Temporary neurological dysfunction after surgery of the thoracic aorta: a predictor of poor outcome and impaired quality of life

Background: Transient neurological dysfunction (TND) consists of postoperative confusion, delirium and agitation. It is underestimated after surgery on the thoracic aorta and its influence on long-term quality of life (QoL) has not yet been studied. This study aimed to assess the influence of TND on short- and long-term outcome following surgery of the ascending aorta and proximal arch. Methods: Nine hundred and seven patients undergoing surgery of the ascending aorta and the proximal aortic arch at our institution were included. Two hundred and ninety patients (31.9%) underwent surgery because of acute aortic dissection type A (AADA) and 617 patients because of aortic aneurysm. In 547 patients (60.3%) the distal anastomosis was performed using deep hypothermic circulatory arrest (DHCA). TND was defined as a Glasgow coma scale (GCS) value <13. All surviving patients had a clinical follow up and QoL was assessed with an SF-36 questionnaire. Results: Overall in-hospital mortality was 8.3%. TND occurred in 89 patients (9.8%). As compared to patients without TND, those who suffered from TND were older (66.4 vs 59.9 years, p<0.01) underwent more frequently emergent procedures (53% vs 32%, p<0.05) and surgery under DHCA (84.3% vs 57.7%, p<0.05). However, duration of DHCA and extent of surgery did not influence the incidence of TND. In-hospital mortality in the group of patients with TND compared to the group without TND was similar (12.0% vs 11.4%; p=ns). Patients with TND suffered more frequently from coronary artery disease (28% vs 20.8%, p=ns) and were more frequently admitted in a compromised haemodynamic condition (23.6% vs 9.9%, p<0.05). Postoperative course revealed more pulmonary complications such as prolonged mechanical ventilation. Additional to their transient neurological dysfunction, significantly more patients had strokes with permanent neurological loss of function (14.6% vs 4.8%, p<0.05) compared to the patients without TND. ICU and hospital stay were significantly prolonged in TND patients (18±13 days vs 12±7 days, p<0.05). Over a mean follow-up interval of 27±14 months, patients with TND showed a significantly impaired QoL. Conclusion: The neurological outcome following surgery of the ascending aorta and proximal aortic arch is of paramount importance. The impact of TND on short- and long-term outcome is underestimated and negatively affects the short- and long-term outcom

Technical advances improved outcome in patients undergoing surgery of the ascending aorta and/or aortic arch: ten years experience

Background: Several technical advances in thoracic aortic surgery, such as the use of antegrade cerebral perfusion, avoidance of cross-clamping and the application of glue, have beneficially influenced postoperative outcome. The aim of the present study was to analyse the impact of these developments on outcome of patients undergoing surgery of the thoracic aorta. Methods and results: Between January 1996 and December 2005, 835 patients (37.6%) out of 2215 aortic patients underwent surgery on the thoracic ascending aorta or the aortic arch at our institution. All in-hospital data were assessed. Two hundred and forty-one patients (28.8%) suffered from acute type A dissection (AADA). Overall aortic caseload increased from 41 patients in 1996 to 141 in 2005 (+339%). The increase was more pronounced for thoracic aortic aneurysms (TAA) (+367.9%), than for acute type A aortic dissections (+276.9%). Especially in TAA, combined procedures increased and the amount of patients with impaired left ventricular function (EF <50%) raised up from 14% in 1996 to 24% in 2005. Average age remained stable. Logistic regression curve revealed a significant decrease in mortality (AADA) and in the overall incidence of neurological deficits. Conclusions: Technical advances in the field of thoracic aortic surgery lead to a decrease of mortality and morbidity, especially in the incidence of adverse neurological events, in a large collective of patients. Long-term outcome and quality of life are better, since antegrade cerebral perfusion has been introduce

Technical advances improved outcome in patients undergoing surgery of the ascending aorta and/or aortic arch: ten years experience

BACKGROUND: Several technical advances in thoracic aortic surgery, such as the use of antegrade cerebral perfusion, avoidance of cross-clamping and the application of glue, have beneficially influenced postoperative outcome. The aim of the present study was to analyse the impact of these developments on outcome of patients undergoing surgery of the thoracic aorta. METHODS AND RESULTS: Between January 1996 and December 2005, 835 patients (37.6%) out of 2215 aortic patients underwent surgery on the thoracic ascending aorta or the aortic arch at our institution. All in-hospital data were assessed. Two hundred and forty-one patients (28.8%) suffered from acute type A dissection (AADA). Overall aortic caseload increased from 41 patients in 1996 to 141 in 2005 (+339%). The increase was more pronounced for thoracic aortic aneurysms (TAA) (+367.9%), than for acute type A aortic dissections (+276.9%). Especially in TAA, combined procedures increased and the amount of patients with impaired left ventricular function (EF <50%) raised up from 14% in 1996 to 24% in 2005. Average age remained stable. Logistic regression curve revealed a significant decrease in mortality (AADA) and in the overall incidence of neurological deficits. CONCLUSIONS: Technical advances in the field of thoracic aortic surgery lead to a decrease of mortality and morbidity, especially in the incidence of adverse neurological events, in a large collective of patients. Long-term outcome and quality of life are better, since antegrade cerebral perfusion has been introduced

Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors

HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an E-box motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression

Genregulation in Herzen Hey-mutierter Mausembryonen und Darstellung der sub-zellulären Verteilung von Hey1

Hey-mutant mouse hearts at embryonic day E14.5 were shown to react to the knock out of Hey2 with several up-regualted genes. This up-regulation is due to the lack of Hey2 and cannot be explained by the structural changes in heart morphology as shown using control animals. Part of the gene regulation was further validated using in situ hybridization. Hey1 was located to the nucleus in immunofluorescence experiments. However, experiments on protein level showed also amount of Hey1 within the cytoplasm. The nuclear localization of Hey1 was unchanged during all cell cycle phases as well as when CaMKII was co-expressed or other cellular pathways were inhibited or stimulated. Hey1 does not seem to interact with the nuclear transport proteins importin-alpha and -beta, therefore it still needs to be elucidated how Hey1 is transported into the nucleus.Am Embryonaltag 14,5 zeigten Herzproben von Hey2-KO-Mäusen eine deutliche Hochregulation mehrerer Gene, die auf das Fehlen von Hey2 zurückzuführen ist, da Kontroll-Tiere gezeigt haben, dass die morphologischen Veränderungen in der Herzstruktur keinen Einfluss auf die Genregulation haben. Vereinzelt wurden die regulierten Gene noch mittels in situ Hybridisierung weiter verdeutlicht. In Immunfloureszenzexperimenten wurde Hey1 im Zellkern lokalisiert. Auf Proteinebene zeigte sich allerdings auch ein Vorhandensein von Hey1 im Cytoplasma der Zellen. Die Kernlokalisaiton von Hey1 veränderte sich während des gesamten Zellzykluses nicht und wurde auch nicht durch die Co-Expression von CaMKII beeinflusst oder die Inhibition oder Stimulation anderer Signalwege in der Zelle. Hey1 scheint nicht mit den Kerntransportproteinen Importin-alpha und -beta zu interagieren, so dass weiterhin nach einem Kernimport-System für Hey1 gesucht werden muss

Temporary neurological dysfunction after surgery of the thoracic aorta: a predictor of poor outcome and impaired quality of life

BACKGROUND: Transient neurological dysfunction (TND) consists of postoperative confusion, delirium and agitation. It is underestimated after surgery on the thoracic aorta and its influence on long-term quality of life (QoL) has not yet been studied. This study aimed to assess the influence of TND on short- and long-term outcome following surgery of the ascending aorta and proximal arch. METHODS: Nine hundred and seven patients undergoing surgery of the ascending aorta and the proximal aortic arch at our institution were included. Two hundred and ninety patients (31.9%) underwent surgery because of acute aortic dissection type A (AADA) and 617 patients because of aortic aneurysm. In 547 patients (60.3%) the distal anastomosis was performed using deep hypothermic circulatory arrest (DHCA). TND was defined as a Glasgow coma scale (GCS) value <13. All surviving patients had a clinical follow up and QoL was assessed with an SF-36 questionnaire. RESULTS: Overall in-hospital mortality was 8.3%. TND occurred in 89 patients (9.8%). As compared to patients without TND, those who suffered from TND were older (66.4 vs 59.9 years, p<0.01) underwent more frequently emergent procedures (53% vs 32%, p<0.05) and surgery under DHCA (84.3% vs 57.7%, p<0.05). However, duration of DHCA and extent of surgery did not influence the incidence of TND. In-hospital mortality in the group of patients with TND compared to the group without TND was similar (12.0% vs 11.4%; p=ns). Patients with TND suffered more frequently from coronary artery disease (28% vs 20.8%, p=ns) and were more frequently admitted in a compromised haemodynamic condition (23.6% vs 9.9%, p<0.05). Postoperative course revealed more pulmonary complications such as prolonged mechanical ventilation. Additional to their transient neurological dysfunction, significantly more patients had strokes with permanent neurological loss of function (14.6% vs 4.8%, p<0.05) compared to the patients without TND. ICU and hospital stay were significantly prolonged in TND patients (18+/-13 days vs 12+/-7 days, p<0.05). Over a mean follow-up interval of 27+/-14 months, patients with TND showed a significantly impaired QoL. CONCLUSION: The neurological outcome following surgery of the ascending aorta and proximal aortic arch is of paramount importance. The impact of TND on short- and long-term outcome is underestimated and negatively affects the short- and long-term outcome

Rivaroxaban in patients with mechanical heart valves: A pilot study.

BACKGROUND Patients with mechanical heart valves are still not eligible for treatment with direct oral anticoagulants (DOAC). We aimed to conduct a proof-of-principle study investigating the anti-Xa inhibitor rivaroxaban as antithrombotic treatment in patients with recent mechanical aortic valve replacement. MATERIALS AND METHODS Low-risk patients scheduled for elective mechanical aortic valve replacement were treated with rivaroxaban 20 mg once daily (OD) in a prospective cohort study, started on day 3 postoperatively and given for 6 months. The study was registered at ClinicalTrials.gov (#NCT02128841). RESULTS Ten patients were included (median age, 48; range 39 to 60). Indication was aortic valve stenosis in 6 patients, aortic root aneurysm with severe aortic valve regurgitation in 3 patients, and mixed stenosis/regurgitation in 1 patient. Neither thromboembolic nor bleeding events were observed, and no patient died. Absence of valve thrombosis was demonstrated in all patients. On day 7, median D-dimers were 2723 μg/L (inter-quartile range [IQR] 1672, 5695 μg/L), median TAT levels were 4.5 μg/L (IQR 4.1, 5.6 μg/L); and median peak thrombin generation was 150 nM (IQR 91, 183). On day 90, median D-dimers were 426 μg/L (IQR 278, 569), median TAT levels were 2.7 μg/L (IQR 2.2, 3.1), and median peak thrombin generation were 66 nM (IQR 62, 87). CONCLUSIONS Rivaroxaban 20 mg OD was safe and effective in a pilot study of 10 low risk patients with mechanical aortic heart valve. Our results justify larger studies investigating the application of anti-Xa inhibitors in patients with mechanical heart valves

Arterial access through the right subclavian artery in surgery of the aortic arch improves neurologic outcome and mid-term quality of life

BACKGROUND: We have shown that selective antegrade cerebral perfusion improves mid-term quality of life in patients undergoing surgical repair for acute type A aortic dissection and aortic aneurysms. The aim of the study was to assess the impact of continuous cerebral perfusion through the right subclavian artery on immediate outcome and quality of life. METHODS: Perioperative data of 567 consecutive patients who underwent surgery of the aortic arch using deep hypothermic circulatory arrest have been analyzed. Patients were divided into three groups, according to the management of cerebral protection. Three hundred eighty-seven patients (68.3%) had deep hypothermic circulatory arrest with pharmacologic protection with pentothal only, 91 (16.0%) had selective antegrade cerebral perfusion and pentothal, and 89 (15.7%) had continuous cerebral perfusion through the right subclavian artery and pentothal. All in-hospital data were assessed, and quality of life was analyzed prospectively 2.4 +/- 1.2 years after surgery with the Short Form-36 Health Survey Questionnaire. RESULTS: Major perioperative cerebrovascular injuries were observed in 1.1% of the patients with continuous cerebral perfusion through the right subclavian artery, compared with 9.8% with selective antegrade cerebral perfusion (p < 0.001) and 6.5% in the group with no antegrade cerebral perfusion (p = 0.007). Average quality of life after an arrest time between 30 and 50 minutes with continuous cerebral perfusion through the right subclavian artery was significantly better than selective antegrade cerebral perfusion (90.2 +/- 12.1 versus 74.4 +/- 40.7; p = 0.015). CONCLUSIONS: Continuous cerebral perfusion through the right subclavian artery improves considerably perioperative brain protection during deep hypothermic circulatory arrest. Irreversible perioperative neurologic complications can be significantly reduced and duration of deep hypothermic circulatory arrest can be extended up to 50 minutes without impairment in quality of life

Impact of new technologies and experience on procedural aspects of surgical aortic valve replacement - a process analysis.

BACKGROUND Surgical aortic valve replacement (SAVR) is the treatment of choice in severe symptomatic aortic valve disease. New techniques and prostheses have been recently developed to facilitate the procedure and reduce aortic cross-clamp time (AOx). The aim of this study was to analyse the different procedural steps in order to identify the most time-consuming part during aortic clamping time and to compare impact of experience on procedural aspects. METHODS AOx during SAVR was divided into five consecutive steps. Duration of each step was measured. The first procedural step started with clamping of the aorta and ended with the beginning of the second step starting with the resection of the native aortic valve. The third step started with placement of the first valve anchoring suture, the fourth step started with tying of the first suture and the fifth and final step started after the cut of the last suture and ended with removal of the aortic clamp. Surgeons were divided into two groups based on their experience, which in our analysis was defined as a total SAVR experience of more than 100 procedures. RESULTS From March 2013 to August 2015 57 nonconsecutive patients (33% female; age, median 71.0 years, interquartile range 65.0-76.0) undergoing isolated SAVR for severe aortic valve stenosis in our institution were included in this process analysis. Two different prostheses were implanted. Forty-eight (84%) patients received a tissue valve (Perimount Magna Ease, Edwards Lifesciences, Irvine, USA) and 9 (16%) patients received a mechanical prosthesis (Medtronic AP 360, St-Paul, MN, USA). The mean estimated risk of mortality was 1.1% (0.7-1.6) according to the logistic EUROScore II. Overall duration of AOx was 50.5 ± 13.8 min, with 32.3% (16.4 ± 5.9 min) accounting for placing the sutures into the native annulus and the prosthetic sewing ring and 18.5% (9.2 ± 3.0min) accounting for tying and cutting the sutures. Surgeons with more experience performed 35 operations (61.4%) and needed an average of 44.1 ± 11.5 min versus 60.6 ± 11.0 min (p <0.001) for less experienced surgeons. Surgeons with more experience needed 14.0 ± 5.0 min for the suturing step and 8.4 ± 2.8 min for tying the sutures compared with 20.2 ± 5.2 min and 10.5 ± 3.0 min, respectively, for the less experienced surgeons with (p <0.001 and p = 0.010). CONCLUSION Placing and tying sutures in the prostheses accounts for over half (50.8%) of AOx during isolated SAVR. Experienced surgeons have significantly reduced AOx. This shortening is equally distributed between all five procedural steps