Search

ZusammenfassungDie interventionelle Therapie der Mitralklappe stellt im Gegensatz zur Aortenklappenintervention eine größere Herausforderung dar. Die Therapie mittels Mitra-Clip zur Rekonstruktion der Mitralklappe wurde erstmals im Jahr 2003 durchgeführt und ist seit dem Jahr 2008 in Europa zugelassen. Die erste Implantation der einzig zugelassenen interventionellen Mitralklappe erfolgte im Jahr 2014, die Zulassung in Europa erfolge im Jahr 2020. Es befinden sich zahlreiche andere Klappensysteme in klinischer Prüfung und werden das Portfolio wahrscheinlich erweitern. In diesem Artikel werden die Indikation für diese neue Therapieform, die technische Umsetzung sowie die spezifischen Herausforderungen für die perioperative Betreuung besprochen.

Fourteen novel quinoline-4-carboxylic acid-chalcone hybrids were obtained via Claisen–Schmidt condensation and evaluated as potential human dihydroorotate dehydrogenase (hDHODH) inhibitors. The ketone precursor 2 was synthesized by the Pfitzinger reaction and used for further derivatization at position 3 of the quinoline ring for the first time. Six compounds showed better hDHODH inhibitory activity than the reference drug leflunomide, with IC50 values ranging from 0.12 to 0.58 μM. The bioactive conformations of the compounds within hDHODH were resolved by means of molecular docking, revealing their tendency to occupy the narrow tunnel of hDHODH within the N-terminus and to prevent ubiquinone as the second cofactor from easily approaching the flavin mononucleotide as a cofactor for the redox reaction within the redox site. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that 4d and 4h demonstrated the highest cytotoxic activity against the A375 cell line, with IC50 values of 5.0 and 6.8 µM, respectively. The lipophilicity of the synthesized hybrids was obtained experimentally and expressed as logD7.4 values at physiologicalpH while the solubility assay was conducted to define physicochemical characteristics influencing the ADMET properties.

Mitral regurgitation (MR) recurrence following annuloplasty can lead to high-risk reoperations impacting long-term outcome. Transcatheter, transapical mitral valve replacement (TMVR) is a novel alternative to treat severe MR without the use of cardiopulmonary bypass. We introduce the case of an 80-year old male, who had undergone a mitral annuloplasty in 2006 and now presented with severe recurrent MR. We performed a TMVR using the Tendyne system©, showing that TMVR following annuloplasty can be a safe method, reducing the procedural time and providing an alternative to the MitraClip© in-the-ring and the transcatheter aortic valve in-the-ring concept.

Background The aim of the study was to assess the indications, surgical strategies, and outcomes after reoperative aortic arch surgery performed generally under mild hypothermia. Methods Ninety consecutive patients (60 males, mean age, 55 ± 16 years) underwent open reoperative aortic arch surgery after previous cardiac aortic surgery. The indications included chronic-progressive arch aneurysm (55.5%), chronic aortic dissection (17.8%), contained arch rupture (16.7%), and graft infection (10%). The reoperation was performed through a repeat sternotomy (96%) or clamshell thoracotomy (4%) using antegrade cerebral perfusion under mild systemic hypothermia (28.9 ± 2.5°C) in all except three patients. Results The surgery comprised hemiarch or total arch replacement in 41 (46%) and 49 (54%) patients, respectively. The distal extension included classic or frozen elephant trunk technique, each in 12 patients, and total descending aorta replacement in 4 patients. Operative mortality was 6 (6.7%) among all patients, with age identified as the only independent predictor of operative mortality (p = 0.05). Permanent and transient neurologic deficits occurred in 1% and 9% of the patients, respectively. Estimated survival at 8 years was 59 ± 8% with advanced heart failure predictive for late mortality (p = 0.014). Freedom from second reoperation or intervention on the aorta was 78 ± 6% at 8 years, with most of these events occurring downstream in patients with chronic degenerative aneurysms. Conclusion Aortic arch reoperations performed using antegrade cerebral perfusion under mild systemic hypothermia offer favorable operative outcomes with an exceptionally low rate of neurologic morbidity without any difference between hemiarch and complex arch procedures.

This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (OKG) and the Austrian Society of Cardiac Surgery (OGTHG) for transfemoral transcatheter aortic valve implantation. Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the OKG and the OGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.

OBJECTIVES Percutaneous pulmonary valve prostheses and right ventricle-to-pulmonary artery conduits are at risk for infective endocarditis (IE). In children and adults with a congenital heart disease, a pulmonary valve implant is frequently necessary. Prosthetic valve endocarditis is a conservatively barely manageable, serious life-threatening condition. We investigated the results of surgical pulmonary valve replacements in patients with IE. METHODS A total of 20 patients with congenital heart disease with the definite diagnosis of IE between March 2013 and July 2020 were included in this single institutional, retrospective review. Infected conduits were 11 Melody, 5 Contegra, 3 homografts and 1 Matrix P Plus. All of the infected prosthetic material was removed from the right ventricular outflow tract up to the pulmonary bifurcation. Pulmonary homografts were implanted after pulmonary root resection as right ventricle-to-pulmonary artery conduits. RESULTS All patients survived and were discharged infection-free. The mean time from the conduit implant to the operation for IE was 4.9 years [95% confidence interval (CI), 3.0–6.9]. The median intensive care unit stay was 3.0 days (95% CI, 2.0–4.7), and the median hospital time was 25.0 days (95% CI, 19.2–42.0). Median follow-up time was 204.5 days (range 30 days to 5 years) without death or recurrent endocarditis. CONCLUSIONS The surgical treatment of IE of percutaneous pulmonary valve prostheses and right ventricle-to-pulmonary artery conduits is a safe and effective therapeutic concept. Early surgical referral of patients with suspicion of IE should be pursued to avoid sequelae such as right ventricular failure, septic emboli, intracardiac expansion and antibiotic resistance.

Background Aortic valve repair (AVR) is an attractive alternative to valve replacement for the treatment of aortic valve insufficiency. Here we report on the midterm outcomes after AVR for aortic valve insufficiency with an emphasis on durability of repair. Methods Between 1996 and 2017, 560 consecutive patients (mean age, 57 ± 16 years) underwent various AVR procedures on tricuspid (n = 415, 74%) and bicuspid (n = 145, 26%) aortic valves. In 313 patients (56%) the David procedure was performed, whereas in 247 patients (44%) cusp repair without aortic root procedure was conducted. Concomitant procedures were coronary artery bypass grafting in 82 patients (15%) and mitral valve repair in 47 patients (8%). Clinical and echocardiographic follow-up was complete in 97% of patients. Mean follow-up was 6.3 ± 4.6 years. Results Thirty-day mortality was 1.4% (n = 8). Late mortality was observed in 132 patients with cardiovascular events accounting for mortality in 13 patients: Survival at 10 years was 70%. Reoperation on the aortic valve was performed on 39 patients for recurrent insufficiency, isolated in 25, or combined with valve stenosis in 5 patients; endocarditis accounted for reoperation in 9 patients (0.2% per patient-year). Freedom from reoperation was 88% at 10 years. Cumulative linearized incidence of all valve-related complications was 2% per patient per year. Conclusions AVR for insufficiency is a durable procedure with low valve-related morbidity and mortality in the midterm.

Side-chain-to-side-chain cyclization is frequently used to stabilize the α-helical conformation of short peptides. In a previous study, we incorporated a lactam bridge between the side chains of Lys-i and Asp-i+4 in the nonapeptide 1Y, cyclo-(2,6)-(Ac-VKRLQDLQY-NH

A water-soluble hydrolysate of silk fibroin (SF) (~30 kDa) was esterified with tocopherol, ergocalciferol, and testosterone to form SF aggregates for the controlled delivery of the anticancer drug camptothecin (CPT). Elemental analysis and 1H NMR spectroscopy showed a degree of substitution (DS) on SF of 0.4 to 3.8 mol %. Yields of 58 to 71% on vitamins- and testosterone-grafted SF conjugates were achieved. CPT was efficiently incorporated into the lipophilic core of SF aggregates using a dialysis–precipitation method, achieving drug contents of 6.3–8.5 wt %. FTIR spectra and DSC thermograms showed that tocopherol- and testosterone-grafted SF conjugates predominantly adopted a β-sheet conformation. After the esterification of tyrosine residues on SF chains with the vitamin or testosterone, the hydrodynamic diameters almost doubled or tripled that of SF. The zeta potential values after esterification increased to about −30 mV, which favors the stability of aggregates in aqueous medium. Controlled and almost quantitative release of CPT was achieved after 6 days in PBS at 37 °C, with almost linear release during the first 8 h. MCF-7 cancer cells exhibited good uptake of CPT-loaded SF aggregates after 6 h, causing cell death and cell cycle arrest in the G2/M phase. Substantial uptake of the CPT-loaded aggregates into MCF-7 spheroids was shown after 3 days. Furthermore, all CPT-loaded SF aggregates demonstrated superior toxicity to MCF-7 spheroids compared with parent CPT. Blank SF aggregates induced no hemolysis at pH 6.2 and 7.4, while CPT-loaded SF aggregates provoked hemolysis at pH 6.2 but not at pH 7.4. In contrast, parent CPT caused hemolysis at both pH tested. Therefore, CPT-loaded SF aggregates are promising candidates for chemotherapy.

Transcatheter therapy of the mitral valve is more challenging compared to the aortic valve. Interventional therapy with the Mitra-Clip system, mimicking the surgical edge-to-edge repair, was first introduced in 2003 and received the CE mark in 2008. The first implantation of the Tendyne system, which is currently the only commercially available system for mitral valve replacement, was performed in 2014, and routine clinical use was approved in 2020. Several new valve platforms are in clinical development and will expand the treatment portfolio. This article will discuss the clinical indications, technical challenges and specific requirements for perioperative management.Die interventionelle Therapie der Mitralklappe stellt im Gegensatz zur Aortenklappenintervention eine größere Herausforderung dar. Die Therapie mittels Mitra-Clip zur Rekonstruktion der Mitralklappe wurde erstmals im Jahr 2003 durchgeführt und ist seit dem Jahr 2008 in Europa zugelassen. Die erste Implantation der einzig zugelassenen interventionellen Mitralklappe erfolgte im Jahr 2014, die Zulassung in Europa erfolge im Jahr 2020. Es befinden sich zahlreiche andere Klappensysteme in klinischer Prüfung und werden das Portfolio wahrscheinlich erweitern. In diesem Artikel werden die Indikation für diese neue Therapieform, die technische Umsetzung sowie die spezifischen Herausforderungen für die perioperative Betreuung besprochen.

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.

Jehovah's Witnesses (JW) refuse allogeneic blood transfusions and therefore pose a unique challenge in case of major surgery. This retrospective study reviewed an experience with JW patients who were undergoing open heart surgery.By using patient blood management strategies, 35 adult JW patients underwent cardiac surgery at Kepler University Hospital in Linz, Austria between 2008 and 2017. Outcomes were compared with patients who accepted blood transfusions (non-JW patients) by using propensity score matching.There were no significant differences in clinical and operative data between the groups. Twelve JW patients (34.3%) were pretreated with erythropoietin and iron, with a preoperative increase in mean hemoglobin of 2.0 g/dL. On admission, hemoglobin was 14.1 ± 1.1 g/dL in JW patients, compared with 13.2 ± 2.0 g/dL in non-JW patients (P = .022). The hematocrit in JW patients was higher throughout the hospital stay, even though 51.4% of non-JW patients received allogeneic red blood cell transfusions. The perioperative red blood cell loss was significantly lower in JW patients than in non-JW patients (619 ± 420 mL vs 929 ± 520 mL; P = .010). Major complication rates were not different between the groups. The hemoglobin at discharge was 11.5 ± 1.5 g/dL in JW patients compared with 10.3 ± 1.3 g/dL in non-JW patients (P.001). In-hospital mortality was 2.9% in each group, and long-term survival was comparable.By implementing patient blood management, open heart surgery in JW patients can be performed with low morbidity and mortality. Preoperative optimization of hemoglobin and minimization of perioperative blood loss are cornerstones in the prevention of blood loss, anemia, and transfusions.

Steroid-grafted silk fibroin (SF) conjugates with a degree of substitution of 1.1–4.3 mol% were efficiently synthesised for controlled release of anticancer drug diosgenin and agrochemicals DI31 and S7. The esterification of tyrosine residues in SF conjugates was confirmed using elemental analysis, ATR-FTIR and 1H NMR spectroscopies. The thermal properties of SF conjugates analysed using DSC and TGA confirmed the ATR-FTIR findings on SF conjugates that β-sheet conformation was the predominant one in solid state. DLS revealed the impact of hydrophobic modification of SF on its hydrodynamic parameters, which resulted in more than doubled hydrodynamic sizes and zeta potential values. SF conjugates were observed as 250–600 nm aggregates formed by nanoparticles of 25–41 nm, as depicted using TEM and AFM. Controlled release of 40–50% grafted steroids from SF conjugates at pH 6.0 was achieved after 5 days. Agrochemical-grafted SF conjugates showed better plant growth enhancing effect than parent DI31 and S7 when evaluated on radish plants. SF conjugates showed low cytotoxicity at concentrations below 0.025 mg/mL when applied on MCF-7 and HEK-293 cells. Due to these results, we envisage that the synthesised DI31- and S7-grafted SF conjugates are good candidates for agrochemical use. This work also contributes to progress the use of silk fibroin in sustainable agriculture.

Rationale: Redo surgeries after mitral valve repair are technically demanding. Procedures applying the NeoChord device (NeoChord Inc, St. Louis Park, MN) have proven to be safe and feasible in selected patients requiring mitral valve repair due to a leaflet prolapse or flail. However, its use for redo procedures after conventional surgical repair has not been well established yet. Patient concerns: We report the case of a 57-year-old man who presented with dyspnea upon exertion. The patient had undergone a minimally invasive surgical mitral valve repair because of a flail leaflet of the segments segment 2 of the posterior mitral valve leaflet (P2)/segment 3 of the posterior mitral valve leaflet (P3) 4 years before. Diagnoses: Transesophageal echocardiography identified a relapse of severe mitral valve regurgitation. The recurring regurgitant jet was caused by a flail leaflet due to newly ruptured native chords. Interventions: After discussion in an interdisciplinary heart team, we performed a minimally invasive off-pump redo procedure applying the NeoChord device under three-dimensional transesophageal echocardiographic guidance. Outcomes: The echocardiographic result with only trivial residual mitral regurgitation as well as the further clinical course of the patient were favorable. Lessons: As redo surgery after minimally invasive mitral valve repair is challenging, the NeoChord device represents a novel treatment option that does not require cardiopulmonary bypass.

OBJECTIVES The aim of this study was to evaluate the effects of the coronavirus 2019 pandemic on elective and acute thoracic aortic surgery in the Netherlands. METHODS The Netherlands Heart Registration database was used to compare the volume of elective and acute surgery on the thoracic aorta in 2019 and 2020, starting from week 11 in both years. A sub-analysis was done to assess the impact of the pandemic on high-volume and low-volume aortic centres. RESULTS During the pandemic, the number of elective thoracic aortic operations declined by 18% [incidence rate ratio (IRR) 0.82 [0.73–0.91]; P < 0.01]. The decline in volume of elective surgery was significant in both high-volume (IRR 0.82 [0.71–0.94]; P < 0.01) and low-volume aortic centres (IRR 0.81 [0.68–0.98]; P = 0.03). The overall number of acute aortic operations during the pandemic remained similar to that in 2019 (505 vs 499; P = 0.85), but an increased share of these operations occurred at high-volume centres. The number of acute operations performed in high-volume centres increased by 20% (IRR 1.20 [1.01–1.42]; P = 0.04), while the number of acute operations performed in low-volume centres decreased by 17% (IRR 0.83 [0.69–1.00]; P = 0.04). CONCLUSIONS The coronavirus 2019 pandemic led to a significant decrease in elective thoracic aortic surgery but did not cause a change in the volume of acute thoracic aortic surgery in the Netherlands. Moreover, the pandemic led to a centralization of care for acute thoracic aortic surgery., The coronavirus disease 19 (COVID-19) pandemic has impacted the delivery of health care around the world.

Transcatheter aortic valve replacement is a well-established therapy for severe aortic stenosis in patients with high surgical risk. Transcatheter mitral valve replacement just recently emerged as a novel modality to treat severe mitral regurgitation. We present the first case of a transcatheter, transapical native double valve replacement for severe aortic stenosis and mitral regurgitation. Our case shows that it is a safe and effective method, not requiring cardiopulmonary bypass and drastically reducing the procedural time. Therefore, patients with significant comorbidities that portend a high surgical risk with poor long-term outcome, may stand to benefit from this minimally invasive procedure.

Objective A novel treatment with intravenous levosimendan and vasopressin for new-onset acute pulmonary hypertension after weaning from cardiopulmonary bypass is described. Design Retrospective analysis of a case series. Setting Single-center study. Participants Nineteen patients undergoing cardiac surgery exhibited new-onset acute pulmonary hypertension with acute right ventricular dysfunction after cardiopulmonary bypass. Intervention Pulmonary hypertension with acute right heart dysfunction was treated with levosimendan as inodilator therapy and vasopressin combined with norepinephrine for systemic vasopressor therapy. Measurements and Main Results Mean pulmonary artery pressure decreased from 32 ± 9 to 26 ± 6 mmHg (p = 0.039) in the first 24 hours along with an increase in cardiac output (3.2 ± 1 to 4.2 ± 1.1 L/min; p = 0.012) and resolution of lactic acidosis. The ratio between mean pulmonary artery pressure and mean arterial pressure decreased from 1:2 to 1:3, and Wood units decreased from 3 ± 1 to 1.5 ± 2 (p = 0.042). At 30 days after intervention, 3 patients died. Conclusion The combination of levosimendan for inotropic support of the right ventricle in conjunction with its vasodilatory effect on the pulmonary circulation, along with the combination of vasopressin and norepinephrine for systemic vasopressor therapy, may be an effective alternative for the treatment of acute new-onset pulmonary hypertension and acute right heart dysfunction after cardiopulmonary bypass. Although there are many confounding variables in this case series, these findings justify additional sufficiently powered trials.

Background: Over the years, frozen elephant trunk (FET) has become the treatment of choice for multisegmental thoracic aortic disease. This multicenter study presents the evolution of FET results using the E-vita Open hybrid graft with respect to institutional experience and time. Methods: The data of International E-vita Open registry were studied according to the institutional experience of the participating centers (high- versus low-volume centers) and according to the evolution of FET treatment during time (1st period, 2005-2011 versus 2nd period, 2012-2018). Overall, 1,165 patients were enrolled in the study with a wide variety of multisegmental thoracic aortic pathologies and aortic emergencies. Participating centers determined their own surgical protocol. Results: The overall 30-day mortality was 12%. Short- and long-term survival were higher in high- versus low-volume centers (P=0.048 and P=0.013, respectively). In the 2nd time period, cerebral complications were reduced significantly (P=0.015). Incidence of permanent spinal cord-related symptoms was reduced to 3% in the 2nd time period, but did not reach statistical significance. Hypothermic circulatory arrest time (P

Giant cell arteritis is an inflammatory vasculopathy of unknown etiology that typically affects the carotid artery and its branches. Symptomatic involvement of upper extremity arteries is uncommon. We report a case of a 70-year-old woman with polymyalgia rheumatica who presented with critical arm ischemia, constitutional symptoms, and elevated erythrocyte sedimentation rate. Urgent revascularization by a carotid-brachial artery bypass was performed. Histopathologic evaluation of a specimen obtained intraoperatively from the occluded axillary artery confirmed the diagnosis, and corticosteroid therapy was initiated. Large-vessel vasculitis should be considered a rare differential diagnosis in occlusive disease of the upper extremity. Keywords: Giant cell arteritis, Arm ischemia, Vasculitis

Objective Autograft dilatation is the main long-term complication following the Ross procedure using the freestanding root replacement technique. We reviewed our 25-year experience with the Ross procedure with a special emphasis on valve-sparing reoperations. Methods From 1991 to 2016, 153 patients (29.6 ± 16.6 years; 29.4% pediatric) underwent a Ross operation at our institution with implantation of the autograft as freestanding root replacement. The follow-up is 98.7% complete with a mean of 12.2 ± 5.5 years. Results Mortality at 30-days was 2.0%. Echocardiography documented no or trivial aortic regurgitation in 99.3% of the patients at discharge. Survival probability at 20 years was 85.4%. No case of autograft endocarditis occurred. Autograft deterioration rate was 2.01% per patient-year, and freedom from autograft reoperation was 75.3% at 15 years. A reoperation for autograft aneurysm was required in 35 patients (22.9%) at a mean interval of 11.1 ± 4.6 years after the Ross procedure. A valve-sparing root replacement was performed in 77% of patients, including 10 David and 17 Yacoub procedures with no early mortality. Three patients required prosthetic valve replacement within 2 years after a Yacoub operation. At latest follow-up, 92% of all surviving patients still carry the pulmonary autograft valve. Freedom from autograft valve replacement was 92.1% at 15 years. Conclusions Using the David or Yacoub techniques, the autograft valve can be preserved in the majority of patients with root aneurysms after the Ross procedure. Reoperations can be performed with no early mortality, a good functional midterm result, and an acceptable reintervention rate.

Degenerative femoral artery aneurysms are uncommon and often associated with aneurysm in other distributions. We report a case of a 68-year-old man with multianeurysmal disease involving the aorta, iliac, femoral, and popliteal arteries managed interdisciplinary by stent-graft placement and open surgical repair. Genetic testing revealed a variant in the FBN2 gene encoding fibrillin-2, an important component of microfibrils. We detail arterial reconstruction of the femoral artery and discuss incidence, diagnosis, and therapy of femoral artery aneurysms.

Objectives The optimal hypothermic level during circulatory arrest in aortic arch surgery remains controversial, particularly in frozen elephant trunk (FET) procedures. We describe herein our experience for total arch replacement with FET technique under moderate systemic hypothermic circulatory arrest (≥ 28°C) during selective antegrade cerebral perfusion. Methods Between January 2009 and January 2016, 38 consecutive patients underwent elective total arch replacement for various aortic arch pathologies with FET technique using the E-vita Open hybrid prosthesis (Jotec GmbH, Hechingen, Germany). Selective unilateral or bilateral cerebral perfusion under moderate systemic hypothermic circulatory arrest (28.7°C ± 0.5°C) was used in all patients. Minimally invasive total arch replacement with FET via partial upper sternotomy was performed in 15 patients (39%) and in the remaining 23 patients (61%) via full sternotomy. Mean late follow-up was 3 ± 2 years and was 98% complete. Clinical data were prospectively entered into our institutional database. Results Cardiopulmonary bypass time accounted for 198 ± 58 minutes and the myocardial ischemic time 109 ± 29 minutes. Selective antegrade cerebral perfusion time was 55 ± 6 minutes. Lower body circulatory arrest time was 39 ± 11 minutes. Unilateral cerebral perfusion was performed in 31 patients (82%), and bilateral in 7 patients (18%). Intensive care unit stay was 4 ± 3 days. Thirty-day mortality was 5% (n = 2). Late survival at 3 years was 87 ± 3%. Two patients (5%) required reexploration for bleeding. Patients were discharged after a hospital length of stay of 7 ± 2 days. Postoperative permanent neurologic complication occurred in two patients (5%). Three patients (8%) experienced a transient neurologic disorder. New transient renal replacement therapy was necessary in three patients (8%). No spinal cord injury was noted. Conclusions Our data suggest that moderate systemic hypothermic circulatory arrest (≥ 28°C) in combination with antegrade cerebral perfusion can safely be applied for total aortic arch replacement with FET and offers sufficient neurologic and visceral organ protection.

Aims: Life-threatening complications occur during transcatheter aortic valve implantation (TAVI) which can require emergent cardiac surgery (ECS). Risks and outcomes of patients needing ECS during or immediately after TAVI are still unclear. Methods and results: Incidence, risk factors, management, and outcomes of patients requiring ECS during transfemoral (TF)-TAVI were analysed from a contemporary real-world multicentre registry. Between 2013 and 2016, 27 760 patients underwent TF-TAVI in 79 centres. Of these, 212 (0.76%) patients required ECS (age 82.4 ± 6.3 years, 67.5% females, logistic EuroSCORE: 17.1%, STS-score 5.8%). The risk of ECS declined from 2013 (1.07%) to 2014 (0.70%) but remained stable since. Annual TF-TAVI numbers have more than doubled from 2013 to 2016. Leading causes for ECS were left ventricular perforation by the guidewire (28.3%) and annular rupture (21.2%). Immediate procedural mortality ( 85 years [odds ratio (OR) 1.87, 95% confidence interval (95% CI) (1.02–3.45), P = 0.044], annular rupture [OR 1.96, 95% CI (0.94–4.10), P = 0.060], and immediate ECS [OR 3.12, 95% CI (1.07–9.11), P = 0.037]. One year of survival of the 114 patients surviving the in-hospital period was only 40.4%. Conclusion: Between 2014 and 2016, the need for ECS remained stable around 0.7%. Left ventricular guidewire perforation and annular rupture were the most frequent causes, accounting for almost half of ECS cases. Half of the patients could be salvaged by ECS—nevertheless, 1 year of all-cause mortality was high even in those ECS patients surviving the in-hospital period.

Objective We report our experience with a staged hybrid approach for the treatment of extended aortic disease, also known as "mega aortic syndrome." Methods A total of 15 patients (10 male, 5 female) underwent staged repair of the thoracoabdominal aorta, consisting of 3 separate stages (repair of ascending aorta and aortic arch using the frozen elephant trunk technique and hybrid thoracoabdominal repair with debranching of the renovisceral branches and stent graft implantation). Results The procedure was completed in 14 patients. After the first stage (repair of ascending aorta and aortic arch), no mortality or spinal cord ischemia occurred. One patient required temporary dialysis. After the thoracoabdominal repair, permanent paraplegia developed in 1 patient. One patient died intraoperatively after aneurysm rupture. The in-hospital mortality for the complete repair reached 6.7%. None of the surviving patients required permanent dialysis. Interval aortic events consisted of 1 contained rupture. Conclusions The concept of a staged hybrid repair of the mega aortic syndrome is technically feasible. The frozen elephant trunk technique represents an attractive treatment option, offering an adequate landing zone for later thoracoabdominal repair in patients with extended aortic disease. For completion of the repair, a staged hybrid approach with renovisceral debranching and aneurysm exclusion using off-the-shelf stent grafts shows promising results with low surgical morbidity and mortality.

Background We analyzed our experience with the aortic arch operations performed through a minimally invasive approach, with emphasis on safety and feasibility, early and late outcomes. Material and methods We reviewed the medical records of 71 adult patients with aortic arch aneurysm (58, 82%), dissection (10, 14%) or porcelain aorta (3, 4%) who underwent primary arch surgery through a partial upper sternotomy. Results The aortic arch was replaced partially in 45 (63%), or totally in 26 (37%) patients. The repair was further extended with the elephant trunk procedure, conventional in 8 (11.3%) or frozen in 15 (21.1%) patients. No conversion to full sternotomy was needed. New permanent renal failure occurred in 1 (1.4%), temporary neurologic deficit in 2 (2.8%) and permanent neurologic deficit in 3 (4.2%) patients. Early mortality was observed in 4 (5.6%) patients. Actuarial survival was 79.2 ± 8.3% at 4 years and cumulative reoperation-free survival was 76.4 ± 9.4% at 4 years. Conclusion Minimally invasive aortic arch surgery is safe and feasible. Early outcomes are at the lower range compared to other published series. Late outcomes are not adversely influenced, as the desired extent of aortic resection can be achieved, producing a durable aortic repair.

Objectives Surgery for acute type A aortic dissection (AAD) remains a surgical challenge with considerable risk of morbidity and mortality. Antegrade cerebral perfusion (ACP) has been popularized, offering a more physiologic method of brain perfusion during complex aortic arch repair, often necessary in setting of AAD. The safe limits of this approach under moderate-to-mild systemic hypothermic circulatory arrest (≥ 28°C) are yet to be defined. Thus, the current study investigates our clinical results after surgical treatment for AAD in patients with a selective ACP and systemic circulatory arrest time of ≥ 60 minutes in moderate-to-mild hypothermia (≥ 28°C). Methods Between January 2000 and April 2016, 63 consecutive patients underwent surgical treatment for AAD employing selective ACP during moderate-to-mild systemic hypothermia (≥ 28°C) with prolonged ACP and circulatory arrest times. Patients' mean age was 59 ± 15 years, and 39 patients (62%) were men. Hemiarch replacement and total arch replacement were performed in 13 (21%) and 50 (79%) patients, respectively. Frozen elephant trunk, arch light, and elephant trunk technique were performed in nine (14%), six (10%), and three patients (5%), respectively. Clinical data were prospectively entered into our institutional database. Mean late follow-up was 6 ± 4 years and was 98% complete. Results Cardiopulmonary bypass time accounted for 245 ± 81 minutes and the myocardial ischemic time accounted for 140 ± 43 minutes. Mean duration of ACP was 74 ± 12 minutes. The mean lowest core temperature accounted for 28.9 ± 0.8°C. Unilateral ACP was performed in 44 patients (70%); bilateral ACP was used in the remaining 19 patients (30%). Intensive care unit stay reached 6 ± 5 days. New onset of acute renal failure requiring hemofiltration was observed in 8% of patients (n = 5). New postoperative permanent neurologic deficits were found in five patients (8%) and transient neurologic deficits in six patients (10%). There was one case of paraplegia. Thirty-day mortality and in-hospital mortality were 8 (n = 5) and 11% (n = 7), respectively. Overall survival at 5 years was 76 ± 9%. Conclusion Our preliminary data suggest that selective ACP during moderate-to-mild systemic hypothermic circulatory arrest (≥ 28°C) can safely be applied for more than 1 hour even in the setting of AAD.

Background Whether selective antegrade cerebral perfusion (ACP) during moderate-to-mild systemic hypothermia (≥28°C) is applicable to aortic arch surgery without restrictions including the emergency setting of an acute type A aortic dissection or extensive total arch procedures such as elephant and frozen elephant trunk techniques is an ongoing subject of controversy. Methods Between January 2000 and January 2015, 587 consecutive all-comers underwent aortic arch surgery at our institution uniformly applying selective ACP (unilateral: n = 393 [67%]; bilateral: n = 194 [33%]) during moderate-to-mild systemic hypothermia (28.7 ± 0.6°C). Patients' mean age was 68 ± 16 years, 405 patients (69%) were men, and 219 patients (37%) had acute type A aortic dissection. Hemiarch replacement was performed in 386 patients (66%) whereas the remaining 201 patients (34%) underwent total arch replacement including elephant trunk (n = 74 [13%]) and frozen elephant trunk (n = 37 [6%]) procedures. Fifty-six patients (10%) have had previous aortic arch surgery. Clinical data were prospectively entered into our institutional database. Results Cardiopulmonary bypass time accounted for 183 ± 67 min and myocardial ischemic time reached 110 ± 45 min. Mean duration of selective ACP was 48 ± 21 (range, 12 to 135) min. Chest tube drainage during the first 24 h accounted for 597 ± 438 mL. Mean ventilation time was 31 ± 18 h. Reexploration for bleeding and postoperative renal replacement therapy was necessary in 74 patients (13%) and 49 patients (8%), respectively. Mean intensive care unit stay was 4 ± 5 days. We observed new postoperative permanent neurologic deficits in 34 patients (6%; stroke: n = 33 [6%]; paraplegia: n = 1 [0.17%]) and transient neurologic deficits in 29 patients (5%). Thirty-day mortality was 6% (n = 36). Conclusions Current data suggest that selective ACP in combination with moderate-to-mild systemic hypothermia offers sufficient neurologic and visceral organ protection to all-comers requiring aortic arch surgery without pathological or procedural limitations.

Background Many techniques for repair of bicuspid aortic valves have been described and long-term results differ considerably. The current study evaluates our institutional results using the pericardial patch augmentation technique with the aim of increasing coaptation height. Methods From November 2002 through April 2015, 103 consecutive patients underwent aortic valve repair using pericardial patch augmentation for incompetent bicuspid aortic valve. Of them 26 were referred with an aortic valve regurgitation grade 1+ or 2+ and were excluded from the current report. The remaining 77 patients with a mean age of 42 ± 14 years and aortic valve regurgitation grade of 3+ or higher were included in this retrospective single-center study. The main step of operative technique is the partial correction of leaflet prolapse by leaflet plication and overcorrection of coaptation height augmenting the fused leaflet with an autologous pericardial patch. In 45 patients (58%) an isolated aortic valve repair was performed. The ascending aorta was dilated in 32 cases (42%), and the following procedures were used for correction: reduction aortoplasty (19 patients), the David procedure (11 patients), and ascending aortic replacement (2 patients). Long-term results were evaluated by echocardiography and standardized questionnaire. Mean follow-up was 4.9 ± 4.6 years. Results There was no perioperative or 90-day mortality. Survival at 5 and 10 years was 96.1% and 93.5%, respectively. Freedom from reoperation at 5 and 10 years was 94.8% and 93.5%, respectively. At the latest echocardiographic follow-up, 94% of patients had none to trivial aortic regurgitation and 6% showed aortic regurgitation greater than or equal to 2°. Mean aortic gradients were 12.6 ± 9 mm Hg. One patients developed endocarditis 1 year after the procedure. There were no perioperative or long-term major neurologic events. Conclusions The pericardial patch augmentation technique provides reliable long-term competence of reconstructed bicuspid aortic valves and results in a low reoperation rate, with other valve related complications being rare.

A series of novel 2-substituted quinoline-4-carboxylic acids was synthesized by Doebner reaction starting from freely available protocatechuic aldehyde and vanillin precursors. Human dihydroorotate dehydrogenase (hDHODH) was recognised as a clear molecular target for these heterocycles. All compounds were also tested for their antiproliferative potential against three cancer cells (MCF-7, A549, A375) and one normal cell line (HaCaT) to evaluate the selective cytotoxicity. Quinoline derivatives 3f and 3g were identified as potent hDHODH inhibitors while 3k and 3l demonstrated high cytotoxic activity against MCF-7 and A375 cells and good selectivity. In addition, the logD7.4 values obtained by the experimental method were found to be in the range from -1.15 to 1.69. The chemical structures of all compounds were confirmed by IR, NMR and elemental analysis. The compounds pharmacology on the molecular level was revealed by means of molecular docking, highlighting the structural differences that distinguish highly active from medium and low active hDHODH inhibitors.

The synthesis and characterisation of novel polyphosphazene nanocarriers, based on hydrophilic polyalkylene oxide Jeffamine M1000 and hydrophobic steroids with a glycinate linker for pH-controlled release of diosgenin and two brassinosteroids (DI31 and S7) with agrochemical and potential anticancer activity, is hereby described. Polyphosphazenes carrying approximately 17 wt% of DI31 or S7 self-assembled in water to form 120–150 nm nanoaggregates, which showed an excellent plant growth effect on radish cotyledons due to sustained delivery of approximately 30% of the agrochemicals after 4 days. Cytotoxic evaluation showed that all polymers carrying steroids and Jeffamine M1000 resulted in strong to moderate toxicity to MCF-7 cancer cells and were non-toxic to primary human lung fibroblast cells at 0.1 to 0.025 mg mL−1. Thus, DI31 and S7 bearing polymers applied at 10−4 to 10−6 mg mL−1 for delivery of recommended DI31 or S7 quantities to crops should be harmless to humans. Particularly, DI31 and S7 bearing polymers with strong cytotoxicity on MCF-7 and non-toxicity on primary human lung fibroblasts, good cell uptake after 6 hours, proper hydrodynamic sizes between 100 and 200 nm, and slow sustained release of cytotoxic drugs (DI31, S7) in acidic conditions might potentiate their accumulation in cancer tissues with good antitumour effects and minor side effects. These results demonstrated that preparation of brassinosteroid bearing polymers is a promising strategy for the preparation of better agrochemicals with reduced pollutant impact on sustainable agriculture and potential anticancer formulations based on analogues of brassinosteroids.

Twenty novel 2-substituted quinoline-4-carboxylic acids bearing amide moiety were designed and synthesized by Doebner reaction. Human dihydroorotate dehydrogenase (hDHODH) was recognized as a biological target and all compounds were screened as potential hDHODH inhibitors in an enzyme inhibition assay. The prepared heterocycles were also evaluated for their cytotoxic effects on the healthy HaCaT cell line while lipophilic properties were considered on the basis of experimentally determined logD values at physiological pH. The most promising compound 5j, with chlorine at para-position of terminal phenyl ring, showed good hDHODH inhibitory activity, low cytotoxicity, and optimal lipophilicity. The bioactive conformation of 5j on the hDHODH, determined by means of molecular docking, revealed the compound’s pharmacology and provide guidelines for further lead optimization.

Optimal valve substitute for young patients with aortic valve endocarditis remains controversial. Given its better resistance to infection, the Ross procedure is an attractive alternative to prosthetic valve replacement or homograft implantation. The objective of this study was to assess long-term outcomes of the Ross procedure in this indication. From January 1991 to April 2017, 190 patients underwent a Ross procedure at our institution. Acute endocarditis was the indication for operation in 19 patients, including 6 patients with a bicuspid aortic valve. The pulmonary autograft was implanted as freestanding root replacement in all patients. The clinical follow-up is 100% complete, with a mean of 12.0 ± 5.7 years. The mean age of the study population was 35.9 ± 11.5 years. Moderate or severe aortic regurgitation was present in 84.2% of the patients. Systemic embolization had occurred in 36.8% of the patients. The mean aortic cross-clamp time was 126 ± 24 minutes. The median length of stay on the intensive care unit was 1 day. Mortality at 30 days was 5.3% (1 patient with gastrointestinal bleeding). Echocardiography at hospital discharge documented no or trivial aortic regurgitation in all patients. No case of recurrent endocarditis affecting the autograft occurred. One patient (0.4% per patient-year) was reoperated 1.8 years after the Ross procedure for homograft endocarditis. Three patients (15.8%) were reoperated for autograft aneurysm. The Ross procedure is a safe and effective alternative to prosthetic valve replacement or homograft implantation in selected young patients with acute endocarditis with a low rate of recurrent infection.

Objective Surgery for acute type A aortic dissection remains a surgical challenge because of prolonged operative times, bleeding complications, and a considerable risk of neurological morbidity and mortality. The following study investigates the clinical results after surgical treatment for acute type A aortic dissection using selective antegrade cerebral perfusion and moderate-to-mild systemic hypothermia (≥28 °C). Methods Between January 2000 and January 2015, 453 consecutive patients underwent surgical treatment for acute type A aortic dissection at two aortic referral centres in Germany. Patient mean age was 67 ± 13 years, 298 patients (66%) were male. Selective unilateral or bilateral cerebral perfusion under moderate-to-mild systemic hypothermia was used in all patients. Ascending aortic replacement, hemiarch replacement and total arch replacement was performed in 9 patients (2%), 342 patients (75%) and 102 patients (23%), respectively. Clinical data were prospectively entered into the institutional databases. Mean late follow-up was 6 ± 3 years and was 98% complete. Results Cardiopulmonary bypass time totalled 181 ± 68 min and the myocardial ischaemic time 107 ± 43 min. Mean duration of selective antegrade cerebral was 46 ± 23 min. Mean lowest core temperature amounted to 28.8 ± 0.6 °C. Unilateral cerebral perfusion was performed in 298 patients (66%) and bilateral in 155 patients (34%). Mean intensive care unit stay was 5 ± 7 days. We observed new postoperative permanent neurological deficits in 27 patients (6%) and transient neurological deficits in 31 patients (7%). Thirty-day mortality was 7% (n = 32). Overall survival rate at 5 years was 77 ± 6%. Conclusions Our data suggest that selective antegrade cerebral perfusion in combination with moderate-to-mild systemic hypothermia (≥28 °C) can be safely and reproducibly applied to surgery for acute type A aortic dissection and offers sufficient neurological and visceral organ protection.

Background The aim of the study was to evaluate operative and long-term results after acute type A aorta dissection (AAAD) operation, in which complete resection of all dissected aortic segments (curative repair) was achieved. Methods Among 205 consecutive patients operated on between 2002 and 2014 because of AAAD were 88 patients (42.9%), in whom the dissection did not extend into the downstream aorta. The distal extension of the dissection ended before the origin of the innominate artery in 50 patients of the study cohort (56.8%) or extended throughout the arch, necessitating a total/subtotal arch replacement to achieve a curative distal repair in 38 remaining patients (43.2%). The aortic root was involved in 52 patients (59.1%) and was repaired using valve-sparing repair (31) or replacement with a valve composite graft (21). Combination of root and open arch surgery was reported in 46 patients (52.3%). Results Thirty-day and in-hospital mortalities were 3.4% and 5.7%, respectively. Survival was estimated starting with the operation and was 81.9% ± 4.5% and 56.6% ± 8.7% at 5 and 10 years, respectively. No patient required reoperation on the aortic root and/or distal thoracoabdominal aorta; however 2 cardiac reoperations were unrelated to the primary surgical procedure. Moreover, the freedom of aortic and/or sudden/unknown death was 100%. Conclusions Curative aortic repair can be achieved in a relevant share of AAAD patients and is mostly limited by the distal extension of dissection. This kind of repair is advisable, whenever possible, because it can provide very low risk of aortic complications and/or reoperations over time.

Background Neo-aortic root dilatation accounts for the majority of reoperations needed after the Ross procedure with implantation of the pulmonary autograft as complete root replacement. This study evaluates early results of external prosthetic reinforcement of the autograft. Methods From July 2015 to October 2017, 16 adolescent and adult patients received a Ross procedure at our department by this technique. A congenital-dysplastic valve was present in 13 patients, including 9 patients with a bicuspid aortic valve. Clinical and echocardiographic follow-up is complete with a mean duration of 19.7 ± 5.8 months. Results The mean age at operation was 27.1 ± 16.1 years. Mean aortic cross-clamping time was 102 ± 39 minutes. No bleeding complication occurred. The median stay on the intensive care unit was 2 days. In-hospital mortality was 0%. All patients were discharged with no or trivial aortic regurgitation. In one patient both the autograft and homograft were replaced because of endocarditis 3 months after the primary operation, leading to 93.8% freedom from reoperation at 2 years. There were no late deaths during the study period. The latest echocardiography confirmed absence of aortic regurgitation grade >I in all patients. Neo-aortic root diameters remained stable during follow-up. Conclusion The presented modification of the Ross procedure does not prolong ischemia time, and can be performed with a low operative morbidity and mortality and an excellent early valve function.

We report the case of an 89-year-old man with severe aortic valve stenosis and concomitant severe mitral valve regurgitation. Due to his age and comorbidities, the patient was not accepted for open heart surgery. After interdisciplinary discussion with the heart team, the patient underwent a minimally invasive off-pump procedure combining aortic valve replacement with mitral valve repair. Cardiac surgeons performed a transapical aortic valve replacement, followed by mitral valve repair applying the NeoChord device (NeoChord Inc, St. Louis Park, MN) under three-dimensional transesophageal echocardiographic guidance by an interventional cardiologist. The patient's further clinical course was uneventful, and he did well on follow-up examinations.

Objectives Classically, repair of extensive thoracic aortic pathologies including the aortic arch and descending aorta required two separate major surgical procedures via full sternotomy and a subsequent left lateral thoracotomy. We describe herein our preliminary institutional experience with minimally invasive single-stage extended thoracic aortic replacement employing the frozen elephant trunk (FET) technique via partial upper sternotomy (PUS) in 14 patients. Methods Between December 2013 and January 2015, 14 consecutive patients with elective indications for FET underwent minimally invasive FET via PUS (PUS-FET) during moderate systemic hypothermia (28°C) and selective antegrade cerebral perfusion (ACP) using the E-vita Open® hybrid prosthesis (Jotec GmbH, Hechingen, Germany). The patients' mean age was 66 ± 6 years, and 9 patients (64%) were male. The arch vessels were reimplanted en bloc in all patients. Clinical data were prospectively entered into our institutional database. Results The surgical procedure was successful in all patients with no need for conversion to full sternotomy. An additional David procedure was performed in 1 patient, whereas 2 patients received a concomitant Bentall procedure. There was no perioperative death or 30-day mortality. The mean cardiopulmonary bypass time was 214 ± 35 min, and the myocardial ischaemic time was 125 ± 14 min. The ACP time was 54 ± 9 min, whereas the ventilation time reached 11 ± 4 h. Intensive care unit stay was 2 ± 3 days. Chest tube drainage within the first 24 h was 460 ± 130 ml. None of the 14 patients required re-exploration for bleeding. Patients were discharged after a hospital length of stay of 9 ± 2 days. No postoperative permanent neurological complication occurred. Two patients (14%) experienced temporary delirium with complete resolution of symptoms prior to discharge from the hospital. Conclusions Our preliminary experience suggests that minimally invasive single-stage extended thoracic aortic replacement can safely and reproducibly be performed by employing the concept of PUS-FET.

Introduction The David Procedure may provide an attractive alternative to aortic root replacement in patients with aortic valve insufficiency (AI) even in the emergency setting of an acute type A aortic dissection (AAD). Methods From 1996 to 2011 the David Procedure was performed in 23 patients with AAD in our department. Patients' mean age was 49 ± 15 years and 70% (n = 16) were male. Concomitant hemiarch replacement was performed in 19 patients while the remaining 4 patients underwent full arch replacement. Additional leaflet prolapse was corrected by plication in 5 cases. A modification of the classic David technique was performed by creating a pseudosinus in 6 patients (26%) and a neosinus in 9 patients (39%). Mean follow up was 7.7 ± 3 years. Results Thirty-day mortality was zero. There were 4 late deaths (17%). One patient suffered a perioperative neurologic event (4%). One further patient suffered a late stroke during follow up (0.6%/pt-yr). Three patients (1.7%/pt-yr) required aortic valve reoperation during follow up: in 2 cases leaflet perforation was observed, and one patient had to undergo valve replacement because of endocarditis with severe AI. There were two cases of bleeding events (1.1%/pt-yr) at follow up. The linearized rate for recurrent AI≥2° was 1.1%/pt-yr. Discussion The David Procedure certainly provides a challenging option to treat selected young patients with AI in the presence of AAD. However, current data suggest that it is safe and feasible. Conclusions Long-term valve-related events of the David Procedure applied in emergency cases are rare and aortic valve function remains stable for many years.

Hintergrund Die praoperative Anamie hat in den Industrienationen eine Pravalenz von ungefahr 30 %, ist einer der starksten Pradiktoren fur die perioperative Gabe von Erythrozytenkonzentraten (EK) und zugleich ein eigenstandiger und unabhangiger Risikofaktor fur das Auftreten postoperativer Komplikationen. Im Bereich der Hamotherapie ist weltweit eine breite Variabilitat der Indikationsstellung zum Einsatz von EK auffallend. Vor diesem Hintergrund wird seit 2011 von der Weltgesundheitsorganisation die Implementierung eines Patient-blood-Managements (PBM) gefordert.