Thoracic endovascular aortic repair: Current evidence and challenges

In 1987 Nikolay Volodos performed the world’s first endovascular treatment of aortic aneurysms. Endovascular technology has progressed significantly since then. There are now many thoracic endovascular aortic repair (TEVAR) systems commercially available. By applying them, we can treat many pathologies: aneurysms, dissections, aortic ruptures, and penetrating aortic ulcers. However, TEVAR technology still has its limitations, namely the risk of a retrograde type A dissection, the issue of precise landing in the distal landing zone, and the risk of air embolism and paraplegia. Furthermore, there are no appropriate stent grafts widely available to treat acute dissections. Those currently used are designed for aneurysms, not for dissections. As a result, there are several challenges facing the future TEVAR surgical community, such as the need to develop new and more precise systems with retrograde deployment for the distal landing zone, as well as to introduce flexible stent grafts to treat dissections. The endo-Bentall is being developed as an alternative treatment method for acute type-A aortic dissection

Subsequent cardiac surgery after transcatheter aortic valve implantation: Indications and outcomes.

BACKGROUND Aim of this study was to report on indications and clinical outcomes of patients who underwent subsequent open-cardiac surgery after transcatheter aortic valve implantation TAVI. METHODS Between 01/2011 and 12/2020 our centre performed 4043 TAVI procedures. Twenty-seven patients (including patients in whom TAVI was performed in other centres) underwent subsequent open-heart surgery via cardiopulmonary bypass. Demographic, intraprocedural data, indications for, and outcomes after surgery were evaluated. RESULTS Indications for cardiac surgery (aged 79 [IQR 76-84]; 59.3% male) were endocarditis (n = 11; 40.7%), annular rupture, severe paravalvular leak and severe stenosis in three (11.1%) patients, respectively as well as in one patient each (3.7%) severe tricuspid valve regurgitation, valve thrombosis, valve malposition, valve migration, ostial right coronary artery obstruction, left ventricular rupture and type A aortic dissection. The interval between the index TAVI procedure to open surgery was 3 months (IQR 0-26 months). Eight patients underwent emergent surgical conversions. Immediate procedural and procedural mortality was 25.9% and 40.7%, respectively and all-cause mortality was 51.9% (11/12 died for cardiovascular reasons). No disabling stroke was observed postoperatively. New permanent pacemaker implantation was required in three patients (11.1%). CONCLUSIONS Subsequent open-cardiac surgery after TAVI is rare, but may urgently become necessary due to TAVI related complications or progressing other cardiac pathologies. Despite a substantial early attrition rate clinical outcome is acceptable and a relevant number of these high-risk patients can be discharged even after emergency conversions. The option of subsequent surgical conversion remains

New insights regarding the incidence, presentation and treatment options of aorto-oesophageal fistulation after thoracic endovascular aortic repair: the European Registry of Endovascular Aortic Repair Complications

OBJECTIVES To review the incidence, clinical presentation, definite management and 1-year outcome in patients with aorto-oesophageal fistulation (AOF) following thoracic endovascular aortic repair (TEVAR). METHODS International multicentre registry (European Registry of Endovascular Aortic Repair Complications) between 2001 and 2011 with a total caseload of 2387 TEVAR procedures (17 centres). RESULTS Thirty-six patients with a median age of 69 years (IQR 56-75), 25% females and 9 patients (19%) following previous aortic surgery were identified. The incidence of AOF in the entire cohort after TEVAR in the study period was 1.5%. The primary underlying aortic pathology for TEVAR was atherosclerotic aneurysm formation in 53% of patients and the median time to development of AOF was 90 days (IQR 30-150). Leading clinical symptoms were fever of unknown origin in 29 (81%), haematemesis in 19 (53%) and shock in 8 (22%) patients. Diagnosis could be confirmed via computed tomography in 92% of the cases with the leading sign of a new mediastinal mass in 28 (78%) patients. A conservative approach resulted in a 100% 1-year mortality, and 1-year survival for an oesophageal stenting-only approach was 17%. Survival after isolated oesophagectomy was 43%. The highest 1-year survival rate (46%) could be achieved via an aggressive treatment including radical oesophagectomy and aortic replacement [relative risk increase 1.73 95% confidence interval (CI) 1.03-2.92]. The survival advantage of this aggressive treatment modality could be confirmed in bootstrap analysis (95% CI 1.11-3.33). CONCLUSIONS The development of AOF is a rare but lethal complication after TEVAR, being associated with the need for emergency TEVAR as well as mediastinal haematoma formation. The only durable and successful approach to cure the disease is radical oesophagectomy and extensive aortic reconstruction. These findings may serve as a decision-making tool for physicians treating these complex patient

Multicentre analysis of current strategies and outcomes in open aortic arch surgery: heterogeneity is still an issue

Abstract OBJECTIVES: The study was conducted to evaluate, on the basis of a multicentre analysis, current results of elective open aortic arch surgery performed during the last decade. METHODS: Data of 1232 consecutive patients who underwent aortic arch repair with reimplantation of at least one supra-aortic artery between 2004 and 2013 were collected from 11 European cardiovascular centres, and retrospective statistical examination was performed using uni-and multi-variable analyses to identify predictors for 30-day mortality. Acute aortic dissections and arch surgeries not involving the supra-aortic arteries were not included. RESULTS: Arch repair involving all 3 arch arteries (total), 2 arch arteries (subtotal) or 1 arch artery ( partial) was performed in 956 (77.6%), 155 (12.6%) and 121 (9.8%) patients, respectively. The patients' characteristics as well as the surgical techniques, including the method of cannulation, perfusion and protection, varied considerably between the clinics participating in the study. The in-hospital and 30-day mortality rates were 11.4 and 8.8% for the entire cohort, respectively, ranging between 1.7 and 19.0% in the surgical centres. Multivariable logistic regression analysis identified surgical centre, patient's age, number of previous surgeries with sternotomy and concomitant surgeries as independent risk factors of 30-day mortality. The follow-up of the study group was 96.5% complete with an overall follow-up duration of 3.3 ± 2.9 years, resulting in 4020 patient-years. After hospital discharge, 176 (14.3%) patients died, yielding an overall mortality rate of 25.6%. The actuarial survival after 5 and 8 years was 72.0 ± 1.5% and 64.0 ± 2.0, respectively. CONCLUSIONS: The surgical risk in elective aortic arch surgery has remained high during the last decade despite the advance in surgical techniques. However, the patients' characteristics, numbers of surgeries, the techniques and the results varied considerably among the centres. The incompleteness of data gathered retrospectively was not effective enough to determine advantages of particular cannulation, perfusion, protection or surgical techniques; and therefore, we strongly recommend further prospective multicentre studies, preferably registries, in which all relevant data have to be clearly defined and collected

Die Überexpression vom Endothelin-2 begünstigt die Entwicklung der diabetischen Kardiomyopathie bei Ratten

GesamtdissertationCardiovascular complications are the major causes of morbidity and mortality in patients with diabetes mellitus. Inhibitory interventions using endothelin receptor antagonists have suggested that the endothelin system plays an important role in diabetic cardiomyopathy, although some studies observed no or only a modest effect. In the present study, a stimulatory intervention, i.e. transgenic overexpression of the human endothelin-2 gene in rats, was used to further characterize the morphological and molecular contributions of endothelins to diabetic cardiomyopathy. Diabetes mellitus was induced by streptozotocin injection into male rats expressing the human endothelin-2 transgene and into transgene-negative littermate controls. Non-diabetic transgene-positive and -negative animals were included as well to form a 4-group study design. Insulin treatment was begun 2 weeks after diabetes was confirmed and was administered every second day. After 12 weeks of diabetes, insulin was injected daily. The aim of the insulin treatment was to prevent a blood glucose concentration of higher than 600 mg/dl and rat mortality due to metabolic complications. Heart morphological and molecular changes were analysed following 6 months of hyperglycaemia. Transgenic overexpression of the human endothelin-2 gene significantly intensified diabetic cardiomyopathy in the rats. The most prominent pathological changes were observed in epicardial and intramyocardial vessel hypertrophy and myocardial interstitial fibrosis. These changes were paralleled by a modest, but complex regulation of myocardial endothelin-1, endothelin A and B receptor expression. Six months of diabetes alone (i.e. without endothelin-2 overexpression as co-factor) were insufficient for revealing advanced cardiomyopathy. In diabetic wild-type rats, when compared with diabetic transgenic animals, the myocardial fibrosis markers were significantly lower and there was no hypertrophic remodelling of large coronary arteries. This interventional animal study, overexpressing human endothelin-2 in rats, provides strong complementary support for, and mechanistic insights into, a detrimental, blood pressure-independent role of endothelins in diabetic cardiomyopathy. The endothelin system seems to promote the development of diabetic cardiomyopathy by altering the arterial vessels and through profibrotic action. In conclusion, this study has demonstrated the usefulness of a transgenic model for evaluating the endothelin system s role in the pathogenesis of diabetic end-organ damage. The use of an endothelin antagonist has previously been shown to have beneficial consequences in experimental diabetes. The findings of this stimulatory interventional study correspond to this assessment, as they show the negative effects of endothelin overexpression on diabetic cardiomyopathy. Effective intervention in diabetes, however, has to take into account the complex regulation of the components of the endothelin system on the molecular level, and the observation that endothelins seem to interact with other molecular players in the development of diabetic cardiomyopathy. Thus, further studies are warranted in order to analyze whether endothelins play a role in other diabetic complications, and whether the contribution of endothelins in diabetic cardiomyopathy mechanisms may be pharmacologically modulated in order to yield a long-term beneficial effect on the evolution of this diabetic end-organ damage.Kardiovaskuläre Komplikationen sind die wichtigste Ursache von Morbidität und Mortalität der Patienten mit Diabetes mellitus. Interventionen mit Endothelin- Antagonisten wiesen auf die mögliche Bedeutung des Endothelin-Systems bei der diabetischen Kardiomyopathie hin, obwohl die Ergebnisse entsprechender Studien nicht konsistent waren. In dieser Studie wurde ein transgenes Überexpressionsmodell für humanes Endothelin-2 verwendet, um morphologische und molekulare Auswirkungen von Endothelin auf die diabetische Kardiomyopathie zu charakterisieren. Der Diabetes mellitus wurde mittels Streptozotocin- Injektion induziert. Verwendet wurden männliche Ratten mit transgener Expression von humanem Endothelin-2 und nicht-transgene Kontrolltiere. Nicht- diabetische transgene und nicht-transgene Tiere wurden ebenfalls in die Studie eingeschlossen. Eine Insulintherapie wurde 2 Wochen nach Manifestation des Diabetes begonnen. Nach initialer Insulin-Applikation alle 2 Tage, wurde nach 12 Wochen beginnend Insulin täglich injiziert. Ziel der Insulintherapie war es, den Blutzucker unter 600 mg/dl einzustellen und Mortalität infolge metabolischer Komplikationen zu vermeiden. Die Herzen der Tiere wurden nach sechsmonatiger Hyperglykämie histologisch und molekular analysiert. Die transgene Expression des Gens für humanes Endothelin-2 in Ratten führte zu einer signifikant ausgeprägteren diabetischen Kardiomyopathie. Die deutlichsten Unterschiede betrafen die Hypertrophie epikardialer und intramyokardialer Gefäße und die Fibrose des myokardialen Interstitiums. Parallel zu diesen Veränderungen fand sich eine komplexe transkriptionelle Regulation der myokardialen Expression von Endothelin-1, Endothelin A- und B-Rezeptoren. Sechs Monate Diabetes mellitus alleine (ohne Endothelin- Überexpression als Co-Faktor) waren nicht in der Lage, eine fortgeschrittene Kardiomyopathie auszulösen. In der diabetischen nicht-transgenen Gruppe waren die myokardialen Fibrosemarker signifikant schwächer als in der diabetischen transgenen Gruppe. Diabetes alleine war nicht in der Lage, ein hypertrophes Remodelling der großen Koronargefäße zu bewirken. Die Überexpression von humanem Endothelin-2 bei Ratten mit Diabetes mellitus liefert neue Einblicke in die Bedeutung von Endothelinen für die Pathophysiologie der diabetischen Kardiomyopathie. Das Endothelinsystem begünstigt die Entwicklung der diabetischen Kardiomyopathie durch vaskuläres Remodelling und profibrotische Wirkungen unabhängig vom arteriellen Blutdruck. Die Ergebnisse dieser Arbeit zeigen den Nutzen eines transgenen Modells bei der Untersuchung der Rolle des Endothelin-Systems in der Pathogenese der diabetischen End-Organ-Schäden. Eine positive Wirkung von Endothelin-Antagonisten wurde bereits in experimentellen Arbeiten nachgewiesen. Diese Studie bestätigt diese Arbeiten durch den Nachweis negativer Effekte der Überexpression von Endothelin auf die diabetische Kardiomyopathie. Die komplexe Regulation des Endothelin-Systems und dessen Interaktionen mit anderen molekularen Faktoren der diabetischen Kardiomyopathie müssen berücksichtigt werden, wenn es um pharmakologische Interventionen bei Patienten mit Diabetes mellitus geht. Zukünftige Studien sollten analysieren, ob auch bei anderen diabetischen Komplikationen Endothelin eine Rolle spielt und ob das Fortschreiten der diabetischen Kardiopathie durch pharmakologische Intervention verzögert werden kann