First-time surgical aortic valve replacement: nationwide trends and outcomes from The Netherlands Heart Registration.

OBJECTIVES: The aim of this study was to describe trends and outcomes for patients undergoing surgical aortic valve replacement (SAVR) in the Netherlands. METHODS: The Netherlands Heart Registration database was used to report the number and outcomes of isolated, primary SAVR procedures performed from 2007 to 2018 in adult patients. RESULTS: A total of 17 142 procedures were included, of which 77.9% were performed using a biological prosthesis and 21.0% with a mechanical prosthesis. Median logistic EuroSCORE I decreased from 4.6 [interquartile range (IQR) 2.4-7.7] to 4.0 (IQR 2.6-6.0). The 120-day mortality decreased from 3.3% in 2007 to 0.7% in 2018. The median duration of follow-up was 76 months (IQR 53-111). Ten-year survival, when adjusted for age, EuroSCORE I and body surface area, was 72.4%, and adjusted 10-year freedom from reinvervention was 98.1%. Additional analysis for patients under the age of 60 showed no difference between patients treated with a biological or mechanical prosthesis in adjusted 10-year survival, 89.7% vs 91.9±%, respectively (P = 0.25), but a significant difference in adjusted 10-year freedom from reintervention, 90.0±% vs 95.9%, respectively (P < 0.01). CONCLUSIONS: Between 2007 and 2018, age and risk profile of patients undergoing SAVR decreased, especially for patients treated with a biological prosthesis. The 120-day mortality decreased over time. Patients undergoing SAVR nowadays have a risk of 120-day mortality of <1% and 10-year freedom from valve-related reintervention of >95%.

Validation of the slaughterhouse porcine heart model for ex-situ heart perfusion studies.

INTRODUCTION: To validate slaughterhouse hearts for ex-situ heart perfusion studies, we compared cold oxygenated machine perfusion in less expensive porcine slaughterhouse hearts (N = 7) to porcine hearts that are harvested following the golden standard in laboratory animals (N = 6). METHODS: All hearts received modified St Thomas 2 crystalloid cardioplegia prior to 4 hours of cold oxygenated machine perfusion. Hearts were perfused with homemade modified Steen heart solution with a perfusion pressure of 20-25 mmHg to achieve a coronary flow between 100-200 mL/min. Reperfusion and testing was performed for 4 hours on a normothermic, oxygenated diluted whole blood loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mmHg. RESULTS: Both groups showed 100% functional survival, with laboratory hearts displaying superior cardiac function. Both groups showed similar decline in function over time. CONCLUSION: We conclude that the slaughterhouse heart can be used as an alternative to laboratory hearts and provides a cost-effective method for future ex-situ heart perfusion studies.

Ventilation during ex vivo lung perfusion, a review.

Evidence suggests that ventilation during ex vivo lung perfusion (EVLP) with a 'one-size-fits-all' strategy has the potential to cause lung injury which may only become clinically relevant in marginal lung allografts. EVLP induced- or accelerated lung injury is a dynamic and cumulative process reflecting the interplay of a number of factors. Stress and strain in lung tissue caused by positive pressure ventilation may be exacerbated by the altered properties of lung tissue in an EVLP setting. Any pre-existing injury may alter the ability of lung allografts to accommodate set ventilation and perfusion techniques on EVLP leading to further injury. This review will examine the effects of ventilation on donor lungs in the setting of EVLP. A framework for developing a protective ventilation technique will be proposed.

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands.

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.

Mixed Reality in Modern Surgical and Interventional Practice: Narrative Review of the Literature.

BACKGROUND: Mixed reality (MR) and its potential applications have gained increasing interest within the medical community over the recent years. The ability to integrate virtual objects into a real-world environment within a single video-see-through display is a topic that sparks imagination. Given these characteristics, MR could facilitate preoperative and preinterventional planning, provide intraoperative and intrainterventional guidance, and aid in education and training, thereby improving the skills and merits of surgeons and residents alike. OBJECTIVE: In this narrative review, we provide a broad overview of the different applications of MR within the entire spectrum of surgical and interventional practice and elucidate on potential future directions. METHODS: A targeted literature search within the PubMed, Embase, and Cochrane databases was performed regarding the application of MR within surgical and interventional practice. Studies were included if they met the criteria for technological readiness level 5, and as such, had to be validated in a relevant environment. RESULTS: A total of 57 studies were included and divided into studies regarding preoperative and interventional planning, intraoperative and interventional guidance, as well as training and education. CONCLUSIONS: The overall experience with MR is positive. The main benefits of MR seem to be related to improved efficiency. Limitations primarily seem to be related to constraints associated with head-mounted display. Future directions should be aimed at improving head-mounted display technology as well as incorporation of MR within surgical microscopes, robots, and design of trials to prove superiority.

Minimally invasive surgery or stenting for left anterior descending artery disease - meta-analysis.

Minimally invasive direct coronary artery bypass (MIDCAB) surgery and percutaneous coronary intervention (PCI) are both well-established minimally invasive revascularization strategies in patients with proximal left anterior descending (LAD) lesions. We aimed to evaluate the 20-years' experience by performing a systematic review and meta-analysis comparing MIDCAB versus PCI in adults with proximal LAD disease. We searched MEDLINE, EMBASE and Cochrane on October 1st, 2021 for articles published in the year 2000 or later. The primary outcome was all-cause mortality. Secondary outcomes included cardiac mortality, repeat target vessel revascularization (rTVR), myocardial infarction (MI), and cerebrovascular accident (CVA). Outcomes were analysed at short-term, mid-term, and long-term follow-up. Random effects meta-analyses were performed. Events were compared using risk ratios (RR) with 95% confidence intervals (CI). Our search yielded 17 studies pooling 3847 patients. At short-term follow-up, cardiac mortality was higher with MIDCAB than with PCI (RR 7.30, 95% CI: 1.38 to 38.61). At long-term follow-up, MIDCAB showed a decrease in all-cause mortality (RR 0.66, 95% CI: 0.46 to 0.93). MIDCAB showed a decrease in rTVR at mid-term follow-up (RR 0.16, 95% CI: 0.11 to 0.23) and at long-term follow-up (RR 0.25, 95% CI: 0.17 to 0.38). MI and CVA comparisons were not significant. In conclusion, in patients with proximal LAD lesions, MIDCAB showed a higher short-term mortality in the RCTs, but the cohort studies suggested a lower all-cause mortality at long-term follow-up. We confirm a decreased rTVR at mid-term follow-up in the RCTs and long-term follow-up in the cohort studies.

Application of three-dimensional computed tomography imaging and reconstructive techniques in lung surgery: A mini-review.

Background: Pulmonary surgery is an innovative discipline with increasing demands for minimally invasive techniques in complicated anatomical resections, warranting adequate preoperative imaging of relevant surgical anatomy to ensure safe and radical resection of target lesions. Over the recent years, the emergence of imaging techniques enabling three-dimensional reconstruction has exerted promising influence on pulmonary surgery, facilitating optimal surgical planning and easier identification of the spatial relationship between bronchovascular structures in the individual patient and aiding the safe resection of target pulmonary lesions. The goal of this mini-review is to provide an overview of three-dimensional computed tomography imaging within pulmonary surgery. Methods: The authors performed a targeted qualitative review of the literature to identify current trends and to provide better understanding of three-dimensional reconstruction within the boundaries of pulmonary surgery. Results: Three-dimensional reconstructive techniques can be used for resectability assessment, identification of surgically relevant interindividual anatomic variance and may improve perioperative outcomes. Discussion: Three-dimensional reconstruction using computed tomography imaging improves surgical planning and there is evidence that it results in shorter operative times, less intraoperative blood loss and lower rates of surgical conversion, as it can be applied both pre- and intraoperatively.

Recurrence of a Mediastinal Germ-Cell Tumor as a Somatic-Type Malignancy: A Complex Case Report.

Background and case: An adolescent male presented with a second mediastinal tumor 1.5 years after treatment of a proven malignant germ-cell tumor in that location. The differential diagnosis included a recurrent germ-cell tumor or a non-germ cell malignancy. Serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) were negative. The first biopsy was not informative, and the second biopsy gave a broad differential diagnosis including secondary non-germ cell malignancy using histology and immunohistochemistry. DNA methylation profiling, RNA sequencing, and targeted microRNA371a-3p profiling was subsequently performed, without a supportive result. After resection of the tumor the definitive diagnosis yielded two secondary non-germ cell malignancies in the form of a leiomyosarcoma and a solitary neuro endocrine carcinoma (NEC). In spite of the differences between the molecular profiles of the initial germ-cell tumor, the leiomyosarcoma and large-cell NEC are clonally related, as determined by the presence of identical chromosomal breakpoints. The copy number profiles suggest an initial polyploidization step, followed by various independent chromosomal gains and losses. This case demonstrates that germ-cell tumors must be evaluated carefully, including molecularly, in which the non-germ cell malignancy is negative for miR-371a-3p, both in tissue as well as in serum, in contrast to the primary tumor. We conclude that the patient presented with a primary type II mediastinal GCT and, a year and a half later, followed by a leiomyosarcoma and a large-cell NEC presenting as two secondary somatic-type malignancies clonally related to the original GCT. Conclusions: Malignant germ-cell tumors are known to recur as a somatic-type malignancy in very rare cases. This case report illustrates the challenges faced in defining the nature and clonality of the secondary somatic-type malignancies.

Sarcoma of the Heart Treated with Stereotactic MR-Guided Online Adaptive Radiation Therapy.

We present the first case in the literature of a patient with a histology-proven intimal sarcoma of the heart, recurrent after surgery, treated with stereotactic MR-guided online adaptive radiation therapy on an MR-Linac machine. The treatment was feasible and well tolerated. The CT scan 6 months after the last treatment showed stable disease.

Whole Body CT Imaging in Deceased Donor Screening for Malignancies.

BACKGROUND: In most western countries, the median donor age is increasing. The incidence of malignancies in older populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort. METHODS: This study analyzes the efficacy of a preoperative computed tomography (CT) scan on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017 were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings between donor screening with or without CT-scan were compared. RESULTS: Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3% malignancies were found in the abdominal CT-scan and ultrasound groups, respectively. CONCLUSIONS: Screening by CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands.

Surfactant pretreatment decreases long-term damage after ischemia-reperfusion injury of the lung.

OBJECTIVE: Lung ischemia-reperfusion injury (LIRI) is a risk factor for primary acute graft failure following lung transplantation. LIRI hereby contributes to morbidity and mortality after lung transplantation. We have previously shown that surfactant pretreatment ameliorates LIRI up to 1 week after reperfusion. However, the impact of surfactant pretreatment on long-term outcome following LIRI is unknown. Therefore, the objective of this study was to investigate the effect of surfactant pretreatment on long-term outcome following LIRI. METHODS: Male Sprague-Dawley rats (n=63) were randomized to receive intratracheally administered porcine surfactant (400mg/kg) or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia by clamping the bronchus, pulmonary artery and vein of the left lung. A third group was sham-operated; a fourth group served as unoperated controls. Animals were killed on day 30 or 90 after surgery. Arterial oxygenation and lung compliance were determined. Broncho-alveolar lavage fluid (BALf) was collected to assess surfactant function and alveolar protein. Leukocyte infiltration was determined by flowcytometry in BALf, lung tissue and thoracic lymph nodes. Lungs of three animals per group were used for histological assessment. RESULTS: Lung compliance was lower on day 30 and day 90 after LIRI than in sham-operated controls (day 30 V(max) 6.1+/-2.1 vs 12.6+/-1.3, day 90 6.9+/-3.0 vs 12.1+/-1.6; C(max) day 30 0.49+/-0.17 vs 1.08+/-0.21, day 90 0.67+/-0.31 vs 1.11+/-0.17). Furthermore, the number of CD45RA(+)-lymphocytes in left lung tissue was decreased on day 90 compared to unoperated animals (230.633+/-96.770 vs 696.347+/-202.909) and the number of macrophages elevated in left BALf on day 90. HE slides of LIRI animals were scored as fibroproliferative with moderate atelectasis. Surfactant pretreatment improved lung compliance (V(max) day 30 11.7+/-1.8, day 90 11.1+/-1.2; C(max) day 30 1.04+/-0.23, day 90 1.16+/-0.21) and normalized the number of CD45RA(+)-lymphocytes (769.555+/-421.016) in left lung tissue. Furthermore lung architecture on HE slides was on return to normal. However, more CD5(+)CD4(+)-lymphocytes on day 30 (754.788+/-97.269 vs 430.409+/-109.909) and more macrophages on day 90 (2.144.000+/-630.633 vs 867.454+/-383.220) were measured in pretreated lung tissue compared to LIRI animals. CONCLUSIONS: Severe LIRI caused extensive pulmonary injury up to 90 days postoperatively. Surfactant pretreatment normalized pulmonary function, but resulted in an increased number of CD5(+)CD4(+)-cells and macrophages in lung tissue.

Ischemia of the lung causes extensive long-term pulmonary injury: an experimental study.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is suggested to be a major risk factor for development of primary acute graft failure (PAGF) following lung transplantation, although other factors have been found to interplay with LIRI. The question whether LIRI exclusively results in PAGF seems difficult to answer, which is partly due to the lack of a long-term experimental LIRI model, in which PAGF changes can be studied. In addition, the long-term effects of LIRI are unclear and a detailed description of the immunological changes over time after LIRI is missing. Therefore our purpose was to establish a long-term experimental model of LIRI, and to study the impact of LIRI on the development of PAGF, using a broad spectrum of LIRI parameters including leukocyte kinetics. METHODS: Male Sprague-Dawley rats (n = 135) were subjected to 120 minutes of left lung warm ischemia or were sham-operated. A third group served as healthy controls. Animals were sacrificed 1, 3, 7, 30 or 90 days after surgery. Blood gas values, lung compliance, surfactant conversion, capillary permeability, and the presence of MMP-2 and MMP-9 in broncho-alveolar-lavage fluid (BALf) were determined. Infiltration of granulocytes, macrophages and lymphocyte subsets (CD45RA+, CD5+CD4+, CD5+CD8+) was measured by flowcytometry in BALf, lung parenchyma, thoracic lymph nodes and spleen. Histological analysis was performed on HE sections. RESULTS: LIRI resulted in hypoxemia, impaired left lung compliance, increased capillary permeability, surfactant conversion, and an increase in MMP-2 and MMP-9. In the BALf, most granulocytes were found on day 1 and CD5+CD4+ and CD5+CD8+-cells were elevated on day 3. Increased numbers of macrophages were found on days 1, 3, 7 and 90. Histology on day 1 showed diffuse alveolar damage, resulting in fibroproliferative changes up to 90 days after LIRI. CONCLUSION: The short-, and long-term changes after LIRI in this model are similar to the changes found in both PAGF and ARDS after clinical lung transplantation. LIRI seems an independent risk factor for the development of PAGF and resulted in progressive deterioration of lung function and architecture, leading to extensive immunopathological and functional abnormalities up to 3 months after reperfusion.

Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung.

OBJECTIVE: To investigate whether surfactant pretreatment provides lung protection in an animal model of lung ischemia-reperfusion injury (LIRI). METHODS: Male Sprague-Dawley rats (n=100) were randomised to receive intratracheally administered surfactant or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia of the left lung, or were sham-operated. A third group served as healthy untreated controls. Animals were killed on day 1, 3 or 7. Blood gas values were measured and lung compliance was recorded. Broncho-alveolar lavage fluid (BALf) was obtained to assess the amount of alveolar protein, the ratio of small to large aggregate surfactant phospholipids (SA/LA ratio), and leukocyte infiltration (granulocytes, macrophages and lymphocytes, measured by Flow Cytometry). RESULTS: LIRI resulted in a mortality rate of 17% and significantly decreased lung compliance and PaO(2) (day 1 and 3 P<0.001, day 7 P<0.05) as compared to sham-operated and healthy controls. On day 1 more protein was present in the alveoli of ischemic lungs (P<0.001) than in sham-operated and healthy controls. Furthermore, LIRI resulted in an increased SA/LA ratio in the left lung on day 1 (P<0.05) and caused infiltration of granulocytes (day 1, 3 and 7 (P<0.01)), macrophages (day 3 (P<0.05) and 7 (P<0.01) and lymphocytes (day 3 and 7 (P<0.01)) in the BALf as compared to sham-operated and healthy controls. Surfactant pretreatment improved survival, lung compliance (day 3 P<0.001) and PaO(2) (day 1, 3 (P<0.01 and 7 (P<0.05)). It also reduced protein leakage (P<0.05) and prevented an increase in the SA/LA ratio (P<0.01). Although the number of macrophages and granulocytes in the BALF was increased on day 1 and 3 (P<0.01) after surfactant pretreatment as compared to all other groups, the number of lymphocytes was reduced on day 3 (P<0.05). CONCLUSIONS: The present study shows that surfactant pretreatment enhances recovery of lung function and lung mechanics after LIRI, resulting in normal parameters from day 3 onwards. Surfactant pretreatment in this LIRI model may provide useful information to improve donor lung function after lung transplantation.