A Mechanistic and Preclinical Assessment of BioRestore Bioactive Glass as a Synthetic Bone Graft Extender and Substitute for Osteoinduction and Spine Fusion.

STUDY DESIGN: Preclinical animal study. OBJECTIVE: Evaluate the osteoinductivity and bone regenerative capacity of BioRestore bioactive glass. SUMMARY OF BACKGROUND DATA: BioRestore is a Food and Drug Administration (FDA)-approved bone void filler that has not yet been evaluated as a bone graft extender or substitute for spine fusion. METHODS: In vitro and in vivo methods were used to compare BioRestore with other biomaterials for the capacity to promote osteodifferentiation and spinal fusion. The materials evaluated (1) absorbable collagen sponge (ACS), (2) allograft, (3) BioRestore, (4) Human Demineralized Bone Matrix (DBM), and (5) MasterGraft. For in vitro studies, rat bone marrow-derived stem cells (BMSC) were cultured on the materials in either standard or osteogenic media (SM, OM), followed by quantification of osteogenic marker genes ( Runx2, Osx, Alpl, Bglap, Spp1 ) and alkaline phosphatase (ALP) activity. Sixty female Fischer rats underwent L4-5 posterolateral fusion (PLF) with placement of 1 of 5 implants: (1) ICBG from syngeneic rats; (2) ICBG+BioRestore; (3) BioRestore alone; (4) ICBG+Allograft; or (5) ICBG+MasterGraft. Spines were harvested 8 weeks postoperatively and evaluated for bone formation and fusion via radiography, blinded manual palpation, microCT, and histology. RESULTS: After culture for 1 week, BioRestore promoted similar expression levels of Runx2 and Osx to cells grown on DBM. At the 2-week timepoint, the relative ALP activity for BioRestore-OM was significantly higher ( P <0.001) than that of ACS-OM and DBM-OM ( P <0.01) and statistically equivalent to cells grown on allograft-OM. In vivo, radiographic and microCT evaluation showed some degree of bridging bone formation in all groups tested, with the exception of BioRestore alone, which did not produce successful fusions. CONCLUSIONS: This study demonstrates the capacity of BioRestore to promote osteoinductivity in vitro. In vivo, BioRestore performed similarly to commercially available bone graft extender materials but was incapable of producing fusion as a bone graft substitute. LEVEL OF EVIDENCE: Level V.

Auxochrome Dimethyl-Dihydroacridine Improves Fluorophores for Prolonged Live-Cell Super-Resolution Imaging.

Superior photostability, minimal phototoxicity, red-shifted absorption/emission wavelengths, high brightness, and an enlarged Stokes shift are essential characteristics of top-tier organic fluorophores, particularly for long-lasting super-resolution imaging in live cells (e.g., via stimulated emission depletion (STED) nanoscopy). However, few existing fluorophores possess all of these properties. In this study, we demonstrate a general approach for simultaneously enhancing these parameters through the introduction of 9,9-dimethyl-9,10-dihydroacridine (DMA) as an electron-donating auxochrome. DMA not only induces red shifts in emission wavelengths but also suppresses photooxidative reactions and prevents the formation of triplet states in DMA-based fluorophores, greatly improving photostability and remarkably minimizing phototoxicity. Moreover, the DMA group enhances the fluorophores' brightness and enlarges the Stokes shift. Importantly, the "universal" benefits of attaching the DMA auxochrome have been exemplified in various fluorophores including rhodamines, difluoride-boron complexes, and coumarin derivatives. The resulting fluorophores successfully enabled the STED imaging of organelles and HaloTag-labeled membrane proteins.

The Irish Trainee Emergency Research Network (ITERN): five years of collaboration.

In 2018, a group of Irish emergency medicine (EM) trainees recognised their common interest in collaborative research and the difficulties that trainees can encounter when trying to broaden their research capacity, prompting the beginning of the Irish Trainee Emergency Research Network (ITERN) journey. Trainee-led collaboratives have been shown to be feasible and have the potential to deliver impactful research projects, generating an evidence base that may not have been possible without collaboration. This article describes the successes and achievement of ITERN and describes the processes and challenges that a trainee-led research network can encounter. The authors believe that trainee-led collaboratives can deliver powerful and impactful research for patients and broaden the research capacity of individuals, hospitals, and groups of healthcare professionals.

Attitudes and knowledge of emergency doctors towards end-of-life care in the emergency department: a national survey.

BACKGROUND: Emergency departments (EDs) are seeing an increase in patients requiring end-of-life (EOL) care. There is paucity of data of attitudes and knowledge of physicians providing EOL care in the ED both internationally and in Ireland. OBJECTIVE: The aim of this project was to assess the attitudes and knowledge of ED physicians towards EOL care. METHODS: This was a cross-sectional electronic survey of ED physicians working in Irish EDs and was facilitated through the Irish Trainee Emergency Research Network over a 6-week period. The questionnaire covered the following domains: demographic data, awareness of EOL Care, views and attitudes towards EOL care. RESULTS: Of a potential 679 respondents, 441 responses were received, of which 311 (response rate of 44.8%) had fully completed the survey across 23 participant sites. Majority of the respondents were under the age of 35 (62%), were male (58%) and at Senior House Officer level (36%). In terms of awareness, 32% (98) of respondents were not aware of palliative care services in their hospitals while only 29% (91) were aware of national EOL guidance. Fifty-five percent (172) reported commencing EOL care in the ED, however 75.5% (234) respondents reported their knowledge of EOL care to be limited or non-existent. Only 30.2% respondents felt comfortable commencing EOL care in the ED without speciality team input. There appears to be a lack of clarity on the roles and responsibilities of emergency medicine nurses and doctors in the care of the dying patient in ED with only 31.2% (95) being clear on this role. Significant differences were observed associated with clinical experience and physician grade. CONCLUSION: This study has highlighted a lack of awareness and knowledge of EOL care particularly amongst less experienced emergency medicine doctors. Formalized training and education programs in the provision of EOL care in the ED will improve comfort levels and knowledge amongst the emergency medicine doctors and improve the quality of care provided.

Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

Three birds one stone: an enzyme-activatable theragnostic agent for fluorescence diagnosis, photodynamic and inhibitor therapies.

AX11890, an inhibitor of overexpressed enzyme, KIAA1363, in some breast cancers, was conjugated with a benzo[a]phenothiazinium photosensitizer to develop a tumor micro-environment-responsive photosensitizer NBS-L-AX. In normal cells, the special geometry of NBS-L-AX causes the fluorescence and photodynamic therapeutic (PDT) effect of NBS-L to be quenched. In cancer cells, when allowed to interact with the enzyme KIAA1363, the geometry of NBS-L-AX changes such that it becomes fluorescent and photodynamically active. Thus, the material of NBS-L-AX serves as an activated imaging and PDT treatment agent for breast cancers. In addition, NBS-L-AX also shows a selective inhibition effect against breast cancer cells.

Cardiovascular imaging techniques for the assessment of coronary artery disease.

Coronary artery disease continues to be the leading cause of morbidity and mortality worldwide. Recent clinical trials have not demonstrated any mortality benefit of percutaneous coronary intervention compared to medical management alone in the treatment of stable angina. While invasive coronary angiography remains the gold standard for diagnosing coronary artery disease, it comes with significant risks, including myocardial infarction, stroke and death. There have been significant advances in imaging techniques to diagnose coronary artery disease in haemodynamically stable patients. The latest National Institute for Health and Care Excellence and European College of Cardiology guidelines emphasise the importance of using these imaging techniques first to inform diagnosis. This review discusses these guidelines and imaging techniques, alongside their benefits and drawbacks.

Sex-based Difference in Response to Recombinant Human Bone Morphogenetic Protein-2 in a Rat Posterolateral Fusion Model.

STUDY DESIGN: This was a preclinical study. OBJECTIVE: Evaluate sex-dependent differences in the bone healing response to recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat posterolateral spinal fusion model. SUMMARY OF BACKGROUND DATA: Minimal and conflicting data exist concerning potential sex-dependent differences in rhBMP-2-mediated bone regeneration in the context of spinal fusion. MATERIALS AND METHODS: Forty-eight female and male Sprague-Dawley rats (N=24/group), underwent L4-L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge, each loaded with 5 µg of bone morphogenetic protein-2 (10 µg/animal). At eight weeks postoperative, 10 specimens of each sex were tested in flexion-extension with quantification of range of motion and stiffness. The remaining specimens were evaluated for new bone growth and successful fusion via radiography, blinded manual palpation and microcomputed tomography (microCT). Laboratory microCT quantified bone microarchitecture, and synchrotron microCT examined bone microstructure at the 1 µm level. RESULTS: Manual palpation scores differed significantly between sexes, with mean fusion scores of 2.4±0.4 in females versus 3.1±0.6 in males ( P <0.001). Biomechanical stiffness did not differ between sexes, but range of motion was significantly greater and more variable for females versus males (3.7±5.6° vs. 0.27±0.15°, P <0.005, respectively). Laboratory microCT showed significantly smaller volumes of fusion masses in females versus males (262±87 vs. 732±238 mm 3 , respectively, P <0.001) but significantly higher bone volume fraction (0.27±0.08 vs. 0.12±0.05, respectively, P <0.001). Mean trabecular thickness was not different, but trabecular number was significantly greater in females (3.1±0.5 vs. 1.5±0.4 mm -1 , respectively, P <0.001). Synchrotron microCT showed fine bone structures developing in both sexes at the eight-week time point. CONCLUSIONS: This study demonstrates sex-dependent differences in bone regeneration induced by rhBMP-2. Further investigation is needed to uncover the extent of and mechanisms underlying these sex differences, particularly at different doses of rhBMP-2.

National Emergency Resuscitation Airway Audit (NERAA): a pilot multicentre analysis of emergency intubations in Irish emergency departments.

BACKGROUND: There is paucity of literature on why and how patients are intubated, and by whom, in Irish Emergency Departments (EDs). The aim of this pilot study was to characterise emergency airway management (EAM) of critically unwell patients presenting to Irish EDs. METHODS: A multisite prospective pilot study was undertaken from February 10 to May 10, 2020. This project was facilitated through the Irish Trainee Emergency Research Network (ITERN). All patients over 16 years of age requiring EAM were included. Eleven EDs participated in the project. Data recorded included patients' demographics, indication for intubation, technique of airway management, medications used to facilitate intubation, level of training and specialty of the intubating clinician, number of attempts, success/complications rates and variation across centres. RESULTS: Over a 3-month period, 118 patients underwent 131 intubation attempts across 11 EDs. The median age was 57 years (IQR: 40-70). Medical indications were reported in 83% of patients compared to 17% for trauma. Of the 118 patients intubated, Emergency Medicine (EM) doctors performed 54% of initial intubations, while anaesthesiology/intensive care medicine (ICM) doctors performed 46%. The majority (90%) of intubating clinicians were at registrar level. Emergency intubation check lists, video laryngoscopy and bougie were used in 55, 53 and 64% of first attempts, respectively. The first pass success rate was 89%. Intubation complications occurred in 19% of patients. EM doctors undertook a greater proportion of intubations in EDs with > 50,000 attendance (65%) compared to EDs with < 50,000 attendances (16%) (p < 0.000). CONCLUSION: This is the first study to describe EAM in Irish EDs, and demonstrates comparable first pass success and complication rates to international studies. This study highlights the need for continuous EAM surveillance and could provide a vector for developing national standards for EAM and EAM training in Irish EDs.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

A comparison of intra-operative diagnosis to histopathological diagnosis of acute appendicitis in paediatric and adult cohorts: an analysis of over 1000 patients.

BACKGROUND: Appendicitis is a common general surgical emergency. The role of removing a normal appendix is debated. However, this relies on accurate intra-operative diagnosis of a normal appendix by the operating surgeon. This study aimed to compare surgeon's intra-operative assessment to final histological result acute appendicitis in paediatric and adult patients. METHODS: All patients who underwent appendicectomy over a 14-year period in a general surgical department were identified using the prospective Lothian Surgical Audit system and pathology reports retrieved to identify final histological diagnosis. Open appendicectomy was selected to examine, as the routine practise at our institution is to remove a normal appendix at open appendicectomy. RESULTS: A total of 1035 open appendicectomies were performed for clinically suspected appendicitis. Sensitivity of intra-operative diagnosis of appendicitis with operating surgeon was high at 95.13% with no difference between trainee and consultant surgeon or between adult and paediatric cases. Specificity of intra-operative diagnosis was lower in the paediatric group (32.58%) than in the adult group (40.58%). Women had a higher rate of negative appendicectomy than men. CONCLUSION: The results of this study highlight some discordance between histological evidence of acute appendicitis and intra-operative impression. Therefore other clinical variables and not just macroscopic appearance alone should be used when deciding to perform appendicectomy.

Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors.

The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole 23 (GSK809) and furan 24 (GSK743) that were derived from the pyrrole fragment 6. We transpose the key learnings from a previous pyridone series (GSK620 2 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research.

Psychological distress and trauma in doctors providing frontline care during the COVID-19 pandemic in the United Kingdom and Ireland: a prospective longitudinal survey cohort study.

OBJECTIVES: The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported. DESIGN: A prospective online three-part longitudinal survey. SETTING: Acute hospitals in the UK and Ireland. PARTICIPANTS: Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020. PRIMARY OUTCOME MEASURES: Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised. RESULTS: The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10). CONCLUSION: Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care. TRIAL REGISTRATION NUMBER: ISRCTN10666798.

Psychological distress during the acceleration phase of the COVID-19 pandemic: a survey of doctors practising in emergency medicine, anaesthesia and intensive care medicine in the UK and Ireland.

OBJECTIVE: To quantify psychological distress experienced by emergency, anaesthetic and intensive care doctors during the acceleration phase of COVID-19 in the UK and Ireland. METHODS: Initial cross-sectional electronic survey distributed during acceleration phase of the first pandemic wave of COVID-19 in the UK and Ireland (UK: 18 March 2020-26 March 2020 and Ireland: 25 March 2020-2 April 2020). Surveys were distributed via established specialty research networks, within a three-part longitudinal study. Participants were doctors working in emergency, anaesthetic and intensive medicine during the first pandemic wave of COVID-19 in acute hospitals across the UK and Ireland. Primary outcome measures were the General Health Questionnaire-12 (GHQ-12). Additional questions examined personal and professional characteristics, experiences of COVID-19 to date, risk to self and others and self-reported perceptions of health and well-being. RESULTS: 5440 responses were obtained, 54.3% (n=2955) from emergency medicine and 36.9% (n=2005) from anaesthetics. All levels of doctor seniority were represented. For the primary outcome of GHQ-12 score, 44.2% (n=2405) of respondents scored >3, meeting the criteria for psychological distress. 57.3% (n=3045) had never previously provided clinical care during an infectious disease outbreak but over half of respondents felt somewhat prepared (48.6%, n=2653) or very prepared (7.6%, n=416) to provide clinical care to patients with COVID-19. However, 81.1% (n=4414) either agreed (31.1%, n=2709) or strongly agreed (31.1%, n=1705) that their personal health was at risk due to their clinical role. CONCLUSIONS: Findings indicate that during the acceleration phase of the COVID-19 pandemic, almost half of frontline doctors working in acute care reported psychological distress as measured by the GHQ-12. Findings from this study should inform strategies to optimise preparedness and explore modifiable factors associated with increased psychological distress in the short and long term. TRIAL REGISTRATION NUMBER: ISRCTN10666798.

Axillary artery and brachial plexus injury secondary to blunt trauma.

Rupture of the axillary artery in the absence of a fracture of dislocation is a rare traumatic event. An associated injury to the brachial plexus may accompany an axillary artery injury but has rarely been reported in the literature. We present the case of an elderly female, who fell onto an outstretched arm and sustained an axillary artery rupture, combined with a brachial plexus injury. The patient in this case did well post-operatively. The challenge in these cases is early recognition and diagnosis of a vascular injury. A significant mechanism of injury needs to alert the clinician to the possibility of such injuries and if suspected, early investigation and surgical exploration should be initiated to prevent limb ischemia. Subsequently, if the neurological symptoms do not improve, consideration must be given to the possibility of a nerve injury and early recognition and management to prevent long-term functional deficits.

Cost-effectiveness of cardiovascular imaging for stable coronary heart disease.

OBJECTIVE: To assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD): (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care. METHODS: Using UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016-2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups. RESULTS: CMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (-0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups. CONCLUSIONS: CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.

Feasibility and reproducibility of a cardiovascular magnetic resonance free-breathing, multi-shot, navigated image acquisition technique for ventricular volume quantification during continuous exercise.

BACKGROUND: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise. METHODS: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Images were acquired at 3-stages, baseline and during steady-state exercise at 55% and 75% maximal heart rate (HRmax), based on a prior supine cardiopulmonary exercise test. Intra-and inter-observer variability and inter-scan reproducibility were derived. Clinical feasibility was tested in a separate cohort of patients with severe mitral regurgitation (n=6). RESULTS: End-diastolic volume (EDV) of both LV and RV decreased during exercise at 55% and 75% HRmax, although a reduction in RVEDV index was only observed at 75% HRmax. Ejection fractions (EF) for both ventricles were significantly higher at 75% HRmax compared to their respective baselines (LVEF 68%±3% vs. 58%±5%, P=0.001; RVEF 66%±4% vs. 58%±7%, P=0.02). Intra-observer and inter-observer reproducibility of LV parameters was excellent at all 3-stages. Although measurements of RVESV were more variable during exercise, the reproducibility of both RVEF and RV cardiac index was excellent (CV <10%). Inter-scan LV and RV ejection fraction were highly reproducible at all 3 stages, although inter-scan reproducibility of indexed RVESV was only moderate. The protocol was well tolerated by all patients. CONCLUSIONS: Exercise CMR using a free-breathing, multi-shot, navigated cine imaging method allows simultaneous assessment of left and right ventricular volumes during continuous exercise. Intra- and inter-observer reproducibility were excellent. Inter-scan LV and RV ejection fraction were also highly reproducible.