Sutton-Kadir Syndrome can be treated safely with endovascular embolisation alone.

INTRODUCTION: Sutton-Kadir Syndrome (SKS) describes true inferior pancreaticoduodenal artery (IPDA) aneurysms in the setting of coeliac artery (CA) stenosis or occlusion. Although rare, SKS aneurysms can rupture and cause morbidity. Due to its rarity and lack of controlled treatment data, correct treatment for the CA lesion is currently unknown. Our aim was to assess if endovascular embolisation alone was safe and effective in treatment of SKS aneurysms, in emergent and elective settings. Secondary objectives were to describe presentation and imaging findings. METHODS: A retrospective cohort study of patients treated at Sir Charles Gairdner Hospital between January 2014 and December 2021 was done. Data on presentation, diagnostics, aneurysm characteristics, CA lesion aetiology, treatment and outcomes were extracted from chart review. RESULTS: Twenty-four aneurysms in 14 patients were identified. Rupture was seen in 7/15 patients. Most aneurysms (22/24) were in the IPDA or one of its anterior or posterior branches. Median arcuate ligament (MAL) compression was identified in all. There was no difference in median (IQR) maximal transverse diameter between ruptured and non-ruptured aneurysms (6 mm (9), 12 mm (6), P = 0.18). Of ruptures, 6/7 had successful endovascular embolisation and 1/7 open surgical ligation. Of non-ruptures, 6/7 had successful endovascular embolisation, 1/7 open MAL division then endovascular CA stenting and aneurysm embolisation. No recurrences or new aneurysms were detected with computed tomography or magnetic resonance angiography over a median (IQR) follow-up period of 30 (10) months in 12 patients. CONCLUSION: Endovascular embolisation of SKS aneurysms without treatment of MAL compression is safe and effective in both the emergent and elective settings.

Therapeutic Inertia With Initial Low-Dose Quadruple Combination Therapy for Hypertension: Results From the QUARTET Trial.

BACKGROUND: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain. METHODS: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP). RESULTS: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P=0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P>0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit. CONCLUSIONS: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target. REGISTRATION: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404.

Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication.

BACKGROUND: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail. METHODS: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes. RESULTS: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill. CONCLUSION: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.

3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Emergency Endovascular Repair of Thoracic Aorta Via a Percutaneous Popliteal Approach Following an Iatrogenic Injury.

Iatrogenic arterial injuries are rare but well-recognised complications of spinal surgery. This paper presents a case of an iatrogenic arterial injury during a total en bloc spondylectomy resulting in significant haemorrhage and the patient's haemodynamic instability. The devastating complication was successfully treated with an emergency thoracic endovascular aortic repair via a percutaneous popliteal approach, while the patient remained in prone position. The patient had an uneventful recovery with no subsequent arterial injury or pseudoaneurysm to the access vessel.

The financial burden of diabetes-related foot disease in Australia: a systematic review.

BACKGROUND: Diabetes-related foot disease (DFD) is a common, costly, and severe complication of diabetes mellitus. DFD is associated with high rates of morbidity and mortality and poses a significant burden on patients, healthcare systems and society. While the detrimental impact of DFD is widely recognised, the precise financial implications of its management in Australia remain unclear due to inconsistent and inconclusive contemporary data. Therefore, the aim of this review was to identify, summarise and synthesise existing evidence to estimate the costs associated with DFD management in Australia. METHODS: Searches were conducted in MEDLINE, Embase, AMED, CINAHL, Joanna Briggs Institute EBP, and the Cochrane Library from November 2011 to July 2023. Australian studies investigating costs associated with DFD management were eligible for inclusion. Two independent reviewers performed the study selection, data extraction and quality assessment steps. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklist was used to assess study quality. A descriptive analysis was performed due to limited existing evidence and large heterogeneity between study populations to conduct meta-analyses. RESULTS: Three economic evaluations were included in the review. One study was rated as 'poor', one as 'very good' and one as 'excellent' when assessed against the CHEERS checklist. The estimated cost of DFD management varied between studies and comparisons were not possible due to the different methodological approaches and data sources. The studies were unable to provide an overall cost of DFD with respect to all aspects of care as they did not capture the multi-faceted level of care throughout the entire patient journey between sectors and over time. CONCLUSION: There is limited contemporary evidence for the costs associated with DFD management within Australia, particularly related to direct costs and resource utilisation. Further research into the economic impact of DFD management is needed to inform optimisation of national service delivery and improve health outcomes for individuals with DFD in Australia. Integrating real-world data on impact of clinical interventions with parallel economic evaluation could be a valuable approach for future research, which would offer a more comprehensive understanding of the clinical and economic outcomes beyond solely model-based evaluations. TRIAL REGISTRATION: PROSPERO Registration No. CRD42022290910.

Peripheral Artery Disease: Underappreciated Impact and Residual Cardiovascular Risk Despite Revascularization.

This Commentary highlights the under-recognized prevalence and heavy burden of peripheral artery disease (PAD) and its important role as a harbinger of complications of atherosclerotic cardiovascular disease. Although increasing in prevalence globally, PAD is being further accelerated with diabetes, and patients with advanced PAD are at high risk for chronic limb-threatening ischemia. The need for (repeated) revascularization and amputation places a heavy social burden on patients and family, and a heavy financial burden on the health care system, exceeding the cost of coronary artery and cerebrovascular diseases. Clinical trial research in PAD will be enhanced by widely agreed-upon definitions of major adverse cardiovascular events and major adverse limb events. Antithrombotic and lipid-lowering therapies are recommended but underutilized, while the optimal peri-interventional antithrombotic regimen is still under debate. Additional antiinflammatory treatment is currently an unaddressed strategy in the management of patients with PAD, and there is a strong case for the evaluation of widely available antiinflammatory agents such as colchicine.

Use of Silica Nanoparticles for Drug Delivery in Cardiovascular Disease.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death worldwide. The current CVD therapeutic drugs require long-term treatment with high doses, which increases the risk of adverse effects while offering only marginal treatment efficacy. Silica nanoparticles (SNPs) have been proven to be an efficient drug delivery vehicle for numerous diseases, including CVD. This article reviews recent progress and advancement in targeted delivery for drugs and diagnostic and theranostic agents using silica nanoparticles to achieve therapeutic efficacy and improved detection of CVD in clinical and preclinical settings. METHODS: A search of PubMed, Scopus, and Google Scholar databases from 1990 to 2023 was conducted. Current clinical trials on silica nanoparticles were identified through ClinicalTrials.gov. Search terms include silica nanoparticles, cardiovascular diseases, drug delivery, and therapy. FINDINGS: Silica nanoparticles exhibit biocompatibility in biological systems, and their shape, size, surface area, and surface functionalization can be customized for the safe transport and protection of drugs in blood circulation. These properties also enable effective drug uptake in specific tissues and controlled drug release after systemic, localized, or oral delivery. A range of silica nanoparticles have been used as nanocarrier for drug delivery to treat conditions such as atherosclerosis, hypertension, ischemia, thrombosis, and myocardial infarction. IMPLICATIONS: The use of silica nanoparticles for drug delivery and their ongoing development has emerged as a promising strategy to improve the effectiveness of drugs, imaging agents, and theranostics with the potential to revolutionize the treatment of CVD.

Prone thoracic endovascular aortic repair via the popliteal artery for inadvertent vascular injury during spondylectomy: a case report.

Background: Vascular injury during spinal surgery is a dreaded complication associated with high morbidity and mortality. Repositioning the patient following such an injury could result in significant time delays and haemorrhage. Endovascular repair via popliteal access has never previously been described in the literature. A novel prone thoracic endovascular aortic repair (TEVAR) technique is described here as a safe alternative to manage vascular injury during posterior spinal surgery. Case Description: Here we describe a 63-year-old male where endovascular repair of vascular injury to the aorta by intercostal artery avulsion was performed via popliteal artery access in the prone position during T11 en bloc spondylectomy and posterior fusion. The patient remained haemodynamically unstable following the vascular injury precluding immediate transfer to the angiography suite. Identification of vascular injury to deployment of TEVAR graft was 90 minutes. The spondylectomy was able to be completed without repositioning the patient. Radiological and clinical follow-up revealed no complications at 1 and 2 months respectively following surgery. Conclusions: TEVAR placement via this novel popliteal access route was able to halt the haemorrhage allowing stabilisation of the patient and completion of the spinal procedure. Clinical teams should be made aware this is a viable technique to address vascular injuries during spinal surgery.

Connecting the Dots: How Injury in the Arterial Wall Contributes to Atherosclerotic Disease.

PURPOSE: The occurrence and development of atherosclerotic cardiovascular disease, which can result in severe outcomes, such as myocardial infarction, stroke, loss of limb, renal failure, and infarction of the gut, are strongly associated with injury to the intimal component of the arterial wall whether via the inside-out or outside-in pathways. The role of injury to the tunica media as a pathway of atherosclerosis initiation is an underresearched area. This review focuses on potential pathways to vessel wall injury as well as current experimental and clinical research in the middle-aged and elderly populations, including the role of exercise, as it relates to injury to the tunica media. METHODS: A database search using PubMed and Google Scholar was conducted for research articles published between 1909 and 2023 that focused on pathways of atherogenesis and the impact of mechanical forces on wall injury. The following key words were searched: wall injury, tunica media, atherogenesis, vascular aging, and wall strain. Studies were analyzed, and the relevant information was extracted from each study. FINDINGS: A link between high mechanical stress in the arterial wall and reduced vascular compliance was found. The stiffening and calcification of the arterial wall with aging induce high blood pressure and pulse pressure, thereby causing incident hypertension and cardiovascular disease. In turn, prolonged high mechanical stress, particularly wall strain, applied to the arterial wall during vigorous exercise, results in stiffening and calcification of tunica media, accelerated arterial aging, and cardiovascular disease events. In both scenarios, the tunica media is the primary target of mechanical stress and the first to respond to hemodynamic changes. The cyclical nature of these impacts confounds the results of each because they are not mutually exclusive. IMPLICATIONS: The role of stress in the tunica media appears to be overlooked despite its relevance, and further research into new primary preventive therapies is needed aside from cautioning the role of vigorous exercise in the elderly population.

Cognition and Cerebral Blood Flow After Extracranial Carotid Revascularization for Carotid Atherosclerosis: A Systematic Review.

PURPOSE: Extracranial atherosclerotic carotid stenosis is associated with inadequate cerebral blood flow (CBF) and cognitive dysfunction. The impact of extracranial carotid revascularization on cognition and how any cognitive change relates to changes in CBF are less clear. This review examines the effects of revascularization of extracranial carotid disease by carotid endarterectomy (CEA) or carotid stenting (CAS) on cognition, and how this relates to changes in CBF. METHODS: A systematic review of existing reports in the Medline, Embase, and Cochrane databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement recommendations. All original retrospective or prospective studies and clinical trials that compared pre- and postoperative cognitive function and CBF in patients with extracranial carotid stenosis who underwent CEA or CAS versus a control group, published between January 1985 and December 2022, were identified and considered eligible for inclusion in this study. FINDINGS: Seven studies (661 participants; 460 CEA or CAS) were identified. All were observational studies and of moderate to good methodologic quality. Six studies (619 participants; follow-up range 1 month to 2 years) demonstrated improvement in some cognitive domains following CEA or CAS, improvement in CBF following revascularization, and correlated some of these cognitive changes with changes in CBF. One study (42 participants; 3 months follow-up) found cognitive improvement following CEA, but found no improvement in CBF or any correlation between cognitive and CBF change. The literature however represented heterogenous study populations examining asymptomatic and/or symptomatic carotid stenosis, differing in treatment modality and criteria for control groups ranging from healthy volunteers to those with stenosis but not who underwent surgical revascularization, and finally, differing reporting methods. This heterogeneity precluded meta-analysis. IMPLICATIONS: Definitive conclusions are limited by variation in cognitive function assessment, timing of testing, and how these are correlated to CBF. However, research suggests a potential improvement in cognition which may be associated with improvement in CBF, particularly in those patients who have more significant CBF deficit at baseline. Further studies are required to better understand this association and provide a clearer picture of the cognitive effects of carotid revascularization.

Three-Dimensional Bioprinting in Cardiovascular Disease: Current Status and Future Directions.

Three-dimensional (3D) printing plays an important role in cardiovascular disease through the use of personalised models that replicate the normal anatomy and its pathology with high accuracy and reliability. While 3D printed heart and vascular models have been shown to improve medical education, preoperative planning and simulation of cardiac procedures, as well as to enhance communication with patients, 3D bioprinting represents a potential advancement of 3D printing technology by allowing the printing of cellular or biological components, functional tissues and organs that can be used in a variety of applications in cardiovascular disease. Recent advances in bioprinting technology have shown the ability to support vascularisation of large-scale constructs with enhanced biocompatibility and structural stability, thus creating opportunities to replace damaged tissues or organs. In this review, we provide an overview of the use of 3D bioprinting in cardiovascular disease with a focus on technologies and applications in cardiac tissues, vascular constructs and grafts, heart valves and myocardium. Limitations and future research directions are highlighted.

Cost-effectiveness of ultra-low-dose quadruple combination therapy for high blood pressure.

OBJECTIVE: To determine the cost-effectiveness and cost-utility of a quadpill containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg in comparison with irbesartan 150 mg for people with hypertension who are either untreated or receiving monotherapy. METHODS: We conducted a within-trial and modelled economic evaluation of the Quadruple UltrA-low-dose tReaTment for hypErTension trial. The analysis was preplanned, and medications and health service use captured during the trial. The main outcomes were incremental cost-effectiveness ratios (ICERs) for cost per mm Hg systolic blood pressure (BP) reduction at 3 months, and modelled cost per quality-adjusted life year (QALY) over a lifetime. RESULTS: The within-trial analysis showed no clear difference in cost per mm Hg BP lowering between randomised treatments at 3 months ($A10 (95% uncertainty interval (UI) $A -18 to $A37) per mm Hg per person) for quadpill versus monotherapy. The modelled cost-utility over a lifetime projected a mean incremental cost of $A265 (95% UI $A166 to $A357) and a mean 0.02 QALYs gained (95% UI 0.01 to 0.03) per person with quadpill therapy compared with monotherapy. Quadpill therapy was cost-effective in the base case (ICER of $A14 006 per QALY), and the result was sensitive to the quadpill cost in one-way sensitivity analysis. CONCLUSIONS: Quadpill in comparison with monotherapy is comparably cost-effective for short-term BP lowering. In the long-term, quadpill therapy is likely to be cost-effective. TRIAL REGISTRATION NUMBER: ANZCTRN12616001144404.

The Role of Near Infrared Spectroscopy in Diagnosing Stump Ischaemia in Patients with Below Knee Amputation: Case Reports.

Introduction: Functional near infrared spectroscopy (fNIRS) can be used to quantify stump oxygen saturation (SaO2) as one of many possible causes of pain following major amputation. Although commonly used for cerebral perfusion monitoring during carotid or cardiac surgery, it can also be used to monitor tissue perfusion in the lower limb and predict healing following below knee amputation (BKA). The aim of this study was to measure the SaO2 trend as there is no validated oxygen threshold to diagnose insufficient flow into the arterial collateral network currently. Report: NIRS was used to measure SaO2 while performing treadmill exercise. Two BKA patients with chronic stump pain were asked to perform treadmill exercise while using their prosthesis and NIRS optode applied to the posterior stump to monitor SaO2. Cases 1 and 2 showed a decline in SaO2 of 25% and 18%, respectively, while walking on the prosthesis. After superficial femoral artery (SFA) recanalisation and stenting, Case 1 showed improvement by maintaining SaO2 between 54% and 60% throughout treadmill exercise. In Case 2, perfusion could not be further improved, and the patient underwent through knee amputation. Discussion: fNIRS detected compressive ischaemia and exercise induced ischaemia as mechanisms of stump pain. Findings provided the multidisciplinary team with objective information, aiding decision making to treat stump pain.

Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia.

Background and aims: Fatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media. Methods: Three healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4-12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima. Results: High lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima. Conclusion: The arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

The Use of Extracorporeal Circulation to Facilitate the Resection of a Large Retroperitoneal Sarcoma With Major Vessel Involvement: A Single-Center Review of 20 Cases.

OBJECTIVE: To describe the introduction of extracorporeal corporeal oxygenation (ECMO) to facilitate the surgical resection of large retroperitoneal sarcomas involving major vessels and to report preliminary outcomes. DESIGN: A case series. SETTING: At a tertiary university hospital and state sarcoma center. PARTICIPANTS: Patients undergoing retroperitoneal sarcoma resection requiring inferior vena cava (IVC) reconstruction between June 2018 and March 2022. INTERVENTION: ECMO for retroperitoneal tumor resection requiring IVC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 20 patients underwent ECMO-assisted retroperitoneal sarcoma resection and IVC reconstruction. The median age was 60.5 years (IQR 48-69); 15 women and 5 men. The median procedure and ECMO durations were 10.8 hours (IQR 8.5-12.4 hours) and 2.2 hours (IQR 62-218 minutes), respectively. The median intensive care unit and hospital lengths of stay were 4 days (IQR 3-5 days) and 21 days (IQR 14-31 days), respectively. All 20 patients received packed cell transfusions (median 8 per patient [IQR 4-14]); 11 patients required fresh frozen plasma, 6 required platelets, and 11 required fibrinogen supplementation. One patient required recombinant activated factor VII. Sixteen patients experienced acute kidney injury, with 12 patients progressing to chronic kidney disease. Three patients were required to return to the operating room within 7 days, with no returns within the first 24 hours. There was no in-hospital or 30-day mortality. Survival at 3 years was 84%. CONCLUSIONS: ECMO for resecting large retroperitoneal tumor resection was introduced successfully and facilitated satisfactory outcomes for many patients who might otherwise have been considered too high risk.

Engineering Heart Valve Interfaces Using Melt Electrowriting: Biomimetic Design Strategies from Multi-Modal Imaging.

Interfaces within biological tissues not only connect different regions but also contribute to the overall functionality of the tissue. This is especially true in the case of the aortic heart valve. Here, melt electrowriting (MEW) is used to engineer complex, user-defined, interfaces for heart valve scaffolds. First, a multi-modal imaging investigation into the interfacial regions of the valve reveals differences in collagen orientation, density, and recruitment in previously unexplored regions including the commissure and inter-leaflet triangle. Overlapping, suturing, and continuous printing methods for interfacing MEW scaffolds are then investigated for their morphological, tensile, and flexural properties, demonstrating the superior performance of continuous interfaces. G-codes for MEW scaffolds with complex interfaces are designed and generated using a novel software and graphical user interface. Finally, a singular MEW scaffold for the interfacial region of the aortic heart valve is presented incorporating continuous interfaces, gradient porosities, variable layer numbers across regions, and tailored fiber orientations inspired by the collagen distribution and orientation from the multi-modal imaging study. The scaffold exhibits similar yield strain, hysteresis, and relaxation behavior to porcine heart valves. This work demonstrates the ability of a bioinspired approach for MEW scaffold design to address the functional complexity of biological tissues.