The exercise in pulmonary arterial hypertension (ExPAH) study: A randomized controlled pilot of exercise training and multidisciplinary rehabilitation in pulmonary arterial hypertension.

Pulmonary hypertension (PH) is characterized by progressive dyspnea, fatigue, and reduced exercise capacity. Despite medical treatment, outcomes remain poor. While exercise training is well established in patients with heart failure, it is less established in patients with PH. This single-blind, randomized controlled pilot study examined the feasibility and effect of 12-week outpatient exercise (multidisciplinary rehabilitation or home walking program) on hemodynamics using cardiac magnetic resonance imaging (cMRI) and right heart catheterization (RHC) in patients with pulmonary arterial hypertension (PAH), a subset of PH. Sixteen participants were randomized to either multidisciplinary outpatient rehabilitation or a home walking program for 12 weeks. Primary outcome measures were changes in right ventricular ejection fraction and stroke volume index on cMRI. Secondary outcome measures included hemodynamics on RHC, quality of life (QOL), muscle strength (handgrip and vital capacity) and 6-min walk test. This preliminary, pilot study suggests that outpatient exercise interventions may be associated with improved hemodynamic function (mean pulmonary artery wedge pressure, stroke volume, and stroke volume index), QOL (PH symptoms, depression, and anxiety), and muscular strength (vital capacity and handgrip strength) for people with PAH, but was not adequately powered to make any formal conclusions. However, our outpatient programs were feasible, safe, and acceptable to participants. Future studies are required to further explore the potential hemodynamic benefits of exercise in PAH.

Myocarditis in Crohn's disease: a case report.

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 imaging for structural heart 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.

Evaluating the Effectiveness of an Online Cardiac Rehabilitation Resource (www.svhhearthealth.com.au) in Improving Knowledge and Confidence for Patients With Newly Diagnosed Cardiac Conditions: A Pre-Experimental Pilot Study.

BACKGROUND: 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. METHODS: 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. RESULTS: After interacting with the website, participants rated a 50% improvement in the control they felt over their heart condition (p<0.01). Understanding of investigations, medications and management improved by 38%, 31% and 38%, respectively (all p<0.01). Subjects' understanding of their heart condition improved by 34% and confidence improved by more than 18% (p<0.01). 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. CONCLUSIONS: 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.

Cardiac Steatosis in HIV-A Marker or Mediator of 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.

Patients with HIV and coronary disease: are we meeting national guidelines?

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.

HIV-related cardiovascular disease: closing the gap in mortality.

: 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.

Use of direct oral anticoagulants for treatment of atrial fibrillation in patients with HIV: a review.

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.

Outcomes of patients with spontaneous coronary artery dissection.

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.

High-risk coronary plaque, invasive coronary procedures, and cardiac events among HIV-positive individuals and matched controls.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Patients with HIV more pronounces coronary atherosclerosis on coronary CTA and higher rates of non-ST elevation acute coronary syndromes compared to negative controls.

Improvements in ECG accuracy for diagnosis of left ventricular hypertrophy in obesity.

OBJECTIVES: The electrocardiogram (ECG) is the most commonly used tool to screen for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are insensitive in modern increasingly overweight society. We propose a simple adjustment to improve diagnostic accuracy in different body weights and improve the sensitivity of this universally available technique. METHODS: Overall, 1295 participants were included-821 with a wide range of body mass index (BMI 17.1-53.3 kg/m(2)) initially underwent cardiac magnetic resonance evaluation of anatomical left ventricular (LV) axis, LV mass and 12-lead surface ECG in order to generate an adjustment factor applied to the Sokolow-Lyon criteria. This factor was then validated in a second cohort (n=520, BMI 15.9-63.2 kg/m(2)). RESULTS: When matched for LV mass, the combination of leftward anatomical axis deviation and increased BMI resulted in a reduction of the Sokolow-Lyon index, by 4 mm in overweight and 8 mm in obesity. After adjusting for this in the initial cohort, the sensitivity of the Sokolow-Lyon index increased (overweight: 12.8% to 30.8%, obese: 3.1% to 27.2%) approaching that seen in normal weight (37.8%). Similar results were achieved in the validation cohort (specificity increased in overweight: 8.3% to 39.1%, obese: 9.4% to 25.0%) again approaching normal weight (39.0%). Importantly, specificity remained excellent (>93.1%). CONCLUSIONS: Adjusting the Sokolow-Lyon index for BMI (overweight +4 mm, obesity +8 mm) improves the diagnostic accuracy for detecting LVH. As the ECG, worldwide, remains the most widely used screening tool for LVH, implementing these findings should translate into significant clinical benefit.

Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus.

AIMS: Patients with type 2 diabetes mellitus (T2DM) are known to have impaired resting myocardial energetics and impaired myocardial perfusion reserve, even in the absence of obstructive epicardial coronary artery disease (CAD). Whether or not the pre-existing energetic deficit is exacerbated by exercise, and whether the impaired myocardial perfusion causes deoxygenation and further energetic derangement during exercise stress, is uncertain. METHODS AND RESULTS: Thirty-one T2DM patients, on oral antidiabetic therapies with a mean HBA1c of 7.4 ± 1.3%, and 17 matched controls underwent adenosine stress cardiovascular magnetic resonance for assessment of perfusion [myocardial perfusion reserve index (MPRI)] and oxygenation [blood-oxygen level-dependent (BOLD) signal intensity change (SIΔ)]. Cardiac phosphorus-MR spectroscopy was performed at rest and during leg exercise. Significant CAD (>50% coronary stenosis) was excluded in all patients by coronary computed tomographic angiography. Resting phosphocreatine to ATP (PCr/ATP) was reduced by 17% in patients (1.74 ± 0.26, P = 0.001), compared with controls (2.07 ± 0.35); during exercise, there was a further 12% reduction in PCr/ATP (P = 0.005) in T2DM patients, but no change in controls. Myocardial perfusion and oxygenation were decreased in T2DM (MPRI 1.61 ± 0.43 vs. 2.11 ± 0.68 in controls, P = 0.002; BOLD SIΔ 7.3 ± 7.8 vs. 17.1 ± 7.2% in controls, P < 0.001). Exercise PCr/ATP correlated with MPRI (r = 0.50, P = 0.001) and BOLD SIΔ (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SIΔ. CONCLUSION: The pre-existing energetic deficit in diabetic cardiomyopathy is exacerbated by exercise; stress PCr/ATP correlates with impaired perfusion and oxygenation. Our findings suggest that, in diabetes, coronary microvascular dysfunction exacerbates derangement of cardiac energetics under conditions of increased workload.

No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure.

BACKGROUND: Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation. METHODS AND RESULTS: Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4-6 minutes IV adenosine, 140 µg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using (31)P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%; P=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10; P=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (P=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (R=0.06; P=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06; P=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08; P=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%; P=0.46; Δ 2±1%). CONCLUSIONS: Our results demonstrate dissociation between microvascular dysfunction and oxygenation in DCM, suggesting that the impairment of perfusion is not sufficient to cause deoxygenation during stress. Cardiac energetics are unaffected by oxygen supplementation, indicating the absence of relevant myocardial hypoxia at rest. Our study suggests that novel treatments for nonischemic heart failure should focus on efforts to directly target cardiomyocyte function and metabolism rather than oxygen delivery and microvascular function.

Exacerbation of cardiac energetic impairment during exercise in hypertrophic cardiomyopathy: a potential mechanism for diastolic dysfunction.

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 (31)Phosphorus MR Spectroscopy ((31)P 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: (31)P 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.