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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.

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.

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.

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

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

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.

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.

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.

Hypoxia causes left ventricular dysfunction in the human heart, but the biochemical mechanism is poorly understood. Here, we tested whether short-term normobaric hypoxia leads to changes in cardiac energetics and early cardiac dysfunction. Healthy male volunteers (n=12, age 24±2 yr) were exposed to normobaric hypoxia in a purpose-built hypoxic chamber. The partial pressure of oxygen during end-tidal expiration (P ETO 2) was kept between 50 and 60 mmHg, and peripheral oxygen saturation (SaO 2) was kept above 80%. Cardiac morphology and function were assessed using magnetic resonance imaging and echocardiography, both before and after 20 h of hypoxic exposure, and high-energy phosphate metabolism [measured as the phosphocreatine (PCr)/ATP ratio] was measured using 31P magnetic resonance spectroscopy. During hypoxia, P ETO 2 and SaO 2averaged 55 ± 1 mmHg and 83.6 ± 0.4%, respectively. Hypoxia caused a 15% reduction in cardiac PCr/ATP (from 2.0±0.1 to 1.7

Background: High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations. Objective: We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects. Design: Men (n = 16) aged 22 6 1 y (mean 6 SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 6 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 6 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac 31 P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively. Results: Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P , 0.05), 9% lower cardiac PCr/ATP (P , 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P , 0.01), speed (P , 0.001), and mood (P , 0.01) after the high-fat, low-carbohydrate diet. Conclusion: Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects. Am J Clin Nutr 2011;93:748–55.

Cardiovascular disease (CVD) has a higher incidence in patients with HIV infection. This study sought to determine whether HIV-infected patients with established CVD were being managed according to national guidelines. Data were collected from Australian general practitioners for 77 HIV-infected patients with a median age of 59 (range 54–64). There was good adherence to guidelines with regards to anti-platelet (84%; n = 65; 95% confidence interval (CI) 74–92%) and statin therapy (97%; n = 75; 95% CI 91–100%), despite a failure to meet cholesterol targets, with only 31% (n = 24; 95% CI 21–42%) of the cohort meeting low-density lipoprotein target values. Similarly, there was limited adherence to guidelines regarding the prescriptions of medications for those with established hypertension (66%; n = 51; 95% CI 55–77%), body mass index targets met (40%; n = 31; 95% CI 29–52%), and depression screening (32%; n = 25; 95% CI 22–44%). This Australian audit provides insight into adherence to guidelines for individuals with CVD and HIV, suggesting that current screening and management practices for these patients falls short of guidelines, particularly in relation to cholesterol management.

Background Heart failure (HF) is characterised by alterations in fatty acid and glucose metabolism. We aimed to determine if myocardial lipid is increased in HF with reduced (HFrEF) and preserved (HFpEF) ejection fraction (EF), and assess whether it is related to cardiac structure and function. Methods 25 HFrEF due to dilated cardiomyopathy (DCM), 18 HFpEF (defined by EF >50%, abnormal diastolic function, maximum oxygen consumption

Background Diabetic cardiomyopathy is a well-recognised entity, with multifactorial aetiology. We and others have previously shown impaired myocardial energetics (decreased PCr/ ATP using cardiac 31P Magnetic Resonance Spectroscopy-MRS) in patients with type II diabetes mellitus (T2DM) at rest. Furthermore, diabetic patients are known to have impaired myocardial perfusion reserve even in the absence of epicardial coronary artery disease likely due to microvascular dysfunction. However, it is unknown whether this hypoperfusion is translated to further energetic derangement at stress. Methods 27 patients (13 male, mean age 54±1.5 years; BMI 28±2.7) with T2DM and 24 healthy volunteers of similar age and BMI (13 male, mean age 51±2.6 years; BMI 26±0.84) were studied. Patients were on oral antidiabetic therapies only, with mean HBA1c 7.4±1.3% and no history of diabetic complications. Obstructive coronary artery disease (defined as> 50% lumen diameter reduction) was excluded in all patients by CT coronary angiography. Cardiac 31PMRS (3T) was performed at rest and during 8 minutes of leg exercise lying prone, with 2.5 kg weights attached to both legs. First-pass perfusion images (using a saturation recovery fast-gradient echo sequence and 0.03 mmol/kg bolus of Gadoterate meglumine (Dotarem, Guerbet LLC, France ) were also acquired at stress (3-6 minutes i.v. adenosine, 140 μg/kg/min) and rest at mid ventricular short axis. myocardial perfusion reserve index (MPRI) were measured from perfusion images. Results Left ventricular ejection fraction (LVEF) and mass index (LVMI) were similar in patients with T2DM and healthy volunteers (LVEF 70±1 vs 71±0.9%, p=0.494; LVMI 56.7 ±1.8 vs 52.6±2.4g/m 2 , p=0.168). Increases in rate pressure product with exercise (T2DM 46±36%, healthy volunteers 42±26%, P = 0.69) and adenosine stress (T2DM 40 ± 3%, healthy volunteers 39 ± 3%, P = 0.89) were similar. There was no change in PCr/ATP during exercise in healthy volunteers (rest: 2.03±0.05, exercise

OBJECTIVE Obtaining new details of radial motion of left ventricular (LV) segments using velocity-encoding cardiac MRI. METHODS Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Cine images for navigator-gated phase contrast velocity mapping were acquired using a black blood segmented κ-space spoiled gradient echo sequence with a temporal resolution of 13.8 ms. Peak systolic and diastolic radial velocities as well as radial velocity curves were obtained for 16 ventricular segments. RESULTS Significant differences among peak radial velocities of basal and mid-ventricular segments have been recorded. Particular patterns of segmental radial velocity curves were also noted. An additional wave of outward radial movement during the phase of rapid ventricular filling, corresponding to the expected timing of the third heart sound, appeared of particular interest. CONCLUSION The technique has allowed visualization of new details of LV radial wall motion. In particular, higher peak systolic radial velocities of anterior and inferior segments are suggestive of a relatively higher dynamics of anteroposterior vs lateral radial motion in systole. Specific patterns of radial motion of other LV segments may provide additional insights into LV mechanics. ADVANCES IN KNOWLEDGE The outward radial movement of LV segments impacted by the blood flow during rapid ventricular filling provides a potential substrate for the third heart sound. A biphasic radial expansion of the basal anteroseptal segment in early diastole is likely to be related to the simultaneous longitudinal LV displacement by the stretched great vessels following repolarization and their close apposition to this segment.

Background Cardiovascular magnetic resonance (CMR) is regarded as the gold standard for clinical assessment of the aorta, but normal dimensions are usually referenced to echocardiographic and computed tomography data and no large CMR normal reference range exists. As a result we aimed to 1) produce a normal CMR reference range of aortic diameters and 2) investigate the relationship between regional aortic size and body surface area (BSA) in a large group of healthy subjects with no vascular risk factors. Methods 447 subjects (208 male, aged 19–70 years) without identifiable cardiac risk factors (BMI range 15.7–52.6 kg/m2) underwent CMR at 1.5 T to determine aortic diameter at three levels: the ascending aorta (Ao) and proximal descending aorta (PDA) at the level of the pulmonary artery, and the abdominal aorta (DDA), at a level 12 cm distal to the PDA. In addition, 201 of these subjects had aortic root imaging, allowing for measurements at the level of the aortic valve annulus (AV), aortic sinuses and sinotubular junction (STJ). Results Normal diameters (mean ±2 SD) were; AV annulus male(♂) 24.4 ± 5.4, female (♀) 21.0 ± 3.6 mm, aortic sinus♂32.4 ± 7.7, ♀27.6 ± 5.8 mm, ST-junction ♂25.0 ± 7.4, ♀21.8 ± 5.4 mm, Ao ♂26.7 ± 7.7, ♀25.5 ± 7.4 mm, PDA ♂20.6 ± 5.6, +18.9 ± 4.0 mm, DDA ♂17.6 ± 5.1, ♀16.4 ± 4.0 mm. Aortic root and thoracic aortic diameters increased at all levels measured with BSA. No gender difference was seen in the degree of dilatation with increasing BSA (p > 0.5 for all analyses). Conclusion Across both genders, increasing body size is characterized by a modest degree of aortic dilatation, even in the absence of traditional cardiovascular risk factors.

Aims Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using 31Phosphorus MR Spectroscopy (31P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences. Methods and results 31P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest ( r = 0.48, P = 0.02) and stress ( r = 0.53, P = 0.01). Conclusion During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.

AIMS: As obesity-related cardiovascular mortality, although elevated when compared with normal weight, is lower in females than in males at every body mass index (BMI) level, we aimed to investigate gender-specific differences in left ventricular (LV) hypertrophy in obesity, which themselves have been shown to have varying prognostic value. METHOD AND RESULTS: In total, 741 subjects (female, n = 399) without identifiable cardiovascular risk factors (BMI 15.7-59.2 kg/m(2)) underwent cardiovascular magnetic resonance (1.5 T) to determine LV mass, end-diastolic volume (EDV, mL), and LV mass/volume ratio (LVM/VR). Across both sexes, there was a strong positive correlation between BMI and LV mass (male r = 0.44, female r = 0.57, both P < 0.001), with males showing a greater LV hypertrophic response (male +2.3 vs. female +1.6 g per BMI point increase, P = 0.001). Concentric hypertrophy was present in both sexes and LVM/VR positively correlated to BMI (male r = 0.45, female r = 0.29, both P < 0.001) on linear regression analysis. However, the degree of concentric hypertrophy was greater in males (male +0.13 vs. female +0.06 LVM/VR increase per BMI point increase, P = 0.001). On the other hand, females showed a greater LV cavity dilatory response (female +1.1 vs. male +0.3 mL per BMI point increase, P < 0.001). Indeed, in contrast to females, where BMI and LV-EDV were positively correlated (r = 0.38, P < 0.001), BMI did not correlate with EDV in men (r = 0.03, P = 0.62). CONCLUSION: In the absence of traditional cardiovascular risk factors, obese men show predominantly concentric hypertrophy, whereas obese women exhibit both eccentric and concentric hypertrophy. As concentric hypertrophy is more strongly related to cardiovascular mortality than eccentric hypertrophy, our observations may explain the observed gender difference in obesity-related mortality.

OBJECTIVE: To determine the effects of short-term exercise training on cardiac function and metabolism during rest and physical exercise in patients with heart failure from dilated cardiomyopathy (DCM). DESIGN: Patients with DCM (n=15, age 58±2 years, NYHA class I-III) were studied before and after 8 weeks of cycle exercise for 20 min, five times per week. MAIN OUTCOME MEASURES: Cardiac volumes, function and high energy phosphate metabolism were measured using cardiac magnetic resonance during rest and 7 min of acute physical exercise (leg-raising). RESULTS: At baseline, average left ventricular ejection fraction (LVEF) was 38±3%, which did not alter during 7 min of exercise. After 8 weeks of home exercise training, there was a 16% improvement in resting LVEF to 44±3% (p

Background— Elevated free fatty acid (FFA) levels are known to impair aortic elastic function. In obesity, FFA levels are elevated and aortic distensibility (AD) reduced in a pattern that predominantly affects the distal aorta. Despite this, the role of FFAs in obesity-related aortic stiffness remains unclear. Methods and Results— Using vascular MRI, we aimed to determine if (1) FFA level correlated with AD in obesity; and (2) whether elevating FFA acutely and subacutely in normal-weight subjects reproduced the distal pattern of AD change in obesity. To do this, regional AD was recorded in 35 normal-weight and 70 obese subjects and then correlated with FFA levels. When compared with normal weight, obesity was associated with reduced AD in a pattern predominantly affecting the distal aorta (ascending aorta by −22%, proximal descending aorta by −25%, and abdominal aorta by −35%; P r =−0.43, P Conclusions— Both intralipid infusion and a low-carbohydrate diet resulted in reduced abdominal AD (infusion −22%, diet −28%; both P

Summary Across both genders, obesity, in the absence of traditional cardiovascular risk factors, is characterized by concentric LV remodeling. Whereas males show predominantly concentric remodeling, females exhibit eccentric and concentric hypertrophy. This may explain the observed gender difference in obesity related cardiovascular mortality. Background Obesity related cardiovascular mortality, although elevated when compared to normal weight, is lower in females (♀ )t han males ( ♂ )a t every body mass index (BMI) level. Given the fact that males have less fat tissue than females at each BMI level, the reasons behind this trend are unlikely to be attributable to the effects of excess adiposity alone. As different patterns of left ventricular (LV) remodeling have been shown to have varying prognostic value, with concentric hypertrophy being more strongly predictive of cardiovascular mortality than eccentric hypertrophy, our aim was to investigate whether sex-specific differences in LV remodeling could provide an additional explanation for the observed gender difference in obesity related mortality. Methods 703 subjects (♀ n= 390, ♂ n=313) without identifiable cardiovascular risk factors, (BMI range 15.7-59.2 Kg/ M2) underwent cardiovascular magnetic resonance at 1.5 Tesla for the assessment of LV mass (g), enddiastolic volume (EDV; ml) and LV mass/volume ratio (LVM/VR).

Summary This work demonstrates that cardiac energetcics is further impaired during exercise in hypertrophic cardiomyopathy. This may be a possible reason for exercise related death in HCM. Background In hypertrophic cardiomyopathy (HCM), sarcomere mutations increase the energy cost of contraction. Impaired resting cardiac energetics as measured by phosphocreatine/adenosine triphosphate (PCr/ATP) using 31Phosphorus MR Spectroscopy(31P MRS) has been documented in animal models and patients. We hypothesize that: 1.Cardiac energetics are further impaired acutely during exercise in HCM, which does not occur in normals or athletes (physiological hypertrophy); 2. This impairment is not related to the degree of hypertrophy or late gadolinium enhancement (LGE) burden.

Cardiac magnetic resonance spectroscopy (MRS) is a noninvasive tool for the assessment of myocardial metabolism, without the use of radiation or intravenous contrast agents. Using the intrinsic magnetic resonance signals from nuclei, including (31)Phosphorus, (1)Hydrogen, (23)Sodium, and (13)Carbon and, more recently, hyperpolarization techniques, MRS provides a comprehensive metabolic assessment of cardiac muscle. This highly versatile technique has provided insights into the pathophysiology of cardiac metabolism in a wide range of conditions, including ischemic heart disease, heart failure, genetic cardiomyopathies, heart transplantation, hypertensive heart disease, valvular heart disease, and diabetes. In addition, MRS has value in the assessment of prognosis and for monitoring therapeutic strategies in heart failure. However, because of the low temporal and spatial resolution of the technique, MRS has so far been limited to research applications. With higher field strength magnets and novel hyperpolarization techniques, the promise of using MRS for clinical applications may eventually be fulfilled.

We recently showed that a week-long, high-fat diet reduced whole body exercise efficiency in sedentary men by >10% (Edwards LM, Murray AJ, Holloway CJ, Carter EE, Kemp GJ, Codreanu I, Brooker H, Tyler DJ, Robbins PA, Clarke K. FASEB J 25: 1088–1096, 2011). To test if a similar dietary regime would blunt whole body efficiency in endurance-trained men and, as a consequence, hinder aerobic exercise performance, 16 endurance-trained men were given a short-term, high-fat (70% kcal from fat) and a moderate carbohydrate (50% kcal from carbohydrate) diet, in random order. Efficiency was assessed during a standardized exercise task on a cycle ergometer, with aerobic performance assessed during a 1-h time trial and mitochondrial function later measured using 31P-magnetic resonance spectroscopy. The subjects then underwent a 2-wk wash-out period, before the study was repeated with the diets crossed over. Muscle biopsies, for mitochondrial protein analysis, were taken at the start of the study and on the 5th day of each diet. Plasma fatty acids were 60% higher on the high-fat diet compared with moderate carbohydrate diet ( P < 0.05). However, there was no change in whole body efficiency and no change in mitochondrial function. Endurance exercise performance was significantly reduced ( P < 0.01), most probably due to glycogen depletion. Neither diet led to changes in citrate synthase, ATP synthase, or mitochondrial uncoupling protein 3. We conclude that prior exercise training blunts the deleterious effect of short-term, high-fat feeding on whole body efficiency.

We recently showed that a short-term high-fat diet blunted exercise performance in rats, accompanied by increased uncoupling protein levels and greater respiratory uncoupling. In this study, we investigated the effects of a similar diet on physical and cognitive performance in humans. Twenty sedentary men were assessed when consuming a standardized, nutritionally balanced diet (control) and after 7 d of consuming a diet comprising 74% kcal from fat. Efficiency was measured during a standardized exercise task, and cognition was assessed using a computerized assessment battery. Skeletal muscle mitochondrial function was measured using (31)P magnetic resonance spectroscopy. The diet increased mean ± se plasma free fatty acids by 44% (0.32±0.03 vs. 0.46±0.05 mM; P