Implementation of Patient Blood Management in Orthotopic Heart Transplants: A Single Centre Retrospective Observational Review.

BACKGROUND: Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay, lung injury, and cost. It has an immunomodulatory effect which may cause allo-immunisation. This may influence long-term survival through immune-mediated factors. Targeting coagulation defects to reduce unnecessary or inappropriate transfusions may reduce these complications. METHODS: In 2012, an institution-wide patient blood management evidence-based algorithmic bleeding management protocol was implemented at The Prince Charles Hospital, Brisbane, Australia. The benefit of this has been previously reported in our lung transplant and cardiac surgery (excluding transplants) cohorts. This study aimed to investigate the effect of this on our orthotopic heart transplant recipients. RESULTS: After the implementation of the protocol, despite no difference in preoperative haemoglobin levels and higher risk patients (EuroSCORE 20 vs 26; p=0.013), the use of packed red blood cells (13.0 U vs 4.4 U; p=0.046) was significantly lower postoperatively and fresh frozen plasma was significantly lower both intra- and postoperatively (7.4 U vs 0.6 U; p<0.001, and 3.3 U vs 0.6 U; p=0.011 respectively). Concurrently, the use of prothrombin complex concentrate (33% vs 78%; p<0.001) and desmopressin (5% vs 22%; p=0.0028) was significantly higher in the post-protocol group, while there was less use of recombinant factor VIIa (15% vs 4%; p=0.058). Intraoperative units of cryoprecipitate also rose from 0.9 to 2.0 (p=0.006). CONCLUSIONS: We have demonstrated that a targeted patient blood management protocol with point-of-care testing for heart transplant recipients is correlated with fewer blood products used postoperatively, with some increase in haemostatic products and no evidence of increased adverse events.

Coronary artery bypass grafting is associated with immunoparalysis of monocytes and dendritic cells.

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co-stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co-stimulatory and adhesion molecules (eg HLA-DR), and intracellular mediators (eg IL-6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post-operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post-surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes.

Multivisceral Transplant, The Prince Charles Hospital Experience.

BACKGROUND: Multi-visceral organ transplant is uncommon. As a result of the rarity of these surgeries, there are limited studies, making it difficult to interpret outcomes and identify specific patient complications. We aim to assess the indications for multi-organ transplant, the time on the wait-list and evaluate outcomes including patient survival, graft survival and postoperative complications in an Australian context. METHODS: Patients undergoing multi-organ transplant from 1993 to 2018 at The Prince Charles Hospital, Brisbane, Australia were retrospectively reviewed, looking at baseline characteristics and post-transplant morbidity, mortality and graft survival. RESULTS: A total of 37 patients were included in the study, comprising 22 heart-lung transplants, eight heart-kidney transplants and seven heart-lung-liver transplants. There were six domino heart transplants performed, all in the heart-lung-liver transplant group. The mean age at transplant was 37 years and the mean wait-list time was 10 months. One patient, receiving a heart-lung transplant, required re-transplantation (bilateral lung) at 3 years. One-year (1-year) survival was 91% for heart-lung transplants, 86% for heart-lung-liver transplants and 87.5% for heart-kidney transplants. Five- and ten-year (5- and 10-year) survival was 79% for both in heart-lung transplant, 43% and 29% for heart-lung-liver transplant and 87.5% for both in heart-kidney transplant. CONCLUSION: Patients undergoing multi-organ transplant at our unit had long-term survival and organ function comparable to international data. In addition, waitlist time for multi-organ transplant was not found to be excessive.

Outcomes of the First 300 Cases of Transcatheter Aortic Valve Implantation at a High-Volume Australian Private Hospital.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) was first performed in Australia in 2008 with a steady increase in the number of implanting centres from seven in 2008 to 42 in 2018 (24 private and 18 public hospitals). There is limited published data on outcomes from Australian centres and no published data from Australian private hospitals. We describe outcomes of the first 300 cases at Queensland's first TAVI implanting private hospital. METHODS: From July 2015 to August 2018, 300 patients with severe, symptomatic aortic stenosis underwent TAVI at our centre. A heart team assessed all patients as suitable. All patients underwent computed tomography (CT) assessment of valve sizing and peripheral access. RESULTS: Median age was 85 years, 58% male, mean Society of Thoracic Surgeons' score 4.0%, 49% had New York Heart Association Class III/IV, 28% previous coronary artery bypass grafts, 14% peripheral vascular disease and 3.7% renal impairment (creatinine >177 µmol/L). At 30 days mortality was 1%, stroke 1.3%, myocardial infarction (MI) 0.3%, major vascular complication 3.0%, no life-threatening or disabling bleeding and new permanent pacemaker (PPM) requirement was 9.0%. Paravalvular leak was none, trace and mild in 27%, 53% and 20% respectively with 0.3%≥moderate paravalvular leak. At 1 year, mortality was 4.2%, stroke 2.1%, MI 0.3%, no life-threatening bleeding and PPM 11.4%. Lower rates of mortality, stroke, and major vascular complications were observed compared to the well-established TAVI centres in USA and Germany. CONCLUSION: Excellent TAVI clinical outcomes can be achieved in the Australian private hospital setting. Expert heart team assessment and CT guided procedural planning are key to these outcomes.

Redo Aortic Valve Replacement Following Bio-Bentall's Procedure.

BACKGROUND: Structural valve degeneration is a known sequel of aortic valve replacement with bioprosthetic valves, not infrequently leading to redo valve replacement. Reoperation on the aortic valve is associated with an incumbent increase in perioperative risk, and this risk is further increased when reoperation is performed on an already replaced aortic root. METHODS: We present a technique of opening the aortic graft and explanting the bioprosthesis by dividing the plane between the stent frame and the sewing ring of the bioprosthesis, followed by re-implantation of a bioprosthesis using simple sutures incorporating the remaining valve seat. RESULTS: The patient experienced an uneventful postoperative course and was discharged on the fifth day postoperatively. CONCLUSIONS: The author presents a simple and reproducible technique to replace a degenerated bioprosthetic aortic valve while preserving the previous aortic root replacement.

Heyde syndrome revisited: anaemia and aortic stenosis.

BACKGROUND: The association of anaemia with aortic stenosis (AS) has been recognised for over 50 years; however, although there have been several sporadic reports, there are few data on the prevalence of this syndrome. AIMS: We sought to compare the prevalence of anaemia in adults with AS with that of controls who had undergone coronary artery bypass grafting (CABG). METHODS: We conducted a retrospective cohort study comparing pre-procedural levels of haemoglobin in 1537 adults who underwent aortic valve replacement (AVR) for AS with 8025 contemporaneous patients who had CABG. We hypothesised that the prevalence of anaemia in patients with AS would be significantly higher than in the control group. RESULTS: A total of 30.1% in the AVR group was anaemic compared to 16.2% in the CABG group. The mean haemoglobin concentration measured across the whole population was significantly lower (132 g/L) in AVR patients than in those who underwent CABG (138 g/L). In a multivariable model, haemoglobin levels varied significantly by treatment group, gender and age. The adjusted marginal mean haemoglobin value was 135.6 g/L in AVR patients compared to 137.3 g/L in CABG patients. CONCLUSIONS: The prevalence of anaemia was significantly greater in patients with AS than in a contemporaneous cohort that underwent CABG. This may indicate that Heyde syndrome is more common than has been generally appreciated and should be considered in the evaluation of anaemia in patients with AS.

A Unique Hybrid Approach to Complex Re-Do Aortic Root Surgery.

BACKGROUND: We present the case of a 23-year-old male with ventriculo-aortic dehiscence and a retrosternal false aneurysm communicating to the left ventricular outflow tract (LVOT) and ascending aorta. His history included aortic valve replacement (AVR) and mitral valve (MV) repair remotely, followed by two further operations for endocarditis and aortic root abscess. METHODS: The risk associated with the redo surgery required detailed planning and innovative techniques to allow it to be performed safely. These included femoral cannulation for cardiopulmonary bypass, venting the left ventricular apex via a small left anterior thoracotomy, use of a CODA® (COOK Medical, Bloomington USA) balloon to occlude the distal ascending aorta (placed via left brachial artery) and finally, the use of a PROPLEGE® (Edwards Lifesciences, Irvine, USA) retrograde cardioplegia cannula (placed via right internal jugular vein).

Veno-Arterial ECMO in the Setting of Post-Infarct Ventricular Septal Defect: A Bridge to Surgical Repair.

Extracorporeal membrane oxygenation (ECMO) is a complex rescue therapy utilised to provide circulatory and/or respiratory support to critically ill patients who have failed maximal conventional therapy. The use of ECMO in adult cardiac surgery is not routine, occurring in a minority of critically ill patients, typically postoperatively. Presented here are three cases of post-infarct ventricular septal defect with cardiogenic shock managed preoperatively with ECMO support as a bridge to definitive surgical closure. We present a review of ECMO in the adult cardiac surgical population and highlight the potential role of preoperative ECMO for cardiogenic shock in the setting of post-infarct ventricular septal defect (PI VSD) as a bridge to definitive closure.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY): concept, design and rationale.

BACKGROUND: The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. METHODS: The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. DISCUSSION: The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Long-term outcomes following Medtronic Open Pivot valved conduit.

BACKGROUND AND AIM OF THE STUDY: Aortic root replacement is a complex procedure, though subsequent modifications of the original Bentall procedure have made surgery more reproducible. The study aim was to examine the outcomes of a modified Bentall procedure, using the Medtronic Open PivotTM valved conduit. Whilst short-term data on the conduit and long-term data on the valve itself are available, little is known of the long-term results with the valved conduit. METHODS: Patients undergoing aortic root replacement between February 1999 and February 2010, using the Medtronic Open Pivot valved conduit were identified from the prospectively collected Cardiothoracic Register at The Prince Charles Hospital, Brisbane, Australia. All patients were followed up echocardiographically and clinically. The primary end-point was death, and a Cox proportional model was used to identify factors associated.with survival. Secondary end-points were valve-related morbidity (as defined by STS guidelines) and postoperative morbidity. Predictors of morbidity were identified using logistic regression. RESULTS: A total of 246 patients (mean age 50 years) was included in the study. The overall mortality was 12%, with actuarial 10-year survival 79% and a 10-year estimate of valve-related death of 0.04 (95% CI: 0.004, 0.07). Preoperative myocardial infarction (p = 0.004, HR 4.74), urgency of operation (p = 0.038, HR 2.8) and 10% incremental decreases in ejection fraction (p = 0.046, HR 0.69) were predictive of mortality. Survival was also affected by the valve gradients, with a unit increase in peak gradient reducing mortality (p = 0.021, HR 0.93). Valve-related morbidity occurred in 11 patients. Urgent surgery (p <0.001, OR 4.12), aortic dissection (p = 0.015, OR 3.35), calcific aortic stenosis (p = 0.016, OR 2.35) and Marfan syndrome (p 0.009, OR 3.75) were predictive of postoperative morbidity. The reoperation rate was 1.2%. CONCLUSION: The Medtronic Open Pivot valved conduit is a safe and durable option for aortic root replacement, and is associated with low morbidity and 10-year survival of 79%. However, further studies are required to determine the effect of valve gradient on survival.

Early experience of transaortic TAVI--the future of surgical TAVI?

BACKGROUND: Trans-catheter aortic valve implantation (TAVI) is now a well recognised procedure for the high risk surgical patient with native or bioprosthetic aortic valve stenosis. Transfemoral and transapical implantation techniques are well described. With increasing referral of more marginal transapical patients, we describe our experience of a transaortic TAVI approach which we believe reduces the postoperative wound pain, respiratory complications, operative risk and hospital stay. METHODS: Patients referred for surgical TAVI underwent trans-catheter aortic valve implantation via an upper sternotomy and direct cannulation of the ascending aorta. RESULTS: Thirteen patients with a mean age of 81 years underwent transaortic Edwards SAPIEN valve implantation. There was no in hospital mortality in our series. One patient required insertion of a permanent pacemaker for complete heart block. There were no aortic cannulation complications. CONCLUSION: The transaortic TAVI approach provides good exposure of the distal ascending aorta, a familiar cannulation site for cardiac surgeons. Our initial experience demonstrates the approach to be a safe technique with the potential for faster and less complicated recovery in patients undergoing surgical TAVI procedures. With further experience and greater acceptance, the transaortic approach may ultimately become the procedure of choice for patients unsuitable for a transfemoral approach.

First Australian transapical mitral valve-in-valve implant for a failed mitral bioprosthesis: how to do it.

Transcatheter aortic valve replacements lower mortality in patients not suitable for surgical valve replacement compared to conservative treatment. Transcatheter valve-in-valve implants have been shown to be feasible in failed bioprostheses in aortic, mitral, pulmonary and tricuspid positions. We report the first Australasian experience of a transapical mitral valve-in-valve placement with an Edwards Sapien(®) transcatheter valve for a failed mitral bioprosthesis, focussing on the technical aspects of this novel procedure. Whilst the evidence for this niche indication is limited currently to case reports and case series, further evaluation of its long term outcomes may justify its use in this particularly high risk group of re-do sternotomy patients.

Aorto-carotid bypass for orthostatic mediated hypoperfusion transient ischaemic attacks: A case report.

INTRODUCTION AND IMPORTANCE: Aorto-carotid bypass is a rare procedure. It is reported to be performed for management of cerebral malperfusion in the setting of supra-aortic branch vessel disease. Malperfusion requiring a bypass is largely secondary to dissection or vasculitis. Atherosclerotic disease of the supra-aortic branch vessels is commonly managed via an endovascular approach. We report a rare and atypical presentation of cerebral malperfusion in the setting of atherosclerotic disease of the innominate and carotid arteries managed with an aorto-carotid bypass graft. CASE PRESENTATION: A case report of an 80-year-old female presenting with orthostatic mediated hypoperfusion transient ischaemic attacks with episodes of limb shaking and unilateral weakness with postural changes. The malperfusion was in the setting of severe atherosclerotic disease of the innominate and carotid arteries. CLINICAL DISCUSSION AND CONCLUSION: Our patient was not amendable to endovascular intervention or a less invasive open approach. The patient underwent an aorto-carotid bypass graft with complete resolution of symptoms. This case highlights a rare manifestation of orthostatic mediated cerebral malperfusion and a successful novel treatment method.

Risk Factors for Mortality in Patients Undergoing Cardiothoracic Surgery for Infective Endocarditis.

BACKGROUND: This study aimed to identify risk factors associated with mortality of patients who undergo cardiac surgery for infective endocarditis. METHODS: A retrospective review was performed of patients with infective endocarditis who underwent cardiac surgery at a quaternary Australian hospital between 2004 and 2014. Patient data were collected and prospectively analyzed. RESULTS: In all, 465 patients underwent surgery during the study period, with 30 deaths (6.45%). Factors independently associated with in-hospital mortality were increasing age (odds ratio [OR] 1.04; 95% confidence interval [CI], 1.01 to 1.07; P = .009), active bacterial endocarditis at time of operation (OR 4.91; 95% CI, 1.01 to 23.8; P = .048), preoperative invasive positive pressure ventilation (OR 3.65; 95% CI, 1.18 to 11.27; P = .025), increasing cardiopulmonary bypass time (OR 1.01; 95% CI, 1.006 to 1.014; P < .001), and increasing European System for Cardiac Operative Risk Evaluation score (OR 21.73; 95% CI, 2.12 to 223.11; P < .01). CONCLUSIONS: The in-hospital mortality of patients with infective endocarditis remains significant, with potential risk factors including increasing age, active bacterial endocarditis, preoperative invasive positive pressure ventilation, increasing cardiopulmonary bypass time, and high European System for Cardiac Operative Risk Evaluation score.

Study Protocol for a Pilot, Open-Label, Prospective, and Observational Study to Evaluate the Pharmacokinetics of Drugs Administered to Patients during Extracorporeal Circulation; Potential of In Vivo Cytochrome P450 Phenotyping to Optimise Pharmacotherapy.

Pharmacokinetic alterations of medications administered during surgeries involving cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO) have been reported. The impact of CPB on the cytochrome P450 (CYP) enzymes' activity is the key factor. The metabolic rates of caffeine, dextromethorphan, midazolam, omeprazole, and Losartan to the CYP-specific metabolites are validated measures of in vivo CYP 1A2, 2D6, 3A4, 2C19, and 2C9 activities, respectively. The study aim is to assess the activities of major CYPs in patients on extracorporeal circulation (EC). This is a pilot, prospective, open-label, observational study in patients undergoing surgery using EC and patients undergoing laparoscopic cholecystectomy as a control group. CYP activities will be measured on the day, and 1-2 days pre-surgery/3-4 days post-surgery (cardiac surgery and Laparoscopic cholecystectomy) and 1-2 days after starting ECMO, 1-2 weeks after starting ECMO, and 1-2 days after discontinuation from ECMO. Aforementioned CYP substrates will be administered to the patient and blood samples will be collected at 0, 1, 2, 4, and 6 h post-dose. Major CYP enzymes' activities will be compared in each participant on the day, and before/after surgery. The CYP activities will be compared in three study groups to investigate the impact of CYPs on EC.

Association between post-sternotomy tracheostomy and deep sternal wound infection: a retrospective analysis.

BACKGROUND: Tracheostomy has traditionally been used as a means of facilitated mechanical ventilation in patients requiring respiratory management following cardiac surgery. However in the clinical setting, the advantages of tracheostomy has been questioned by concerns surrounding evidence of its association with increased risk of deep sternal wound infections (DSWI). The present study sought to evaluate retrospectively our experience with post-sternotomy tracheostomy among cardiac surgery patients and association with DSWI. METHODS: Between July 2003 and June 2013, 11,795 patients underwent open cardiac surgery via sternotomy in our department. Among these, 225 underwent post-sternotomy tracheostomy. Data were obtained by reviewing and analyzing the Cardiac Surgical and Cardiac Intensive Care Unit (ICU) databases for adult cardiac patients. RESULTS: Out of the 11,795 sternotomy patients analyzed, 225 (1.9%) underwent tracheostomy. The overall mortality rate for post-sternotomy tracheostomy patients was 21.3%. DSWI developed in 23 patients (10.2%) of the tracheostomy group. Seven of these 23 patients had DSWI after insertion of tracheostomy. DSWI was significantly higher in tracheostomy versus no-tracheostomy patients (10.2% vs. 0.48%; P<0.001). DSWI was also associated with higher mortality rates compared to non-DSWI patients (11.4% vs. 2.3%; P<0.001). CONCLUSIONS: The present study demonstrated that tracheostomy was an independent risk factor for post-sternotomy DSWI, and that DSWI was a predictor of mortality. For tracheostomy patients, coronary artery bypass grafting (CABG) procedures and longer durations of tracheostomy were strong predictors of DSWI. Across all sternotomy patients, tracheostomy, diabetes, urgency status and blood transfusions were significant risk factors for DSWI. As such, the decision for tracheostomy post-sternotomy should be carefully considered on a case by case basis.

Posttraumatic growth in post-surgical coronary artery bypass graft patients.

Recent research in posttraumatic growth has been applied to people with life-threatening illnesses to optimise recovery. There is a lack of research exploring posttraumatic growth in coronary artery bypass graft patients. This article describes the recovery experience of 14 coronary artery bypass graft patients (13 males and 1 female) at their first outpatient review post-surgery. Grounded theory analysis was used to develop a model of distinct and shared pathways to growth depending on whether patients were symptomatic or asymptomatic pre-coronary artery bypass graft. Outcomes of posttraumatic growth in this sample included action-based healthy lifestyle growth and two forms of cognitive growth: appreciation of life and new possibilities. The model of posttraumatic growth developed in this study may be helpful in guiding future research into promoting posttraumatic growth and behaviour change in coronary artery bypass graft patients.

Osteopontin alters endothelial and valvular interstitial cell behaviour in calcific aortic valve stenosis through HMGB1 regulation.

OBJECTIVES: Calcific aortic valve stenosis (CAVS) is an important clinical problem predominantly affecting elderly individuals. Studies suggest that the progression of CAVS is actively regulated with valve endothelial injury leading to inflammation, fibrosis and calcification. The aim of this study was to delineate the possible regulatory role of osteopontin (OPN) on high-mobility group box 1 (HMGB1) function and the associated inflammatory and fibrotic response in CAVS. METHODS: Aortic valve leaflets were collected from CAVS patients undergoing aortic valve replacement (n = 40), and control aortic valve leaflets were obtained from heart transplant recipients (n = 15). Valves and plasma were analysed by quantitative real-time polymerase chain reaction (PCR), immunohistochemical staining and Western blot. Recombinant OPN or neutralizing OPN antibody was added to cultured endothelial and valvular interstitial cells (VICs), and cell proliferation scores and HMGB1 expression were assessed. RESULTS: CAVS valves had a decreased total percentage of VICs but increased numbers of infiltrating macrophages relative to control valves. RT-PCR studies showed higher expression of OPN, the inflammatory cytokine tumour necrosis factor-alpha as well as markers of fibrosis, tissue inhibitor of matrix metalloproteinase 1 and matrix metalloproteinase 2 in CAVS valves. Elevated expression of OPN was also observed in plasma of CAVS patients compared with controls. HMGB1 was detected in the secretory granules of cultured valve endothelial and VICs derived from CAVS valves. The addition of exogenous OPN inhibited the proliferation of cultured endothelial and VICs from CAVS valves and was associated with the extracellular expression of HMGB1, whereas neutralizing OPN had the opposite effect. CONCLUSIONS: We conclude that altered OPN expression in CAVS affects cellular HMGB1 function inducing cytoplasmic translocation and secretion of HMGB1 in endothelial cells and VICs, thus indicating a regulatory role for OPN in the progression of CAVS through alteration of HMGB1 function.