Long-term outcome after the Ross procedure in 173 adults with up to 25 years of follow-up.

OBJECTIVES: The potential risk of autograft dilatation and homograft stenosis after the Ross procedure mandates lifelong follow-up. This retrospective cohort study aimed to determine long-term outcome of the Ross procedure, investigating autograft and homograft failure patterns leading to reintervention. METHODS: All adults who underwent the Ross procedure between 1991 and 2018 at the University Hospitals Leuven were included, with follow-up data collected retrospectively. Autograft implantation was performed using the full root replacement technique. The primary end-point was long-term survival. Secondary end-points were survival free from any reintervention, autograft or homograft reintervention-free survival, and evolution of autograft diameter, homograft gradient and aortic regurgitation grade over time. RESULTS: A total of 173 adult patients (66% male) with a median age of 32 years (range 18-58 years) were included. External support at both the annulus and sinotubular junction was used in 38.7% (67/173). Median follow-up duration was 11.1 years (IQR, 6.4-15.9; 2065 patient-years) with 95% follow-up completeness. There was one (0.6%) perioperative death. Kaplan-Meier estimate for 15-year survival was 91.1% and Ross-related reintervention-free survival was 75.7% (autograft: 83.5%, homograft: 85%). Regression analyses demonstrated progressive neoaortic root dilatation (0.56 mm/year) and increase in homograft gradient (0.72 mmHg/year). CONCLUSIONS: The Ross procedure has the potential to offer excellent long-term survival and reintervention-free survival. These long-term data further confirm that the Ross procedure is a suitable option in young adults with aortic valve disease which should be considered on an individual basis.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale. The cell-scale model consists of a network model, that includes important signaling pathways and relations between relevant transcription factors and their target genes. The resulting gene activity leads to changes in the mechanical properties of the tissue, modeled as a constrained mixture of collagen, elastin and smooth muscle. The multiscale model is calibrated with findings from experiments in which seven sheep underwent the Ross procedure. The model is then validated against a different set of sheep experiments, for which a qualitative agreement between model and experiment is found. Model outcomes at the cell scale, including the activity of genes and transcription factors, also match experimentally obtained transcriptomics data.

Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function, and their interplay have accumulated, resulting in advanced knowledge on the complex functional characteristics of the aortic valve (AV) and root. This has shifted our vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved, with a similar shift towards treatments options that are more hemodynamically centered, such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress-related stimuli. Many of these physiological and hemodynamical processes are under-acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision making.

Aortic valve replacement in non-elderly: the gap between reality, guidelines and evidence.

OBJECTIVES: There are several treatment options for non-elderly adults (18-60 years) in need of aortic valve replacement (AVR): a mechanical or biological substitute, a homograft, the Ross procedure or nowadays even transcatheter aortic valve replacement. This study evaluated the current opinions and practices of cardiac surgeons and cardiologists concerning AVR strategies in this patient group. METHODS: A 43-item online survey was sent out to several scientific organizations, individual cardiac surgeons, cardiologists and residents/fellows worldwide. RESULTS: Two hundred twenty-two physicians from 33 different countries answered the survey. The UK (24%), Belgium (23%) and North America (22%) are best represented. A mechanical valve is the most frequently used substitute in non-elderly. With increasing patient age, the popularity of a biological valve increases. Transcatheter aortic valve replacement and the Ross procedure are each used in <10% of this cohort. Only 12% of the cardiac surgeons has experience with the Ross surgery. In 23%, the patient seems not to be involved in the decision on the type of valve substitute. CONCLUSIONS: The preferred surgical treatment for non-elderly patients in need of AVR differs widely. To enable a shared decision-making process including patient preferences, there is more need for collaboration between cardiac departments, as well as education and scientific research about patient-centred outcomes of the different AVR techniques.

In vivo performance of a tri-leaflet mechanical heart valve prosthesis in an ovine model.

OBJECTIVES: We present the long-term results of a trileaflet (Triflo) versus bileaflet (On-X) mechanical valve in both aortic and pulmonary positions in a sheep model. METHODS: The Triflo valve was implanted in 21 female sheep in aortic (n = 8) and pulmonary position (n = 13). The On-X valve was implanted in 7 female sheep in aortic (n = 1) and pulmonary (n = 6) positions. No antithrombotic medication of any kind was given postoperatively. In the aortic group, survival cohorts were 3 and 5 months. In the pulmonary group, survival cohorts were 10 and 20 weeks. Valve performance was assessed using haematology, echocardiography and acoustic measurements combined with post-mortem pathology analysis of the downstream organs. RESULTS: The mean gradients were lower for the Triflo valve in both pulmonary [4.30 mmHg (3.70-5.73) vs 6.80 mmHg (4.63-7.96), P = 0.012] and aortic [5.1 mmHg (4.2-7.7) vs 10.7 mmHg (8.7-12.9), P = 0.007] positions. Peak gradients were lower for the Triflo valve in both pulmonary [8.05 mmHg (6.75-10.23) vs 13.15 mmHg (9.20-14.76), P = 0.005] and aortic [8.7 mmHg (7.5-12.5) vs 16.5 mmHg (14.2-19.6), P = 0.009] positions. In both positions, leaflets and housing surface were free from any deposits macro- and microscopically and comparable to nonimplanted control valves. Peripheral organs showed no signs of thrombo-embolic damage. Biochemical and haematological were comparable to preoperative. The closing click sound pressure level of the Triflo was significantly lower in both aortic [108.4 sound pressure level (102.0-115.7) vs 111.7 sound pressure level (105.5-117.0), P < 0.001] and pulmonary [103.6 sound pressure level (99.1-108.9) vs 118.5 sound pressure level (116.7-120.2), P < 0.001] position. CONCLUSIONS: Preliminary in vivo results of the Triflo valve are promising in both aortic and pulmonary positions in an ovine model. Excellent haemodynamics, stable long-term function, low valve noise and no thrombo-embolic events in the absence of antithrombotic medication lay the foundation to a future clinical first-in-man trial.

A Large-Diameter Vascular Graft Replacing Animal-Derived Sealants With an Elastomeric Polymer.

INTRODUCTION: To assess the safety and efficacy of an experimental large-diameter vascular graft externally sealed with an elastomeric polymer when used as an interposition graft in the descending aorta of sheep. METHODS: The experimental vascular grafts as well as control gelatin sealed interposition grafts were inserted into the descending aorta of juvenile sheep. The grafts were assessed by time to hemostasis and blood loss during surgery and hematology and biochemistry panels at distinct time points. Magnetic resonance imaging (MRI) was performed at 3 and at 6 mo after surgery, after which the animals were euthanized and necropsies were carried out including macroscopic and microscopic examination of the grafts, anastomoses, and distal organs. RESULTS: All animals survived the study period. There was no perceivable difference in the surgical handling of the grafts. The median intraoperative blood loss was 27.5 mL (range 10.0-125.0 mL) in the experimental group and 50.0 mL (range 10.0-75.0 mL) in the control group. The median time to hemostasis was 5.0 min (range 2.0-16.0 min) minutes in the experimental group versus 6.0 min (range 4.0-6.0 min) in the control group. MRI showed normal flow and graft patency in both groups. Healing and perianastomotic endothelialization was similar in both groups. CONCLUSIONS: The experimental graft has a similar safety and performance profile and largely comparable necropsy results, in comparison to a commonly used prosthetic vascular graft, with the experimental grafts eliciting a nonadherent external fibrous capsule as the major difference compared to the control grafts that were incorporated into the periadventitia. Survival, hemostatic sealing, and hematologic and radiologic results were comparable between the study groups.

Neurodevelopmetal effects of maternal blood pressure management with noradrenaline during general anaesthesia for nonobstetric surgery in the pregnant rabbit model.

In pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, the rationale being to maintain uterine perfusion pressure and thereby uterine blood flow. Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent. To analyse the effects of treating anaesthesia-induced hypotension with noradrenaline on brain development of rabbit foetuses of mothers subjected to general anaesthesia for nonobstetric surgery. We hypothesised that treatment of maternal hypotension would improve foetal outcomes. Randomised controlled laboratory study using 21 pregnant rabbits (does) at 28 days of gestation. Two hours of sevoflurane anaesthesia for a laparotomy without treatment of anaesthesia-induced hypotension (hypotension group) or with maintaining maternal mean arterial pressure above 80% of the awake value using noradrenaline (noradrenaline group). In the control group, does remained untouched. At term, all pups were delivered by caesarean section. One day later, the neurobehaviour of the pups was assessed and brains were harvested. Neuron density in the frontal cortex for the comparison of noradrenaline groups versus hypotension groups was the primary outcome; the neurobehavioural scores and other histological outcomes were secondary outcomes. In the noradrenaline groups and hypotension groups, neuron density in the frontal cortex was similar (1181 ±â€Š162 versus 1189 ±â€Š200 neurons mm-2, P  = 0.870). However, significantly less foetal survival, lower sensory scores in neurobehavioural assessment and less proliferation were observed in the noradrenaline group when compared with the hypotension group. Neuron densities in other regions, total cell densities, biometrics and synaptogenesis were not affected. There were no differences between the control group and hypotension group. During general anaesthesia for nonobstetric surgery in rabbits, treatment of anaesthesia-induced hypotension using noradrenaline did not affect neuron densities but was associated with impaired foetal outcomes according to several secondary outcome parameters. Further studies are needed to investigate any clinical relevance and to determine the target blood pressure in pregnant women during general anaesthesia.KEY POINTSIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, with the rationale to maintain uterine perfusion pressure and thereby uterine blood flow.Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.We investigated the effects of treating anaesthesia-induced hypotension with noradrenaline on the brain development of rabbit foetuses, of mothers subjected to general anaesthesia for nonobstetric surgery.We hypothesised that treatment of maternal hypotension would improve foetal outcomes.Neuron densities were similar but significantly less foetal survival, impaired neurobehaviour and less proliferation were observed after treatment of anaesthesia-induced hypotension with noradrenaline, compared with untreated hypotension.

Apixaban in a porcine model of mechanical valve thrombosis in pulmonary position-a pilot study.

OBJECTIVES: The newest mechanical valves have low thrombogenicity, making them candidates for anticoagulation with a direct oral anticoagulant. While these drugs hold great promise to replace warfarin, clinical trials have been disappointing so far. We aimed to evaluate apixaban in a porcine model of mechanical valve thrombosis with On-X® (CryoLife) aortic valves implanted in pulmonary position. METHODS: On-X® valves were implanted in pulmonary valve position in 9 Yucatan pigs. Animals received prophylactic enoxaparin 40 mg for 1 week. Pigs in the low-dose group received 5 mg apixaban twice daily for 10 weeks. The intermediary-dose group received 5 mg twice daily for 6 weeks and then 10 mg twice daily afterwards. The high-dose group received 15 mg twice daily for 10 weeks. After sacrifice, valves were macroscopically evaluated and thrombus weight was documented. RESULTS: The median weight of the 9 animals was 64.3 kg, range 52.5-70.9. In the low-dose group (2 animals), both valves showed manifest, chronic thrombosis with blocked hinges. In the intermediary-dose group, a normal functioning valve without thrombosis was seen in 2/4 animals. In the high-dose group (3 pigs), there was no valve thrombosis. No bleeding events occurred. In all animals, apixaban plasma levels were low compared to clinical target levels. CONCLUSIONS: The pulmonary position seems to be an aggressive model for mechanical valve thrombosis in pigs. Apixaban has the potential to prevent valve thrombosis, even in these thrombogenic conditions. Detailed pharmacokinetic studies are needed to determine the ideal apixaban dosage for future experiments and to enable extrapolation to the clinical situation.

Back to the root: a large animal model of the Ross procedure.

The excellent clinical outcomes of the Ross procedure and previous histological studies suggest that the pulmonary autograft has the potential to offer young patients a permanent solution to aortic valve disease. We aim to study the early mechanobiological adaptation of the autograft. To this end, we have reviewed relevant existing animal models, including the canine models which enabled Donald N Ross to perform the first Ross procedure in a patient in 1967. Two research groups recently evaluated the isolated effect of systemic pressures on pulmonary arterial tissue in an ovine model of a pulmonary artery interposition graft in the descending aorta. While this model is ideal to study the artery's biological response and the effect of external support, it does not recreate the complex environment of the aortic root. The freestanding Ross procedure has been performed in pigs and sheep before. These studies offered valuable insights into leaflet growth and histological remodeling, yet may be less relevant to adults undergoing the Ross procedure, as pronounced autograft dilatation was achieved by using small, rapidly growing animals. Therefore, a large animal model remains needed to determine the ideal conditions and surgical technique to ensure long-term autograft remodeling and valve function. We set out to develop an ovine model of the Ross procedure performed as a freestanding root replacement, acknowledging that the sheep's specific anatomy and the setting of an animal laboratory would mandate several modifications in surgical strategy. This article describes the development, surgical technique and early outcomes of our animal model while highlighting opportunities for further research.

Antithrombotic Treatment After Surgical and Transcatheter Heart Valve Repair and Replacement.

New antithrombotic drugs have been developed, new valve types have been designed and minimally invasive transcatheter techniques have emerged, making the choice of antithrombotic therapy after surgical or transcatheter heart valve repair and replacement increasingly complex. Moreover, due to a lack of large randomized controlled trials many recommendations for antithrombotic therapy are based on expert opinion, reflected by divergent recommendations in current guidelines. Therefore, decision-making in clinical practice regarding antithrombotic therapy for prosthetic heart valves is difficult, potentially resulting in sub-optimal patient treatment. This article compares the 2017 ESC/EACTS and 2020 ACC/AHA guidelines on the management of valvular heart disease and summarizes the available evidence. Finally, we established a convenient consensus on antithrombotic therapy after valve interventions based on over 800 annual cases of surgical and transcatheter heart valve repair and replacement and a multidisciplinary team discussion between the department of cardiovascular diseases and cardiac surgery of the University Hospitals Leuven, Belgium.

Personalised external aortic root support for elective treatment of aortic root dilation in 200 patients.

BACKGROUND AND OBJECTIVES: In personalised external aortic root support (PEARS), a custom-made, macroporous mesh is used to stabilise a dilated aortic root and prevent dissection, primarily in patients with genetically driven aortopathies. Data are needed on the safety and postoperative incidence of aortic events. METHODS: We present a multicentre cohort study evaluating the first 200 consecutive patients (median age 33 years) undergoing surgery with an intention to perform PEARS for aortic root dilatation in 23 centres between 2004 and 2019. Perioperative outcomes were collected prospectively while clinical follow-up was retrieved retrospectively. Median follow-up was 21.2 months. RESULTS: The main indication was Marfan syndrome (73.5%) and the most frequent concomitant procedure was mitral valve repair (10%). An intervention for myocardial ischaemia or coronary injury was needed in 11 patients, 1 case resulting in perioperative death. No ascending aortic dissections were observed in 596 documented postoperative patient years. Late reoperation was performed in 3 patients for operator failure to achieve complete mesh coverage. Among patients with at least mild aortic regurgitation (AR) preoperatively, 68% had no or trivial AR at follow-up. CONCLUSIONS: This study represents the clinical history of the first 200 patients to undergo PEARS. To date, aortic dissection has not been observed in the restrained part of the aorta, yet long-term follow-up is needed to confirm the potential of PEARS to prevent dissection. While operative mortality is low, the reported coronary complications reflect the learning curve of aortic root surgery in patients with connective tissue disease. PEARS may stabilise or reduce aortic regurgitation.

Remote Heart Rhythm Monitoring by Photoplethysmography-Based Smartphone Technology After Cardiac Surgery: Prospective Observational Study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery, yet the precise incidence and significance of arrhythmias after discharge home need to be better defined. Photoplethysmography (PPG)-based smartphone apps are promising tools to enable early detection and follow-up of arrhythmias. OBJECTIVE: By using a PPG-based smartphone app, we aimed to gain more insight into the prevalence of AF and other rhythm-related complications upon discharge home after cardiac surgery and evaluate the implementation of this app into routine clinical care. METHODS: In this prospective, single-center trial, patients recovering from cardiac surgery were asked to register their heart rhythm 3 times daily using a Food and Drug Administration-approved PPG-based app, for either 30 or 60 days after discharge home. Patients with permanent AF or a permanent pacemaker were excluded. RESULTS: We included 24 patients (mean age 60.2 years, SD 12 years; 15/23, 65% male) who underwent coronary artery bypass grafting and/or valve surgery. During hospitalization, 39% (9/23) experienced postoperative AF. After discharge, the PPG app reported AF or atrial flutter in 5 patients. While the app notified flutter in 1 patient, this was a false positive, as electrocardiogram revealed a 2nd-degree, 2:1 atrioventricular block necessitating a permanent pacemaker. AF was confirmed in 4 patients (4/23, 17%) and interestingly, was associated with an underlying postoperative complication in 2 participants (pneumonia n=1, pericardial tamponade n=1). A significant increase in the proportion of measurements indicating sinus rhythm was observed when comparing the first to the second month of follow-up (P<.001). In the second month of follow-up, compliance was significantly lower with 2.2 (SD 0.7) measurements per day versus 3.0 (SD 0.8) measurements per day in the first month (P=.002). The majority of participants (17/23, 74%), as well as the surveyed primary care physicians, experienced positive value by using the app as they felt more involved in the postoperative rehabilitation. CONCLUSIONS: Implementation of smartphone-based PPG technology enables detection of AF and other rhythm-related complications after cardiac surgery. An association between AF detection and an underlying complication was found in 2 patients. Therefore, smartphone-based PPG technology may supplement rehabilitation after cardiac surgery by acting as a sentinel for underlying complications, rhythm-related or otherwise.

Screening and follow-up of pregestational diabetes and gestational diabetes mellitus: A survey of primary care physicians in Belgium.

AIMS: Consensus regarding the best screening and follow-up strategy for gestational diabetes mellitus (GDM) is lacking, resulting in heterogeneity in clinical practice. We aimed to evaluate screening and follow-up practices for pregestational type 2 diabetes (T2DM) and GDM in primary care in Belgium. METHODS: We performed an online survey among primary care physicians (PCPs) in the northern part of Belgium, Flanders. RESULTS: Responses were obtained from 379 PCPs. Approximately two thirds of participants estimated the prevalence of pregestational T2DM and GDM in Flanders at 5% and <10%, respectively. The risk of developing T2DM within 10 years after a history of GDM was estimated at <30% by nearly half of all participants. The majority of interviewed PCPs screen for pre-existing T2DM and GDM. For T2DM, fasting glycaemia was used by 92.2% whereas for GDM, 75.2% used the 50g glucose challenge test (GCT). Fasting glycaemia was the preferred test for postpartum follow-up. CONCLUSIONS: While overall guideline adherence appears favourable, the prevalence of GDM is underestimated. Increased awareness on the long-term risk for women with a history of GDM is needed. The overall preference for the two-step strategy with GCT indicates that the 2019 Flemish guidelines on GDM screening are attainable in primary care.

The Belgian experience with concomitant surgical ablation of atrial fibrillation: a multi-centre prospective registry.

Background: The Belgian 'National Institute for Health and Disability Insurance (RIZIV-INAMI)' requested prospective collection of data on all ablations in Belgium to determine the outcomes of surgical ablation of atrial fibrillation (AF) during concomitant cardiac surgery.Methods: 890 patients undergoing concomitant ablation for AF between 2011 and 2016 were prospectively followed. Freedom from AF with and without anti-arrhythmic drugs was calculated for 817 patients with follow-up beyond the 3-month blanking period and for 574 patients with sufficient rhythm-related follow-up consisting of at least one Holter registration or a skipped Holter due to AF being evident on ECG. Besides preoperative AF type, concomitant procedure and ablation, potential covariates were entered into uni- and multivariable regression models to determine predictors of outcome.Results: The overall freedom from AF beyond 3 months was 69.9% (571/817) and without anti-arrhythmic drugs at last follow-up 51.0% (417/817), respectively, 61.3% (352/574) and 44.4% (255/574) for patients with sufficient rhythm-related follow-up. Using a Kaplan-Meier estimate, freedom from AF was 89.3%, 74.9% and 59%, without antiarrhythmic drugs 74.4%, 47.8% and 32.3% at 6, 12 and 24 months, respectively. In-hospital mortality was 1.7% (15/890) and the overall survival was 95.0% at 1 year and 92.3% at 2 years. Preoperative left atrial diameter and AF type were significant predictive factors of freedom from AF in a multivariable analysis.Conclusion: Analysis of the Belgian national registry shows that concomitant surgical ablation of atrial fibrillation is safe, achieves favourable freedom from AF and, therefore, deserves to be performed in accordance to the guidelines.

Support of the aortic wall: a histological study in sheep comparing a macroporous mesh with low-porosity vascular graft of the same polyethylene terephthalate material.

OBJECTIVES: Wrapping with various materials was an early treatment for aortic aneurysms. Wrapping with low-porosity vascular grafts has been associated with graft migration and vascular erosion. An alternative is to use a macroporous mesh (MPM) made of the same polymer (polyethylene terephalate). We compared the histological outcome 1 year after wrapping sheep aortas with low-porosity grafts versus MPM fabrics. METHODS: The 2 different fabrics were wrapped around the aorta of 3 sheep. After 1 year the aortas were excised. The 2 wrapped segments of aorta were compared with each other and control aorta. Histological examinations and measurements were made of the layers of the aortic wall in 36 prespecified locations in each of the 3 sheep. RESULTS: Both fabrics were consistently surrounded by foreign body reaction and well-vascularized fibrosis. This was more pronounced with the low-porosity vascular graft material which was poorly incorporated and caused buckling at the transition between wrapped and unwrapped aorta. Conversely, the MPM was fully incorporated, resulting in a composite mesh/biological aortic wall. There was reduction of medial thickness with both materials but it was locally more extreme due to the corrugations in the vascular graft material. The findings were consistent between sampled locations and were similar in the 3 animals. CONCLUSIONS: The different porosity and rigidity of the materials influences their incorporation into the aortic wall. The incorporation of the pliable MPM precludes the complications of migration and erosion which are seen after wrapping with low-porosity prosthetic vascular graft material.