Evolution of T cells in the cancer-resistant naked mole-rat.

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.

Cultivating Competency in Cardiac Sonography: Aligning Entrustable Professional Activities With Industry Expectations.

BACKGROUND & AIM: Echocardiography education involves the teaching and assessment of multiple competencies to ensure work-ready graduates. To connect these competency standards to professional practice, it is important that the industry expectation around specific entrustable professional activities (EPAs) is determined. In Australia, echocardiography examinations are eligible for Medicare reimbursement when performed by sonographers listed on the Australian Sonographers Accreditation Registry (ASAR), either as an Accredited Medical Sonographer or as an Accredited Student Sonographer. A key criterion for acceptance onto the registry is the completion of, or active enrolment in, an accredited cardiac sonography course. Eligible courses apply for accreditation and are assessed by ASAR against their Standards for Accreditation of Sonographer Courses. This study sought to investigate the existing cardiac EPAs and provide insights into the industry's expectations for graduate cardiac sonographers in Australia. METHODS: Using an anonymous online survey tool, an invitation to participate was circulated via professional sonography groups and social media platforms. Accredited Medical Sonographers, Accredited Student Sonographers or interested stakeholders (academic, employer, medical specialist) working in Australia or New Zealand were invited to complete the survey. Survey questions were structured around the existing EPAs and knowledge items described in published sonography competency documents. Participants were asked if each individual EPA should be considered appropriate at the threshold of graduation, or at a higher level following a period of working in the profession. RESULTS: There were 211 cardiac sonographers who completed the survey. The majority of respondents (148 of 211, 72.2%) indicated that the current EPAs should be updated. At 80% agreement, the following EPAs were considered essential for the graduate: left ventricular structure and function, right ventricular structure and function, atrial size, valvular disease, systemic hypertension, cardiomyopathies, diseases of the aorta, coronary artery disease, pulmonic hypertension, and basic congenital heart disease. This list is more extensive than the current ASAR-endorsed EPAs, and the findings in this research will guide the revision of current ASAR-endorsed EPAs for graduate-level cardiac sonography. CONCLUSIONS: The results of this study show Accredited Medical Sonographers completing a cardiac sonography course in Australia should be entrusted to perform a wide range of examinations however, greater alignment between educational providers, ASAR and industry is still required.

Impact of Aerobic Training on Cardiovascular Function, Fitness, and Patient Reported Outcomes During Anthracycline Chemotherapy: A Case Series in Women With Breast Cancer.

BACKGROUND: Chemotherapy for breast cancer can increase the risk of cancer therapy related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD, however, research to date has indicated high degrees of individual variability following exercise interventions in this population. AIM: This study aimed to explore the impact of regular, individualized aerobic exercise on CTRCD incidence (defined by global longitudinal strain [GLS]) during and immediately upon the completion of dose-dense anthracycline (DDAC) chemotherapy in 5 women with breast cancer. METHODS: Five women receiving DDAC with stage I-III breast cancer enrolled. Participants underwent resting echocardiography and exercise testing before, during, upon the completion of, and 3 months after the completion of DDAC treatment to measure GLS and aerobic fitness (VO2peak). Participants opted-in to an individualized 8-week aerobic exercise intervention (3 sessions per week, 24 sessions total) or standard care for the duration of their DDAC treatment. Data for each participant were presented descriptively. RESULTS: Four of the 5 participants completed the exercise intervention during DDAC treatment (adherence 79.2%-91.7%). Mild asymptomatic CTRCD occurred in 2 of the 4 exercising participants, of whom both were at an increased risk (one was >65 years of age and diagnosed with hypertension, with the other receiving trastuzumab prior to DDAC treatment). Varied responses in VO2peak were observed and did not align with changes in GLS. The only participant not to complete the exercise intervention reported poorer health related quality of life and increased cancer related fatigue at all measurement timepoints. CONCLUSION: This study details the individual variability in cardiovascular responses to exercise that can occur during DDAC treatment in women with breast cancer, which can inform exercise professionals and researchers when designing individualized exercise programs for this population.

How do practitioners prescribe exercise to patients with breast cancer? Professional perspectives on the key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy.

OBJECTIVES: This study aimed to understand the key factors experienced accredited exercise physiologists (AEPs) and medical professionals consider when prescribing/recommending aerobic exercise to patients with breast cancer undergoing chemotherapy. DESIGN: Modified Delphi Survey. METHODS: A four-round, two-phase survey was conducted. Following a Delphi approach, four cancer-specific AEPs, four oncologists, and one breast cancer surgeon (median 13-yr breast-cancer-specific experience) completed phase one. Eighty-four AEPs (median 5-yr experience) completed phase two. Phase one participants answered open- and close-ended questions regarding key considerations for aerobic exercise in patients with breast cancer undergoing chemotherapy, and what information should be collected to guide exercise prescription. All questions and considerations agreed upon in phase one (>70 % rating 7-9 on a 0-9 Likert Scale) were rated by AEPs in phase two. RESULTS: Key considerations for exercise assessment and prescription aligned closely with exercise guidelines for cancer survivors. Common strategies for exercise individualisation were identified by AEPs, including separating aerobic exercise into 5-to--9-minute bouts when required and avoiding exercising to complete exhaustion. Exercise intensity and duration should be adjusted throughout chemotherapy to improve tolerance and adherence. Novel considerations for subjective questioning and objective assessments to tailor exercise prescription were outlined. CONCLUSIONS: This study identifies how professionals approach exercise assessment and prescription in patients with breast cancer undergoing chemotherapy. Findings can guide AEPs in practice when prescribing tailored exercise to breast cancer patients undergoing chemotherapy and inform future guidelines.

Including Community Partners in the Development and Adaptation of Intervention Strategies to Prevent Initiation or Escalation of Opioid Misuse.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

Acute Aortic Injury and Bilateral Pulmonary Emboli in the Setting of COVID-19.

In this report, we present the case of a 72-year-old female diagnosed with an aortic dissection variant and bilateral pulmonary emboli (PE) in the setting of Coronavirus Disease of 2019 (COVID-19) infection. The patient was transported from home to the emergency department (ED) via emergency medical services (EMS) with acute chest pain and dyspnea. After arriving at the ED, she was hypoxic on her baseline supplemental O2 requirement and tachycardic and tachypneic. Computed tomography (CT) angiogram of the chest showed evidence of possible thoracic aortic dissection and bilateral PE. The patient was ultimately transported to a tertiary center for operative aortic repair and bilateral embolectomy and, fortunately, survived the procedures. Interestingly, during operative repair of the aorta, no obvious dissection flap was noted, but rather evidence of a limited tear in the intimal layer of the aorta. This is an interesting case as acute aortic injuries in the setting of COVID-19 infection have not been as widely documented as PE in the setting of COVID and highlight the need for further research on the possible association between them.

Improving Research on Racial Disparities in Access to Medications to Treat Opioid Use Disorders.

OBJECTIVES: The aims of the study are to review the current research on the association between access to medications for opioid use disorders (MOUD) and race, to identify gaps in research methods, and to propose new approaches to end racialized disparities in access to MOUD. METHODS: We conducted a literature review of English language peer-reviewed published literature from 2010 to 2021 to identify research studies examining the association between race and use of, or access to, MOUD. RESULTS: We reviewed 21 studies related to access to MOUD for Black and White populations. Of the 21 studies, 16 found that Black individuals had lower use of, or access to, MOUD than White individuals, 2 found the opposite among patients in specialty addiction treatment, 1 found that the difference changed over time, and 2 found that distance to opioid treatment programs was shorter for Black residents than for White residents. CONCLUSIONS: To improve future research, we recommend that researchers (1) be clearer on how race is conceptualized and interpreted; (2) explicitly evaluate the intersection of race and other factors that may influence access such as income, insurance status, and geography; (3) use measures of perceived racism, unconscious bias, and self-identified race; (4) collect narratives to better understand why race is associated with lower MOUD access and identify solutions; and (5) evaluate the effect of policies, programs, and clinical training on reducing racial disparities. A multitude of studies find that Black individuals have lower access to MOUD. Researchers must now identify effective solutions for reducing these disparities.

Atypical Presentation of Carbon Monoxide Poisoning With Aphasia.

We present a patient with carbon monoxide poisoning with a single focal neurological deficit. The patient was found by emergency medical services (EMS) to be resting in his truck with a generator running nearby. On arrival, the patient was hemodynamically stable. The patient was aphasic but did not exhibit any other focal or lateralizing deficits. He was able to communicate by writing clearly and coherently on a sheet of paper. His initial carboxyhemoglobin was 29%, confirming the diagnosis of carbon monoxide poisoning. He was treated with 100% O2 via a non-rebreather mask and regained his speech during his ED (emergency department) course. The patient was ultimately hospitalized for continued oxygen treatment and serial examinations. This case highlights the varied presenting symptoms of carbon monoxide poisoning as well as the importance of including a broad differential diagnosis while working up patients with a focal neurologic deficit.

Entrustable professional activities of graduate accredited General Medical Sonographers in Australia - Industry perceptions.

INTRODUCTION: Linking individual competencies to entrustable professional tasks provides a holistic view of Sonography graduate work readiness. The Australian Sonographers Accreditation Registry (ASAR) publishes a set of entrustable professional activities (EPAs) as part of its Standards for Accreditation of Sonography Courses. EPAs are distinct ultrasound examinations grouped within six critical practice units. This study reports on industry perspectives of current EPAs and their classification for graduates completing general sonography courses in Australia. The article also examines the value of EPAs and links their function to the assessment of graduate competency. METHODS: An online survey tool elicited stakeholder feedback on graduate EPAs across six critical practice units and the potential for including a new Paediatric unit. From an original sample size of 655, 309 responded to questions about general sonography courses. RESULTS: A majority (55.3%) recommended no changes to the existing EPA list, and 44.7% recommended amending the list. From respondents that recommended changes (138/309), all current EPAs received >80% agreement to be retained; in addition, nine new examinations received >70% agreement for inclusion at the graduate level. Whilst 42.7% (132/309) supported the current ASAR model requiring competency in five out of six critical practice units, 45.6% (141/309) recommended increasing it to all six. There was limited support, 11.7% (36/309), to reduce this number. Responding to the potential to add a new Paediatric specific critical practice unit, 61.8% (181/293) recommended its inclusion. CONCLUSIONS: The findings demonstrate that the current list of EPAs aligns with industry expectations. In contrast, there are divergent views on the modelling and grouping of critical practice units. The article's critical analysis of the results and implications provides stakeholders with a practical approach to clinical teaching and EPA assessment, and helps to inform any review of accreditation standards.

Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.

BACKGROUND: Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. METHODS: In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. RESULTS: Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. CONCLUSIONS: Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.

Impact of Left Ventricular Ejection Fraction on Clinical Outcomes in Bicuspid Aortic Valve Disease.

BACKGROUND: The prognostic impact of left ventricular ejection fraction (LVEF) in patients with bicuspid aortic valve (BAV) disease has not been previously studied. OBJECTIVES: The purpose of this study was to determine the prognostic impact of LVEF in BAV patients according to the type of aortic valve dysfunction. METHODS: We retrospectively analyzed the data collected in 2,672 patients included in an international registry of patients with BAV. Patients were classified according to the type of aortic valve dysfunction: isolated aortic stenosis (AS) (n = 749), isolated aortic regurgitation (AR) (n = 554), mixed aortic valve disease (MAVD) (n = 190), or no significant aortic valve dysfunction (n = 1,179; excluded from this analysis). The study population was divided according to LVEF strata to investigate its impact on clinical outcomes. RESULTS: The risk of all-cause mortality and the composite endpoint of aortic valve replacement or repair (AVR) and all-cause mortality increased when LVEF was <60% in the whole cohort as well as in the AS and AR groups, and when LVEF was <55% in MAVD group. In multivariable analysis, LVEF strata were significantly associated with increased rate of mortality (LVEF 50%-59%: HR: 1.83 [95% CI: 1.09-3.07]; P = 0.022; LVEF 30%-49%: HR: 1.97 [95% CI: 1.13-3.41]; P = 0.016; LVEF <30%: HR: 4.20 [95% CI: 2.01-8.75]; P < 0.001; vs LVEF 60%-70%, reference group). CONCLUSIONS: In BAV patients, the risk of adverse clinical outcomes increases significantly when the LVEF is <60%. These findings suggest that LVEF cutoff values proposed in the guidelines to indicate intervention should be raised from 50% to 60% in AS or AR and 55% in MAVD.

Infants With Torticollis Who Changed Head Presentation During A Physical Therapy Episode.

PURPOSE: The purpose of this study is to describe infants with congenital muscular torticollis (CMT) who changed head presentation during an episode of physical therapy. METHODS: Data were extracted from electronic medical records between January 2015 and December 2018 to describe infants with CMT who changed presentation. RESULTS: Eighty-nine infants met criteria (predominantly male, non-Hispanic, White, with private insurance). Torticollis symptoms were noticed by 3 months in 90% of infants with a physical therapy examination before 6 months in 100% of infants. Most infants had early mild CMT with abnormal head shape and greater limitation in active cervical range of motion (ROM) than passive cervical ROM. Clinicians frequently recommended weekly physical therapy that included first- choice and supplemental interventions. Episodes of care averaged 7 visits over 64 days with 73% of infants meeting goals. CONCLUSION: Physical therapists should recognize that infants with CMT may change presentation but benefit from physical therapy to resolve symptoms.Digital Abstract available at: http://links.lww.com/PPT/A366.

The effect of exercise on left ventricular global longitudinal strain.

Exercise improves measures of cardiovascular (CV) health and function. But as traditional measures improve gradually, it can be difficult to identify the effectiveness of an exercise intervention in the short-term. Left ventricular global longitudinal strain (LVGLS) is a highly sensitive CV imaging measure that detects signs of myocardial dysfunction prior to more traditional measures, with reductions in LVGLS a strong prognostic indicator of future CV dysfunction and mortality. Due to its sensitivity, LVGLS may offer useful method of tracking the effectiveness of an exercise intervention on CV function in the short-term, providing practitioners useful information to improve patient care in exercise settings. However, the effect of exercise on LVGLS is unclear. This systematic review and meta-analysis aimed to determine the effect exercise has on LVGLS across a range of populations. Included studies assessed LVGLS pre-post an exercise intervention (minimum 2 weeks) in adults 18 years and over, and were published in English from 2000 onwards. Study-level random-effects meta-analyses were performed using Stata (v16.1) to calculate summary standardized mean differences (SMD) and 95% confidence intervals (CI). 39 studies met selection criteria, with 35 included in meta-analyses (1765 participants). In primary analyses, a significant improvement in LVGLS was observed in populations with CV disease (SMD = 0.59; 95% CI 0.16-1.02; p = 0.01), however, no significant effect of exercise was observed in CV risk factor and healthy populations. In populations with CV disease, LVGLS could be used as an early biomarker to determine the effectiveness of an exercise regime before changes in other clinical measures are observed.

The impact of breast cancer on fears of exercise and exercise identity.

OBJECTIVES: Low exercise adherence is common amongst breast cancer (BC) patients. This study aimed to understand BC patients exercise identity and fears of exercise to identify barriers to exercise participation. METHODS: Women (18 years plus) currently undergoing, or completed (in remission), chemotherapy for BC, and women (18 years plus) with no cancer history completed three validated questionnaires: Exercise Identity Scale (EI), Exercise Fear Avoidance Scale (EFAS) and Fear of Physical Activity/Exercise Scale - Breast Cancer. RESULTS: 86 women were included (BC: n = 51 - non-cancer: n = 35). There were no significant differences between groups when comparing overall EI (p = 0.240; d=0.127) and EFAS (p = 0.060; d=0.203) scores. BC reported significantly higher scores on specific questions related to fear during exercise (EFAS 2,3, and 5; p = <0.005). Associations were observed between EI and EFAS questionnaire scores in BC (r = -0.342; p = 0.014), and EI scores and exercise levels in both groups (BC, r = 0.527; p = <0.001; non-cancer, r = 0.639; p = <0.001). CONCLUSION: Results suggest women with BC may have specific concerns and fears of exercise compared to age-matched controls. Education may mitigate fears, increase exercise identity, and promote exercise uptake. PRACTICAL IMPLICATIONS: Education provided by clinicians at BC diagnosis regarding the benefits and safety of exercise may help mitigate fear and promote exercise identity.

A Case Report on Gastric Remnant Intussusception.

We present a case of intussusception of a gastric remnant in a patient years after undergoing a Billroth II procedure that was treated with esophagogastroduodenoscopy. Although rare in adults, intussusception has been documented with increasing frequency in adult patients who have undergone Billroth II, mini-gastric bypass, and Roux-en-Y gastric bypass surgery. Timely management can decrease damage due to ischemia.

The role of exercise in the prevention of cancer therapy-related cardiac dysfunction in breast cancer patients undergoing chemotherapy: systematic review.

AIMS: Breast cancer (BC) patients undergoing chemotherapy are at risk of developing cancer therapy-related cardiac dysfunction (CTRCD). Exercise has been proposed to prevent CTRCD; however, its effectiveness remains unclear. The aim of this systematic review was to establish the effect of exercise on global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) in BC patients undergoing chemotherapy, to determine if exercise can prevent the development of CTRCD. METHODS AND RESULTS: Four databases (Medline, Scopus, eMbase, SPORTDiscus) were searched. Studies were eligible for inclusion if they measured GLS or LVEF prior to and following an exercise intervention of any length in BC patients undergoing chemotherapy and were published in English from 2000 onwards. Risk of bias was evaluated using the QUADAS-2 tool. Of the 398 studies screened, eight were eligible. Changes were similar in exercising (EX) and non-exercising (CON) groups for GLS (EX: pre: -19.6 ± 0.4, post: -20.1 ± 1.0, CON: pre: -20.0 ± 0.4, post: -20.1 ± 1) and LVEF (EX: pre: 58.5 ± 4.1%, post: 58.6 ± 2%, CON: pre: 56.6 ± 4.2%, post: 55.6 ± 4.6%). Exercise maintained or improved peak oxygen uptake (VO2peak) during chemotherapy, while declines were observed in non-exercising groups. The included studies were limited by methodological deficiencies. CONCLUSION: The ability of exercise to prevent CTRCD is unclear. However, exercise positively impacts cardiorespiratory fitness in BC patients undergoing chemotherapy. Future research must address the methodological limitations of current research to understand the true effect of exercise in the prevention of CTRCD.

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

OBJECTIVE: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). METHODS: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. RESULTS: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. CONCLUSIONS: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Left ventricular remodelling in bicuspid aortic valve disease.

AIMS: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction. METHODS AND RESULTS: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD. CONCLUSIONS: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.

Right ventricular myocardial deoxygenation in patients with pulmonary artery hypertension.

BACKGROUND: In pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters. METHODS: We prospectively recruited 42 patients with right heart catheter (RHC) proven PAH and 11 healthy age matched controls. The CMR examination involved standard functional imaging, OS-CMR imaging and native T1 mapping. An ΔOS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at the inferior RV segment. RESULTS: The inferior RV ΔOS-CMR SI index was significantly lower in PAH patients compared with healthy controls (9.5 (- 7.4-42.8) vs 12.5 (9-24.6)%, p = 0.02). The inferior RV ΔOS-CMR SI had a significant correlation to RV inferior wall thickness (r = - 0.7, p < 0.001) and RHC mean pulmonary artery pressure (mPAP) (r = - 0.4, p = 0.02). Compared to healthy controls, patients with PAH had higher native T1 in the inferior RV wall: 1303 (1107-1612) vs 1232 (1159-1288)ms, p = 0.049. In addition, there was a significant difference in the inferior RV T1 values between the idiopathic PAH and systemic sclerosis associated PAH patients: 1242 (1107-1612) vs 1386 (1219-1552)ms, p = 0.007. CONCLUSION: Blunted OS-CMR SI suggests the presence of in-vivo microvascular RV dysfunction in PAH patients. The native T1 in the inferior RV segments is significantly increased in the PAH patients, particularly among the systemic sclerosis associated PAH group.

Atrial fibrosis and substrate based characterization in atrial fibrillation: Time to move forwards.

Atrial fibrillation (AF) is the most commonly encountered cardiac arrhythmia in clinical practice. However, current therapeutic interventions for atrial fibrillation have limited clinical efficacy as a consequence of major knowledge gaps in the mechanisms sustaining atrial fibrillation. From a mechanistic perspective, there is increasing evidence that atrial fibrosis plays a central role in the maintenance and perpetuation of atrial fibrillation. Electrophysiologically, atrial fibrosis results in alterations in conduction velocity, cellular refractoriness, and produces conduction block promoting meandering, unstable wavelets and micro-reentrant circuits. Clinically, atrial fibrosis has also linked to poor clinical outcomes including AF-related thromboembolic complications and arrhythmia recurrences post catheter ablation. In this article, we review the pathophysiology behind the formation of fibrosis as AF progresses, the role of fibrosis in arrhythmogenesis, surrogate markers for detection of fibrosis using cardiac magnetic resonance imaging, echocardiography and electroanatomic mapping, along with their respective limitations. We then proceed to review the current evidence behind therapeutic interventions targeting atrial fibrosis, including drugs and substrate-based catheter ablation therapies followed by the potential future use of electro phenotyping for AF characterization to overcome the limitations of contemporary substrate-based methodologies.