAVI in a high-risk patient with an extremely tortuous iliofemoral system and a significant S-type bend in the descending aorta. With careful preprocedure planning and using all the techniques available, TAVI can be performed in the most challenging patients.
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Management of cardiac surgery health human resources (HHR) has been challenging, with recent graduates struggling to secure employment and a shortage of cardiac surgeons predicted as early as 2020. The length of cardiac surgery training prevents HHR supply from adapting in a timely fashion to changes in demand, resulting in a critical need for active workforce management. This study details the results of the 2015 Canadian Society of Cardiac Surgeons (CSCS) workforce survey undertaken as part of the CSCS strategy for active workforce management. The 38-question survey was administered electronically to all 96 trainees identified as being registered in a Canadian cardiac surgery residency program for the 2015-2016 academic year. Eighty-four of 96 (88%) trainees responded. The majority of participants were satisfied with their training experience. However, 29% stated that their clinical and operative exposure needed improvement, and 57% of graduating trainees did not believe that they would be competent to practice independently at the conclusion of their training. Although 51% of participants believe the job market is improving, 94% of senior trainees found it competitive or extremely difficult to secure an attending staff position. Participants highlighted a need for improved career counselling and formal mentorship. Although the job market is perceived to be improving, a mismatch in the cardiac surgery workforce supply and demand remains because current trainees continue to experience difficulty securing employment after the completion of residency training. Trainees have identified improved career counselling and mentorship as potential strategies to aid graduates in securing employment.
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Procedimientos Quirúrgicos Cardíacos/educación , Selección de Profesión , Educación de Postgrado en Medicina/métodos , Internado y Residencia , Cirujanos/educación , Encuestas y Cuestionarios , Cirugía Torácica , Actitud del Personal de Salud , Canadá , Humanos , Satisfacción en el Trabajo , Recursos HumanosRESUMEN
Conventional surgical techniques for acute Type A aortic dissection (ATAAD) generally fail to address residual dissection in the descending aorta. The persistence of a false lumen is associated with visceral malperfusion in the acute setting and adverse aortic remodeling in the chronic setting. Hybrid aortic arch repair techniques may improve perioperative and long-term mortality by expanding the true lumen and obliterating the false lumen. However, there is a limit to the extent of aortic coverage due to the concomitant risk of spinal cord ischemia. In Type B dissection, the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique, which entails stent graft coverage of the primary intimal tear followed by bare metal stent placement distally, may improve true lumen caliber and promote false lumen thrombosis without increasing the risk of spinal cord ischemia, as intercostal branches remain perfused through the bare metal stents. The technique of hybrid arch with surgical creation of a Dacron landing zone covering a stent graft in the proximal descending aorta and bare metal stents in the thoraco-abdominal aorta is a promising concept in the treatment of ATAAD.
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Aorta/cirugía , Oclusión de Injerto Vascular/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Implantación de Prótesis/instrumentación , Trombosis/diagnóstico por imagen , Ultrasonografía Intervencional , Anciano , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Cateterismo Cardíaco , Angiografía por Tomografía Computarizada , Remoción de Dispositivos , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/cirugía , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Hemólisis , Humanos , Valor Predictivo de las Pruebas , Diseño de Prótesis , Falla de Prótesis , Implantación de Prótesis/efectos adversos , Trombosis/etiología , Trombosis/fisiopatología , Trombosis/cirugía , Resultado del Tratamiento , Función VentricularRESUMEN
Acute type A aortic dissections still present a major challenge to cardiac surgeons. Although surgical management remains the gold standard, operative mortality remains high, including in experienced centres. Nevertheless, recent advances in the understanding and management of various aspects of these complex operations are expected to improve overall patient outcomes. The Canadian Thoracic Aortic Collaborative (CTAC) represents a group of surgeons with interest and expertise in the management of patients with aortic diseases. The purpose of this state-of-the-art review is to detail our approach to the contemporary surgical management of acute type A aortic dissections. We focus specifically on cannulation strategies, cerebral protection, and extent of proximal and distal resection. In addition, specific clinical scenarios-including malperfusion, intramural hematomas, and surgery in octogenarians-are explored.
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Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Procedimientos Quirúrgicos Vasculares/métodos , Procedimientos Quirúrgicos Vasculares/normas , HumanosRESUMEN
BACKGROUND: Endovascular options to repair the arch and ascending aorta are rapidly evolving. Little is known about the durability of endovascular devices deployed at this location. This report describes a single-centre experience with the novel application of thoracic endovascular aortic repair (TEVAR) by examining clinical and radiological outcomes. METHODS: A retrospective review was performed for a cohort of patients undergoing TEVAR of the arch or ascending aorta, or both, at a single centre from November 2008-July 2012. RESULTS: Sixteen patients were included in the study, with mean imaging follow-up of 38 months (range, 15-72 months). Two complications at the proximal landing zone in the ascending aorta were identified: 1 endoleak and 1 infolding identified at 3 and 24 months postoperatively, respectively. Clinically, both these complications were attributed to the bird-beak configuration at the proximal landing zone site. At up to 72 months of follow-up, there were no cases of retrograde dissection of the native sinus of Valsalva. There were no cases of stent graft migration, graft fracture, open surgical reintervention for aortic pathologic conditions, or late mortality. CONCLUSIONS: Early outcomes suggest that the current generation of thoracic aortic endografts can be placed in the complex anatomy of the ascending aorta and aortic arch without a high incidence of early graft fracture or migration. Future endeavors will need to focus on techniques to achieve optimal apposition with the curves of the ascending aorta. These findings are important as indications for endovascular aortic therapies expand to address proximal aortic pathologic conditions.
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Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Implantación de Prótesis Vascular/métodos , Prótesis Vascular , Procedimientos Endovasculares/métodos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Aortografía/métodos , Implantación de Prótesis Vascular/mortalidad , Estudios de Cohortes , Bases de Datos Factuales , Procedimientos Endovasculares/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Seguridad del Paciente , Diseño de Prótesis , Falla de Prótesis , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Thoracic endovascular aortic repair, a minimally invasive technique is replacing the maximally invasive gold standard of thoracotomy and replacement of the descending thoracic aorta. With experience, indications have expanded to encroach on the arch and even ascending aorta. This review highlights the current state of technology, discusses controversies, and takes the perspective of a forward-thinking review to describe novel, innovative techniques that might make the entire thoracic aorta amenable to minimally invasive repair.
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Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Procedimientos Endovasculares/métodos , Guías de Práctica Clínica como Asunto , Humanos , Toracotomía/métodosRESUMEN
Nucleoside transporters (NTs) are integral membrane transport proteins that modulate the flux of nucleosides such as adenosine across cell membranes. Two families of NTs exist, the concentrative NTs (CNTs, SLC28) and the equilibrative NTs (ENTs, SLC29). CNTs and ENTs transport anti-cancer and anti-viral nucleoside analog drugs and ENTs are also targets of drugs used to treat cardiac pathologies. Levels of some NT profiles have been shown to relate to clinical outcomes in the use of nucleoside analog drugs. However, currently, patient NT profile is not assessed prior to pharmacological administration of analog drugs. Here we describe a reliable method to determine a complete individual NT expression profile from human tissue using quantitative real-time PCR. We developed this assay on tissue (right atrial appendage, left internal mammary, aorta) from individuals undergoing cardiac surgery and compared these findings to the NT expression profiles in pooled whole heart tissue (normal and diseased). Data show that hENT1 is the most abundantly expressed NT, with highest expression levels in the aorta. However, NT expression profiles are highly variable among individuals and changes in NT expression between normal and diseased tissues were observed. These data are the first to describe the RNA expression patterns of all seven NT isoforms in the human heart. The methodology described here may be useful for quantitatively characterizing complete NT expression profiles in any human target tissue.
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Bioensayo/métodos , Tranportador Equilibrativo 1 de Nucleósido/genética , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Miocardio/metabolismo , Adenosina/metabolismo , Adulto , Anciano , Aorta/metabolismo , Transporte Biológico , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Nucleósidos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoAsunto(s)
Anatomía/historia , Atlas como Asunto , Bibliografías como Asunto , Libros Ilustrados , Historia del Siglo XVI , Edición/historia , Libros Raros , Anatomía/economía , Anatomía/métodos , Anatomía/tendencias , Atlas como Asunto/historia , Libros Ilustrados/historia , Inglaterra , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Italia , Bibliotecas/historia , Edición/economía , Edición/provisión & distribución , Libros Raros/historia , Investigación/historia , Proyectos de Investigación , SuizaRESUMEN
BACKGROUND: Alveolar hypoxia acutely elicits pulmonary vasoconstriction (HPV). Chronic hypoxia (CH), despite attenuating HPV, causes pulmonary hypertension (CH-PHT). HPV results, in part, from inhibition of O2-sensitive, voltage-gated potassium channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). CH decreases Kv channel current/expression and depolarizes and causes Ca2+ overload in PASMCs. We hypothesize that Kv gene transfer would normalize the pulmonary circulation (restore HPV and reduce CH-PHT), despite ongoing hypoxia. METHODS AND RESULTS: Adult male Sprague-Dawley rats were exposed to normoxia or CH for 3 to 4 weeks and then nebulized orotracheally with saline or adenovirus (Ad5) carrying genes for the reporter, green fluorescent protein reporter+/-human Kv1.5 (cloned from normal PA). HPV was assessed in isolated lungs. Hemodynamics, including Fick and thermodilution cardiac output, were measured in vivo 3 and 14 days after gene therapy by use of micromanometer-tipped catheters. Transgene expression, measured by quantitative RT-PCR, was confined to the lung, persisted for 2 to 3 weeks, and did not alter endogenous Kv1.5 levels. Ad5-Kv1.5 caused no mortality or morbidity, except for sporadic, mild elevation of liver transaminases. Ad5-Kv1.5 restored the O2-sensitive K+ current of PASMCs, normalized HPV, and reduced pulmonary vascular resistance. Pulmonary vascular resistance decreased at day 2 because of increased cardiac output, and remained reduced at day 14, at which time there was concomitant regression of right ventricular hypertrophy and PA medial hypertrophy. CONCLUSIONS: Kv1.5 is an important O2-sensitive channel and potential therapeutic target in PHT. Kv1.5 gene therapy restores HPV and improves PHT. This is, to the best of our knowledge, the first example of K+ channel gene therapy for a vascular disease.