Left ventricular assist devices for treatment of refractory advanced heart failure: the Western Australian experience.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can prolong survival and improve quality of life in end-stage heart failure. AIMS: Review outcomes of the Western Australian LVAD programme. METHODS: Retrospective database and medical record review. RESULTS: One hundred forty-seven LVADs have been implanted in 23 years, of which 95 were newer-generation devices (HeartWare HVAD [HW], HeartMate II and HeartMate 3). Presented data refer to these devices only. Most patients (94%) were classed as bridge-to-transplant or -candidacy/decision, with the remainder classed as 'destination therapy' (DT). Mean LV ejection fraction was 20%, and 36% had severe right ventricular dysfunction. Sixty-two percent of patients had a nonischaemic cardiomyopathy. Following LVAD implant, the median length of stay in intensive care was 2 days, and in the hospital overall was 23 days. Ninety-six percent of patients survived to hospital discharge, and, following discharge, 98% of days with LVAD were spent as an outpatient. The median number of hospital readmissions was 1.5 per patient per year. LVAD-associated infection requiring admission or intravenous antibiotics at any time after implant occurred in 36%, significant gastrointestinal bleeding in 19% and stroke in 11%. The percentage of patients alive with LVAD still in situ at 1, 2 and 5 years was 94%, 88% and 62% respectively, which exceeds current international registry outcomes. All DT patients survived at least 4 years, spending 97% of days with LVAD as an outpatient. The two longest-surviving HW DT patients worldwide (11.3 and 10.5 years) are among this cohort. CONCLUSIONS: Excellent outcomes can be achieved with LVADs in appropriately selected patients.

Evaluation of an artificial intelligence coronary artery calcium scoring model from computed tomography.

OBJECTIVES: Coronary artery calcium (CAC) scores derived from computed tomography (CT) scans are used for cardiovascular risk stratification. Artificial intelligence (AI) can assist in CAC quantification and potentially reduce the time required for human analysis. This study aimed to develop and evaluate a fully automated model that identifies and quantifies CAC. METHODS: Fully convolutional neural networks for automated CAC scoring were developed and trained on 2439 cardiac CT scans and validated using 771 scans. The model was tested on an independent set of 1849 cardiac CT scans. Agatston CAC scores were further categorised into five risk categories (0, 1-10, 11-100, 101-400, and > 400). Automated scores were compared to the manual reference standard (level 3 expert readers). RESULTS: Of 1849 scans used for model testing (mean age 55.7 ± 10.5 years, 49% males), the automated model detected the presence of CAC in 867 (47%) scans compared with 815 (44%) by human readers (p = 0.09). CAC scores from the model correlated very strongly with the manual score (Spearman's r = 0.90, 95% confidence interval [CI] 0.89-0.91, p < 0.001 and intraclass correlation coefficient = 0.98, 95% CI 0.98-0.99, p < 0.001). The model classified 1646 (89%) into the same risk category as human observers. The Bland-Altman analysis demonstrated little difference (1.69, 95% limits of agreement: -41.22, 44.60) and there was almost excellent agreement (Cohen's κ = 0.90, 95% CI 0.88-0.91, p < 0.001). Model analysis time was 13.1 ± 3.2 s/scan. CONCLUSIONS: This artificial intelligence-based fully automated CAC scoring model shows high accuracy and low analysis times. Its potential to optimise clinical workflow efficiency and patient outcomes requires evaluation. KEY POINTS: • Coronary artery calcium (CAC) scores are traditionally assessed using cardiac computed tomography and require manual input by human operators to identify calcified lesions. • A novel artificial intelligence (AI)-based model for fully automated CAC scoring was developed and tested on an independent dataset of computed tomography scans, showing very high levels of correlation and agreement with manual measurements as a reference standard. • AI has the potential to assist in the identification and quantification of CAC, thereby reducing the time required for human analysis.

Testosterone and exercise: effects on fitness, body composition, and strength in middle-to-older aged men with low-normal serum testosterone levels.

As men age, serum testosterone (T) concentrations decrease, as do fitness, strength, and lean mass. Whether testosterone treatment confers additive benefit to reverse these changes when combined with exercise training in middle-to-older aged men remains unclear. We assessed the effects of T treatment and exercise, alone and in combination, on aerobic capacity (V̇o2peak), body composition, and muscular strength in men 50-70 yr, waist circumference ≥95 cm and low-normal serum T (6-14 nmol·L-1). Participants (n = 80) were randomized to AndroForte5 (testosterone 5.0% wt/vol, 100 mg/2 mL) cream (T), or matching placebo (P), applied transdermally daily, and supervised center-based exercise (Ex) or no additional exercise (NEx), for 12-wk. Exercise increased V̇o2peak and strength versus nonexercise (V̇o2peak: T + Ex: +2.5 mL·kg-1·min-1, P + Ex: +3.2 mL·kg-1·min-1, P < 0.001; leg press: T + Ex: +31 kg, P + Ex: +24 kg, P = 0.006). T treatment did not affect V̇o2peak or strength. Exercise decreased total (T + Ex: -1.7, P + Ex: -2.3 kg, P < 0.001) and visceral fat (T + Ex: -0.1 kg, P + Ex: -0.3 kg, P = 0.003), and increased total (T + Ex: +1.4 kg, P + Ex: +0.7 kg, P = 0.008) and arm lean mass (T + Ex: +0.5 kg, P + Ex: +0.3 kg, P = 0.024). T treatment did not affect total or visceral fat, but increased total (T + Ex: +1.4 kg, T + NEx: +0.7 kg, P = 0.015), leg (T + Ex: +0.3 kg, T + NEx: +0.2 kg, P = 0.024), and arm lean mass (T + Ex: +0.5 kg, T + NEx: +0.2 kg, P = 0.046). T + Ex increased arm lean mass (T + Ex: +0.5 kg vs. P + NEx: -0.0 kg, P = 0.001) and leg strength (T + Ex: +31 kg vs. P + NEx: +12 kg, P = 0.032) compared with P + NEx, with no other additive effects. Exercise training was more effective than T treatment in increasing aerobic capacity and decreasing total and visceral fat mass. T treatment at therapeutic doses increased lean mass but conferred limited additional benefit when combined with exercise. Exercise should be evaluated as an antiaging intervention in preference to testosterone treatment in men.NEW & NOTEWORTHY We illustrate that exercise training generates superior outcomes to testosterone treatment for improving aerobic fitness, muscular strength, and total and visceral fat mass in men 50-70 yr with low-normal serum testosterone concentrations. Adding testosterone treatment to exercise did not provide any additive benefit for these variables. Testosterone treatment alone and exercise alone had similar impacts on lean mass. Therefore, men unable to exercise may obtain benefit from testosterone treatment alone to improve lean mass.

The Utility of Whole Body 18F-FDG PET-CT in Diagnosing Isolated Cardiac Sarcoidosis: The Western Australian Cardiac Sarcoid Study.

BACKGROUND: It is reported that up to 29-52% of patients with cardiac sarcoidosis (CS) may have isolated cardiac sarcoidosis (ICS). The wide variation in prevalence may be related to the diagnostic methods for assessing extracardiac involvement. Whole-body 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging is a useful and increasingly used technique for screening for extracardiac involvement in cases of suspected ICS. This study aims to determine the rate of isolated cardiac involvement with clinically manifest CS using cardiac 18F-FDG PET-CT. METHODS: We performed a retrospective analysis of data in the West Australian Cardiac Sarcoid (WACaS) Database. After cardiologist review and workup, all cases of proven or probable CS, based on either current Heart Rhythm Society criteria for the diagnosis of CS or local expert consensus were included. Only patients who underwent whole body 18F-FDG PET-CT were included in the final analysis. RESULTS: Fifty-two (52) cases of CS were identified. Data on symptoms, imaging findings, treatment and outcomes were collected. Of the 42 patients who underwent diagnostic 18F-FDG PET-CT, 32 demonstrated changes consistent with CS. Of the 32, 69% were male, mean age 50 years at diagnosis. Only 3/32 (9.4%) patients had ICS. Pulmonary involvement occurred in 91% with varied involvement in other organs. The mean number of extracardiac sites at diagnosis was 2.2. CONCLUSIONS: This study demonstrates the utility of 18F-FDG PET-CT in diagnosing extracardiac organ involvement in cases of CS. With the use of this modality, ICS may be rarer than previously reported.

COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ).

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

Successful Heart Transplant after Ten Hours Out-of-body Time using the TransMedics Organ Care System.

OBJECTIVE: We report the successful transplantation of a heart following an out-of-body time of 611 minutes into a recipient with dilated cardiomyopathy and left ventricular assist device implant. PATIENTS: Our patient was urgently waiting for a cardiac transplant whilst receiving LVAD support. Recurrent VF and repeated AICD shocks necessitated this action. RESULTS: Although requiring ECMO and inotropic support in the first 17 hours post-transplant, the patient was discharged from hospital on day 15 post-transplant with normal cardiac function. CONCLUSION: We report some of the salient points of the process and discuss the utility of this technology to an Australian transplant unit.

Primary care Adherence To Heart Failure guidelines IN Diagnosis, Evaluation and Routine management (PATHFINDER): a randomised controlled trial protocol.

INTRODUCTION: General practitioners (GPs) routinely provide care for patients with heart failure (HF); however, adherence to management guidelines, including titrating medication to optimal dose, can be challenging in this setting. This study will evaluate the effectiveness of a multifaceted intervention to support adherence to HF management guidelines in primary care. METHODS AND ANALYSIS: We will undertake a multicentre, parallel-group, randomised controlled trial of 200 participants with HF with reduced ejection fraction. Participants will be recruited during a hospital admission due to HF. Following hospital discharge, the intervention group will have follow-up with their GP scheduled at 1 week, 4 weeks and 3 months with the provision of a medication titration plan approved by a specialist HF cardiologist. The control group will receive usual care. The primary endpoint, assessed at 6 months, will be the difference between groups in the proportion of participants being prescribed five guideline-recommended treatments; (1) ACE inhibitor/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor at least 50% of target dose, (2) beta-blocker at least 50% of target dose, (3) mineralocorticoid receptor antagonist at any dose, (4) anticoagulation for patients diagnosed with atrial fibrillation, (5) referral to cardiac rehabilitation. Secondary outcomes will include functional capacity (6-minute walk test); quality of life (Kansas City Cardiomyopathy Questionnaire); depressive symptoms (Patient Health Questionnaire-2); self-care behaviour (Self-Care of Heart Failure Index). Resource utilisation will also be assessed. ETHICS AND DISSEMINATION: Ethical approval was granted by the South Metropolitan Health Service Ethics Committee (RGS3531), with reciprocal approval at Curtin University (HRE2020-0322). Results will be disseminated via peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: ACTRN12620001069943.

Left Ventricular Adaptation to Exercise Training via Magnetic Resonance Imaging: Studies of Twin Responses to Understand Exercise THerapy.

PURPOSE: Changes in left ventricular mass (LVM) and end-diastolic volume (EDV) in response to exercise training are important determinants of functional capacity in health and disease, but the impact of different exercise modalities remains unclear. METHODS: Using a randomized crossover design we studied the impact of resistance (RES) and endurance (END) training using cardiac magnetic resonance imaging in previously untrained monozygotic (MZ) and dizygotic (DZ) twin pairs (n = 72; 22 MZ pairs, 14 DZ same-sex pairs; 26.1 ± 5.4 yr). Twins, as pairs, undertook 3 months of RES and 3 months of END training (order randomized), separated by a 3-month washout. RESULTS: Group results revealed that END increased LVM (P < 0.001) and EDV (P = 0.007), whereas RES did not (P > 0.05). A higher proportion of individuals responded to END than RES for LVM (72% vs 38%, P < 0.001) and EDV (67% vs 40%, P = 0.003). Baseline cross-sectional intraclass correlations were higher for MZ than DZ twin pairs for all variables (e.g., LVM heritability = 0.42), but no significant correlations were apparent between pairs for change in any variable in response to either RES or END (P > 0.05). CONCLUSIONS: Our findings indicate that cardiac adaptation in response to exercise is modality-specific and that low responders to one mode of exercise can be high responders to an alternative. Heritability estimates based on cross-sectional data, which suggested a genetic contribution to LVM, do not accord with estimates based on training effects, which indicated limited genetic impact on adaptation in this 3-month study of exercise training. This study has implications for understanding the physiological and health impacts of typically used exercise modalities on cardiac adaptation in previously untrained individuals.

A prospective randomised longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise training in humans.

The principle that 'concentric' cardiac hypertrophy occurs in response to strength training, whilst 'eccentric' hypertrophy results from endurance exercise has been a fundamental tenet of exercise science. This notion is largely based on cross-sectional comparisons of athletes using echocardiography. In this study, young (27.4 ± 1.1 years) untrained subjects were randomly assigned to supervised, intensive, endurance (END, n = 10) or resistance (RES, n = 13) exercise and cardiac MRI scans and myocardial speckle tracking echocardiography were performed at baseline, after 6 months of training and after a subsequent 6 weeks of detraining. Aerobic fitness increased significantly in END (3.5 to 3.8 l min(-1), P < 0.05) but was unchanged in RES. Muscular strength significantly improved compared to baseline in both RES and END ( = 53.0 ± 1.1 versus 36.4 ± 4.5 kg, both P < 0.001) as did lean body mass (2.3 ± 0.4 kg, P < 0.001 versus 1.4 ± 0.6 kg P < 0.05). MRI derived left ventricular (LV) mass increased significantly following END (112.5 ± 7.3 to 121.8 ± 6.6 g, P < 0.01) but not RES, whilst training increased end-diastolic volume (LVEDV, END: +9.0 ± 5.0 versus RES +3.1 ± 3.6 ml, P = 0.05). Interventricular wall thickness significantly increased with training in END (1.06 ± 0.0 to 1.14 ± 0.06, P < 0.05) but not RES. Longitudinal strain and strain rates did not change following exercise training. Detraining reduced aerobic fitness, LV mass and wall thickness in END (P < 0.05), whereas LVEDV remained elevated. This study is the first to use MRI to compare LV adaptation in response to intensive supervised endurance and resistance training. Our findings provide some support for the 'Morganroth hypothesis', as it pertains to LV remodelling in response to endurance training, but cast some doubt over the proposal that remodelling occurs in response to resistance training.

Sex Differences in Cardiac Adaptation to Distinct Modalities of Exercise: A Cardiac Magnetic Resonance Study.

PURPOSE: No previous study has described sex differences in chronic cardiac adaptation in response to distinct modalities of exercise training in humans. METHODS: Cardiac magnetic resonance imaging (1.5 T) was used to assess left ventricular (LV) outcomes in 78 untrained subjects (46F, 26 M; 26.1 ± 5.4 yr). Subjects underwent 3 months of closely supervised and monitored resistance (RES) and endurance (END) training, separated by a 3-month washout period. RESULTS: LV mass (LVM) increased in response to END in both sexes (females △3.98 ± 7.98 g, P = 0.002; males △5.99 ± 10.67 g, P = 0.005), whereas LV end-diastolic volume (EDV) increased in males (△7.48 ± 11.91 mL, P = 0.002) but not females (△1.54 ± 10.49 mL, P = 0.373). In response to RES, LVM and EDV did not increase in either sex. The proportion of subjects exhibiting a positive response to training (i.e., a change >0) for LVM and EDV did not differ between sexes for either training modality. CONCLUSION: Eccentric hypertrophy in response to END training was more apparent in males than females, whereas there were no notable cardiac changes between sexes for RES training. The proportion of low versus high responders to training was not sex specific for LVM or EDV in response to either commonly prescribed exercise training modality.

Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion.

This study investigated the nitric oxide (NO) dependence of radial artery (RA) flow-mediated dilation (FMD) in response to three different reactive hyperemia (RH) shear stimulus profiles. Ten healthy males underwent the following three RH trials: 1) 5 min occlusion (5 trial), 2) 10 min occlusion (10 trial), and 3) 10 min occlusion with cuff reinflation at 30 s (10-30 trial). Trials were performed during saline infusion and repeated during N(G)-monomethyl-L-arginine (L-NMMA) infusion in the brachial artery. RA blood flow velocity was measured with Doppler ultrasound, and B-mode RA images were analyzed using automated edge detection software. Shear rate estimation of shear stress was calculated as the blood flow velocity/vessel diameter. L-NMMA decreased baseline vascular conductance by 35%. L-NMMA infusion did not affect the peak shear rate stimulus (P = 0.681) or the area under the curve (AUC) of shear rate to peak FMD (P = 0.088). The AUC was significantly larger in the 10 trial vs. the 10-30 or 5 trial (P < 0.001). Although percent FMD (%change in diameter) in the 10 trial was larger than that in the 5 trial (P = 0.035), there was no significant difference in %FMD between the saline and L-NMMA conditions in any trial: 5 trial, 5.62 +/- 1.48 vs. 5.63 +/- 1.27%; 10 trial, 9.07 +/- 1.16 vs. 11.22 +/- 2.21%; 10-30 trial, 6.52 +/- 1.43 vs. 7.98 +/- 1.51% for saline and L-NMMA, respectively (P = 0.158). We conclude the following: 1) RH following 10 min of occlusion results in an enhanced stimulus and %FMD compared with 5 min of occlusion. 2) When the occlusion cuff is reinflated 30 s postrelease of a 10 min occlusion, it does not result in an enhanced %FMD compared with that which results from RH following 5 min of occlusion. 3) The lack of effect of L-NMMA on FMD suggests that NO may not be obligatory for radial artery FMD in response to either 5 or 10 min of occlusion in healthy volunteers.

Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a single-center experience.

Gastrointestinal (GI) bleeding in ventricular assist devices (VADs) has been reported with rotary devices. The pathophysiological mechanisms and treatments are in evolution. We performed a retrospective review of GI bleeding episodes for all VADs implanted at our institution. Five male patients experienced GI bleeding-age 63.6 ± 3.64 years. VAD type VentrAssist n = 1, Jarvik 2000 n = 2, and HeartWare n = 2. All patients were anticoagulated as per protocol with antiplatelet agents (aspirin and/or clopidogrel bisulfate [Plavix] and warfarin (therapeutic international normalized ratio 2.0-3.5). There was no prior history of gastric bleeding in this group. Ten episodes of bleeding requiring blood transfusion occurred in five patients. Some patients had multiple episodes (1 × 5, 1 × 2, 3 × 1). The events occurred at varying times post-VAD implantation (days 14, 21, 26, 107, 152, 189, 476, 582, 669, and 839). Octreotide (a long-acting somatostatin analogue that reduces splanchnic arterial and portal blood flow) was administered subcutaneously or intravenously. Three patients received infusions of adrenaline at 1 µg/min to enhance pulsatility. Anticoagulation was interrupted during bleeding episodes but successfully introduced post bleeding event. GI bleeding is a significant complication of VAD therapy. In this article, we discuss diagnosis and management options.

Physical Activity Is Higher in Patients with Left Ventricular Assist Device Compared with Chronic Heart Failure.

PURPOSE: Left ventricular assist devices (LVAD) are associated with an increased aerobic capacity in patients with chronic heart failure (CHF). However, studies evaluating the impact of LVAD implantation on physical activity (PA) are lacking. The aim of this study was to compare daily PA levels in participants with LVAD with well-matched CHF participants. METHODS: Sixteen participants with an LVAD (age, 59.1 ± 10.8 yr) were case-matched to 16 participants with advanced CHF (age, 58.3 ± 8.7 yr), who were listed or being considered for cardiac transplantation. Participants underwent a cardiopulmonary exercise test to determine peak oxygen consumption (V˙O2 peak). Physical activity was monitored continuously for seven consecutive days with an Actiheart monitor. RESULTS: V˙O2 peak in the CHF group (12.3 ± 3.5 mL·kg·min) was not significantly different to the LVAD group before LVAD implantation (10.4 ± 2.1 mL·kg·min), but was lower than in the LVAD group after implantation (15.8 ± 4.3 mL·kg·min; P < 0.05). Physical activity was higher in the LVAD (19.7 ± 6.4 kJ·kg·d) compared with the CHF group (11.6 ± 6.9 kJ·kg·d; P = 0.001). The LVAD participants spent more time performing moderate-intensity PA than their CHF counterparts (median, 26 min·d; interquartile range, 24-40 min·d vs median, 12 min·d; interquartile range, 9-16 min·d; P < 0.001). Physical activity was correlated with V˙O2 peak (r = 0.582; P = 0.001) across participants in the CHF and LVAD groups. CONCLUSIONS: Higher levels of PA were observed in participants with LVAD compared with patients with advanced CHF. This may be due to a higher V˙O2 peak, resulting in an improved capacity to perform activities of daily living with less symptoms.

Cerebral blood flow responses to exercise are enhanced in left ventricular assist device patients after an exercise rehabilitation program.

Cerebral blood flow during exercise is impaired in patients with heart failure implanted with left ventricular assist devices (LVADs). Our aim was to determine whether a 3-mo exercise training program could mitigate cerebrovascular dysfunction. Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental cycle ergometer exercise protocol in 12 LVAD participants (5 female, 53.6 ± 11.8 yr; 84.2 ± 15.7 kg; 1.73 ± 0.08) pre- (PreTR) and post- (PostTR) completion of a 3-mo supervised exercise rehabilitation program. At rest, only PCAv was different PostTR (38.1 ± 10.4 cm/s) compared with PreTR (43.0 ± 10.8 cm/s; P < 0.05). PreTR, the reduction in PCAv observed from rest to exercise (5.2 ± 1.8%) was mitigated PostTR (P < 0.001). Similarly, exercise training enhanced ICA flow during submaximal exercise (~8.6 ± 13.7%), resulting in increased ICA flow PostTR compared with a reduced flow PreTR (P < 0.001). Although both end-tidal partial pressure of carbon dioxide and mean arterial pressure responses during incremental exercise were greater PostTR than PreTR, only the improved PETCO2 was related to the improved ICA flow (R2 = 0.14; P < 0.05). Our findings suggest that short-term exercise training improves cerebrovascular function during exercise in patients with LVADs. This finding should encourage future studies investigating long-term exercise training and cerebral and peripheral vascular adaptation.NEW & NOTEWORTHY Left ventricular assist devices, now used as destination therapy in end-stage heart failure, enable patients to undertake rehabilitative exercise training. We show, for the first time in humans, that training improves cerebrovascular function during exercise in patients with left ventricular assist devices. This finding may have implications for cerebrovascular health in patients with heart failure.

High-intensity interval training in patients with left ventricular assist devices: A pilot randomized controlled trial.

BACKGROUND: Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure. To date, studies evaluating the impact of aerobic training in patients with LVADs have focused on moderate-intensity exercise. METHODS: This pilot randomized controlled trial compared the effects of high-intensity interval training (HIIT) with those of moderate-intensity continuous training (MICT) on peak oxygen consumption (V̇O2 peak) in patients with LVADs. Secondary outcomes included 6-minute walk test distance, flow-mediated dilation, and anthropometry. Assessments were conducted at baseline and after 12 weeks of supervised training performed 3 times weekly. Participants were randomized to HIIT (4 sets of 4 minutes at 80%-90% V̇O2 reserve, alternating with 3 minutes at 50%-60% V̇O2 reserve) or MICT groups (28 minutes continuously at 50%-60% V̇O2 reserve). Within and between-group differences were analyzed using linear mixed models. Data are expressed as marginal means with 95% confidence intervals or as mean ± SD. RESULTS: A total of 21 participants were randomized (HIIT: age 57.7 ± 13.1 years; n = 11 and MICT: age 55.6 ± 14.2 years; n = 10) (mean ± SD). No major adverse events occurred in response to training in either group. HIIT significantly improved V̇O2 peak (15.6 [13.2-17.8] to 18.4 [16.0-20.8] ml/kg/min) (marginal mean [95% CI]) compared with MICT (16.2 [13.8-18.7] to 17.2 [14.6-19.7] ml/kg/min; p < 0.05 between groups). No significant group differences were detected in secondary outcomes. CONCLUSION: In patients with LVADs, HIIT was well tolerated and increased aerobic capacity more than MICT. These preliminary findings support the prescription of high-intensity exercise in clinically stable patients with LVADs but warrant validation in a larger sample and across a broader range of physiologic and clinical outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au, unique identifier: ACTRN12616001596493.

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy.

BACKGROUND: Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracycline-mediated cardiac injury may lie latent for years following cessation of treatment and is therefore often not detected until disease is advanced and aggressive therapy is required. Symptomatic CVD may be preceded by subclinical cardiac and vascular dysfunction. This study aimed to determine whether such dysfunction could be detected in healthy, anthracycline-treated survivors of childhood leukaemia. METHODS: Cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement and endothelial function were used to characterise pre-clinical stages of CVD. Twenty-two long-term (>5 years survival; age 21 ± 3 years) childhood leukaemia survivors were assessed. All survivors were asymptomatic and had normal resting echocardiography. To exclude potential confounding effects of radiotherapy, no survivors had received this treatment. Twenty-two similarly aged (25 ± 3 years) gender-matched controls were recruited for comparison. RESULTS: Left ventricular ejection fraction was lower in the survivors (55.0 ± 4.6%) compared to the controls (59.4 ± 6.2%; p = 0.010). Further, five survivors (23%) had clinically reduced (<50%) left ventricular ejection fraction. Normalised left ventricular end systolic volume was augmented in survivors (40.0 ± 9.1 mL·m2 vs. 34.5 ± 7.5 mL·m2; p = 0.038). Cardiac MRI did not show any late gadolinium enhancement. High resolution, ultrasound-derived flow mediated dilation was impaired in survivors (6.7 ± 2.1% vs. 8.60 ± 1.91%, p = 0.005). CONCLUSIONS: We detected subclinical changes in cardiovascular structure and function indicative of early disease in anthracycline-treated childhood leukaemia survivors with normal echocardiography. Early detection and characterisation of underlying disease allows for timely intervention and improved outcomes in this at-risk population.

Cerebral Blood Flow during Exercise in Heart Failure: Effect of Ventricular Assist Devices.

INTRODUCTION: In healthy individuals, cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL) or assessed the effects of left ventricular assist devices (LVAD). We hypothesized that subjects implanted with LVAD would exhibit impaired cerebrovascular responses to cycle exercise when compared with age- and sex-matched healthy CTRL subjects but would have enhanced responses relative to subjects with HF. METHODS: Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in nine LVAD participants (58 ± 15 yr, 87 ± 16 kg, 172 ± 8 cm, six females), nine age- and sex-matched subjects with HF (58 ± 8 yr, 84 ± 11 kg, 177 ± 6 cm), and nine CTRL (55 ± 14 yr, 74 ± 16 kg, 168 ± 10 cm). RESULTS: At rest, ICA hemodynamics (velocity, shear rate, and flow) were greater in CTRL and LVAD than that in HF (P < 0.05). Higher MCAv (+5.52 ± 1.59 cm·s, P = 0.003) and PCAv (+5.82 ± 1.41 cm·s, P = 0.001) were also observed in LVAD subjects than healthy CTRL. During exercise, ICA flow increased at all workloads in CTRL, but not in HF or LVAD groups. MCAv increased from baseline in both HF and CTRL participants (P = 0.0001), but not in LVAD subjects. Nonetheless, CTRL and LVAD showed higher MCAv (P = 0.006) and PCAv (P < 0.0001) values throughout exercise than HF. CONCLUSION: Our findings indicate that LVAD subjects exhibit higher CBF at rest and during exercise than matched HF participants but attenuated brain blood flows during exercise when compared with healthy subjects. CBF should be considered when designing exercise training interventions in patients with HF and LVAD.

Eccentric Cycling: A Promising Modality for Patients with Chronic Heart Failure.

PURPOSE: Chronic heart failure (CHF) is characterized by dyspnea and poor exercise tolerance, which decreases aerobic capacity (V˙O2peak), a measure strongly correlated with quality of life and mortality. In healthy populations, eccentric (ECC) cycling can be performed at a lower oxygen demand for matched workload, compared with concentric (CON) cycling, but few studies have previously investigated ECC cycling in CHF. We hypothesized that, when matched for external workload (W), an ECC cycling bout would be performed at a lower cardiorespiratory load (V˙O2) than CON in patients with CHF. METHODS: Eleven CHF patients (10 males) with impaired left ventricular systolic function (ejection fraction 31% ± 12%) completed a CON V˙O2peak test, with the subsequent ECC and CON protocols set at 70% of individual maximal CON power (W). Oxygen consumption (V˙O2), RER, minute ventilation (V˙E), HR, and rate pressure product were compared between conditions. RESULTS: ECC was performed at a lower V˙O2 (12.3 ± 1.3 vs 14.1 ± 0.8 mL·kg·min, P = 0.01), RER (0.92 ± 0.02 vs 0.96 ± 0.01, P = 0.01), and V˙E (36.5 ± 4.4 vs 40.2 ± 2.0 L·min, P = 0.04) in comparison with CON, despite both conditions being performed at matched workloads. HR (101 ± 5 vs 96 ± 1 bpm, P = 0.06) and rate pressure product (13,539 ± 788 vs 11,911 ± 227 bpm·mm Hg, P = 0.15) were not significantly different between conditions. CONCLUSION: When matched for external workload, ECC cycling can be performed with a lower oxygen demand than CON in patients with CHF. Eccentric cycling is a promising modality for cardiac rehabilitation in severely deconditioned patients with CHF.

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF are scant. Eccentric (ECC) cycling is a novel exercise modality that may be particularly suited to patients with CHF, but the acute impacts of ECC cycling on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow-mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC cycling increased baseline artery diameter (pre: 4.0 ± 0.8 mm vs. post: 4.2 ± 0.7 mm; P = 0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for, the decrease in FMD post-ECC cycling was no longer significant. No changes were apparent after CON. Neither ECC nor CON cycling resulted in changes to any platelet-function measures (all P > 0.05). These results suggest that both ECC and CON cycling, at a moderate intensity and short duration, can be performed by patients with HFrEF without detrimental impacts on vascular or platelet function.NEW & NOTEWORTHY This is the first evidence to indicate that eccentric (ECC) cycling can be performed relatively safely by patients with chronic heart failure (CHF), as it did not result in impaired vascular or platelet function compared with conventional cycling. This is important, as acute exercise can transiently increase atherothrombotic risk, and ECC cycling is a novel exercise modality that may be particularly suited to patients with CHF.