Cost-Effectiveness of Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation in the Australian Health Care System.

BACKGROUND: Heart transplantation is an effective treatment for end-stage congestive heart failure, however, achieving the right balance of immunosuppression to maintain graft function while minimising adverse effects is challenging. Serial endomyocardial biopsies (EMBs) are currently the standard for rejection surveillance, despite being invasive. Replacing EMB-based surveillance with cardiac magnetic resonance (CMR)-based surveillance for acute cardiac allograft rejection has shown feasibility. This study aimed to assess the cost-effectiveness of CMR-based surveillance in the first year after heart transplantation. METHOD: A prospective clinical trial was conducted with 40 orthotopic heart transplant (OHT) recipients. Participants were randomly allocated into two surveillance groups: EMB-based, and CMR-based. The trial included economic evaluations, comparing the frequency and cost of surveillance modalities in relation to quality-adjusted life years (QALYs) within the first year post-transplantation. Sensitivity analysis encompassed modelled data from observed EMB and CMR arms, integrating two hypothetical models of expedited CMR-based surveillance. RESULTS: In the CMR cohort, 238 CMR scans and 15 EMBs were conducted, versus (vs) 235 EMBs in the EMB group. CMR surveillance yielded comparable rejection rates (CMR 74 vs EMB 94 events, p=0.10) and did not increase hospitalisation risk (CMR 32 vs EMB 46 events, p=0.031). It significantly reduced the necessity for invasive EMBs by 94%, lowered costs by an average of AUD$32,878.61, and enhanced cumulative QALY by 0.588 compared with EMB. Sensitivity analysis showed that increased surveillance with expedited CMR Models 1 and 2 were more cost-effective than EMB (all p<0.01), with CMR Model 1 achieving the greatest cost savings (AUD$34,091.12±AUD$23,271.86 less) and utility increase (+0.62±1.49 QALYs, p=0.011), signifying an optimal cost-utility ratio. Model 2 showed comparable utility to the base CMR model (p=0.900) while offering the benefit of heightened surveillance frequency during periods of elevated rejection risk. CONCLUSIONS: CMR-based rejection surveillance in orthotopic heart transplant recipients provides a cost-effective alternative to EMB-based surveillance. Furthermore, it reduces the need for invasive procedures, without increased risk of rejection or hospitalisation for patients, and can be incorporated economically for expedited surveillance. These findings have important implications for improving patient care and optimising resource allocation in post-transplant management.

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.

Cardiovascular Magnetic Resonance for Rejection Surveillance After Cardiac Transplantation.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard method for surveillance of acute cardiac allograft rejection (ACAR) despite its invasive nature. Cardiovascular magnetic resonance (CMR)-based myocardial tissue characterization allows detection of myocarditis. The feasibility of CMR-based surveillance for ACAR-induced myocarditis in the first year after heart transplantation is currently undescribed. METHODS: CMR-based multiparametric mapping was initially assessed in a prospective cross-sectional fashion to establish agreement between CMR- and EMB-based ACAR and to determine CMR cutoff values between rejection grades. A prospective randomized noninferiority pilot study was then undertaken in adult orthotopic heart transplant recipients who were randomized at 4 weeks after orthotopic heart transplantation to either CMR- or EMB-based rejection surveillance. Clinical end points were assessed at 52 weeks. RESULTS: Four hundred one CMR studies and 354 EMB procedures were performed in 106 participants. Forty heart transplant recipients were randomized. CMR-based multiparametric assessment was highly reproducible and reliable at detecting ACAR (area under the curve, 0.92; sensitivity, 93%; specificity, 92%; negative predictive value, 99%) with greater specificity and negative predictive value than either T1 or T2 parametric CMR mapping alone. High-grade rejection occurred in similar numbers of patients in each randomized group (CMR, n=7; EMB, n=8; P=0.74). Despite similarities in immunosuppression requirements, kidney function, and mortality between groups, the rates of hospitalization (9 of 20 [45%] versus 18 of 20 [90%]; odds ratio, 0.091; P=0.006) and infection (7 of 20 [35%] versus 14 of 20 [70%]; odds ratio, 0.192; P=0,019) were lower in the CMR group. On 15 occasions (6%), patients who were randomized to the CMR arm underwent EMB for clarification or logistic reasons, representing a 94% reduction in the requirement for EMB-based surveillance. CONCLUSIONS: A noninvasive CMR-based surveillance strategy for ACAR in the first year after orthotopic heart transplantation is feasible compared with EMB-based surveillance. REGISTRATION: HREC/13/SVH/66 and HREC/17/SVH/80. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12618000672257.

Atrial Septal Aneurysms - A Clinically Relevant Enigma?

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.

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.

The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure.

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.

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.

Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Native T1 Mapping in the Diagnosis of Cardiac Allograft Rejection: A Prospective Histologically Validated Study.

OBJECTIVES: This study aimed to determine the role of T1 mapping in identifying cardiac allograft rejection. BACKGROUND: Endomyocardial biopsy (EMBx), the current gold standard to diagnose cardiac allograft rejection, is associated with potentially serious complications. Cardiac magnetic resonance (CMR)-based T1 mapping detects interstitial edema and fibrosis, which are important markers of acute and chronic rejection. Therefore, T1 mapping can potentially diagnose cardiac allograft rejection noninvasively. METHODS: Patients underwent CMR within 24 h of EMBx. T1 maps were acquired at 1.5-T. EMBx-determined rejection was graded according to International Society of Heart and Lung Transplant (ISHLT) criteria. RESULTS: Of 112 biopsies with simultaneous CMR, 60 were classified as group 0 (ISHLT grade 0), 35 as group 1 (ISHLT grade 1R), and 17 as group 2 (2R, 3R, clinically diagnosed rejection, antibody-mediated rejection). Native T1 values in patients with grade 0 biopsies and left ventricular ejection fraction >60% (983 ± 42 ms; 95% confidence interval: 972 to 994 ms) were comparable to values in nontransplant healthy control subjects (974 ± 45 ms; 95% confidence interval: 962 to 987 ms). T1 values were significantly higher in group 2 (1,066 ± 78 ms) versus group 0 (984 ± 42 ms; p = 0.0001) and versus group 1 (1,001 ± 54 ms; p = 0.001). After excluding patients with an estimated glomerular filtration rate <50 ml/min/m2, there was a moderate correlation of log-transformed native T1 with high-sensitivity troponin T (r = 0.54, p < 0.0001) and pro-B-type natriuretic peptide (r = 0.67, p < 0.0001). Using a T1 cutoff value of 1,029 ms, the sensitivity, specificity, and negative predictive value were 93%, 79%, and 99%, respectively. CONCLUSIONS: Myocardial tissue characterization with T1 mapping displays excellent negative predictive capacity for the noninvasive detection of cardiac allograft rejection and holds promise to reduce substantially the EMBx requirement in cardiac transplant rejection surveillance.

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.

The interplay between metabolic alterations, diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study.

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.

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.