Exercise Cardiac Magnetic Resonance Imaging Research Articles

Cardiac and intramuscular adaptations following short-term exercise prehabilitation in unfit patients scheduled to undergo hepatic or pancreatic surgery: study protocol of a multinuclear MRI study

IntroductionShort-term exercise prehabilitation programmes have demonstrated promising results in improving aerobic capacity of unfit patients prior to major abdominal surgery. However, little is known about the cardiac and skeletal muscle...

Anatomical/Physiological Correlates of Functional Capacity in Adults With Repaired and Nonsevere Coarctation of the Aorta

BackgroundThere is limited data regarding the interplay of anatomic and physiologic parameters with exercise capacity in adults with native or recurrent nonsevere coarctation of the aorta (CoA). ObjectivesThe objective of this study was to use exercise stress echocardiography and cardiac magnetic resonance imaging to identify anatomic and physiologic correlates of exercise capacity in these patients. MethodsWe conducted a single-center retrospective analysis of 54 adults with nonsevere CoA (repaired or unrepaired) followed at our institution between 2015 and 2020. Resting coarctation gradients were obtained using echocardiography. Exercise gradients and functional capacity were assessed using exercise stress echocardiography. Aorta anatomy was obtained using magnetic resonance imaging. ResultsCoarctation-to-diaphragm ratio correlated with minutes of exercise (r = 0.56, P < 0.01) and metabolic equivalents (r = 0.49, P < 0.01). These relationships remained significant after controlling for use of beta-blockers, valvular disease, and type of coarctation repair. Minutes of exercise correlated with mean resting gradients (r = −0.39, P < 0.05). Coarctation-to-diaphragm ratio correlated with peak and mean resting gradients (r = −0.34, P < 0.05; r = −0.48, P < 0.01). Patients with coarctation-to-diaphragm ratio ≤0.7 achieved fewer metabolic equivalents (11.1 ± 1.9 vs 12.8 ± 2.2, P < 0.05) and minutes of exercise (10.3 ± 2.0 vs 12.6 ± 2.7, P < 0.05). ConclusionsIn patients with nonsevere native or recurrent CoA, reduced exercise capacity is correlated with coarctation severity by anatomic size and gradients. Those with a coarctation-to-diaphragm ratio ≤0.7 may represent a subset of patients with nonsevere CoA whose clinical symptoms are only elicited with exercise stress testing. Exercise stress testing and cross-sectional imaging may help identify those who could be considered for earlier coarctation intervention.

Preliminary results of whole exome sequencing in a clinical hypertrophic cardiomyopathy cohort in India

Abstract Funding Acknowledgements Type of funding sources: None. Background Hypertrophic cardiomyopathy (HCM), characterized by unexplained left ventricular hypertrophy and outcomes ranging from normal life expectancy to heart failure and sudden cardiac death, has a global prevalence of about 1 in 500. Genetic testing helps to improve care of patients with HCM and their family members as children of carriers have a 50% chance of inheriting the disease. However, there is limited availability, awareness and application of genetic testing modalities, particularly whole exome sequencing (WES), in the management of HCM in India. Purpose This study aimed to analyze the results of WES in a clinical HCM cohort in India. Methods Patients with unexplained moderate to severe cardiomyopathy presenting to our centre from 2017 to 2022 and consenting for genetic testing were included in the study. Following a thorough clinical diagnostic process including 3-generational family history, electrocardiogram and echocardiogram in all patients and exercise stress test, Holter monitoring and cardiac magnetic resonance imaging where applicable, pre-test counseling was provided and WES performed using genomic DNA isolated from whole blood samples. A total of 33 affected individuals including 1 affected family member from 32 families were processed for genetic testing. A multidisciplinary team comprising of cardiologist, cardiothoracic surgeon, physician with expertise in cardiogenetics, geneticist and genetic counselor carried out the study in a tertiary cardiac centre. Results Age of the probands (n=32) at the time of the study was 47.8±15.9 years and 24 (75%) were males. There was concomitant hypertension in 11 (34%), type 2 diabetes mellitus in 6 (19%), arrhythmias in 6 (19%) and coronary artery disease in 2 (6%) probands. Obstructive HCM was present in 2 (6%) probands. Disease-causing significant variants (Pathogenic/Likely pathogenic) were detected in 8 (25%, Table), variants of uncertain significance in 17 (53%) and no significant variants were detected in 7 cases. Cascade genetic testing of significant variants among 7 family members of 4 probands showed segregation of the pathogenic variant in 4 asymptomatic carriers. Conclusions The yield of whole exome sequencing in a clinical HCM cohort in India was 25%. Of note the rare variants of uncertain significance in the cardiomyopathy genes makes genetic counseling and disease management challenging. However, large-scale studies in the context of Indian population are expected to bring clarity on the role of these variants in disease manifestation. A multidisciplinary team approach incorporating genetic testing modalities such as whole exome sequencing and cascade screening is the way forward in the comprehensive management of patients with HCM and their families.

Association of symptoms with myocardial fibrosis in adults with Fontan circulation

The extent and significance of cardiac remodeling in Fontan patients are unclear. The aim of this study was to measure myocardial fibrosis in single ventricle (SV) and to determine its relationship with Fontan failure. A prospective cross-sectional study was performed in 25 patients (mean age 32 ± 9 years, 48% male) with SV. Echocardiography, cardiopulmonary exercise test, BNP measurement and cardiac magnetic resonance imaging (CMR) were performed within the same day. Assessment of late gadolinium enhancement in combination with T1 mapping to quantify diffuse myocardial fibrosis with assessment of myocardial extracellular volume (ECV) were performed. Associations between parameters of SV remodeling, BNP and exercise performances were evaluated. Ten patients (40%) showed clinical signs of Fontan failure. SV volumes and mass were significantly increased in these patients compared to asymptomatic patients ( P < 0.01), while there was no difference in SV ejection fraction. Compared to asymptomatic Fontan patients, those with failing Fontan had significantly higher native T1 (1030 ± 29 ms vs. 982 ± 25 ms, P < 0.001) and ECV (32% (interquartile range (IQR) 30–36) vs. 27% IQR [25–30], P = 0.002). Amongst CMR parameters, only native T1 was significantly correlated with the peak VO2 [r = −0.49, P = 0.017] and BNP (r = 0.41, P = 0.046). No association was observed with echocardiographic parameters of SV systolic and diastolic function. Diffuse myocardial fibrosis is a determinant of Fontan circulation failure independently of systolic ventricular function.

Preventing the adverse cardiovascular consequences of allogeneic stem cell transplantation with a multi-faceted exercise intervention: the ALLO-Active trial protocol

BackgroundAllogeneic stem cell transplantation (allo-SCT) is a potentially lifesaving treatment for high-risk hematological malignancy, but survivors experience markedly elevated rates of cardiovascular disease and associated functional impairment. Mounting evidence suggests regular exercise, combined with a reduction in sedentary time through replacement with light exercise may be a useful therapeutic strategy for the prevention of cardiovascular comorbidities. However, this type of intervention has yet to be evaluated in patients undergoing allo-SCT. The ALLO-Active study will evaluate the efficacy of a ~ 4 month multi-faceted exercise intervention, commenced upon admission for allo-SCT, to preserve peak oxygen uptake (VO2peak) and peak cardiac output, compared with usual care. The study will also evaluate the effect of the intervention on functional independence, quality of life, and symptoms of fatigue.MethodsSixty adults with hematological malignancy scheduled for allo-SCT will be randomly assigned to usual care (n = 30) or the exercise and sedentary behaviour intervention (n = 30). Participants assigned to the intervention will complete a thrice weekly aerobic and progressive resistance training program and concomitantly aim to reduce daily sedentary time by 30 min with short, frequent, light-intensity exercise bouts. Participants will undergo testing prior to, immediately after inpatient discharge, and 12 weeks after discharge. To address aim 1, VO2peak and peak cardiac output (multiple primary outcomes, p < 0.025) will be assessed via cardiopulmonary exercise testing and exercise cardiac magnetic resonance imaging, respectively. Secondary outcomes include functional independence (defined as VO2peak ≥ 18.mL.kg−1.min−1), quality of life, and fatigue (assessed via validated questionnaire). Exploratory outcomes will include indices of resting cardiac, vascular, and skeletal muscle structure and function, cardiovascular biomarkers, anxiety and depression, transplant outcomes (e.g., engraftment, graft-versus-host disease), and habitual physical activity, sedentary time, and sleep.DiscussionMulti-faceted exercise programs are a promising approach for ameliorating the cardiovascular consequences of allo-SCT. If this intervention proves to be effective, it will contribute to the development of evidence-based exercise guidelines for patients undergoing allo-SCT and assist with optimising the balance between acute cancer management and long-term health.Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ID: 12619000741189. Registered 17 May 2019.

Resuming Training in High-Level Athletes After Mild COVID-19 Infection: A Multicenter Prospective Study (ASCCOVID-19)

BackgroundThere is a paucity of data on cardiovascular sequelae of asymptomatic/mildly symptomatic SARS-Cov-2 infections (COVID).ObjectivesThe aim of this prospective study was to characterize the cardiovascular sequelae of asymptomatic/mildly symptomatic COVID-19 among high/elite-level athletes.Methods950 athletes (779 professional French National Rugby League (F-NRL) players; 171 student athletes) were included. SARS-Cov-2 testing was performed at inclusion, and F-NRL athletes were intensely followed-up for incident COVID-19. Athletes underwent ECG and biomarker profiling (D-Dimer, troponin, C-reactive protein). COVID(+) athletes underwent additional exercise testing, echocardiography and cardiac magnetic resonance imaging (CMR).Results285/950 athletes (30.0%) had mild/asymptomatic COVID-19 [79 (8.3%) at inclusion (COVID(+)prevalent); 206 (28.3%) during follow-up (COVID(+)incident)]. 2.6% COVID(+) athletes had abnormal ECGs, while 0.4% had an abnormal echocardiogram. During stress testing (following 7-day rest), COVID(+) athletes had a functional capacity of 12.8 ± 2.7 METS with only stress-induced premature ventricular ectopy in 10 (4.3%). Prevalence of CMR scar was comparable between COVID(+) athletes and controls [COVID(+) vs. COVID(−); 1/102 (1.0%) vs 1/28 (3.6%)]. During 289 ± 56 days follow-up, one athlete had ventricular tachycardia, with no obvious link with a SARS-CoV-2 infection. The proportion with troponin I and CRP values above the upper-limit threshold was comparable between pre- and post-infection (5.9% vs 5.9%, and 5.6% vs 8.7%, respectively). The proportion with D-Dimer values above the upper-limit threshold increased when comparing pre- and post-infection (7.9% vs 17.3%, P = 0.01).ConclusionThe absence of cardiac sequelae in pauci/asymptomatic COVID(+) athletes is reassuring and argues against the need for systematic cardiac assessment prior to resumption of training (clinicaltrials.gov; NCT04936503).

Oxygen Pathway Limitations in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation/perfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention. Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared with healthy participants (n=10). Furthermore, we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10). Peak Vo2 (oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted; P<0.0001). The difference was attributable to impairments in multiple steps of the O2 cascade, including O2 delivery (product of cardiac output and arterial O2 content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O2 extracted in the periphery (ie, ΔAVo2 [arteriovenous O2 content difference]) was not different. After pulmonary vascular intervention, peak Vo2 increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min]; P=0.036) but remained below age-predicted levels (70±11%). The O2 delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVo2 was unchanged, as was skeletal muscle diffusion capacity. We demonstrated that patients with CTEPH have significant impairment of all steps in the O2 use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak Vo2 by partly correcting O2 delivery but had no effect on abnormalities in peripheral O2 extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.

Cardiovascular sequalae in uncomplicated COVID-19 survivors.

BackgroundA high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.MethodsWe performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1–4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.ResultsThe mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.ConclusionCardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.

Exercise Cardiac Magnetic Resonance Imaging in Boys With Duchenne Muscular Dystrophy Without Cardiac Disease

BackgroundDuchenne muscular dystrophy is caused by mutations in the DMD gene, resulting in cardiomyopathy in all affected children by 18 years. Although cardiomyopathy is now the leading cause of mortality in these children, there is ongoing debate regarding timely diagnosis, secondary prevention, and treatment of this condition. The purpose of this study was to use exercise cardiac magnetic resonance imaging in asymptomatic young boys with Duchenne muscular dystrophy to describe their heart function and compare this with healthy controls. MethodsWe studied 11 boys with Duchenne muscular dystrophy aged 8.6 to 13.9 years and 11 healthy age- and sex-matched controls. ResultsCompared with the controls, boys with Duchenne muscular dystrophy had lower ejection fraction at rest (57% versus 63%; P = 0.004). During submaximal exercise, they reached similar peak tachycardia but increased their heart rate and cardiac output only half as much as controls (P = 0.003 and P = 0.014, respectively). End-systolic volume remained higher in boys with Duchenne muscular dystrophy both at rest and during exercise. When transthoracic echocardiography was compared with cardiac magnetic resonance imaging, 45% of the echocardiograms had suboptimal or poor views in the Duchenne muscular dystrophy group. ConclusionsBoys with Duchenne muscular dystrophy had abnormalities in left ventricular systolic function that were exaggerated by exercise stress. Exercise cardiac magnetic resonance imaging is feasible in a select population of children with Duchenne muscular dystrophy, and it has the potential to unmask early signs of cardiomyopathy.

Exercise cardiac magnetic resonance imaging to assess dynamic right ventricular outflow tract obstruction in congenital heart disease: a case report.

BackgroundRight ventricular outflow tract obstruction in patients with congenital heart disease is usually assessed using echocardiographic peak instantaneous gradient at rest. Since right ventricular outflow tract obstruction may change during exercise (dynamic right ventricular outflow tract obstruction), we present a case emphasizing the potential use of exercise cardiac magnetic resonance imaging (CMR).Case summaryWe discuss a 15-year-old patient with repaired mid-ventricular sub-pulmonary stenosis type double-chambered right ventricle causing right ventricular outflow tract obstruction and symptoms on exertion. In this case, exercise CMR imaging provided additional information, allowing adequate surgical planning.DiscussionThe additional value of exercise CMR imaging in a case of right ventricular outflow tract obstruction was described. Although exercise cardiac magnetic resonance imaging did not show a significant increase in peak gradient across the right ventricular outflow tract obstruction, shifting and D-shaping of the interventricular septum with subsequent insufficient left ventricular filling (preload) was observed in the patient with recurrent double-chambered right ventricle. This case demonstrates how exercise CMR imaging can be helpful in the clinical decision beyond standard echocardiographic evaluation by providing additional evidence of adverse haemodynamics during exercise.

Hemodynamic and Ventilatory Responses during Exercise in Pediatric Patients with Pulmonary Embolism

Background Pediatric patients with pulmonary embolism (PE) suffer from exercise intolerance and dyspnea on exertion, often without right heart dysfunction or pulmonary hypertension - at least at rest. The pathophysiology of the exercise limitation following pediatric PE therefore remains incompletely understood. Objectives To extend our understanding of exercise intolerance in pediatric patients with PE by examining ventilatory and hemodynamic responses to exercise. Methods To accomplish our goal, we instituted a standardized institutional protocol to systematically assess exercise capacity in pediatric PE patients in the first 3 months following diagnosis. Between February 2019- June 2020, 15 patients underwent resting pulmonary function tests and an incremental symptom-limited cardiopulmonary exercise testing (CPET) to obtain peak exercise in 8-12 minutes. All patients had received anticoagulation for at least 3 months. In all patients, right and left ventricular systolic and/or diastolic dysfunction at rest was ruled out by transthoracic echocardiography. Continuous measurements were made of minute ventilation (VE), oxygen uptake (VO2), carbon dioxide production (VCO2), heart rate (HR), and blood pressure. Predicted values for peak VO2 and work rate were generated from predictive equations. Patients with impaired exercise capacity, defined as &amp;lt;80% of age-, sex- and ideal lean body mass predicted, and dyspnea on exertion underwent further exercise cardiac magnetic resonance (exCMR) imaging using an MR compatible ergometer. Biventricular volumes and contractility, RV longitudinal strain, and RV to pulmonary artery coupling were assessed at rest and with exercise. Results Baseline, clinical characteristics, and CPET data are shown in Tables 1 and 2. Forced Vital Capacity was normal without signs of airway obstruction. Three patients failed to reach their predicted physiologic limits during exercise, and CPET was terminated by the patient prematurely (e.g., muscular exertion, fatigue, &amp; dyspnea, respectively). The mean exercise duration was 9.85 min. The mean ventilatory reserve was within normal limits (&amp;gt;15%) in all but 1 patient. VO2/work rate was normal with normal VO2 at the anaerobic threshold (mean 1541ml/kg/min, SD:731). Exercise capacity, as measured by peak VO2 was reduced, that is, &amp;lt;80% of predicted, in 5 out of the 15 patients (30%). Of these, three patients had echocardiography evidence of RV dysfunction at PE diagnosis, which had resolved at the time of CPET. There were no differences in the mean exercise time and maximal work rate achieved in those with low exercise capacity relative to normal capacity. The ventilatory equivalent for CO2 (VE/VCO2) at peak exercise was elevated (&amp;gt;35) in three of the five patients with decreased exercise capacity. The O2 pulse was attenuated in patients with decreased exercise capacity when compared to those with normal exercise capacity (7.5 mL.beat -1 vs. 12.9-1; p=0.037). Of the two patients who underwent exCMR; one showed reduced right ventricular ejection fraction (38%), abnormal RV strain (-11.3%), elevated right sided pressures signified by interventricular flattening upon inspiration during free breathing scan and an uncoupled RV to the pulmonary circulation. Conclusions Reduced exercise capacity is common after PE and not evident by resting evaluations. Pediatric PE patients with low exercise capacity and dyspnea seem to be characterized by either an abnormal pulmonary vascular response to exercise or decreased ventilatory efficiency. Larger studies are needed to better understand exercise pathophysiology after pediatric PE. Disclosures No relevant conflicts of interest to declare.

Exercise cardiac MRI unmasks cardiac dysfunction in childhood and adolescent cancer survivors with reduced cardiopulmonary fitness

Abstract Background Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk. Purpose To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve Methods Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value &amp;lt;85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging. Results 12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71). Conclusions Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation

Exercise as a diagnostic and therapeutic tool for preventing cardiovascular morbidity in breast cancer patients\u2013 the BReast cancer EXercise InTervention (BREXIT) trial protocol

BackgroundAnthracycline chemotherapy (AC) is an efficacious (neo) adjuvant treatment for early-stage breast cancer (BCa), but is associated with an increased risk of cardiac dysfunction and functional disability. Observations suggest that regular exercise may be a useful therapy for the prevention of cardiovascular morbidity but it is yet to be interrogated in a large randomised trial.The primary aims of this study are to: 1) determine if 12-months of ET commenced at the onset of AC can reduce the proportion of BCa patients with functional disability (peak VO2, < 18 ml/kg/min), and 2) compare current standard-of-care for detecting cardiac dysfunction (resting left-ventricular ejection fraction assessed from 3-dimensional echocardiography) to measures of cardiac reserve (peak exercise cardiac output assessed from exercise cardiac magnetic resonance imaging) for predicting the development of functional disability 12-months following AC. Secondary aims are to assess the effects of ET on VO2peak, left ventricular morphology, vascular stiffness, cardiac biomarkers, body composition, bone mineral density, muscle strength, physical function, habitual physical activity, cognitive function, and multidimensional quality of life.MethodsOne hundred women with early-stage BCa (40–75 years) scheduled for AC will be randomized to 12-months of structured exercise training (n = 50) or a usual care control group (n = 50). Participants will be assessed at baseline, 4-weeks following completion of AC (4-months) and at 12-months for all measures.DiscussionWomen diagnosed with early-stage BCa have increased cardiac mortality. More sensitive strategies for diagnosing and preventing AC-induced cardiovascular impairment are critical for reducing cardiovascular morbidity and improving long-term health outcomes in BCa survivors.Trial registrationAustralia & New Zealand Clinical Trials Registry (ANZCTR), ID: 12617001408370. Registered on 5th of October 2017.

Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing

BackgroundVaried detection methods have resulted in conflicting reports on the prevalence of cardiac disease in Duchenne and Becker muscular dystrophy carriers (MDC). MethodsWe performed a prospective cohort study of 77 genetically-confirmed MDC mothers, 22 non-carrier mothers, and 25 controls. All participants underwent Cardiopulmonary Exercise Testing (CPET) and Cardiac Magnetic Resonance imaging (CMR). Results25% of carriers had ventricular ectopy in recovery of exercise (RecVE) as compared to 1 non-carrier and no controls (p = .003). No difference in age or maximal oxygen consumption was noted. 11 carriers had abnormal (<55%) left ventricular ejection fraction by CMR. Evidence of late gadolinium enhancement (LGE) was noted in 48% of MDC, 1 non-carrier patient and no control subjects (p < .0001). Subset analysis of LGE+ and LGE- subjects revealed differences in age (44.1 v 38.6 yrs.; p = .005), presence of RecVE, (38.9% v 10.5%, p = .004), and high serum creatine kinase (CK) (> 289 U/l; 52.8% v 31.6%, p = .065). ConclusionWe describe the prevalence of disease using CPET and CMR in genetically-proven MDC. 49% of carriers had fibrosis, opposed to 5% of non-carriers, highlighting the importance of genetic testing in this population. Despite cardiomyopathy, functional assessment by treadmill was normal, illustrating the discrepancy in cardiac and skeletal muscle impacts. Age, RecVE and serum CK appear to have an important role in predicting cardiomyopathy. Serum CK levels suggest that a systemic higher global disease severity and not tissue heterogeneity may be the etiology for greater cardiac disease and relatively spared skeletal muscle disease in this population.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02972580?term=mendell&cond=Duchenne+Muscular+Dystrophy&rank=5; ClinicalTrials.gov Identifier: NCT02972580

Prospective, Comprehensive Cardiac Assessment in Patients Receiving BTK Inhibitor Therapy

The development of Bruton Kinase Inhibitors (BTKi) has been a major advance in the treatment of chronic lymphocytic leukaemia and related B cell malignancies, but atrial fibrillation (AF) and sudden cardiac deaths are emerging as unique side effects of BTKi. The pathophysiology of cardiac side effects in BTKi treated patients is not known, and an excess of cardiac diseases is not exhibited in the congenital BTK deficiency population. Our group has previously shown in cell models that ibrutinib inhibits the phosphoinositide 3-kinase (PI3K)-AKT pathway in the heart, providing a potential explanation for cardiotoxicity. The PI3K pathway is the major cardioprotective mechanism in the heart under stress conditions, and mice with cardiomyopathy and reduced PI3K can display AF, ventricular arrhythmias and develop severe cardiomyopathy. Concerningly, given the above information, cardiac surveillance has not been routinely incorporated in BTKi trials. We therefore sought to prospectively and systemically assess cardiac function and rhythm in patients commencing BTKi therapy. Method: This is a prospective, multicentre study with the aim of conducting comprehensive cardiac assessment of patients commencing BTKi. This assessment involved 2 domains: 1) detection of subclinical arrhythmias by performing baseline and 3 month follow-up Holter Monitor testing, 2) quantification of subclinical structural changes including dynamic atrial and ventricular contractile function using transthoracic echocardiogram (TTE) and exercise cardiac magnetic resonance imaging (MRI) at baseline and 3 months. The primary outcome assessed was significant reduction in left atrial(LA) volume as a measure of ibrutinib-induced myocardial dysfunction. A 12.5% difference in LA volume is clinically meaningful given that it has been associated with greater AF risk in predisposed individuals. A sample size of 40 provides adequate power of 0.8, α = 0.05 for detecting a 12.5% increase in LA volume from an expected baseline of -18±3. Secondary outcomes measured were: 1) Reduction in ventricular ejection fraction during exercise cardiac MRI, 2) reduction in VO2 max on cardiopulmonary exercise testing. Results: A total number of 40 patients with median age of 68 years were recruited over median follow-up of 12 months (Table 1). 6/40 patients demonstrated significant reduction in left atrial volume at 3 month follow-up. They were not clinically symptomatic and did not have co-existing history of AF. Functional testing with VO2 max on cardiopulmonary exercise testing showed significant reduction in VO2 max in 8/40 patients. There were no significant reduction in ventricular ejection fraction during exercise cardiac MRI. 1/40 patients developed symptomatic AF 257 days after commencing ibrutinib and symptoms were controlled with a beta blocker. He had normal baseline TTE but was found to have enlargement of LA volume during follow-up. One patient with Waldenstrom Macroglobulinameia with normal baseline cardiac testing died from presumed ventricular tachycardia 3 months after commencing trial drug, before reassessment could be conducted. Overall, our data indicated that despite thorough cardiac surveillance, no significant cardiac abnormalities were detected at 3 month follow-up. Conclusion: This prospective and comprehensive cardiac study demonstrated no significant evidence of functional, structural or rhythm abnormalities at 3 month follow-up of patients commencing BTKiinhibitor, as assessed by Holter monitor, exercise cardiac MRI, cardiopulmonary testing and transthoracic echocardiography. Longer follow-up and additional electrophysiological studies may be required to further delineate the cause of BTKi induced cardiotoxicity. Disclosures McMullen: CLL Global Research Funding: Research Funding. Handunnetti:Gilead: Honoraria; Abbvie: Other: Travel Grant. Tam:Abbvie, Janssen: Research Funding; Abbvie, Janssen, Beigene, Roche, Novartis: Honoraria.

P591Insights from Exercise Cardiac Magnetic Resonance Imaging (ExMR) With Cardiopulmonary Testing in HIV Patients

Abstract Background Cardiac magnetic resonance imaging in conjunction with exercise (exMR) and cardiopulmonary testing (CPET) to evaluate cardiopulmonary function has the potential of uncovering poorly understood mechanisms of dyspnea in patients that cannot be otherwise discerned with a single imaging modality. Purpose We prospectively evaluated the value of this technique in dyspneic patients with HIV without obvious cardiopulmonary etiologies to comprehensively assess mechanisms of dyspnea. Methods Thirty-six HIV patients with dyspnea without obvious cardiopulmonary causes [normal chest x-ray, normal resting LVEF and resting pulmonary artery (PA) pressures &lt;40 mm Hg on echo] and exercise limitation [Modified Medical Research Council (MMRC) dyspnea scale &gt;2] underwent testing using a novel combined exMR/CPET platform (Figure 1). Resting and exercise magnetic resonance imaging (MRI), including flow velocities across the pulmonary artery together with CPET was evaluated at pre and post peak stress. We analyzed the correlation between CPET and MRI pre and peak exercise variables. Results The mean age was 51 years; 60% were male; and mean absolute CD4 count was 718. Ventilator efficiency at peak exercise (Peak VO2) did not correlate with exMR parameters. Peak VE/VCO2 was negatively associated with peak LV and RV stroke volume (p values 0.002 &amp; 0.005 respectively). There was a positive relationship between peak petCO2and LV cardiac output (p=0.02), peak exercise RV stroke volume (p=0.003), peak exercise LV stroke volume (p=0.02). Absolute CD4 count was positively correlated with post exercise pulmonary artery velocity (p=0.045). We found no correlation between absolute CD8 count and CMR and CPET exercise parameters. Figure 1. MRI-CPET setting Conclusion HIV patients appear to have an impairment of ventilatory efficiency, exemplified by the association of VE/VCO2and PetCO2 with exMR parameters in the context of normal RV/LV contractile reserve and no evidence of Pulmonary arterial hypertension. A combined CPET/exMRI platform may provide new insight into cardiopulmonary function and the factors influencing exercise tolerance in symptomatic HIV patients. Acknowledgement/Funding 7R01HL125060-03

Quantification of biventricular strain and assessment of ventriculo-ventricular interaction in pulmonary arterial hypertension using exercise cardiac magnetic resonance imaging and myocardial feature tracking.

Right ventricular (RV) failure is the main cause of mortality in pulmonary arterial hypertension (PAH). Exercise testing helps identify early RV maladaptation and systolic dysfunction and facilitates therapy. Myocardial strain has been shown to be more sensitive than ejection fraction (EF) in detecting subclinical ventricular contractile dysfunction. Chronic pressure overload in PAH had been associated with changes in left ventricular (LV) filling. To compare biventricular strains and ventriculo-ventricular interaction in PAH and controls using cardiac magnetic resonance feature tracking (cMRI-FT) and to determine the reproducibility of strain analysis. Prospective. Nine PAH and nine control subjects. 1.5T MRI balanced steady state free precession. RV and LV longitudinal strain (EllRV and EllLV ) were derived using the mid-axial images. Radial (ErrLV ) and circumferential strain (EccLV ) were derived using the mid-ventricular short-axis images. Relationships between strain and volumetric parameters were assessed at rest and during submaximal in-magnet exercise. Comparison of rest-to-exercise data between PAH and controls was analyzed using two-way repeated measures analysis of variance. The relationship between volumetric parameters and cMRI-FT were assessed using Pearson's correlation. Reproducibility was assessed by using Bland-Altman plots. PAH had significantly lower EllRV at rest (-16.6 ± 2.7 vs. -20.1 ± 3.6, P = 0.03) despite normal RVEF. During exercise, RV systolic contractile reserve measured by EllRV was significantly reduced in PAH (PInteraction = 0.02). In PAH, indexed RV end-systolic volume (ESVi) significantly correlated with EccLV and ErrLV at rest (r = -0.65 and r = -0.70, P < 0.05) and with ErrLV during exercise (r = -0.43, P < 0.05). High observer agreement was demonstrated. Despite normal resting RVEF, RV systolic function and contractile reserve as measured by EllRV was significantly reduced in PAH. The close relation between RVESVi with EccLV and ErrLV provides evidence of systolic ventriculo-ventricular interaction in PAH. Exercise cMRI-FT may provide a quantitative metric for detection of subclinical RV dysfunction in PAH. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1427-1436.

Long-Term Cardiac Function After Peripartum Cardiomyopathy and Preeclampsia: A Danish Nationwide, Clinical Follow-Up Study Using Maximal Exercise Testing and Cardiac Magnetic Resonance Imaging.

BackgroundLong‐term clinical studies of peripartum cardiomyopathy (PPCM) are few. We aimed to measure the long‐term effect of PPCM on cardiac function in comparison with the long‐term effects of severe preeclampsia and uncomplicated pregnancy.Methods and ResultsA nationwide Danish cohort of women diagnosed with PPCM from 2005 to 2014 (PPCMgroup) were invited to participate in a clinical follow‐up study including maximal cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Matched women with previous severe preeclampsia (preeclampsia group) and previous uncomplicated pregnancies (uncomplicated pregnancies group) served as comparison groups. A total of 84 women with 28 in each group participated. Median time to follow‐up after PPCM was 91 months. Most women (85%) in the PPCM group reported no symptoms of heart failure. Mean left ventricular ejection fraction in the PPCM group was normal at 62%, but significantly lower than in the preeclampsia group and the uncomplicated pregnancies group where mean left ventricular ejection fraction was 69% and 67%, respectively (P<0.0001). Women in the PPCM group also had impaired diastolic function with reduced left ventricular peak filling rate, left atrial passive emptying volume, and left atrial passive emptying fraction. Maximal exercise capacity (peak VO 2) was also reduced in the PPCM group compared with the preeclampsia group and the uncomplicated pregnancies group, and PPCM, high body mass index, and low left ventricular ejection fraction independently predicted reduced peak VO 2. Only 1 woman with PPCM had late gadolinium enhancement.ConclusionsWomen generally recovered left ventricular ejection fraction and were asymptomatic 7 years after PPCM, but had subtle diastolic dysfunction on cardiac magnetic resonance imaging and reduced peak VO 2. Focal myocardial fibrosis assessed with late gadolinium enhancement was, however, uncommon.

Exercise cardiac magnetic resonance imaging: a feasibility study and meta-analysis.

Cardiac stress testing improves detection and risk assessment of heart disease. Magnetic resonance imaging (MRI) is the clinical gold-standard for assessing cardiac morphology and function at rest; however, exercise MRI has not been widely adapted for cardiac assessment because of imaging and device limitations. Commercially available magnetic resonance ergometers, together with improved imaging sequences, have overcome many previous limitations, making cardiac stress MRI more feasible. Here, we aimed to demonstrate clinical feasibility and establish the normative, healthy response to supine exercise MRI. Eight young, healthy subjects underwent rest and exercise cinematic imaging to measure left ventricular volumes and ejection fraction. To establish the normative, healthy response to exercise MRI we performed a comprehensive literature review and meta-analysis of existing exercise cardiac MRI studies. Results were pooled using a random effects model to define the left ventricular ejection fraction, end-diastolic, end-systolic, and stroke volume responses. Our proof-of-concept data showed a marked increase in cardiac index with exercise, secondary to an increase in both heart rate and stroke volume. The change in stroke volume was driven by a reduction in end-systolic volume, with no change in end-diastolic volume. These findings were entirely consistent with 17 previous exercise MRI studies (226 individual records), despite differences in imaging approach, ergometer, or exercise type. Taken together, the data herein demonstrate that exercise cardiac MRI is clinically feasible, using commercially available exercise equipment and vendor-provided product sequences and establish the normative, healthy response to exercise MRI.