Aortic Stenosis: Haemodynamic Benchmark and Metric Reliability Study.

Aortic stenosis is a condition which is fatal if left untreated. Novel quantitative imaging techniques which better characterise transvalvular pressure drops are being developed but require refinement and validation. A customisable and cost-effective workbench valve phantom circuit capable of replicating valve mechanics and pathology was created. The reproducibility and relationship of differing haemodynamic metrics were assessed from ground truth pressure data alongside imaging compatibility. The phantom met the requirements to capture ground truth pressure data alongside ultrasound and magnetic resonance image compatibility. The reproducibility was successfully tested. The robustness of three different pressure drop metrics was assessed: whilst the peak and net pressure drops provide a robust assessment of the stenotic burden in our phantom, the peak-to-peak pressure drop is a metric that is confounded by non-valvular factors such as wave reflection. The peak-to-peak pressure drop is a metric that should be reconsidered in clinical practice. The left panel shows manufacture of low cost, functional valves. The central section demonstrates circuit layout, representative MRI and US images alongside gross valve morphologies. The right panel shows the different pressure drop metrics that were assessed for reproducibility.

Non-invasive cardiovascular magnetic resonance assessment of pressure recovery distance after aortic valve stenosis.

BACKGROUND: Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pressure recovery along the ascending aorta which is mainly caused by turbulence energy dissipation. Currently, pressure recovery is considered to occur within the first 40-50 mm distally from the aortic valve, albeit there is inconsistency across interventionist centers on where/how to position the catheter to capture the net pressure drop. METHODS: We developed a non-invasive method to assess the pressure recovery distance based on blood flow momentum via 4D Flow cardiovascular magnetic resonance (CMR). Multi-center acquisitions included physical flow phantoms with different stenotic valve configurations to validate this method, first against reference measurements and then against turbulent energy dissipation (respectively n = 8 and n = 28 acquisitions) and to investigate the relationship between peak and net pressure drops. Finally, we explored the potential errors of cardiac catheterisation pressure recordings as a result of neglecting the pressure recovery distance in a clinical bicuspid aortic valve (BAV) cohort of n = 32 patients. RESULTS: In-vitro assessment of pressure recovery distance based on flow momentum achieved an average error of 1.8 ± 8.4 mm when compared to reference pressure sensors in the first phantom workbench. The momentum pressure recovery distance and the turbulent energy dissipation distance showed no statistical difference (mean difference of 2.8 ± 5.4 mm, R2 = 0.93) in the second phantom workbench. A linear correlation was observed between peak and net pressure drops, however, with strong dependences on the valvular morphology. Finally, in the BAV cohort the pressure recovery distance was 78.8 ± 34.3 mm from vena contracta, which is significantly longer than currently accepted in clinical practise (40-50 mm), and 37.5% of patients displayed a pressure recovery distance beyond the end of the ascending aorta. CONCLUSION: The non-invasive assessment of the distance to pressure recovery is possible by tracking momentum via 4D Flow CMR. Recovery is not always complete at the ascending aorta, and catheterised recordings will overestimate the net pressure drop in those situations. There is a need to re-evaluate the methods that characterise the haemodynamic burden caused by aortic stenosis as currently clinically accepted pressure recovery distance is an underestimation.

Blood speckle imaging compared with conventional Doppler ultrasound for transvalvular pressure drop estimation in an aortic flow phantom.

BACKGROUND: Transvalvular pressure drops are assessed using Doppler echocardiography for the diagnosis of heart valve disease. However, this method is highly user-dependent and may overestimate transvalvular pressure drops by up to 54%. This work aimed to assess transvalvular pressure drops using velocity fields derived from blood speckle imaging (BSI), as a potential alternative to Doppler.  METHODS: A silicone 3D-printed aortic valve model, segmented from a healthy CT scan, was placed within a silicone tube. A CardioFlow 5000MR flow pump was used to circulate blood mimicking fluid to create eight different stenotic conditions. Eight PendoTech pressure sensors were embedded along the tube wall to record ground-truth pressures (10 kHz). The simplified Bernoulli equation with measured probe angle correction was used to estimate pressure drop from maximum velocity values acquired across the valve using Doppler and BSI with a GE Vivid E95 ultrasound machine and 6S-D cardiac phased array transducer. RESULTS: There were no significant differences between pressure drops estimated by Doppler, BSI and ground-truth at the lowest stenotic condition (10.4 ± 1.76, 10.3 ± 1.63 vs. 10.5 ± 1.00 mmHg, respectively; p > 0.05). Significant differences were observed between the pressure drops estimated by the three methods at the greatest stenotic condition (26.4 ± 1.52, 14.5 ± 2.14 vs. 20.9 ± 1.92 mmHg for Doppler, BSI and ground-truth, respectively; p < 0.05). Across all conditions, Doppler overestimated pressure drop (Bias = 3.92 mmHg), while BSI underestimated pressure drop (Bias = -3.31 mmHg). CONCLUSIONS: BSI accurately estimated pressure drops only up to 10.5 mmHg in controlled phantom conditions of low stenotic burden. Doppler overestimated pressure drops of 20.9 mmHg. Although BSI offers a number of theoretical advantages to conventional Doppler echocardiography, further refinements and clinical studies are required with BSI before it can be used to improve transvalvular pressure drop estimation in the clinical evaluation of aortic stenosis.

The Menopause Alters Aerobic Adaptations to High-Intensity Interval Training.

INTRODUCTION: Postmenopausal women have lower resting cardiac function than premenopausal women, but whether the menopause influences maximal cardiac output and hence exercise capacity is unclear. It is possible that premenopausal and postmenopausal women achieve similar improvements in maximal aerobic capacity (V˙O2max) and cardiac output with exercise training via different regional left ventricular muscle function ("LV mechanics"), as suggested by in vitro and animal studies. The aim of this study was to investigate the effects of the menopause on LV mechanics and adaptations to exercise training. METHODS: Twenty-five healthy untrained middle-age women (age, 45-58 yr; 11 premenopausal, 14 postmenopausal) completed 12 wk of exercise training. Before and after exercise training, (i) V˙O2max and blood volume were determined, and (ii) LV mechanics were assessed using echocardiography at rest and during two submaximal physiological tests - lower-body negative pressure and supine cycling. RESULTS: The increase in V˙O2max after exercise training was 9% smaller in postmenopausal than premenopausal women, concomitant with a smaller increase in blood volume (P < 0.05). However, cardiac output and LV volumes were not different between premenopausal and postmenopausal women (P > 0.05) despite altered regional LV muscle function, as indicated by higher basal mechanics in premenopausal women during the physiological tests after exercise training (P < 0.05). CONCLUSIONS: These findings are the first to confirm altered LV mechanics in postmenopausal women. In addition, the reduced aerobic adaptability to exercise training in postmenopausal women does not appear to be a central cardiac limitation and may be due to altered blood volume distribution and lower peripheral adaptations.

Optimal Control of SonoVue Microbubbles to Estimate Hydrostatic Pressure.

The measurement of cardiac and aortic pressures enables diagnostic insight into cardiac contractility and stiffness. However, these pressures are currently assessed invasively using pressure catheters. It may be possible to estimate these pressures less invasively by applying microbubble ultrasound contrast agents as pressure sensors. The aim of this study was to investigate the subharmonic response of the microbubble ultrasound contrast agent SonoVue (Bracco Spa, Milan, Italy) at physiological pressures using a static pressure phantom. A commercially available cell culture cassette with Luer connections was used as a static pressure chamber. SonoVue was added to the phantom, and radio frequency data were recorded on the ULtrasound Advanced Open Platform (ULA-OP). The mean subharmonic amplitude over a 40% bandwidth was extracted at 0-200-mmHg hydrostatic pressures, across 1.7-7.0-MHz transmit frequencies and 3.5%-100% maximum scanner acoustic output. The Rayleigh-Plesset equation for single-bubble oscillations and additional hysteresis experiments were used to provide insight into the mechanisms underlying the subharmonic pressure response of SonoVue. The subharmonic amplitude of SonoVue increased with hydrostatic pressure up to 50 mmHg across all transmit frequencies and decreased thereafter. A decreasing microbubble surface tension may drive the initial increase in the subharmonic amplitude of SonoVue with hydrostatic pressure, while shell buckling and microbubble destruction may contribute to the subsequent decrease above 125-mmHg pressure. In conclusion, a practical operating regime that may be applied to estimate cardiac and aortic blood pressures from the subharmonic signal of SonoVue has been identified.

The female human heart at rest and during exercise: a review.

Sexual dimorphism exists in numerous aspects of exercise physiology. One area that has long been debated is the potential of sex differences in cardiac structure and function. Anthropometric differences exist between males and females, and the relationship between absolute body size and cardiac structure dictate that men typically have larger hearts than women. However, increasing evidence suggests that males and females may also demonstrate different cardiac structure and function independent of body size, and it is likely that female sex hormones play a role in these differences. The purpose of this review is to draw together and examine the literature that has compared cardiac structure and function in men and women at rest and during exercise. We make specific reference to the influence of female sex hormones, and discuss the confounding effects of age and training status. Wherever possible, we provide conclusive remarks. Due to the paucity of data in this field, and general lack of consensus, the review concludes by making recommendations for future work.

Lactose-free milk prolonged endurance capacity in lactose intolerant Asian males.

BACKGROUND: Several studies on Caucasian volunteers have proven that milk is an effective recovery drink for athletes. Such benefit, however, cannot be directly applied to the lactose-intolerant Asian population. This study investigated the effects of ingesting water (WT), sports drink (SPD) and lactose-free milk (LFM) on cycling capacity. METHODS: Ten healthy young men completed 3 randomized experimental trials. Each trial consisted of an intermittent glycogen depleting session, a 2 h recovery period during which they ingested the test drink, followed by cycling at 70% of their maximum oxygen consumption (VO2max) to volitional exhaustion. Each trial was separated by at least one week. RESULTS: There were no complaints or symptoms of lactose intolerance during any of the trials. The cycling periods were different (p < 0.05) amongst the 3 trials, namely, lactose-free milk (LFM; 69.6 ± 14.0 min), sports drink (SPD; 52.1 ± 11.6 min), and water (WT; 36.0 ± 11.1 min), respectively. The VO2 and VCO2 of LFM (30 ± 4 and 29 ± 4 ml/kg/min) were lower (p < 0.05) than that of SPD (34 ± 4 and 34 ± 4 ml/kg/min) and WT (35 ± 4 and 33 ± 5 ml/kg/min). There were no differences (p = 0.45) in VO2 and VCO2 between SPD and WT. Mean rating of perceived exertion was lowest in LFM (14 ± 5; p < 0.05), while no difference was found between the other two trials (SPD: 16 ± 4 and WT: 16 ± 4; p = 0.18). CONCLUSION: Lactose-free milk is likely to be an effective recovery drink for enhancing subsequent cycling capacity in lactose intolerant Asian males.

Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P < 0.05). Sherpa had smaller right-ventricular (RV) and LV stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function.

Neck cooling and cognitive performance following exercise-induced hyperthermia.

PURPOSE: To assess the efficacy of neck cooling on cognitive performance following exertional hyperthermia. METHODS: Twelve healthy men completed two experimental trials [control (CON) and neck cooling collar (NCC)] in a counter-balanced design. They ran on a treadmill at 70% VO2peak under warm and humid conditions (dry bulb temperature: 30.2 ± 0.3 °C, relative humidity: 71 ± 2 %) for 75 min or until volitional exhaustion. Gastrointestinal, neck and skin temperatures, heart rate and subjective ratings were assessed. Serum brain-derived neurotrophic factor (BDNF) levels were measured before and after each run. Cognitive performance comprising symbol digit matching, search and memory, digit span, choice reaction time and psychomotor vigilance test (PVT) were assessed before and after exercise. RESULTS: Mean gastrointestinal temperature was similar after exercise between trials (CON: 39.5 ± 0.4 °C vs. NCC: 39.6 ± 0.3 °C; p = 0.15). Mean neck temperature was lowered in NCC compared to CON after the run (36.4 ± 1.6 °C vs. NCC: 26.0 ± 0.3 °C; p < 0.001). Exercise-induced hyperthermia improved mean reaction time in the symbol digit matching test (-134 ± 154 ms; p < 0.05) and the PVT (-18 ± 30 ms; p < 0.05). Maximum span was increased in the digit span test (1 ± 2; p < 0.05). Application of NCC reduced the number of search errors made in level 3 of the search and memory test (p < 0.05). Mean serum BDNF levels were increased following exercise-induced hyperthermia in both trials (p < 0.05). CONCLUSION: Exercise-induced hyperthermia improves working memory and alertness. Neck cooling may only enhance performance in tasks of higher complexity.

Thermoregulation, pacing and fluid balance during mass participation distance running in a warm and humid environment.

Deep body temperature (T(c)), pacing strategy and fluid balance were investigated during a 21-km road race in a warm and humid environment. Thirty-one males (age 25.3 +/- 3.2 years; maximal oxygen uptake 59.1 +/- 4.2 ml kg(-1) min(-1)) volunteered for this study. Continuous T(c) responses were obtained in 25 runners. Research stations at approximately 3-km intervals permitted accurate assessment of split times and fluid intake. Environmental conditions averaged 26.4 degrees C dry bulb temperature and 81% relative humidity. Peak T(c) was 39.8 +/- 0.5 (38.5-40.7) degrees C with 24 runners achieving T(c) > 39.0 degrees C, 17 runners > or = 39.5 degrees C, and 10 runners > or = 40.0 degrees C. In 12 runners attaining peak T(c) > or = 39.8 degrees C, running speed did not differ significantly when T(c) was below or above this threshold (208 +/- 15 cf. 205 +/- 24 m min(-1); P = 0.532). Running velocity was the main significant predictor variable of T(c) at 21 km (R(2) = 0.42, P < 0.001) and was the main discriminating variable between hyperthermic (T(c) > or = 39.8 degrees C) and normothermic runners (T(c) < 39.8 degrees C) up to 11.8 km. A reverse J-shaped pacing profile characterised by a marked reduction in running speed after 6.9 km and evidence of an end-spurt in 16 runners was observed. Variables relating to fluid balance were not associated with any T(c) parameters or pacing. We conclude that hyperthermia, defined by a deep body temperature greater than 39.5 degrees C, is common in trained individuals undertaking outdoor distance running in environmental heat, without evidence of fatigue or heat illness.