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Background Mobile valvular masses are often considered pathognomonic for infective endocarditis. We present a case of a young patient with mobile valvular masses in the context of myocarditis likely secondary to active ileal Crohn’s disease. Cardiac magnetic resonance (CMR) imaging was crucial in diagnosing and monitoring our patient. Case summary A 27-year-old woman presented with pleuritic chest pain, dyspnoea, and a 3-day history of fevers. She also reported a 2-month history of intermittent visual loss in her right eye. She had a history of histologically proven ileal Crohn’s disease, diagnosed 5 months prior. She was haemodynamically unstable on presentation. Abnormalities on a transthoracic echocardiogram necessitated a transoesophageal echocardiogram. After blood cultures were sent, the patient was commenced on empirical treatment for infective endocarditis with gentamicin and flucloxacillin. Eight days after her initial presentation, all blood cultures remained negative and she was changed to empirical treatment for culture negative endocarditis with ceftriaxone and vancomycin, according to local protocol. Despite 8 days of treatment for infective endocarditis she remained febrile. A CMR was organized on Day 9 and this showed myocarditis, which changed the treatment paradigm. She responded swiftly to steroids and anti-coagulation. Discussion In this case, echo-dense valvular lesions are not pathognomonic for infective endocarditis and a careful diagnostic process involving multi-modality imaging, including CMR, occurred to arrive at a diagnosis of myocarditis likely secondary to Crohn’s disease.

Cardiovascular magnetic resonance (CMR) has increasingly become a powerful imaging technique over the past few decades due to increasing knowledge about clinical applications, operator experience and technological advances, including the introduction of high field strength magnets, leading to improved signal-to-noise ratio. Its success is attributed to the free choice of imaging planes, the wide variety of imaging techniques, and the lack of harmful radiation. Developments in CMR have led to the accurate evaluation of cardiac structure, function and tissues characterisation, so this non-invasive technique has become a powerful tool for a broad range of cardiac pathologies. This review will provide an introduction of magnetic resonance imaging (MRI) physics, an overview of the current techniques and clinical application of CMR in structural heart disease, and illustrated examples of its use in clinical practice.

Atrial septal aneurysms (ASAs) are often seen during routine cardiac imaging, though their clinical relevance has been poorly defined. The aneurysmal, and often mobile, inter-atrial septum is frequently associated with other clinically relevant structural cardiac abnormalities, particularly patent foramen ovale (PFO). Whilst ASAs have previously been considered an incidental finding, a well-endowed atrial septum provides more than visual interest, including insights into atrial function and intra-atrial pressures, and has important clinical implications in PFO-associated stroke, migraines, and arrhythmias. This review outlines diagnostic challenges when assessing ASAs using all imaging modalities and the clinical implications of this common anatomical variant.

Background: People living with HIV (PLHIV) have a higher incidence of cardiovascular disease and complications after intervention, including in-stent thrombosis. The frequency of potential drug-drug interactions in the setting of acute coronary syndrome (ACS) with antiretroviral therapy (ART) and dual-antiplatelet therapy (DAPT) regimens remains unclear. We sought to determine the frequency of potential drug-drug interactions in a cohort of people living with HIV who were investigated for coronary disease and initiated on DAPT as per Australian ACS Guidelines. Methods: A retrospective audit was performed in a single tertiary hospital in PLHIV presenting with symptomatic coronary artery disease (CAD) receiving DAPT. Patients were grouped based on exposure to a protease inhibitor or efavirenz and etravirine, given that these were found to have the greatest potential interactions with DAPT. Results: Fifty-three patients received DAPT, of which 31 (58%) had a potential drug-drug interaction. Clopidogrel was the most frequent P2Y12 inhibitor prescribed, accounting for 47 (87%) of the interactions. Twenty-six patients were on a protease inhibitor, of which 21 (81%) had a potential drug-drug interaction. There were 11 instances of efavirenz and 3 of etravirine use, of which all resulted in potential drug-drug interactions (100%, respectively). Conclusion: Potential drug-drug interactions were very common in PLHIV needing DAPT. The widespread use of clopidogrel in DAPT regimens resulted in a high rate of drug-drug interactions. An awareness of interactions and guidelines around P2Y12 inhibitor selection may help reduce the rate of in-stent thrombosis for PLHIV and improve clinical outcomes.

Highlights • Aerobic exercise has been proposed to improve cognitive health, via brain structure. • 12-weeks of aerobic exercise did not change cognitive, grey or white matter measures. • Interventions may need to be longer lasting or multifactorial., While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% female), we compared the effects of a twelve-week aerobic training programme to a waitlist control condition on cardiorespiratory fitness, cognition and magnetic resonance imaging (MRI) outcomes. Cardiorespiratory fitness was assessed by VO2 max testing. Cognitive assessments spanned executive function, memory and processing speed. Structural MRI analysis included examination of hippocampal volume, and voxel-wise assessment of grey matter volumes using voxel-based morphometry. Diffusion tensor imaging analysis of fractional anisotropy, axial diffusivity and radial diffusivity was performed using tract-based spatial statistics. While the intervention successfully increased cardiorespiratory fitness, there was no evidence that the aerobic training programme led to changes in cognitive functioning or measures of brain structure in older adults. Interventions that are longer lasting, multi-factorial, or targeted at specific high-risk populations, may yield more encouraging results.

Purpose of review Atrial fibrillation is increasingly common in the ageing population. Patients with atrial fibrillation and HIV have a higher stroke risk, with guidelines recommending anticoagulation in the majority. Whilst anticoagulation options have diversified in the last decade for the general population, there is limited evidence for the safety and efficacy of these medications when used concurrently with antiretroviral therapy. We review the potential for patients with HIV on antiretroviral therapy to have direct-acting oral anticoagulations (DOACs). Recent findings Several case reports have been published in the past 5 years, as well as theoretical analyses of anticipated drug interactions, which provide a starting point to guide use of DOACs with antiretroviral medications. Summary Caution is needed when prescribing DOACs in patients with atrial fibrillation and HIV due to potential drug interactions. Studies are lacking and current advice is based on case reports, expert opinion and knowledge of theoretical interactions.

This series of review articles outlines the complex cause of HIV-related cardiovascular diseases (CVDs) particularly the interactions of viral factors, complications of antiviral therapy such as metabolic derangement, and chronic systemic inflammation. These factors, directly stemming from chronic HIV infection, are important in the pathogenesis of HIV-related CVD. Addressing each issue has likely underpinned the improved morbidity and increased life expectancy enjoyed by patients in the modern era of HIV management. The global management of HIV-related CVD may, however, be simpler than previously imagined, as the disease likely follows a pathway shared by multiple systemic diseases. Other chronic systemic diseases, including diabetes, rheumatoid arthritis, and autoimmune disease, share numerous pathophysiological mechanisms with HIV and provoke similar cardiac complications. CVD risk management in patients living with HIV (PLHIV) may be optimized by drawing upon existing knowledge of chronic systemic diseases which may open up new concepts in treatment and address the current shortfalls in cardiovascular management of PLHIV.

The indication for cardiac pacing has been reliant on electrocardiography and the severity of bradycardia symptom correlation ([1][1]). Cardiovascular magnetic resonance (CMR) is routinely used in the assessment and prognostication of cardiac disease, but the clinical usefulness in patients with

Background There is increasing evidence that patients with spontaneous coronary artery dissection (SCAD) have an underlying genetic susceptibility (Goel et al JAMA Intern Med175:821–826, 2015). Moreover, in a collaborative study involving 1,055 SCAD cases and 7,190 controls, we recently reported the first risk allele for SCAD, a variant (rs9349379-A) in the PHACTR1/EDN1 genetic locus (Adlam et al J Amer Coll Cardiol73:58–66, 2019). Purpose We sought to determine the clinical characteristics and initial genetic data for 11 families, in which more than one member has had an episode of SCAD. Methods Participants were recruited largely via a social media platform. Informed consent was obtained in all cases for analysis of genetic information using whole genome sequencing, as well as collection of clinical information. SCAD was confirmed by review of coronary angiogram images and clinical data collected by phone interview, as well as review of specialist letters and hospital records. Results Of 235 participants recruited to date, 23 cases showed familial clustering involving sister-sister pairs in six families, three first-degree cousins in one family (picture), two first-degree cousins in two families, a mother-son pair, and a family with concordant monozygotic twins, that is both twins having had SCAD. In an additional family, SCAD is discordant in monozygotic twins. A comparison of symptoms, age at SCAD, clinical syndrome, cardiovascular risk factors, SCAD risk factors, environmental triggers, SCAD location, acute management, left ventricular function and recurrent SCAD events in these families versus isolated cases, will be presented. Three sister-sister pairs have undergone whole genome sequencing and these data sets are undergoing segregation analysis to identify rare variants that are present exclusively in affected family members. Family E Pedigree. Shaded circles represent first cousins affected with SCAD. The top number represents age (in years) of the SCAD event and the bottom number represents current age (in years). Conclusions To our knowledge, this is the largest assembly of SCAD cases with familial clustering reported to date. It provides strong evidence supporting an underlying genetic basis for SCAD, which most likely is a multi-genic disorder that also involves important gene-environment interactions.

OBJECTIVES Theoretical and untested interactions between antiretrovirals and direct-acting oral anticoagulants have limited the use of this new class of anticoagulant in people with HIV infection. This case series, the first of its kind, reports on the successful concurrent use of the direct-acting oral anticoagulant dabigatran and antiretroviral therapy. METHODS This series involved 14 patients requiring anticoagulation for management of atrial fibrillation, who were either unable or unwilling to take warfarin, and who were receiving concurrent treatment for HIV infection. Participants were treated with dabigatran with dose monitoring to establish the safety and efficacy of concurrent use with antiretrovirals. All were commenced on 110 mg twice daily, increased to 150 mg twice daily if the trough level was < 69.3 ng/mL. RESULTS In the 14 patients treated with dabigatran and antiretrovirals, there were no thromboembolic or bleeding complications. Dabigatran treatment was discontinued in one patient because of undetectable dabigatran levels despite dose escalation. Dabigatran levels fell within the fivefold variance seen in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study at a dose of either 110 or 150 mg twice daily. CONCLUSIONS This case series represents the largest published population to date successfully receiving antiretroviral and direct-acting oral anticoagulant therapy. Given the significant health care burden faced by people living with HIV, the availability of safe anticoagulant therapy without the requirement for monitoring is an important option in this patient population.

Background Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity. Methods Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate. Results When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max. Conclusions Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

HIV infection is now considered a chronic, treatable disease, although treatment is associated with increased rates of coronary artery disease (CAD). Increased risk of CAD in HIV-infected patients has been associated with the inflammatory sequelae of the infection as well as the greater prevalence of cardiac risk factors in HIV-positive populations and the side effects of life-prolonging antiretroviral therapies. Patients with HIV infection now have a 1.5 to 2-fold greater risk of developing CAD compared with noninfected individuals, raising the independent risk of CAD in HIV infection to levels similar to those in diabetes. Despite this increased risk, screening and other adjuvant assessment tools are lacking. In this paper we explore the current climate of CAD in the contemporary HIV-infected population and look at the tools used in the assessment and management of patients as well as the limitations of these approaches for this at-risk population group.

Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.

Although people living with HIV (PLHIV) are approaching normal life expectancy, a limitation to achieving this goal is managing the higher prevalence of co-morbidities, including cardiovascular disease. Whilst ischaemic heart disease likely contributes to a large proportion of cardiac disease in the modern era of treatment, cardio-metabolic disease, including cardiac steatosis, akin to obesity-related heart disease, is also a possible mechanism of increased cardiac morbidity and mortality. HIV and other metabolic and inflammatory diseases affecting the heart, including obesity, share many cardio-metabolic abnormalities, with increased pericardial and myocardial fat content, in association with chronic systemic inflammatory changes and alterations in cardiac metabolism. Understanding the mechanisms of HIV-associated cardiac steatosis remains an important challenge, as managing the untreated metabolic and inflammatory precipitants may substantially improve cardiac outcomes for PLHIV.

Holloway, Cameron J., Andrew J. Murray, Kay Mitchell, Daniel S. Martin, Andrew W. Johnson, Lowri E. Cochlin, Ion Codreanu, Sundeep Dhillon, George W. Rodway, Tom Ashmore, Denny Z.H. Levett, Stefan Neubauer, Hugh E. Montgomery, Michael P.W. Grocott, and Kieran Clarke, on behalf of the Caudwell Xtreme Everest 2009 Investigators. Oral Coenzyme Q supplementation does not prevent cardiac alterations during a high altitude trek to Everest Base Camp. High Alt Med Biol 15:000—000, 2014.—Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure. Twenty-three volunteers (10 male, 13 female, 46±3 years) were recruited from the 2009 Caudwell Xtreme Everest Research Treks and studied before, and within 48 h of return from, a 17-day trek to Everest Base Camp, with subjects receiving either no intervention (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac morphology and function. Following altitude exposure, body mass fell by 3 kg in all subjects (p

Cardiac rehabilitation (CR) is an important tool for the secondary prevention of cardiac disease. Despite its proven effectiveness, CR remains vastly under-utilised especially amongst the most disadvantaged patients. As an adjunct to CR, the St Vincent's Heart Health website (SVHHH) was created by the St Vincent's Hospital CR team to provide information via simplified medical text, videos and animations. We evaluated the effectiveness of the website in educating patients about their heart condition.Patients with a newly diagnosed cardiac condition were recruited from St Vincent's Hospital inpatient wards and outpatient clinics (n=67, age 63+/-11) and given 30minutes to interact with our online resource. Using a pre-test post-test design we evaluated the success of the website in improving patients' knowledge of their condition using a modified Brief Illness Perception Questionnaire and Patient Activation Questionnaire.After interacting with the website, participants rated a 50% improvement in the control they felt over their heart condition (p0.01). Understanding of investigations, medications and management improved by 38%, 31% and 38%, respectively (all p0.01). Subjects' understanding of their heart condition improved by 34% and confidence improved by more than 18% (p0.01). These improvements were seen irrespective of age and primary place of residence. While older subjects had the lowest confidence using the internet, they demonstrated the greatest self-reported improvement in knowledge. There was no improvement in patients' perceived concern about their illness.The St Vincent's Heart Health website shows real promise as an educational tool for patients, as an adjunct to standard CR and for patients in remote settings. Online health resources will likely become an important adjunct to traditional teaching methods across all medical specialties to improve patient outcomes.

Introduction Pulmonary hypertension (PH) is a potentially life-threatening condition characterised by elevated pulmonary artery pressure. Early stage PH patients are often asymptomatic. Disease progression is associated with impairment of right ventricular function and progressive dyspnoea. Current guidelines recommend exercise training (grade IIa, level B). However, many questions remain regarding the mechanisms of improvement, intensity of supervision and optimal frequency, duration and intensity of exercise. This study will assess the effect of an outpatient rehabilitation programme on haemodynamics and cardiac right ventricular function in patients with pulmonary arterial hypertension (PAH), a subgroup of PH. Methods and analysis This randomised controlled trial involves both a major urban tertiary and smaller regional hospital in New South Wales, Australia. The intervention will compare an outpatient rehabilitation programme with a control group (home exercise programme). Participants will be stable on oral PAH-specific therapy. The primary outcome measure will be right ventricular ejection fraction measured by cardiac MRI. Secondary outcomes will include haemodynamics measured by right heart catheterisation, endurance, functional capacity, health-related quality of life questionnaires and biomarkers of cardiac function and inflammation. Ethics approval and dissemination Ethical approval has been granted by St Vincent9s Hospital, Sydney (HREC/14/SVH/341). Results of this study will be disseminated through presentation at scientific conferences and in scientific journals. Trial registration number ACTRN12615001041549; pre-results.

The majority of display devices used in visualization are 2D displays. Inevitably, it is often necessary to overlay one piece of visual information on top of another, especially in applications such as multi-field visualization and geo-spatial information visualization. In this paper, we present a conceptual framework for studying the mechanisms for overlaying multiple pieces of visual information while allowing users to recover occluded information. We adopt the term 'multiplexing' from tele- and data communication to encompass all such overlapping mechanisms. We establish 10 categories of visual multiplexing mechanisms. We draw support evidence from both perception literature and existing works in visualization to support this conceptual framework. We examine the relationships between multiplexing and information theoretic measures. This new conceptual categorization provides the much-needed theory of visualization with an integral component.

With widespread access to high-quality medical care as in Australia, human immunodeficiency virus (HIV) is now considered a chronic, treatable condition, with a good life expectancy. The use of combined highly active antiretroviral therapy has enabled effective suppression of the virus, but has also been associated with increased cardiac morbidity and mortality. Over representation of traditional cardiac risk factors, such as hyperlipidaemia and diabetes, as well as an increased incidence of ischaemic and non-ischaemic heart disease is now considered a major concern of treatment with antiretroviral therapy. Therefore, a contemporary management strategy for patients with HIV must include active prevention and treatment of cardiovascular risk. This review will outline the complex interplay between HIV infection, antiretroviral drug regimens and accelerated cardiovascular disease, with a particular focus on screening, prevention and treatment options in a contemporary Australian HIV population.

Objective Treated HIV infection is associated with a higher incidence of coronary artery disease and myocardial infarction, although the mechanisms remain unclear. We sought to characterise the burden of coronary artery disease in men with HIV using retrospective data from invasive coronary angiograms in patients presenting with acute coronary syndrome (ACS). Methods Demographic and coronary angiographic data were obtained from 160 men with ST elevation myocardial infarction, non-STEMI or high-risk chest pain; 73 HIV-infected cases and 87 age-matched controls. The burden of coronary disease was calculated using the Gensini Angiographic Scoring System by 2 independent cardiologists blinded to HIV status. Results The 2 groups were matched for age, sex and cardiac event subtype and there was no difference in rates of smoking or cholesterol levels. Compared with control participants, patients with HIV had higher usage of antihypertensives (46 (63%) vs 30 (35%), p

The proximal thoracic aorta—composed of the ascending aorta, aortic arch, and upper descending aorta—plays the major role in accepting blood from the left ventricle (LV), cushioning flow pulsations and passing blood to the body’s tissues and organs with minimal energy loss [(1)][1]. The load

Objectives This study sought to test the diagnostic performance of native T1 mapping in acute myocarditis compared with cardiac magnetic resonance (CMR) techniques such as dark-blood T2-weighted (T2W)-CMR, bright-blood T2W-CMR, and late gadolinium enhancement (LGE) imaging. Background The diagnosis of acute myocarditis on CMR often requires multiple techniques, including T2W, early gadolinium enhancement, and LGE imaging. Novel techniques such as T1 mapping and bright-blood T2W-CMR are also sensitive to changes in free water content. We hypothesized that these techniques can serve as new and potentially superior diagnostic criteria for myocarditis. Methods We investigated 50 patients with suspected acute myocarditis (age 42 ± 16 years; 22% women) and 45 controls (age 42 ± 14 years; 22% women). CMR at 1.5-T (median 3 days from presentation) included: 1) dark-blood T2W-CMR (short-tau inversion recovery); 2) bright-blood T2W-CMR (acquisition for cardiac unified T2 edema); 3) native T1 mapping (shortened modified look-locker inversion recovery); and 4) LGE. Image analysis included: 1) global T2 signal intensity ratio of myocardium compared with skeletal muscle; 2) myocardial T1 relaxation times; and 3) areas of LGE. Results Compared with controls, patients had significantly higher global T2 signal intensity ratios by dark-blood T2W-CMR (1.73 ± 0.27 vs. 1.56 ± 0.15, p Conclusions Native T1 mapping as a novel criterion for the detection of acute myocarditis showed excellent and superior diagnostic performance compared with T2W-CMR. It also has a higher sensitivity compared with T2W and LGE techniques, which may be especially useful in detecting subtle focal disease and when gadolinium contrast imaging is not feasible.

Background— Aortic stenosis (AS) leads to left ventricular (LV) hypertrophy and dysfunction. We hypothesized that cardiac steatosis is involved in the pathophysiology and also assessed whether it is reversible after aortic valve replacement. Methods and Results— Thirty-nine patients with severe AS (symptomatic=25, asymptomatic=14) with normal LV ejection fraction and no significant coronary artery disease and 20 age- and sex-matched healthy controls underwent cardiac 1H-magnetic resonance spectroscopy and imaging for the determination of steatosis (myocardial triglyceride content) and cardiac function, including circumferential strain (measured by magnetic resonance tagging). Strain was lower in both symptomatic and asymptomatic AS (−16.4±2.5% and −18.1±2.9%, respectively, versus controls −20.7±2.0%, both P P Conclusions— Pronounced myocardial steatosis is present in severe AS, regardless of symptoms, and is independently associated with the degree of LV strain impairment. Myocardial triglyceride content measured by magnetic resonance spectroscopy correlates with histological quantification. Steatosis and strain impairment are reversible after aortic valve replacement. Our findings suggest a novel pathophysiological mechanism in AS, myocardial steatosis, which may be amenable to treatment, thus potentially delaying onset of LV dysfunction.

Interleukin-10 (IL-10) plays a key role in regulating proinflammatory immune responses to infection but can interfere with pathogen clearance. Although IL-10 is upregulated throughout HIV-1 infection in multiple cell subsets, whether this is a viral immune evasion strategy or an appropriate response to immune activation is unresolved. Analysis of IL-10 production at the single cell level in 51 chronically infected subjects (31 antiretroviral (ART) naive and 20 ART treated) showed that a subset of CD8(+) T cells with a CD25(neg) FoxP3(neg) phenotype contributes substantially to IL-10 production in response to HIV-1 gag stimulation. The frequencies of gag-specific IL-10- and IFN-γ-producing T cells in ART-naive subjects were strongly correlated and the majority of these IL-10(+) CD8(+) T cells co-produced IFN-γ; however, patients with a predominant IL-10(+) /IFN-γ(neg) profile showed better control of viraemia. Depletion of HIV-specific CD8(+) IL-10(+) cells from PBMCs led to upregulation of CD38 on CD14(+) monocytes together with increased IL-6 production, in response to gag stimulation. Increased CD38 expression was positively correlated with the frequency of the IL-10(+) population and was also induced by exposure of monocytes to HIV-1 in vitro. Production of IL-10 by HIV-specific CD8(+) T cells may represent an adaptive regulatory response to monocyte activation during chronic infection.

The purpose of this study was to evaluate normal values for regional and global myocardial wall motion parameters in young and elderly individuals, as detected by navigator gated high temporal resolution tissue phase mapping. Radial, longitudinal and circumferential ventricular wall motion, as well as ventricular torsion and longitudinal strain rates, were assessed in two age groups of volunteers, 23±3 (n=14) and 66±7 years old (n=9), respectively. All subjects were healthy, non-smokers without known cardiac disease. An increased global left ventricular (LV) torsion rate (peak systolic torsion rate 20.6±2.0 versus 14.5±1.0°/s/cm, peak diastolic torsion rate -25.2±1.8 versus -14.1±1.3°/s/cm) and a decrease in longitudinal LV motion (peak systolic values at mid-ventricle 5.9±0.5 versus 8.5±0.8 cm/s, peak diastolic values -10.7±0.7 versus -15.2±0.9 cm/s) in the older age group were the most prominent findings. Lower peak diastolic radial velocities with a longer time-to-peak values, most pronounced at the apex, are consistent with reduced diastolic function with ageing. Lower peak clockwise and counter-clockwise velocities at all LV levels revealed limitations in resting LV rotational motions in the older group. Significant changes in the undulating pattern of the rotational motions of the left ventricle were also observed. The results demonstrate distinct changes in regional and global myocardial wall motion in elderly individuals. Increased LV torsion rate and reduced LV longitudinal motion were particularly prominent in the older group. These parameters may have a role in the assessment of global LV contractility and help differentiate age-related changes from cardiac disease. © American Aging Association 2013.

OBJECTIVES: This study sought to assess myocardial perfusion and tissue oxygenation during vasodilator stress in patients with overt hypertrophic cardiomyopathy (HCM), as well as in HCM mutation carriers without left ventricular (LV) hypertrophy, and to compare findings to those in athletes with comparable hypertrophy and normal controls. BACKGROUND: Myocardial perfusion under vasodilator stress is impaired in patients with HCM. Whether this is associated with impaired myocardial oxygenation and tissue ischemia is unknown. Furthermore, it is not known whether perfusion and oxygenation are impaired in HCM mutation carriers without left ventricular hypertrophy (LVH). METHODS: A total of 27 patients with overt HCM, 10 HCM mutation carriers without LVH, 11 athletes, and 20 healthy controls underwent cardiovascular magnetic resonance (CMR) scanning at 3-T. Myocardial function, perfusion (perfusion reserve index [MPRI]), and oxygenation (blood-oxygen level dependent signal intensity [SI] change) under adenosine stress were assessed. RESULTS: MPRI was significantly reduced in HCM (1.3 ± 0.1) compared to controls (1.8 ± 0.1, p < 0.001) and athletes (2.0 ± 0.1, p < 0.001), but remained normal in HCM mutation carriers without LVH (1.7 ± 0.1; p = 0.61 vs. controls, p = 0.02 vs. overt HCM). Oxygenation response was attenuated in overt HCM (SI change 6.9 ± 1.4%) compared to controls (18.9 ± 1.4%, p < 0.0001) and athletes (18.7 ± 2.0%, p < 0.001). Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine (10.4 ± 2.0%; p = 0.001 vs. controls, p = 0.16 vs. overt HCM, p = 0.003 vs. athletes). CONCLUSIONS: In overt HCM, both perfusion and oxygenation are impaired during vasodilator stress. However, in HCM mutation carriers without LVH, only oxygenation is impaired. In athletes, stress perfusion and oxygenation are normal. CMR assessment of myocardial oxygenation has the potential to become a novel risk factor in HCM.

Objective As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. Methods In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4] ≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen = 0.11, 1 hour). Results In the high-altitude studies, headache burden correlated with both RVD (Spearman rho = 0.55, p = 0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r = -0.56, p = 0.03). It also related inversely to both the lateral + third ventricle summed volumes (Spearman rho = -0.5, p = 0.05) and pericerebellar CSF volume (r = -0.56, p = 0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r = -0.66, p < 0.05 and r = -0.75, p < 0.05, respectively). Interpretation Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur. ANN NEUROL 2013;73:381-389 Copyright © 2013 American Neurological Association.

Background Spontaneous coronary artery dissection (SCAD) is an uncommon but serious condition presenting as an acute coronary syndrome (ACS) or cardiac arrest. The pathophysiology and outcomes are poorly understood. We investigated the characteristics and outcomes of patients presenting with SCAD. Methods In a retrospective study of a large cohort of patients with SCAD, data were collected regarding clinical presentation, patient characteristics, vascular screening, coronary artery involvement and clinical outcomes. Results 40 patients with SCAD (95% women, mean age 45±10 years) were included. At least 1 traditional cardiovascular risk factor was present in 40% of patients. Migraine was reported in 43% of patients. Events preceding SCAD included parturition (8%), physical stress (13%), emotional stress (10%) and vasoconstrictor substance-use (8%). 65% of patients had a non-ST elevation ACS (NSTEACS) at presentation, 30% had an ST elevation myocardial infarction (STEMI) and 13% had a cardiac arrest. The left anterior descending artery was most frequently involved (68% of patients), and 13% had involvement of multiple coronary territories. Fibromuscular dysplasia (FMD) was identified in 7 (37%) of 19 patients screened. 68% of patients were managed medically, 30% had percutaneous coronary intervention and 5% had coronary artery bypass grafting. Over a median 16-month follow-up period, 8% of patients had at least 1 recurrent SCAD event. There were no deaths. Conclusions Patients with SCAD in this study often had multiple coronary territories involved (13%) and extracardiac vascular abnormalities, suggesting a systemic vascular process, which may explain the high incidence of migraine. All patients with SCAD should be screened for FMD and followed closely due to the possibility of recurrence.

Right ventricular strain assessment by feature tracking from cine images shows acceptable levels of agreement with echocardiography

Background: Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds. Methods. We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE. Results: Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis. Conclusion: Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In addition, T1-mapping offers significant incremental diagnostic value, detecting additional areas of myocardial involvement beyond T2W and LGE imaging and identified extra cases when these conventional methods failed to identify abnormalities. In the future, it may be possible to perform gadolinium-free CMR using cine and T1-mapping for tissue characterization and may be particularly useful for patients in whom gadolinium contrast is contraindicated. © 2014 Ferreira et al.; licensee BioMed Central Ltd.

We thank Ellims et al for their query about the consistency of results from the T1 mapping literature on hypertrophic cardiomyopathy. The letter serves well to highlight an important issue: the fundamental differences between native (or precontrast) T1 mapping and postcontrast T1 mapping as distinct techniques. Native myocardial T1 increases with conditions involving an increase in free water content, whereas postcontrast T1 typically decreases. Results and correlations derived from studies using these different biomarkers should not be expected to demonstrate a direct relationship. Single-time-point postcontrast T1 constitutes a momentary snapshot of the transient effect of …

Background— Noncontrast magnetic resonance T1 mapping reflects a composite of both intra- and extracellular signal. We hypothesized that noncontrast T1 mapping can characterize the myocardium beyond that achieved by the well-established late gadolinium enhancement (LGE) technique (which detects focal fibrosis) in both hypertrophic (HCM) and dilated (DCM) cardiomyopathy, by detecting both diffuse and focal fibrosis. Methods and Results— Subjects underwent Cardiovascular Magnetic Resonance imaging at 3T (28 HCM, 18 DCM, and 12 normals). Matching short-axis slices were acquired for cine, T1 mapping, and LGE imaging (0.1 mmol/kg). Circumferential strain was measured in the midventricular slice, and 31 P magnetic resonance spectroscopy was acquired for the septum of the midventricular slice. Mean T1 relaxation time was increased in HCM and DCM (HCM 1209±28 ms, DCM 1225±42 ms, normal 1178±13 ms, P r =0.32, P P P P r =0.42, P r =0.56, P =0.04). Finally, there was also a statistically significant negative correlation between T1 values and phosphocreatine/adenosine triphosphate ratios ( r =−0.59, P Conclusions— In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.

Background— Obesity is characterized by impaired cardiac energetics, which may play a role in the development of diastolic dysfunction and inappropriate shortness of breath. We assessed whether, in obesity, derangement of energetics and diastolic function is further altered during acute cardiac stress. Methods and Results— Normal-weight (body mass index, 22±2 kg/m 2 ; n=9–17) and obese (body mass index, 39±7 kg/m 2 ; n=17–46) subjects underwent assessment of diastolic left ventricular function (cine magnetic resonance imaging volume-time curve analysis) and cardiac energetics (phosphocreatine/ATP ratio; 31 P-magnetic resonance spectroscopy) at rest and during dobutamine stress (heart rate increase, 65±22% and 69±14%, respectively; P =0.61). At rest, obesity was associated with a 22% lower peak filling rate ( P P =0.048). Peak filling rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio, and phosphocreatine/ATP ratio. On multivariable analysis, phosphocreatine/ATP was the only independent predictor of peak filling rate (β=0.50; P =0.03). During stress, a further reduction in phosphocreatine/ATP occurred in obese (from 1.73±0.40 to 1.53±0.50; P =0.03) but not in normal-weight (from 1.98±0.24 to 2.04±0.34; P =0.50) subject. For similar levels of inotropic stress, there were smaller increases in peak filling rate in obesity (38% versus 70%; P =0.01). Conclusions— In obesity, cardiac energetics are further deranged during inotropic stress, in association with continued diastolic dysfunction. Myocardial energetics may play a key role in the impairment of diastolic function in obesity.

Human immunodeficiency virus (HIV) infection is considered a chronic, treatable disease, although treatment is associated with increased rates of coronary artery disease (CAD). We analyzed the utility of coronary CTA in the assessment of CAD among HIV patients and explored whether HIV patients are at greater risk of associated morbidity and mortality compared to HIV-negative controls.In a retrospective, single center cohort study 97 males without history of previous coronary artery disease who had undergone coronary CTA between 2011 and 2014 was analyzed, including 32 HIV positive patients and 65 matched HIV negative controls. Presence and composition of coronary plaque was determined by coronary CTA. Data on subsequent coronary events and coronary intervention was collected.Patients with HIV had higher rates of non-calcified plaque (0.8 ± 1.5 versus 0.3 ± 0.7, p = 0.03) compared to negative controls. At a median follow-up of 38 months, patients with HIV were at greater risk of non-ST elevation acute coronary syndrome (16% versus 3%, p 0.04), although there was no difference in the combined endpoint of all acute coronary syndromes (19% versus 6%, p = 0.08). Following baseline coronary TCA, there was a higher rate of coronary intervention in patients without HIV (mean time to event 9.9 ± 3.3 versus 20.6 ± 4.9 months, p 0.04).Patients with HIV more pronounces coronary atherosclerosis on coronary CTA and higher rates of non-ST elevation acute coronary syndromes compared to negative controls.

Background— Patients with treated HIV infection have clear survival benefits although with increased cardiac morbidity and mortality. Mechanisms of heart disease may be partly related to untreated chronic inflammation. Cardiovascular magnetic resonance imaging allows a comprehensive assessment of myocardial structure, function, and tissue characterization. We investigated, using cardiovascular magnetic resonance, subclinical inflammation and myocardial disease in asymptomatic HIV-infected individuals. Methods and Results— Myocardial structure and function were assessed using cardiovascular magnetic resonance at 1.5-T in treated HIV-infected individuals without known cardiovascular disease (n=103; mean age, 45±10 years) compared with healthy controls (n=92; mean age, 44±10 years). Assessments included left ventricular volumes, ejection fraction, strain, regional systolic, diastolic function, native T1 mapping, edema, and gadolinium enhancement. Compared with controls, subjects with HIV infection had 6% lower left ventricular ejection fraction ( P P =0.02), 29% lower peak diastolic strain rate ( P P =0.02), and higher native T1 values (969 versus 956 ms in controls; P =0.01). Pericardial effusions and myocardial fibrosis were 3 and 4× more common, respectively, in subjects with HIV infection (both P Conclusions— Treated HIV infection is associated with changes in myocardial structure and function in addition to higher rates of subclinical myocardial edema and fibrosis and frequent pericardial effusions. Chronic systemic inflammation in HIV, which involves the myocardium and pericardium, may explain the high rate of myocardial fibrosis and increased cardiac dysfunction in people living with HIV.