Hypertrophic cardiomyopathy with anteriorly directed mitral regurgitation is a red flag for concomitant pathology: a case report.

Background: Hypertrophic cardiomyopathy (HCM) is often linked to systolic anterior motion (SAM) of the mitral valve, typically resulting in a posteriorly directed mitral regurgitation (MR) jet. An anteriorly directed MR jet suggests additional mitral valve pathology that may not be resolved by myectomy alone. Case summary: A 58-year-old construction worker with no significant medical history experienced a syncopal event and was admitted to the emergency department with acute pulmonary oedema. A systolic murmur was investigated with a trans-thoracic echocardiogram that revealed severe MR with an unusual anteriorly directed MR jet and a possible flail segment of the posterior leaflet. This finding was further characterized with a trans-oesophageal echocardiogram that revealed severe asymmetric septal hypertrophy with SAM of the mitral valve, severe mitral regurgitation into a dilated left atrium with pulmonary vein flow reversal not caused by HCM-associated SAM, and a markedly abnormal mitral valve with flail and prolapse. The patient underwent successful cardiac surgery, including mitral valve repair and septal myectomy. The patient's recovery was uneventful, allowing for a return to work within a month post-surgery. Discussion: The anteriorly directed MR jet served as a red flag, leading to the discovery of an independent mitral valve pathology that required surgical intervention beyond the expected treatment for SAM-associated HCM. This case highlights the complexity of assessing MR in patients with HCM and underscores the importance of characterizing MR jet direction in diagnosing additional mitral valve diseases.

Differential responses of cerebral and renal oxygenation to altered perfusion conditions during experimental cardiopulmonary bypass in sheep.

We tested whether the brain and kidney respond differently to cardiopulmonary bypass (CPB) and to changes in perfusion conditions during CPB. Therefore, in ovine CPB, we assessed regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy and renal cortical and medullary tissue oxygen tension (PO2 ), and, in some protocols, brain tissue PO2 , by phosphorescence lifetime oximetry. During CPB, rSO2 correlated with mixed venous SO2 (r = 0.78) and brain tissue PO2 (r = 0.49) when arterial PO2 was varied. During the first 30 min of CPB, brain tissue PO2 , rSO2 and renal cortical tissue PO2 did not fall, but renal medullary tissue PO2 did. Nevertheless, compared with stable anaesthesia, during stable CPB, rSO2 (66.8 decreasing to 61.3%) and both renal cortical (90.8 decreasing to 43.5 mm Hg) and medullary (44.3 decreasing to 19.2 mm Hg) tissue PO2 were lower. Both rSO2 and renal PO2 increased when pump flow was increased from 60 to 100 mL kg-1 min-1 at a target arterial pressure of 70 mm Hg. They also both increased when pump flow and arterial pressure were increased simultaneously. Neither was significantly altered by partially pulsatile flow. The vasopressor, metaraminol, dose-dependently decreased rSO2 , but increased renal cortical and medullary PO2 . Increasing blood haemoglobin concentration increased rSO2 , but not renal PO2 . We conclude that both the brain and kidney are susceptible to hypoxia during CPB, which can be alleviated by increasing pump flow, even without increasing arterial pressure. However, increasing blood haemoglobin concentration increases brain, but not kidney oxygenation, whereas vasopressor support with metaraminol increases kidney, but not brain oxygenation.

Point-of-care diagnosis of tissue fibrosis: a review of advances in vibrational spectroscopy with machine learning.

Histopathology is the gold standard for diagnosing fibrosis, but its routine use is constrained by the need for additional stains, time, personnel and resources. Vibrational spectroscopy is a novel technique that offers an alternative atraumatic approach, with short scan times, while providing metabolic and morphological data. This review evaluates vibrational spectroscopy for the assessment of fibrosis, with a focus on point-of-care capabilities. OVID Medline, Embase and Cochrane databases were systematically searched using PRISMA guidelines for search terms including vibrational spectroscopy, human tissue and fibrosis. Studies were stratified based on imaging modality and tissue type. Outcomes recorded included tissue type, machine learning technique, metrics for accuracy and author conclusions. Systematic review yielded 420 articles, of which 14 were relevant. Ten of these articles considered mid-infrared spectroscopy, three dealt with Raman spectroscopy and one with near-infrared spectroscopy. The metrics for detecting fibrosis were Pearson correlation coefficients ranging from 0.65-0.98; sensitivity from 76-100%; specificity from 90-99%; area under receiver operator curves from 0.83-0.98; and accuracy of 86-99%. Vibrational spectroscopy identified fibrosis in myeloproliferative neoplasms in bone, cirrhotic and hepatocellular carcinoma in liver, end-stage heart failure in cardiac tissue and following laser ablation for acne in skin. It also identified interstitial fibrosis as a predictor of early renal transplant rejection in renal tissue. Vibrational spectroscopic techniques can therefore accurately identify fibrosis in a range of human tissues. Emerging data show that it can be used to quantify, classify and provide data about the nature of fibrosis with a high degree of accuracy with potential scope for point-of-care use.

Near-infrared spectroscopy as a novel method of ex vivo bladder cancer tissue characterisation.

OBJECTIVE: To evaluate near-infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. PATIENTS AND METHODS: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. RESULTS: A two-group algorithm comparing low- vs high-grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three-group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. CONCLUSIONS: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point-of-care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re-resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre-optic probes offer the potential for in vivo assessment.

Point-of-care detection of fibrosis in liver transplant surgery using near-infrared spectroscopy and machine learning.

Introduction: Visual assessment and imaging of the donor liver are inaccurate in predicting fibrosis and remain surrogates for histopathology. We demonstrate that 3-s scans using a handheld near-infrared-spectroscopy (NIRS) instrument can identify and quantify fibrosis in fresh human liver samples. Methods: We undertook NIRS scans on 107 samples from 27 patients, 88 from 23 patients with liver disease, and 19 from four organ donors. Results: Liver disease patients had a median immature fibrosis of 40% (interquartile range [IQR] 20-60) and mature fibrosis of 30% (10%-50%) on histopathology. The organ donor livers had a median fibrosis (both mature and immature) of 10% (IQR 5%-15%). Using machine learning, this study detected presence of cirrhosis and METAVIR grade of fibrosis with a classification accuracy of 96.3% and 97.2%, precision of 96.3% and 97.0%, recall of 96.3% and 97.2%, specificity of 95.4% and 98.0% and area under receiver operator curve of 0.977 and 0.999, respectively. Using partial-least square regression machine learning, this study predicted the percentage of both immature (R 2 = 0.842) and mature (R 2 = 0.837) with a low margin of error (root mean square of error of 9.76% and 7.96%, respectively). Conclusion: This study demonstrates that a point-of-care NIRS instrument can accurately detect, quantify and classify liver fibrosis using machine learning.

Ambulatory short-term mechanical circulatory support: facilitates recovery and prepares patients for definitive therapy.

Short-term mechanical circulatory support (ST-MCS) devices have been traditionally deployed in patients with cardiogenic shock, advanced heart failure, cardiovascular collapse, and cardiorespiratory failure. Limitations of the mechanical support devices are typically related to mobility of the patient since the access is frequently through femoral vasculature. This limits the time the patient can be supported by mechanical circulatory support (MCS). We describe deployment of ST-MCS using alternate access such as the subclavian/axillary artery that facilitates ambulation of the patient. These include the deployment of intra-aortic balloon pump (IABP) through the subclavian artery, Impella pump through the axillary/subclavian artery, and extracorporeal membrane oxygenation (ECMO) using the subclavian artery and jugular vein.

Australian Donation and Transplantation Biobank: A Research Biobank Integrated Within a Deceased Organ and Tissue Donation Program.

We aimed to facilitate the donation of tissue samples for research by establishing a centralized system integrated in the organ donation program for collection, storage, and distribution of samples (the Australian Donation and Transplantation Biobank [ADTB]). Methods: Feasibility of a research biobank integrated within the deceased organ and tissue donation program was assessed. DonateLife Victoria sought consent for ADTB donation after consent was received for organ donation for transplantation from the donor's senior available next of kin. ADTB samples were collected during donation surgery and distributed fresh to researchers or stored for future research. The main outcome measures were ADTB donation rates, ADTB sample collection, ADTB sample use, and to identify ethical considerations. Results: Over 2 y, samples were collected for the ADTB from 69 donors (28% of 249 donors). Samples were obtained from the spleen (n = 59, 86%), colon (n = 57, 83%), ileum (n = 56, 82%), duodenum (n = 55, 80%), blood (n = 55, 80%), bone marrow (n = 55, 80%), skin (n = 54, 78%), mesenteric lymph nodes (n = 56, 81%), liver (n = 21, 30%), lung (n = 29, 42%), and lung-draining lymph node (n = 29, 42%). Heart (n = 20), breast (n = 1), and lower urinary tract (n = 1) samples were obtained in the second year. Five hundred fifty-six samples were used in 19 ethics-approved research projects spanning the fields of immunology, microbiology, oncology, anatomy, physiology, and surgery. Conclusions: The integration of routine deceased donation and transplantation activities with a coordinated system for retrieval and allocation of donor samples for use in a range of research projects is feasible and valuable.

Brian Fowell Buxton (15/04/1940-20/05/2022)-Outstanding Achievements and Personal Memories.

Brian F. Buxton, one of Australia's greatest cardiac surgeons, died in May 2022, aged 82 years. In June 2022, a memorial celebration of Brian's life was held in Melbourne, Australia, attended by 550 colleagues and friends from many walks of life-not only "medical people" but also friends involved in Brian's sailing and hiking activities. This Special Article includes an introduction from Professor Jayme Bennetts, President of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS), an abridged version of a memorial address by Professor James Tatoulis and contributions from two other long-term professional colleagues and personal friends of Buxton, Professor Jaishankar Raman and Professor Franklin Rosenfeldt, founding editor of Heart, Lung and Circulation. Buxton was an outstanding and pioneering surgeon, clinical leader, and good friend to many. The Brian F. Buxton Cardiac and Thoracic Aortic Surgery Unit in Melbourne, Australia, is now so named in honour of his outstanding achievements and as a legacy. Vale Brian F. Buxton.

The Effects of Targeted Changes in Systemic Blood Flow and Mean Arterial Pressure on Urine Oximetry During Cardiopulmonary Bypass.

OBJECTIVES: Poor medullary oxygenation is implicated in the evolution of acute kidney injury. The authors sought to determine if increasing systemic flow and mean arterial pressure could improve urine oxygen tension (PuO2) measured in the bladder, a surrogate of kidney medullary oxygenation, in patients undergoing on-pump cardiac surgery. DESIGN: Randomized crossover study. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty adult patients undergoing cardiopulmonary bypass (CPB) with expected cross-clamp time of >60 minutes and estimated glomerular filtration rate of >30 mL/min/1.73m2. INTERVENTIONS: Sequential 20-minute periods of 2 interventions: Intervention H ("High") or Intervention N ("Normal"). The order of interventions was determined by randomization. Intervention H: targeted CPB flow 3.0 L/min/m2 and mean arterial pressure (MAP) 80 mmHg. Intervention N: targeted CPB flow 2.4 L/min/m2 and MAP 65 mmHg. MEASUREMENTS AND MAIN RESULTS: PuO2 was measured by an oxygen sensor introduced into the bladder via a urinary catheter. Clear separation was achieved in CPB flow and MAP between intervention periods (p < 0.001 for group-time interaction). PuO2 during Intervention H was higher than during Intervention N (p < 0.001 for group-time interaction). After 17 minutes, PuO2 was statistically higher in Intervention H at each time point. There were no differences in markers of hemolysis between interventions. CONCLUSIONS: PuO2 was higher when systemic flow and MAP were increased during CPB. These findings suggest that PuO2 is responsive to changes in hemodynamics and that higher flow and pressure may improve medullary oxygenation.

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-ll (HAS FLAIR-II) trial.

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, setting, participants and intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, openlabel, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main outcome measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised. Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN No. 12620000137998).

Opioid Prescription After Cardiac Surgery.

OBJECTIVES: To characterise short-term and long-term opioid prescription patterns after cardiac surgery. DESIGN, SETTING AND PARTICIPANTS: We obtained data from a single Australian tertiary hospital from November 2012 to July 2019 and included 2,205 patients who underwent a primary cardiac surgical procedure. MAIN OUTCOME AND MEASURES: The primary outcome was the dose of opioids at hospital discharge. Secondary outcomes included factors associated with high dose opioid prescriptions and persistent opioids use after cardiac surgery. RESULTS: Overall, 76.4% of study patients were prescribed opioids at hospital discharge, with a median discharge prescription of 150 mg oral morphine equivalents. Moreover, 52.8% of discharge opioid prescriptions were as slow-release formulations and 60.0% of all discharge prescriptions were for patients who had received no opioids the day before discharge. In the subset of our patients with long-term data, 14.0% were still receiving opioids at 3-12 months after cardiac surgery. CONCLUSIONS: In cardiac surgical patients, opioid prescriptions at discharge were common, most were at higher than recommended doses and more than half were slow-release formulations. Such prescription was associated with one in seven patients continuing to receive opioids 3-12 months after surgery.

Factor Xa Inhibition for the Treatment of Venous Thromboembolism Associated With Cancer: A Meta-Analysis of the Randomised Controlled Trials.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Until recently, guidelines recommended the use of low-molecular weight heparin (LMWH) as standard of care for VTE in patients with cancer. Despite the proven efficacy of direct oral anticoagulants (DOACs) for treatment of VTE, there is equipoise supporting their use in cancer patients. METHODS: A systematic review of PubMed, Medline and EMBASE identified four randomised controlled trials (RCTs) in patients with cancer and VTE comparing a factor Xa inhibitor (FXaI) to LMWH. A meta-analysis was performed with a primary outcome of VTE recurrence and key secondary outcomes of major bleeding, clinically relevant non-major bleeding (CRNMB) and gastrointestinal (GI) bleeding. RESULTS: Four RCTs with 2,907 patients were included. 1,451 patients were randomised to FXaI and 1,456 to LMWH. VTE recurrence was lower in the FXaI group (RR 0.62, 95%CI 0.44-0.87; p=0.01; I2=24.90), with an absolute risk difference of -4% equating to a number needed to treat of 25 for prevention of recurrent VTE with FXaI. No significant difference in major bleeding was noted between groups (RR 1.33, 95%CI 0.84-2.11; p=0.23). Rates of GI bleeding (RR 1.87, 95%CI 1.06-3.29; p=0.03) and CRNMB (RR 1.57, 95%CI 1.11-2.23; p=0.01) were greater with FXaIs. CONCLUSION: In patients with cancer and VTE, the rate of VTE recurrence was significantly lower with FXaI than with LMWH without an increased risk of major bleeding. Our data supports the use of FXaIs as the standard of care for the treatment of VTE in this population.

SMARTphone Based Cardiovascular Risk Reduction in BREAST Cancer Patients (SMART-BREAST): A Randomised Controlled Trial Protocol.

INTRODUCTION: Breast cancer survivors are at greater risk for cardiovascular-related mortality compared to women without breast cancer. Accordingly, attention to reducing the risk of cardiovascular disease must be a priority in the long-term management of these patients. With the exponential rise in cancer survivors, there is a need for innovative cardio-oncology programs. This paper describes the study design of a randomised controlled trial assessing the effectiveness of a smartphone-based cardiovascular risk reduction program in improving physical activity and cardiovascular health in patients undergoing treatment for breast cancer. METHODS AND ANALYSIS: The aim of this study is to assess the efficacy and usability of a smartphone-based model of care for exercise promotion, cardiovascular risk reduction and community engagement in women undergoing treatment for breast cancer. This will be achieved by testing our personalised smartphone application "BreastMate", as an adjunct to standard care in a single-blinded, parallel, randomised controlled trial. The primary outcome of the trial is change in exercise capacity, as measured by the 6-minute walk test distance at 12 months compared to baseline. Secondary endpoints include improvements in cardiovascular risk factor status and quality of life, received dose intensity of chemotherapy and major adverse cardiovascular events. ETHICS: Multicentre ethical approval has been granted by the Austin Hospital (HREC/47081/Austin/2018). DISSEMINATION OF RESULTS: The analysed results will be published in a peer reviewed journal on completion of the clinical trial. REGISTRATION DETAILS: SMART-BREAST has been prospectively registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR12620000007932).

Extracorporeal membrane oxygenation in the management of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) is a type of systematic vasculitis that primarily involves the lung and kidney. Diffuse alveolar hemorrhage (DAH) and associated acute respiratory failure are uncommon but devastating complications of GPA. Experience in using extracorporeal membrane oxygenation (ECMO) to manage DAH caused by GPA is limited. We report two GPA patients with DAH that were successfully managed using ECMO support. Examining 13 cases identified in the literature and two of our own, we observed that most patients experienced rapid deterioration in respiratory function in conjunction with a precedent respiratory infection. All 15 patients received veno-venous ECMO support. The median duration of ECMO support was 11 days (interquartile range: 7.5-20.75 days). Bleeding was the most common complication, seen in four (26.7%) cases. All patients were successfully weaned off ECMO after a median length of hospital stay of 42 days (interquartile range: 30-78 days). We demonstrated that the use of ECMO is a reasonable and effective support option in the management of GPA patients with DAH. The risk of bleeding is high but maybe reduced using a lower anticoagulation goal.

Extracorporeal Membrane Oxygenation Bridges Inoperable Patients to Definitive Cardiac Operation.

Extracorporeal membrane oxygenation (ECMO) offers an opportunity for patient recovery through complete cardiopulmonary support but is associated with complications that limit duration and overall utility. We examine the role of ECMO as a potential bridge to high-risk cardiac surgery in otherwise inoperable cases. This study reports a retrospective, multi-institution experience examining all patients for whom ECMO was used preoperatively as a bridge to definitive cardiac surgery without exception. A consecutive patient database (December 2011 through August 2017) was utilized. European System for Cardiac Risk Evaluation (EuroSCORE) 2 was calculated as a metric of patient acuity and risk assessment. Observed and expected mortality were compared. Twelve adult patients fit inclusion criteria and were supported with ECMO during the study period. There were five males and seven females. Average age was 56 (39-77) years. All 12 patients were supported with venoarterial ECMO for cardiogenic shock. This was done in preparation for corrective conventional cardiac surgery. Definitive cardiac surgical procedures included complex valve (n = 5), left ventricular assist device (n = 3), coronary artery bypass grafting (CABG; n = 2), CABG/ventricular septal defect repair (n = 1), and mitral valve replacement/CABG (n = 1). Average time of ECMO support was 200 (range 113-379) hours. Three patients were decannulated from ECMO at the conclusion of definitive cardiac surgery. Risk assessed by Logistic EuroSCORE 2 ranged from 64% to 89%. Average EuroSCORE 2-predicted mortality representing all 12 patients was 77%. Thirty day mortality was 25% (3/12), and hospital mortality was 33% (4/12). Seven patients are still alive today, with a mean survival of 37 (range 2-64) months. Two deaths were associated with gastrointestinal bleeding and two with evolving liver failure. Mean difference between the EuroSCORE 2 prediction model and actual observed 30 day mortality rate was 42.33 (95% CI 36.86-47.98) with a two-tailed, one-sample t test value of p < 0.001. ECMO can successfully be utilized as a bridge to conventional cardiac surgical procedures in critically ill patients, with a historically high mortality.

Routine Papillary Muscle Realignment and Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: Septal myectomy has been the mainstay of the surgical treatment of obstructive hypertrophic cardiomyopathy (HCM); however, recently there is growing appreciation for associated mitral valve abnormalities that contribute to left ventricular outflow tract (LVOT) obstruction. In this study, we describe our experience with combined papillary muscle realignment (PMR) and septal myectomy for the treatment of obstructive HCM. METHODS: We identified 44 patients undergoing surgery for obstructive HCM whose anatomy was amenable to combined PMR and septal myectomy at our institution over a 20-month period. All patients underwent resting and stress echocardiography preoperatively and postoperatively. Demographic, clinical, and imaging data were prospectively collected in a cardiac surgery database. RESULTS: Patient age ranged broadly, with mean age of 54 (range, 18 to 76) years. Preoperatively, 70% of patients were New York Heart Association functional class III or IV, the mean stress LVOT gradient was 144 mm Hg, and severe mitral regurgitation (MR) with stress was seen in 81%. Additional procedures included division of myocardial bands (50%) and chordae (43%) and resection of accessory papillary muscles (25%). Following the procedure, mean resting and stress gradients were reduced to normal (12 and 27 mm Hg, respectively; p < 0.0001). No patient had severe MR and only 3 (6.8%) had moderate MR (p < 0.0001). Mean length of stay was 6 days and there were no mortalities. CONCLUSIONS: Septal myectomy combined with PMR is a safe, highly effective, and reproducible procedure that reliably relieves LVOT obstruction and corrects MR without the need for mitral valve repair or replacement.