Short-latency afferent inhibition is reduced in people with multiple sclerosis during fatiguing muscle contractions.

Understanding how inhibitory pathways influence motor cortical activity during fatiguing contractions may provide valuable insight into mechanisms associated with multiple sclerosis (MS) muscle activation. Short-latency afferent inhibition (SAI) reflects inhibitory interactions between the somatosensory cortex and the motor cortex, and although SAI is typically reduced with MS, it is unknown how SAI is regulated during exercise-induced fatigue. The current study examined how SAI modulates motor evoked potentials (MEPs) during fatiguing contractions. Fourteen people with relapsing-remitting MS (39 ± 6 years, nine female) and 10 healthy individuals (36 ± 6 years, six female) participated. SAI was induced by stimulation of the median nerve that was paired with TMS over the motor representation of the abductor pollicis brevis. A contraction protocol was employed that depressed force generating capacity using a sustained 3-min 15% MVC, immediately followed by a low-intensity (15% MVC) intermittent contraction protocol so that MEP and SAI could be measured during the rest phases of each duty cycle. Similar force, electromyography and MEP responses were observed between groups. However, the MS group had significantly reduced SAI during the contraction protocol compared to the healthy control group (p < .001). Despite the MS group reporting greater scores on the Fatigue Severity Scale and Modified Fatigue Impact Scale, these scales did not correlate with inhibitory measures. As there were no between-group differences in SSEPs, MS-related SAI differences during the fatiguing contractions were most likely associated with disease-related changes in central integration.

High-Intensity Small Muscle Mass Training in Patients With Heart Failure: Rationale and Design of a Randomized Controlled Trial.

OBJECTIVE: Small muscle mass training localized to the quadriceps femoris muscle group has been proposed as an intervention to reverse heart failure-related skeletal muscle impairments. Although this training paradigm has demonstrated efficacy in heart failure, it remains to be evaluated in a conventional clinical context. Hence, the aim of this proposed study is to determine the effects of integrating high-intensity small muscle mass training (HISMT) isolated to the knee extensor muscles within a standard heart failure rehabilitation program. METHODS: This single-blind, randomized controlled trial will aim to recruit 70 participants with heart failure. Participants will be randomized to either (1) standard training: combination of upper and lower extremity cardiovascular and resistance-based exercises, or (2) HISMT plus modified standard training: bilateral knee extensor HISMT and a modified version of the standard training, so that the total volume of work will be similar to standard training alone. The training interventions will be undertaken twice weekly for 12 weeks in an outpatient clinical setting. Outcome measurements will be performed at baseline and after the 12-week intervention period. The primary outcome will be exercise capacity (6-Minute Walk Test), with secondary outcomes being physical performance measures, muscle strength, and health-related quality of life. Data will be analyzed using the intention-to-treat principle. IMPACT: This study will address a gap in the literature regarding the efficacy of small muscle training under routine clinical conditions for individuals with heart failure. The findings will also provide insight into the effects of HISMT within a heart failure rehabilitation program, thus enabling the optimization of exercise prescription for this patient population.

Voluntary muscle activation in people with multiple sclerosis is reduced across a wide range of forces following maximal effort-fatiguing contractions.

Although multiple sclerosis (MS) is frequently associated with motor impairment, little is known about how muscle activation is affected with MS. The aim of this study was to use transcranial magnetic stimulation (TMS) and motor nerve stimulation to investigate voluntary muscle activation in people with MS across a range of contraction forces. Ten people with MS (39 ± 7 yr) and 10 healthy controls (40 ± 5 yr) performed elbow flexions at target contraction forces of 25%, 50%, 75%, 90%, and 100% maximal voluntary contraction (MVC) while electromyography (EMG) of the biceps brachii was recorded. Sustained elbow flexion MVCs were then performed until force declined to 60% of baseline MVC, where the target contraction forces were again examined but after the sustained MVC. Following the sustained MVC, there was a reduction in biceps EMG amplitude (P < 0.01) and motor cortical voluntary activation (P < 0.01) for the MS group across all contraction intensities. There was also an increase in the rate of torque development for motor nerve-resting twitches in the MS group following the sustained MVC (P = 0.03). Despite the MS group reporting higher fatigue severity scale scores (P < 0.01), disease duration was a better predictor of muscle activation for the MS group (r = -0.757, P = 0.01). These findings indicate that voluntary muscle activation is compromised in people with MS following maximal effort contractions, which may be associated with disease duration rather than self-reports of fatigue.NEW & NOTEWORTHY We use transcranial magnetic stimulation to demonstrate that people with relapsing-remitting multiple sclerosis (MS) have a reduced ability to activate muscles following maximal effort-fatiguing contractions. A reduced ability to activate the elbow flexor muscles after a fatiguing contraction was associated with disease duration and not self-reported levels of fatigue.

Fixed-intensity exercise tests to measure exertional dyspnoea in chronic heart and lung populations: a systematic review.

INTRODUCTION: Exertional dyspnoea is the primary diagnostic symptom for chronic cardiopulmonary disease populations. Whilst a number of exercise tests are used, there remains no gold standard clinical measure of exertional dyspnoea. The aim of this review was to comprehensively describe and evaluate all types of fixed-intensity exercise tests used to assess exertional dyspnoea in chronic cardiopulmonary populations and, where possible, report the reliability and responsiveness of the tests. METHODS: A systematic search of five electronic databases identified papers that examined 1) fixed-intensity exercise tests and measured exertional dyspnoea, 2) chronic cardiopulmonary populations, 3) exertional dyspnoea reported at isotime or upon completion of fixed-duration exercise tests, and 4) published in English. RESULTS: Searches identified 8785 papers. 123 papers were included, covering exercise tests using a variety of fixed-intensity protocols. Three modes were identified, as follows: 1) cycling (n=87), 2) walking (n=31) and 3) other (step test (n=8) and arm exercise (n=2)). Most studies (98%) were performed on chronic respiratory disease patients. Nearly all studies (88%) used an incremental exercise test. 34% of studies used a fixed duration for the exercise test, with the remaining 66% using an exhaustion protocol recording exertional dyspnoea at isotime. Exertional dyspnoea was measured using the Borg scale (89%). 7% of studies reported reliability. Most studies (72%) examined the change in exertional dyspnoea in response to different interventions. CONCLUSION: Considerable methodological variety of fixed-intensity exercise tests exists to assess exertional dyspnoea and most test protocols require incremental exercise tests. There does not appear to be a simple, universal test for measuring exertional dyspnoea in the clinical setting.

Modulation of red blood cell nitric oxide synthase phosphorylation in the quiescent and exercising human forearm.

In vitro investigations demonstrate that human erythrocytes synthesize nitric oxide via a functional isoform of endothelial nitric oxide synthase (NOS) (RBC-NOS). We tested the hypothesis that phosphorylation of RBC-NOS at serine residue 1177 (RBC-NOS1177) would be amplified in blood draining-active skeletal muscle. Furthermore, given hypoxemia modulates local blood flow and thus shear stress, and nitric oxide availability, we performed duplicate experiments under normoxia and hypoxia. Nine healthy volunteers performed rhythmic handgrip exercise at 60% of individualized maximal workload for 3.5 min while breathing room air (normoxia) and after being titrated to an arterial oxygen saturation ≈80% (hypoxemia). We measured brachial artery blood flow by high-resolution duplex ultrasound, while continuously monitoring vascular conductance and mean arterial pressure using finger photoplethysmography. Blood was sampled during the final 30 s of each stage from an indwelling cannula. Blood viscosity was measured to facilitate calculation of accurate shear stresses. Erythrocytes were assessed for levels of phosphorylated RBC-NOS1177 and cellular deformability from blood collected at rest and during exercise. Forearm exercise increased blood flow, vascular conductance, and vascular shear stress, which coincided with a 2.7 ± 0.6-fold increase in RBC-NOS1177 phosphorylation (P < 0.0001) and increased cellular deformability (P < 0.0001) under normoxia. When compared with normoxia, hypoxemia elevated vascular conductance and shear stress (P < 0.05) at rest, while cellular deformability (P < 0.01) and RBC-NOS1177 phosphorylation (P < 0.01) increased. Hypoxemic exercise elicited further increases in vascular conductance, shear stress, and cell deformability (P < 0.0001), although a subject-specific response in RBC-NOS1177 phosphorylation was observed. Our data yield novel insights into the manner that hemodynamic force and oxygen tension modulate RBC-NOS in vivo.

Single-night continuous positive airway pressure treatment improves blood fluid properties in individuals recently diagnosed with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation. While CPAP effectively ameliorates nocturnal hypoxic events and associated arousals, it remains unclear whether CVD risk factors are positively impacted. The aim of the present study was thus to assess the effects of an acute CPAP therapy on sleep quality and the physical properties of blood that determine blood fluidity. Sixteen participants with suspected OSA were recruited into the current study. Participants attended the sleep laboratory for two visits: an initial diagnostic visit that included confirmation of OSA severity and comprehensive assessments of blood parameters, followed by a subsequent visit where participants were administered an individualised, acute CPAP therapy session and had their blood assessments repeated. Holistic appraisal of blood rheological properties included assessment of blood and plasma viscosity, red blood cell (RBC) aggregation, deformability, and osmotic gradient ektacytometry. Acute CPAP treatment significantly improved sleep quality parameters, which were associated with decreased nocturnal arousals and improved blood oxygen saturation. Whole blood viscosity was significantly decreased following acute CPAP treatment, which might be explained by the improved RBC aggregation during this visit. Although an acute increase in plasma viscosity was observed, it appears that the alterations in RBC properties that mediate cell-cell aggregation, and thus blood viscosity, overcame the increased plasma viscosity. While deformability of RBC was unaltered, CPAP therapy had mild effects on the osmotic tolerance of RBC. Collectively, novel observations demonstrate that a single CPAP treatment session acutely improved sleep quality, which was accompanied by improved rheological properties.

Exertional dyspnea responses to the Dyspnea Challenge in heart failure: Comparison to chronic obstructive pulmonary disease.

BACKGROUND: In heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease. OBJECTIVES: The purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD). METHODS: The study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics. RESULTS: Twenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P<.01) and COPD (0.95, P<.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·h-1) and gradient (10.3 ± 2.8 vs. 9.6 ± 2.8%) and a greater oxygen uptake (P<.01) and ventilation (P<.01) than those with COPD. While achieving similar cardiac outputs (P=.98), stroke volumes (P=.97), and heart rates (P=.83), those with HF displayed a larger arteriovenous oxygen difference (P<.01), while those with COPD exhibited greater decreases in inspiratory capacity (P=.03), arterial oxygen saturation (P=.02), and breathing reserve (P<.01). CONCLUSIONS: The Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.

Prognostic Value of Left and right ventricular deformation strain analysis on Acute Cellular rejection in Heart Transplant recipients: A 6-year outcome study.

PURPOSE: Two-dimensional (2D) strain analysis is a sensitive method for detecting myocardial dysfunction in acute cellular rejection (ACR) from post-transplant complications. This study aims to evaluate the utility of novel left (LV) and right ventricular (RV) strain parameters for prognostic risk stratification associated with ACR burden at 1-year post transplantation. METHODS: 128 Heart transplant patients, assessed between 2012 and 2018, underwent transthoracic echocardiography and endomyocardial biopsy. 2D strain analysis was performed and history of rejection burden was assessed and grouped according to ACR burden at 1-year post transplantation. The primary endpoint was all-cause mortality at 6-years follow up. RESULTS: 21 patients met primary the endpoint. Multivariate analysis of 6-year all-cause mortality showed LV global longitudinal strain (LV GLS) (Hazard Ratio [HR] = 1.21, CI = 1.06-1.49), LV early diastolic strain rate (LV ESr) (HR = 1.31, CI = 1.12-1.54), RV GLS (HR = 1.12, CI = 1.02-1.25) and RV ESr (HR = 1.26, CI = 1.12-1.47) were significant predictors of outcome. Univariate analysis also showed LV GLS, LV ESr, RV GLS and RV ESr were significant predictors of outcome. Optimal cut-off for predicting 6-year mortality for LV GLS by receive operator characteristic was 15.5% (sensitivity: 92%, specificity: 79%). Significant reductions (p < 0.05) in LV GLS, RV GLS and LV and RV ESr between rejection groups were seen. CONCLUSIONS: Non-invasive LV and RV strain parameters are predictors of mortality in post-transplant patient with ACR. LV GLS and LV ESr are superior to other strain and conventional echo parameters.

Exertional Dyspnoea responses reported in the Dyspnoea Challenge and measures of disease severity in COPD.

BACKGROUND: The Dyspnoea Challenge has been developed to facilitate the field-based measure of exertional dyspnoea(ED). To further validate the test, we aimed to; investigate the relationship between end-exercise ED, generated by a fixed-intensity Dyspnoea Challenge(DCFIX), and measures of disease severity (Forced expiratory volume in 1 s(FEV1), six-minute walk distance(6MWD), breathing reserve(V̇E/MVV), modified medical research council dyspnoea scale (mMRC), Body-mass index, airflow Obstruction, Dyspnoea, and Exercise (BODE index) and compare the physiological response of the DCFIX to a six-minute walk test(6MWT). METHODS: Thirty-two individuals (15 female) with COPD (GOLD II-IV) (age: 69.7 ± 9.4 yrs; FEV1: 49.1 ± 18.2 %) performed 2×6MWT and 2xDCFIX at a treadmill speed of 3 km h-1 and gradient of 4 %. The intensity of ED was measured using the modified Borg dyspnoea scale at baseline and end-exercise with heart rate (HR) and oxygen saturation (SpO2) monitored continuously. During 1×6MWT and 1xDCFIX pulmonary gas exchange, cardiac output (Q̇) and dynamic hyperinflation were measured. RESULTS: End-exercise ED measured during the DCFIX was not correlated to FEV1, but moderately correlated to; 6MWD(rs = -0.54, P < .01), V̇E/MVV (rs = 0.46, P = .02), mMRC(rs = 0.45, P = .01), and the BODE index(rs = 0.53, P < .01). When comparing the DCFIX and 6MWT, participants walked to comparable levels of oxygen consumption(P = .38), ventilation(P = .37), Q̇(P = .20), V̇E/MVV(P = .83), maximum HR percentages(P = .67) and dynamically hyperinflated to a similar degree(P = .37). CONCLUSIONS: The Dyspnoea Challenge is correlated to different parameters of disease severity and produces a similar physiological and ED response to that of the 6MWT with the added benefit of being appropriate for longitudinal assessment of ED.

Effects of Acute Sleep Loss on Physical Performance: A Systematic and Meta-Analytical Review.

BACKGROUND: Sleep loss may influence subsequent physical performance. Quantifying the impact of sleep loss on physical performance is critical for individuals involved in athletic pursuits. DESIGN: Systematic review and meta-analysis. SEARCH AND INCLUSION: Studies were identified via the Web of Science, Scopus, and PsycINFO online databases. Investigations measuring exercise performance under 'control' (i.e., normal sleep, > 6 h in any 24 h period) and 'intervention' (i.e., sleep loss, ≤ 6 h sleep in any 24 h period) conditions were included. Performance tasks were classified into different exercise categories (anaerobic power, speed/power endurance, high-intensity interval exercise (HIIE), strength, endurance, strength-endurance, and skill). Multi-level random-effects meta-analyses and meta-regression analyses were conducted, including subgroup analyses to explore the influence of sleep-loss protocol (e.g., deprivation, restriction, early [delayed sleep onset] and late restriction [earlier than normal waking]), time of day the exercise task was performed (AM vs. PM) and body limb strength (upper vs. lower body). RESULTS: Overall, 227 outcome measures (anaerobic power: n = 58; speed/power endurance: n = 32; HIIE: n = 27; strength: n = 66; endurance: n = 22; strength-endurance: n = 9; skill: n = 13) derived from 69 publications were included. Results indicated a negative impact of sleep loss on the percentage change (%Δ) in exercise performance (n = 959 [89%] male; mean %Δ = - 7.56%, 95% CI - 11.9 to - 3.13, p = 0.001, I2 = 98.1%). Effects were significant for all exercise categories. Subgroup analyses indicated that the pattern of sleep loss (i.e., deprivation, early and late restriction) preceding exercise is an important factor, with consistent negative effects only observed with deprivation and late-restriction protocols. A significant positive relationship was observed between time awake prior to the exercise task and %Δ in performance for both deprivation and late-restriction protocols (~ 0.4% decrease for every hour awake prior to exercise). The negative effects of sleep loss on different exercise tasks performed in the PM were consistent, while tasks performed in the AM were largely unaffected. CONCLUSIONS: Sleep loss appears to have a negative impact on exercise performance. If sleep loss is anticipated and unavoidable, individuals should avoid situations that lead to experiencing deprivation or late restriction, and prioritise morning exercise in an effort to maintain performance.

People with multiple sclerosis have reduced TMS-evoked motor cortical output compared with healthy individuals during fatiguing submaximal contractions.

People with multiple sclerosis (PwMS) typically experience greater levels of exercise-induced fatigue compared with healthy individuals. Therefore, this study examined performance fatigability in PwMS when executing a prolonged submaximal contraction. Nine PwMS (38 ± 7 yr, 6 females) and nine healthy controls (35 ± 6 yr, 4 females) performed an elbow flexion at 15% maximal voluntary contraction (MVC) for 26 min. MVCs were performed every 2 min during, and following, the contraction to determine if maximal force was impaired by the low-intensity contraction. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the primary motor cortex with a circular coil during each MVC and during the submaximal contraction. Superimposed and resting twitches were calculated from elbow flexion torque, whereas motor-evoked potentials were calculated from biceps brachii electromyography. Ratings of perceived exertion (RPE) were obtained before each MVC. During the fatiguing contraction protocol, the MS group exhibited a reduced MVC torque compared with the healthy control group (P = 0.044), which aligned with group differences in biceps brachii EMG activity (P = 0.022) and superimposed twitch amplitude (P = 0.016). Fatigue-related decrements in MVC torque (P = 0.044) and biceps brachii EMG activity (P = 0.043) demonstrated in the MS group persisted throughout recovery. However, MS did not affect the RPE during the fatigue task. These findings suggest that PwMS may have greater levels of performance fatigability due to decreased voluntary drive from the motor cortex, which is not associated with greater ratings of perceived exertion.NEW & NOTEWORTHY By combining TMS and motor nerve stimulation during a low-intensity exercise task, we were able to uncover the contribution that different levels of the CNS have during fatiguing exercise in PwMS. Our findings are novel and revealed that PwMS experienced decreased voluntary drive from the motor cortex during a low-intensity sustained fatiguing task that was associated with heightened levels of performance fatigability.

Optimising the Dyspnoea Challenge: exertional dyspnoea responses to changing treadmill gradients.

BACKGROUND: The Dyspnoea Challenge is a two-minute treadmill walk designed to measure exertional dyspnoea(ED). To efficiently individualise workload, we aimed to assess; 1) whether the Dyspnoea Challenge is responsive to 1% changes in treadmill gradient and 2) the minimum gradient variation necessary to generate a clinically meaningful change in ED (≥1 modified Borg scale). METHODS: Thirty individuals with COPD(GOLD II-IV) (age: 69.2 ± 9.2 years; FEV1: 49.3 ± 19.1%) completed six Dyspnoea Challenges at a fixed treadmill speed of 3 km·h-1 and at a gradient of between 3% and 8%, performed in random order. ED intensity and leg fatigue were measured using the 0-10 modified Borg scale. Heart rate(HR) and oxygen saturation(SpO2) were monitored continuously. A multidimensional dyspnoea profile(MDP) was used to quantify the discomfort, physical, e.g., work/effort and breathing frequency, and emotional components of ED. RESULTS: Higher treadmill gradients generated stronger intensities of ED (3%:2.6 ± 1.8; 4%:2.8 ± 2.2; 5%:3.2 ± 2.2; 6%:3.4 ± 2.2; 7%:3.7 ± 1.8; 8%:4.0 ± 2.1units). Statistical changes were observed in ED(e.g.,3 vs. 5%: P = .03) and the MDP discomfort data(e.g.,4 vs. 6%: P = .04) at ≥ a 2% variation in treadmill gradient. Linear regression found a 4% variation in treadmill gradient corresponded to a rise in ED ≥ 1unit. Increases in ED intensity corresponded to heightened sensations of work/effort(P < .01) and breathing frequency(P < .01). There were no changes in emotional constructs(P = .27). While there was an increase in HR with increasing gradient(P < .01), no differences were observed in end-exercise SpO2(P = .79) or leg fatigue(P = .06). CONCLUSION: To significantly change ED, the treadmill gradient must be manipulated by ≥ 2%, with a ≥ 4% change in gradient required to induce a clinically meaningful change in ED.

The influence of exercise training volume alterations on the gut microbiome in highly-trained middle-distance runners.

The aim of this study was to determine the influence of training volume alterations on diversity and composition of the gut microbiome in a free-living cohort of middle-distance runners. Fourteen highly-trained middle-distance runners (n = 8 men; V˙O2peak = 70.1 ± 4.3 ml·kg·min-1; n = 6 women, V˙O2peak: 59.0 ± 3.2 ml·kg·min-1) completed three weeks of normal training (NormTr), three weeks of high-volume training (HVolTr; a 10, 20 and 30% increase in training volume during each successive week from NormTr), and a one-week taper (TaperTr; 55% exponential reduction in training volume from HVolTr week three). Faecal samples were collected before and immediately after each training phase to quantify alpha-diversity and composition of the gut microbiome. A three-day diet record was collected during each training phase and a maximal incremental running test was completed after each training phase. Results showed no significant changes in nutritional intake, alpha-diversity, or global microbial composition following HVolTr or TaperTr compared to NormTr (p's > 0.05). Following HVolTr, there was a significant decrease in Pasterellaceae (p = 0.03), Lachnoclostridium (p = 0.02), Haemophilus (p = 0.03), S. parasagunis (p = 0.02), and H. parainfluenzae (p = 0.03), while R. callidus (p = 0.03) significantly increased. These changes did not return to NormTr levels following TaperTr. This study shows that the alpha-diversity and global composition of the gut microbiome were unaffected by changes in training volume. However, an increase in training volume led to several changes at the lower taxonomy levels that did not return to pre-HVolTr levels following a taper period.

Examining the repeatability of a novel test to measure exertional dyspnoea in chronic obstructive pulmonary disease.

BACKGROUND: Exertional dyspnoea(ED) is a hallmark of chronic obstructive pulmonary disease(COPD). We examined the repeatability and face validity of the end-exercise ED(EDend) response during the Dyspnoea Challenge and compared those to the six-minute walk test (6MWT) in COPD. METHODS: Twenty-six individuals with COPD(13 Females, age:69 ± 5.5yrs, FEV1:63.4 ± 11.9 %) completed 2 × 6MWTs and 4 x Dyspnoea Challenges on three occasions. The challenge consisted of a two-minute treadmill walk at 80 % of 6MWT speed(3.9 ± 0.5 km·hr-1) at either a low(LIDC:5.3 ± 2%) or high angle of incline(HIDC:9.5 ± 3%). Dyspnoea(0-10 scale), heart rate(HR) and oxygen saturation(SpO2) were monitored continuously. RESULTS: Mean 6MWT distance was 488 ± 58 m. End-exercise ED and HR were higher in the HIDC(EDend 6.2 ± 2.0; HR: 123 ± 17beats·min-1) compared to the LIDC(EDend 4.2 ± 2.0; HR: 119 ± 15beats·min-1) and the 6MWT(EDend 4.3 ± 2.0; HR: 115 ± 16beats·min-1)(P < 0.01). SpO2 was not different between 6MWT, LIDC or HIDC(P = 0.34). The intraclass correlation coefficient(ICC) for each intensity was excellent (HIDC, ICC = 0.88, LIDC, ICC = 0.93, P < 0.001) with neither reporting bias(HIDC, P = 0.63; LIDC, P = 0.94). CONCLUSIONS: The Dyspnoea Challenge is a simple measure of ED that appears to have both repeatability and face validity. With further optimisation, this test may enhance the field-based clinical assessment of ED.

Advantage and validation of vendor-independent software for myocardial strain analysis compared to vendor-specific software.

INTRODUCTION: One of the main limitations incorporating strain imaging into widespread clinical practice is inter-vendor incompatibility. This poses a problem when serial strain measurements are required in a multi-vendor echocardiography laboratory. METHODS: This study sought to compare the variability of two-dimensional speckle-tracking global and regional longitudinal strain using vendor-specific software and vendor-independent software from images acquired by two different commercially available ultrasound systems. Forty subjects underwent two sequential echocardiographic acquisitions using different ultrasound systems (GE Vivid E9 and Philips iE33). Global longitudinal strain and regional peak longitudinal strain were derived using vendor-specific software (EchoPAC BT 13 v201 and QLAB version 10.3) and vendor-independent software (TomTec Image Arena version 4.6). Agreement and reproducibility of global and regional strain between vendor-specific and vendor-independent software were assessed by independent blinded observers. RESULTS: Global longitudinal strain derived from vendor-independent software was comparable to global longitudinal strain derived from vendor-specific software, whilst regional strain was lower in agreement compared to global longitudinal strain. There was good overall agreement and high inter- and intra-observer reproducibility using vendor-independent software for global longitudinal strain and regional strain. CONCLUSIONS: Vendor-independent software provides good agreement with vendor-specific software for global longitudinal strain. However, minor variability exists for regional strain measurements between vendor-independent and vendor-specific software. Good agreement of strain measurements derived by vendor-independent software suggests vendor-independent software could potentially be useful for serial follow-up of global longitudinal strain.

Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation.

OBJECTIVE: This study sought to determine the contractile reserve (CR) response to exercise stress echocardiography (ESE) quantified by the novel parameter, non-invasive myocardial work (MW), in subjects with angiographically proven coronary artery disease (CAD). METHODS: CR was measured by the relative change in ejection fraction (EF), global longitudinal strain (GLS) and MW indices from rest to peak exercise in 304 patients referred for clinically indicated ESE. Positive ESE patients proceeded to coronary angiography and further risk stratified based on either percutaneous or surgical intervention. RESULTS: CRGLS and global work index (CRGWI ) significantly decreased with exercise induced ischemia and angiographically proven significant CAD (CRGLS -1.6±3.5%; CRGWI -8.6±511 mm Hg% decrement, p < 0.001) compared to non-ischemic patients (CRGLS 1.4±2.2%; CRGWI 398±404 mm Hg% improvement). Global constructive work (CRGCW ) was significantly higher (p < 0.0001) in non-ischemic (818±457 mm Hg%) and blunted in ischemic patients (208±550 mm Hg%). CRGCW (AUC .81; 95%CI:.75-.86) demonstrated the most association for inducible ischemia followed by CRGLS (AUC .75; 95%CI:.69-.80), CRGWI (AUC .73, 95%CI:.67-.79) and CREF (AUC .71; 95%CI:.65-.77, p < 0.001). Subgroup analysis showed patients requiring surgical revascularization demonstrated a significantly lower CRGWE (-11.5±7.6%, p < 0.05) as a result of reduced CRGCW (281±573 mm Hg%, p < 0.05) and increased global wasted work (CRGWW , 289±151 mm Hg%, p = 0.09). CONCLUSION: Multivessel disease requiring surgical revascularization have the greatest reduction in CR. MW may potentially improve detection of ischemia and further risk stratification during ESE to maximize the benefits of revascularization.

Safety and Efficacy of Scientist Led Exercise Stress Testing for Arrhythmia Provocation and Chronotropic Competence.

For many years, non physician led exercise stress testing performed for the investigation of coronary artery disease has been endorsed by many cardiovascular (CV) societies and associations around the world. The safety guidelines don't currently include the performing of these tests for arrhythmia provocation or chronotropic assessment. Therefore, the aim of this study was to assess the safety and efficacy of non physician led EST performed for suspected arrhythmias, chronotropic competence, long QT, and accessory pathway conduction (APC) assessment. A total of 486 patients performed an exercise stress test for either of the above suspected conditions and were followed for 1.8 years ± 1.5 years. Tests were performed by a trained cardiac scientist with all reports over-read by a consultant Cardiologist. There were no significant adverse events (myocardial infarction, arrhythmia causing hemodynamic compromise or syncope) at time of testing. A total of 12.1% of patients required further follow up consisting of either a cardiac pacemaker, an implantable cardioverter defibrillator, radiofrequency ablation, Direct-Current cardioversion or a change in medications. Interobserver agreement between the Cardiologist and cardiac scientist was 98.4% indicating excellent agreement. In conclusion, the present study demonstrates that cardiac scientists can safely perform non physician led EST for the investigation of suspected arrhythmias, chronotropic competence, long QT, and APC assessment with a diagnostic interpretation equivalent to that of a consultant Cardiologist.

Resting global myocardial work can improve interpretation of exercise stress echocardiography.

Sensitivity and specificity of ESE to determine hemodynamically significant coronary artery disease (CAD) is limited by subjective qualitative interpretation resulting in false-positive results. The objective of this study was to determine whether resting myocardial work estimated from non-invasive left ventricular pressure-strain loops can help improve the interpretation of exercise stress echocardiography (ESE). Resting global myocardial work was performed on 288 patients referred for clinically indicated ESE with no resting regional wall motion abnormalities and normal ejection fraction (≥ 55%). Coronary angiography was used to validate the presence of significant CAD in those with a positive ESE. Resting global myocardial work index (GWI) was significantly reduced (p < 0.001) in patients with true-positive (1544 ± 354 mmHg%) compared to negative (1819 ± 317 mmHg%) and false-positive (1857 ± 344 mmHg%) ESE. A GWI of ≤ 1391 mmHg (AUC 0.73; sensitivity 94%; specificity 73%) predicted true-positive ESE. Predictors of a true-positive ESE were (1) lower myocardial work efficiency (odds ratio 0.731, 95% CI 0.58-0.92, p = 0.007), (2) lower GWI (odds ratio 0.997, 95% CI 0.996-0.999, p = 0.006) (3) male gender (odds ratio 5.47, 95% CI 1.84-16.31, p = 0.002) and (4) E/e' ratio (odds ratio 1.15, CI 1.01-1.31, p = 0.032). Myocardial work is a potentially valuable quantitative parameter that provides incremental value over qualitative ESE interpretation and improves appropriate patient selection for coronary angiography.

Shear Stress and RBC-NOS Serine1177 Phosphorylation in Humans: A Dose Response.

Red blood cells (RBC) express a nitric oxide synthase isoform (RBC-NOS) that appears dependent on shear stress for Serine1177 phosphorylation. Whether this protein is equally activated by varied shears in the physiological range is less described. Here, we explored RBC-NOS Serine1177 phosphorylation in response to shear stress levels reflective of in vivo conditions. Whole blood samples were exposed to specific magnitudes of shear stress (0.5, 1.5, 4.5, 13.5 Pa) for discrete exposure times (1, 10, 30 min). Thereafter, RBC-NOS Serine1177 phosphorylation was measured utilising immunofluorescence labelling. Shear stress exposure at 0.5, 1.5, and 13.5 Pa significantly increased RBC-NOS Serine1177 phosphorylation following 1 min (p < 0.0001); exposure to 4.5 Pa had no effect after 1 min. RBC-NOS Serine1177 phosphorylation was significantly increased following 10 min at each magnitude of shear stress (0.5, 1.5, 13.5 Pa, p < 0.0001; 4.5 Pa, p = 0.0042). Shear stress exposure for 30 min significantly increased RBC-NOS Serine1177 phosphorylation at 0.5 Pa and 13.5 Pa (p < 0.0001). We found that RBC-NOS phosphorylation via shear stress is non-linear and differs for a given magnitude and duration of exposure. This study provides a new understanding of the discrete relation between RBC-NOS and shear stress.