Risk Prediction Models for Long-Term Survival after Cardiac Surgery: A Systematic Review.

BACKGROUND: The reporting of alternative postoperative measures of quality after cardiac surgery is becoming increasingly important as in-hospital mortality rates continue to decline. This study aims to systematically review and assess risk models designed to predict long-term outcomes after cardiac surgery. METHODS: The MEDLINE and Embase databases were searched for articles published between 1990 and 2020. Studies developing or validating risk prediction models for long-term outcomes after cardiac surgery were included. Data were extracted using checklists for critical appraisal and systematic review of prediction modeling studies. RESULTS: Eleven studies were identified for inclusion in the review, of which nine studies described the development of long-term risk prediction models after cardiac surgery and two were external validation studies. A total of 70 predictors were included across the nine models. The most frequently used predictors were age (n = 9), peripheral vascular disease (n = 8), renal disease (n = 8), and pulmonary disease (n = 8). Despite all models demonstrating acceptable performance on internal validation, only two models underwent external validation, both of which performed poorly. CONCLUSION: Nine risk prediction models predicting long-term mortality after cardiac surgery have been identified in this review. Statistical issues with model development, limited inclusion of outcomes beyond 5 years of follow-up, and a lack of external validation studies means that none of the models identified can be recommended for use in contemporary cardiac surgery. Further work is needed either to successfully externally validate existing models or to develop new models. Newly developed models should aim to use standardized long-term specific reproducible outcome measures.

Morphologically intact airways in lung fibrosis have an abnormal proteome.

Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression.

The circadian clock protein REVERBα inhibits pulmonary fibrosis development.

Pulmonary inflammatory responses lie under circadian control; however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the little-understood transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinß1 focal-adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of 2 human cohorts. In the UK Biobank, circadian strain markers (sleep length, chronotype, and shift work) are associated with pulmonary fibrosis, making them risk factors. In a separate cohort, REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, thus suggesting that targeting of REVERBα could be a viable therapeutic approach.

Management of ganciclovir resistance cytomegalovirus infection with CMV hyperimmune globulin and leflunomide in seven cardiothoracic transplant recipients and literature review.

Cytomegalovirus (CMV) disease caused by genetically resistant CMV poses a major challenge in solid organ transplant recipients, and the development of resistance is associated with increased morbidity and mortality. Antiviral resistance affects 5%-12% of patients following ganciclovir (GCV) therapy, but is more common in individuals with specific underlying risk factors. These include the CMV D+R- serostatus, type of transplanted organ, dose and duration of (Val)GCV ([V]GCV) prophylaxis, peak viral loads, and the intensity of immunosuppressive therapy. Guideline recommendations for the management of GCV resistance (GanR) in solid organ transplant recipients are based on expert opinion as there is a lack of data from controlled trials. Second-line options to treat GanR include foscarnet (FOS) and cidofovir (CDV), but these drugs are often poorly tolerated due to high rates of toxicity, such as renal dysfunction and neutropenia. Here, we report seven cardiothoracic transplant recipients with GCV resistance CMV infection from our centre treated with CMV immunoglobulin (CMVIG) +/- leflunomide (LEF) and reviewed the literature on the use of these agents in this therapeutic setting.

An early evaluation of the HISTO SPOT® AB ID Class I & II test in cardiothoracic transplant patients.

The HISTO SPOT® AB ID assay (BAG Diagnostics GmbH) is a novel single antigen HLA Class I & II antibody definition test used with the MR.SPOT® processor. We compared this assay with Luminex® -based assays to assess its potential application in defining unacceptable antigens for transplantation in patients awaiting transplants with cardiothoracic organs. A cohort of 40 sensitized cardiothoracic patients were identified, and one sample was selected from each patient. The required screening was based on the patients' antibody profiles (Class I, n = 17, Class II, n = 11, Class I & II, n = 12). Samples were screened with LABScreen™ Single Antigen (SAg), LIFECODES® LSA™, HISTO SPOT® AB ID, and an acid modified LABScreen™ SAg test for detecting antibodies against denatured HLA. Results indicated that HISTO SPOT® AB ID had reduced sensitivity (68% for Class I; 69% for Class II). When compared to LABScreen™ and LIFECODES® , HISTO SPOT® AB ID failed to detect Luminex® -defined antibodies with median fluorescence intensity (MFI) ranging from 1114 to 24,489. The HISTO SPOT® AB ID panel used in the study had reduced antigen representation compared with Luminex® -based assays which further compromised its capacity for antibody detection and definition. Further work is needed to evaluate the clinical relevance of these differences between the performance of HISTO SPOT® and Luminex® -based methods.

Venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock-A six-year service evaluation.

Only a small number of English hospitals provide postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) and there are doubts about its efficacy and safety. The aim of this service evaluation was to determine local survival rates and report on patient demographics. This was a retrospective service evaluation of prospectively recorded routine clinical data from a tertiary cardiothoracic center in the United Kingdom offering services including cardiac and thoracic surgery, heart and lung transplantation, venovenous extracorporeal membrane oxygenation (VV-ECMO) for respiratory failure, and all types of mechanical circulatory support. In six years, 39 patients were supported with VA-ECMO for refractory postcardiotomy cardiogenic shock (PCCS). We analyzed survival data and looked for associations between survival rates and patient characteristics. The intervention was venoarterial-ECMO in patients with PCCS either following weaning from cardiopulmonary bypass or following a trial of inotropes and intra-aortic balloon counterpulsation on the intensive care unit. 30-day, hospital discharge, 1-year and 2-year survivals were 51.3%, 41%, 37.5%, and 38.5%, respectively. The median (IQR [range]) duration of support was 6 (4-9 [1-35]) days. Nonsurvival was associated with advanced age, shorter intensive care length of stay, and the requirement for postoperative hemofiltration. Reasonable survival rates can be achieved in selected patients who may have been expected to have a worse mortality without VA-ECMO. We suggest postoperative VA-ECMO should be available to all patients undergoing cardiac surgery be it in their own center or through an established pathway to a specialist center.

The use of CMVIg rescue therapy in cardiothoracic transplantation: A single-center experience over 6 years (2011-2017).

Cytomegalovirus (CMV) is the most important infectious agent in solid organ transplant recipients and has a major impact on morbidity and mortality. Most cases are well managed with antiviral agents, but CMV hyperimmune globulin (CMVIg) can be used alongside antiviral therapy for prophylaxis in high-risk thoracic organ recipients and to treat life-threatening CMV infection or disease. CMVIg may also improve antiviral host defences when genetic resistance to antivirals or unwanted side effects occur. In this single-center, retrospective study, we reviewed the CMVIg use to supplement antiviral therapy as a "rescue therapy" in cardiothoracic transplant recipients. These comprised 12 single lung, 11 double lung, and 12 heart transplant recipients. Patients received a median of 2 doses of CMVIg, most often in combination with ganciclovir or valganciclovir, and reduced immunosuppression. One week after rescue therapy was initiated, CMV DNA levels were significantly reduced, and after four weeks, CMV DNA was undetectable in 73% patients. Only one patient died as a result of CMV-related disease. No significant adverse effects were observed. We conclude that CMVIg rescue therapy is safe, well tolerated, and effective at controlling viral replication in cardiothoracic transplant recipients.

Study Comparing Vein Integrity and Clinical Outcomes in Open Vein Harvesting and 2 Types of Endoscopic Vein Harvesting for Coronary Artery Bypass Grafting: The VICO Randomized Clinical Trial (Vein Integrity and Clinical Outcomes).

BACKGROUND: Current consensus statements maintain that endoscopic vein harvesting (EVH) should be standard care in coronary artery bypass graft surgery, but vein quality and clinical outcomes have been questioned. The VICO trial (Vein Integrity and Clinical Outcomes) was designed to assess the impact of different vein harvesting methods on vessel damage and whether this contributes to clinical outcomes after coronary artery bypass grafting. METHODS: In this single-center, randomized clinical trial, patients undergoing coronary artery bypass grafting with an internal mammary artery and with 1 to 4 vein grafts were recruited. All veins were harvested by a single experienced practitioner. We randomly allocated 300 patients into closed tunnel CO2 EVH (n=100), open tunnel CO2 EVH (n=100), and traditional open vein harvesting (n=100) groups. The primary end point was endothelial integrity and muscular damage of the harvested vein. Secondary end points included clinical outcomes (major adverse cardiac events), use of healthcare resources, and impact on health status (quality-adjusted life-years). RESULTS: The open vein harvesting group demonstrated marginally better endothelial integrity in random samples (85% versus 88% versus 93% for closed tunnel EVH, open tunnel EVH, and open vein harvesting; P<0.001). Closed tunnel EVH displayed the lowest longitudinal hypertrophy (1% versus 13.5% versus 3%; P=0.001). However, no differences in endothelial stretching were observed between groups (37% versus 37% versus 31%; P=0.62). Secondary clinical outcomes demonstrated no significant differences in composite major adverse cardiac event scores at each time point up to 48 months. The quality-adjusted life-year gain per patient was 0.11 (P<0.001) for closed tunnel EVH and 0.07 (P=0.003) for open tunnel EVH compared with open vein harvesting. The likelihood of being cost-effective, at a predefined threshold of £20 000 per quality-adjusted life-year gained, was 75% for closed tunnel EVH, 19% for open tunnel EVH, and 6% for open vein harvesting. CONCLUSIONS: Our study demonstrates that harvesting techniques affect the integrity of different vein layers, albeit only slightly. Secondary outcomes suggest that histological findings do not directly contribute to major adverse cardiac event outcomes. Gains in health status were observed, and cost-effectiveness was better with closed tunnel EVH. High-level experience with endoscopic harvesting performed by a dedicated specialist practitioner gives optimal results comparable to those of open vein harvesting. CLINICAL TRIAL REGISTRATION: URL: https://www.isrctn.com. International Standard Randomised Controlled Trial Registry Number: 91485426.

Validation of Three Postoperative Risk Prediction Models for Intensive Care Unit Mortality after Cardiac Surgery.

BACKGROUND: Several cardiac surgery risk prediction models based on postoperative data have been developed. However, unlike preoperative cardiac surgery risk prediction models, postoperative models are rarely externally validated or utilized by clinicians. The objective of this study was to externally validate three postoperative risk prediction models for intensive care unit (ICU) mortality after cardiac surgery. METHODS: The logistic Cardiac Surgery Scores (logCASUS), Rapid Clinical Evaluation (RACE), and Sequential Organ Failure Assessment (SOFA) scores were calculated over the first 7 postoperative days for consecutive adult cardiac surgery patients between January 2013 and May 2015. Model discrimination was assessed using receiver operating characteristic curve analyses. Calibration was assessed using the Hosmer-Lemeshow (HL) test, calibration plots, and observed to expected ratios. Recalibration of the models was performed. RESULTS: A total of 2255 patients were included with an ICU mortality rate of 1.8%. Discrimination for all three models on each postoperative day was good with areas under the receiver operating characteristic curve of >0.8. Generally, RACE and logCASUS had better discrimination than SOFA. Calibration of the RACE score was better than logCASUS, but ratios of observed to expected mortality for both were generally <0.65. Locally recalibrated SOFA, logCASUS and RACE models all performed well. CONCLUSION: All three models demonstrated good discrimination for the first 7 days after cardiac surgery. After recalibration, logCASUS and RACE scores appear to be most useful for daily risk prediction after cardiac surgery. If appropriately calibrated, postoperative cardiac surgery risk prediction models have the potential to be useful tools after cardiac surgery.

Rheumatoid nodule on the anterior mitral valve leaflet.

Symptomatic cardiac rheumatoid nodules are a rare but recognized manifestation of rheumatoid arthritis. We describe the surgical management of a rheumatic nodule involving the anterior leaflet of the mitral valve.

Durable left ventricular assist device as a bridge to recovery for addisonian crisis related cardiomyopathy.

A 19-year-old female with addisonian crisis-related cardiomyopathy underwent temporary mechanical circulatory support followed by insertion of a durable left ventricular assist device. Successful device explanation was possible 2.5 years following implantation.

Enhancing the implantation of mechanical circulatory support devices using computational simulations.

Introduction: Patients with end-stage heart failure (HF) may need mechanical circulatory support such as a left ventricular assist device (LVAD). However, there are a range of complications associated with LVAD including aortic regurgitation (AR) and thrombus formation. This study assesses whether the risk of developing aortic conditions can be minimised by optimising LVAD implantation technique. Methods: In this work, we evaluate the aortic flow patterns produced under different geometrical parameters for the anastomosis of the outflow graft (OG) to the aorta using computational fluid dynamics (CFD). A three-dimensional aortic model is created and the HeartMate III OG positioning is simulated by modifying (i) the distance from the anatomic ventriculo-arterial junction (AVJ) to the OG, (ii) the cardinal position around the aorta, and (iii) the angle between the aorta and the OG. The continuous LVAD flow and the remnant native cardiac cycle are used as inlet boundaries and the three-element Windkessel model is applied at the pressure outlets. Results: The analysis quantifies the impact of OG positioning on different haemodynamic parameters, including velocity, wall shear stress (WSS), pressure, vorticity and turbulent kinetic energy (TKE). We find that WSS on the aortic root (AoR) is around two times lower when the OG is attached to the coronal side of the aorta using an angle of 45° ± 10° at a distance of 55 mm. Discussion: The results show that the OG placement may significantly influence the haemodynamic patterns, demonstrating the potential application of CFD for optimising OG positioning to minimise the risk of cardiovascular complications after LVAD implantation.

Clinical-radiological-pathological correlation in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is defined by the presence of a mean pulmonary arterial pressure >20 mmHg. Current guidelines describe five groups of PH with shared pathophysiological and clinical features. In this paper, the first of a series covering all five PH classification groups, the clinical, radiological and pathological features of pulmonary arterial hypertension (PAH) will be reviewed. PAH may develop in the presence of associated medical conditions or a family history, following exposure to certain medications or drugs, or may be idiopathic in nature. Although all forms of PAH share common histopathological features, the presence of certain pulmonary arterial abnormalities, such as plexiform lesions, and extent of co-existing pulmonary venous involvement differs between the different subgroups. Radiological investigations are key to diagnosing the correct form of PH and a systematic approach to interpretation, especially of computed tomography, is essential.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom.

BACKGROUND: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. METHODS: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. RESULTS: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46). CONCLUSION: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Axillary intra-aortic balloon pump, biventricular assist device implantation and subsequent orthotopic heart transplantation in a patient with sickle cell trait.

A 38-year-old male with sickle cell trait and acute refractory heart failure received an axillary intra-aortic balloon pump and short-term biventricular assist device. He underwent orthotopic heart transplantation 45 days later, which was complicated by major bleeding necessitating significant intra-operative transfusion. Support with veno-arterial extracorporeal membrane oxygenation was provided and successfully weaned five days later. He made a full recovery and remains alive and well 34 months after discharge. We hypothesize that the protective peri-operative measures undertaken, including normothermia during surgery and post-operative haemodynamic stability due to the use of mechanical circulatory support, conveyed a degree of protection against complications associated with sickle cell dysfunction and contributed to the successful outcome.

Veno-venous extracorporeal membrane oxygenation used as an adjunct in the surgical management of acquired and iatrogenic tracheobronchial pathology.

BACKGROUND: Surgical repair of tracheobronchial tree injuries is challenging due to the difficulties associated with providing perioperative ventilatory support. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a recognized treatment modality for managing respiratory failure. Its use has expanded to include offering respiratory support for patients requiring surgery on the tracheobronchial tree. This study presents our experience with V-V ECMO support for elective and emergency surgery for acquired and iatrogenic tracheobronchial pathology. METHODS: A retrospective review of our single-center experience of surgical tracheobronchial repairs where V-V ECMO was employed between 2017 and 2020 was undertaken. Preoperative patient characteristics, intraoperative findings, details of ECMO support and postoperative outcomes were collected and analyzed. RESULTS: Five patients underwent surgery with V-V ECMO support during the study period. Indications for surgery included repair of iatrogenic tracheal tear (N.=2), repair of iatrogenic gastro-bronchial fistula (N.=1), elective tracheoplasty (N.=1) and elective resection of tracheal tumor (N.=1). The median duration of V-V ECMO was 17 hours (range: 4-543 hours), and the median postoperative length of stay was 9 days (range: 7-19 days). In-hospital and 90-day mortality were both 0% (N.=0). Postoperative complications included reoperation for bleeding (N.=1) and thrombotic complications (N.=2). CONCLUSIONS: We have shown how V-V ECMO can be safely utilized to manage patients with a range of tracheobronchial injuries with low rates of postoperative morbidity. Acceptable postoperative outcomes can be achieved for this cohort of clinically complex patients when treatment is provided with a multidisciplinary team approach in high-volume specialist centers.

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.

Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.

The challenges of venoarterial extracorporeal membrane oxygenation for postcardiotomy cardiogenic shock.

Postcardiotomy cardiogenic shock describes the syndrome of refractory cardiac performance following cardiac surgery. The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for the management of postcardiotomy cardiogenic shock is controversial, and there are at least three scenarios where it may be necessary: first, pre-emptive postoperative VA-ECMO, where the decision for postoperative mechanical support is made prior to surgery, for example, in the context of poor pre-operative cardiac function; second, early yet unplanned post-cardiopulmonary bypass VA-ECMO following a long duration of cardiopulmonary bypass due to, for example, unexpected surgical complications; third, late rescue VA-ECMO following several attempts at weaning, either immediately following cardiopulmonary bypass or following transfer to the intensive care unit. The use of mechanical circulatory support for postcardiotomy cardiogenic shock is further complicated by the wide range of available devices, the availability of VA-ECMO in different centres, variations in experience and expertise as a function of local VA-ECMO workload, and regional variations in the diagnosis and management of postcardiotomy cardiogenic shock. Furthermore, survival appears to be low for such patients and it is not yet possible to predict who will survive. Many questions remain, however, such as those in relation to practices around patient selection, how best to study long-term outcomes, the ethics and efficacy of ECMO in such patients, and on all aspects of clinical decision-making. This review sets these clinical challenges in the context of the available evidence, including that from our centre.

Traversing the Learning Curve Associated with a New Minimal Access Aortic Valve Replacement Service.

OBJECTIVE: Isolated aortic valve replacement is a safe and frequently performed cardiac surgical procedure. Although minimal access approaches including right anterior thoracotomy and partial sternotomy have been adopted by some surgeons in recent years, concerns about additional procedural morbidity and mortality during the early phase of the learning curve persist. The aim of this study was to assess the impact of the learning curve on outcomes for a single surgeon implementing a new minimal access aortic valve replacement service. METHODS: Ninety-three patients undergoing minimal access aortic valve replacement performed by a single surgeon in our institution between October 2014 and March 2019 were analysed. Patients were divided into tertiles according to procedure order. Endpoints included peri-operative mortality and post-operative complications, and these were compared across tertiles to assess the impact of the learning curve on procedural outcomes. RESULTS: Overall in-hospital mortality was 2.15% (n=2). Despite significantly longer cardiopulmonary bypass and cross-clamp duration in the early tertile, there was no significant difference in the rate of post-operative complications, post-operative length of stay or in-hospital mortality between tertiles. CONCLUSIONS: Although our results have demonstrated a significant learning curve effect associated with the introduction of this minimally invasive approach to aortic valve replacement, as demonstrated by the significant reduction in cardiopulmonary bypass and cross-clamp duration over time, our findings suggest that a minimal access aortic valve replacement service can be safely commenced by an experienced surgeon without concerns about the learning curve significantly affecting post-operative morbidity and mortality.