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.

Hemofiltration Improves Blood Perfusate Conditions Leading to Improved Ex Situ Heart Perfusion.

The aim was to optimize the perfusate composition by including a hemofiltrator to the PhysioHeartplatform for ex situ heart perfusion of porcine slaughterhouse hearts. Fourteen hearts were harvested from Dutch Landrace pigs and slaughtered for human consumption. All hearts were preserved for 4 hours using static cold storage before reperfusion for 4 hours on the PhysioHeart platform. Seven hearts were assigned to the hemofiltration group, where a hemofiltrator was added to the perfusion circuit, while the control group did not receive hemofiltration. In the hemofiltration group, the perfusion fluid was filtrated for 1 hour with a flow of 1 L/hour before reperfusion. After mounting the heart, hemofiltration was maintained at 1 L/hour, and cardiac function and blood samples were analyzed at multiple time points. Preserved cardiac function was defined as a cardiac output >3.0 L/min with a mean aortic pressure >60 mm Hg and a left atrial pressure <15 mm Hg. Hemofiltration resulted in a significantly reduced potassium concentration at all time points ( p < 0.001), while sodium levels remained at baseline values ( p < 0.004). Furthermore, creatinine and ammonia levels decreased over time. Functional assessment demonstrated a reduced left atrial pressure ( p < 0.04) and a reduction of the required dobutamine dose to support myocardial function ( p < 0.003) in the hemofiltration group. Preserved cardiac function did not differ between groups. Hemofiltration results in an improved biochemical composition of the whole blood perfusate and preserves cardiac function better during normothermic perfusion based on a reduced left atrial pressure (LAP) and dobutamine requirement to support function.

Monitoring left ventricular assist device parameters to detect flow- and power-impacting complications: a proof of concept.

Aims: The number of patients on left ventricular assist device (LVAD) support increases due to the growing number of patients with end-stage heart failure and the limited number of donor hearts. Despite improving survival rates, patients frequently suffer from adverse events such as cardiac arrhythmia and major bleeding. Telemonitoring is a potentially powerful tool to early detect deteriorations and may further improve outcome after LVAD implantation. Hence, we developed a personalized algorithm to remotely monitor HeartMate3 (HM3) pump parameters aiming to early detect unscheduled admissions due to cardiac arrhythmia or major bleeding. Methods and results: The source code of the algorithm is published in an open repository. The algorithm was optimized and tested retrospectively using HeartMate 3 (HM3) power and flow data of 120 patients, including 29 admissions due to cardiac arrhythmia and 14 admissions due to major bleeding. Using a true alarm window of 14 days prior to the admission date, the algorithm detected 59 and 79% of unscheduled admissions due to cardiac arrhythmia and major bleeding, respectively, with a false alarm rate of 2%. Conclusion: The proposed algorithm showed that the personalized algorithm is a viable approach to early identify cardiac arrhythmia and major bleeding by monitoring HM3 pump parameters. External validation is needed and integration with other clinical parameters could potentially improve the predictive value. In addition, the algorithm can be further enhanced using continuous data.

Gene therapy during ex situ heart perfusion: a new frontier in cardiac regenerative medicine?

Ex situ organ preservation by machine perfusion can improve preservation of organs for transplantation. Furthermore, machine perfusion opens up the possibilities for selective immunomodulation, creation of tolerance to ischemia-reperfusion injury and/or correction of a pathogenic genetic defect. The application of gene modifying therapies to treat heart diseases caused by pathogenic mutations during ex situ heart perfusion seems promising, especially given the limitations related to delivery of vectors that were encountered during clinical trials using in vivo cardiac gene therapy. By isolating the heart in a metabolically and immunologically favorable environment and preventing off-target effects and dilution, it is possible to directly control factors that enhance the success rate of cardiac gene therapy. A literature search of PubMed and Embase databases was performed to identify all relevant studies regarding gene therapy during ex situ heart perfusion, aiming to highlight important lessons learned and discuss future clinical prospects of this promising approach.

Successful aortic arch cannulation and perfusion of a heart donated after circulatory death: A case report.

INTRODUCTION: We describe successful aortic arch cannulation and perfusion of a heart donated after circulatory death using the Transmedics Organ Care System™. CASE REPORT: A 47-year old man developed advanced heart failure symptoms after prior mustard operation for transposition of the great arteries. He matched a DCD-donor and required an elongated aorta for implantation due to his altered anatomy. The donor heart was retrieved and successfully perfused via aortic arch cannulation for 4.5 h with satisfactory perfusion parameters. DISUSSION: Although Transmedics advises against aortic arch cannulation due to concerns regarding malperfusion, satisfactory and safe perfusion can be achieved by careful positioning of the heart. Awareness and attention to the occurrence of malperfusion is mandatory, especially during transport, to achieve satisfactory outcome. CONCLUSION: Aortic arch cannulation is feasible without compromising quality of perfusion. This is relevant for patient that require an elongated aorta after surgically corrected congenital heart disease.

Pre-Operative SARS-CoV-2 Testing in Asymptomatic Heart Transplantation Recipients.

INTRODUCTION: From the start of the coronavirus disease 2019 (COVID-19) pandemic, international guidelines have recommended pre-operative screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before heart transplantation (HTx). Due to the changing prevalence of COVID-19, the chances of false positive results have increased. Because of increased immunity in the population and evolution of SARS-CoV-2 to current Omicron variants, associated mortality and morbidity have decreased. We set out to investigate the yield and side effects of SARS-CoV-2 screening in our center. METHODS: We performed a retrospective cohort study in the University Medical Center Utrecht. The study period was from March 2019 to January 2023. All data from patients who underwent HTx were collected, including all pre-operative and post-operative SARS-CoV-2 tests. Furthermore, all clinical SARS-CoV-2 tests for the indication of potential HTx were screened. RESULTS: In the period under study, 51 patients underwent HTx. None of the recipients reported any symptoms of a viral infection. Fifty HTx recipients were screened for SARS-CoV-2. Forty-nine out of fifty patients tested negative. One patient had a false positive result, potentially delaying the HTx procedure. There were no cancelled HTx procedures due to a true positive SARS-CoV-2 test result. CONCLUSION: Pre-operative SARS-CoV-2 screening in asymptomatic HTx recipients did not lead to any true positive cases. In 2% of the cases, screening resulted in a false positive test result. With the current Omicron variants, in combination with a low-prevalence situation, we propose to abandon pre-operative SARS-CoV-2 screening and initiate a symptom-driven approach for the general viral testing of patients who are called in for a potential HTx.

Cold Oxygenated Machine Perfusion Improves Functional Survival of Slaughterhouse Porcine Hearts.

The aim of our study was to explore the effect of cold oxygenated machine perfusion in slaughterhouse porcine hearts on functional myocardial survival compared to static cold storage (SCS). Seventeen hearts were harvested from Dutch Landrace Hybrid pigs, which were sacrificed for human consumption and randomly assigned to the 4 hours SCS group (N = 10) or the 4 hours cold oxygenated machine perfusion group (N = 7). Hearts were perfused with a homemade Heart Solution with a perfusion pressure of 20-25 mm Hg to achieve a coronary flow between 100 and 200 ml/minute. After 4 hours of preservation, all hearts were functionally assessed during 4 hours on a normothermic, oxygenated diluted whole blood (1:2) loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mm Hg. Survival was significantly better in the cold oxygenated machine perfusion group, where 100% of the hearts reached the 4 hours end-point, as compared with 30% in the SCS group ( p = 0.006). Interestingly, warm ischemic time was inversely related to survival in the SCS group with a correlation coefficient of -0.754 ( p = 0.012). Cold oxygenated machine perfusion improves survival of the slaughterhouse porcine heart.

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.

Data-driven monitoring in patients on left ventricular assist device support.

INTRODUCTION: Despite an increasing population of patients supported with a left ventricular assist device (LVAD), it remains a complex therapy, and patients are frequently admitted. Therefore, a strict follow-up including frequent hospital visits, patient self-management and telemonitoring is needed. AREAS COVERED: The current review describes the principles of LVADs, the possibilities of (tele)monitoring using noninvasive and invasive devices. Furthermore, possibilities, challenges, and future perspectives in this emerging field are discussed. EXPERT OPINION: Several studies described initial experiences on telemonitoring in LVAD patients, using mobile phone applications to collect clinical data and pump data. This may replace frequent hospital visits in near future. In addition, algorithms were developed aiming to early detect pump thrombosis or driveline infections. Since not all complications are reflected by pump parameters, data from different sources should be combined to detect a broader spectrum of complications in an early stage. We need to focus on the development of sophisticated but understandable algorithms and infrastructure combining different data sources, while addressing essential aspects such as data safety, privacy, and cost-effectiveness.

[Heart donation after circulatory death: ethical and emotional aspect of central normothermic regional perfusion]. / Hoe behoud je een donorhart na circulatoir overlijden?

Heart transplantation after circulatory death is possible in different countries with the use of ex situ normothermic perfusion of the donor heart. Central normothermic regional perfusion, where the circulation in the donor is restarted using an extracorporeal life support system after circulatory death, may give a better 1-years survival and a reduction in costs compared to ex situ normothermic perfusion of the donor heart. However, restarting circulation in a donor that was just declared death by circulatory criteria may be controversial. The advantages described are, in our view, reason to consider central normothermic regional perfusion, in which case a debate on ethical and emotional aspects is of great importance. In this article, we describe two point of views and hope in this way to start the debate on central normothermic regional perfusion in the Netherlands.

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.

Propensity score-based analysis of long-term outcome of patients on HeartWare and HeartMate 3 left ventricular assist device support.

AIMS: Left ventricular assist device therapy has become the cornerstone in the treatment of end-stage heart failure and is increasingly used as destination therapy next to bridge to transplant or recovery. HeartMate 3 (HM3) and HeartWare (HVAD) are centrifugal continuous flow devices implanted intrapericardially and most commonly used worldwide. No randomized controlled trials have been performed yet. Analysis based on large registries may be considered as the best alternative but has the disadvantage of different standard of care between centres and missing data. Bias is introduced, because the decision which device to use was not random, even more so because many centres use only one type of left ventricular assist device. Therefore, we performed a propensity score (PS)-based analysis of long-term clinical outcome of patients that received HM3 or HVAD in a single centre. METHODS AND RESULTS: Between December 2010 and December 2019, 100 patients received HVAD and 81 patients HM3 as primary implantation at the University Medical Centre Utrecht. We performed PS matching with an extensive set of covariates, resulting in 112 matched patients with a median follow-up of 28 months. After PS matching, survival was not significantly different (P = 0.21) but was better for HM3. The cumulative incidences for haemorrhagic stroke (P = 0.01) and pump thrombosis (P = 0.02) were significantly higher for HVAD patients. The cumulative incidences for major bleeding, ischaemic stroke, right heart failure, and driveline infection were not different between the groups. We found no interaction between the surgeon who performed the implantation and survival (P = 0.59, P = 0.78, and P = 0.89). Sensitivity analysis was performed, by PS matching without patients on preoperative temporary support resulting in 74 matched patients. This also resulted in a non-significant difference in survival (P = 0.07). The PS-adjusted Cox regression showed a worse but non-significant (P = 0.10) survival for HVAD patients with hazard ratio 1.71 (95% confidence interval 0.91-3.24). CONCLUSIONS: Survival was not significantly different between both groups after PS matching, but was better for HM3, with a significantly lower incidence of haemorrhagic stroke and pump thrombosis for HM3. These results need to be interpreted carefully, because matching may have introduced greater imbalance on unmeasured covariates. A multicentre approach of carefully selected centres is recommended to enlarge the number of matched patients.