Improved Exercise-Related Skeletal Muscle Oxygen Consumption Following Uptake of Endurance Training Measured Using Near-Infrared Spectroscopy

Skeletal muscle metabolic function is known to respond positively to exercise interventions. Developing non-invasive techniques that quantify metabolic adaptations and identifying interventions that impart successful response are ongoing challenges for research. Healthy non-athletic adults (18–35 years old) were enrolled in a study investigating physiological adaptations to a minimum of 16 weeks endurance training prior to undertaking their first marathon. Before beginning training, participants underwent measurements of skeletal muscle oxygen consumption using near-infrared spectroscopy (NIRS) at rest (resting muscleV˙O2) and immediately following a maximal exercise test (post-exercise muscleV˙O2). Exercise-related increase in muscleV˙O2 (ΔmV˙O2) was derived from these measurements and cardio-pulmonary peakV˙O2 measured by analysis of expired gases. All measurements were repeated within 3 weeks of participants completing following the marathon and marathon completion time recorded. MuscleV˙O2 was positively correlated with cardio-pulmonary peakV˙O2 (r = 0.63, p < 0.001). MuscleV˙O2 increased at follow-up (48% increase; p = 0.004) despite no change in cardio-pulmonary peakV˙O2 (0% change; p = 0.97). Faster marathon completion time correlated with higher cardio-pulmonary peakV˙O2 (rpartial = −0.58, p = 0.002) but not muscleV˙O2 (rpartial = 0.16, p = 0.44) after adjustment for age and sex [and adipose tissue thickness (ATT) for muscleV˙O2 measurements]. Skeletal muscle metabolic adaptions occur following training and completion of a first-time marathon; these can be identified non-invasively using NIRS. Although the cardio-pulmonary system is limiting for running performance, skeletal muscle changes can be detected despite minimal improvement in cardio-pulmonary function

Evaluating semi-supervision methods for medical image segmentation: applications in cardiac magnetic resonance imaging

PURPOSE: Purpose Neural networks have potential to automate medical image segmentation but require expensive labeling efforts. While methods have been proposed to reduce the labeling burden, most have not been thoroughly evaluated on large, clinical datasets or clinical tasks. We propose a method to train segmentation networks with limited labeled data and focus on thorough network evaluation. APPROACH: We propose a semi-supervised method that leverages data augmentation, consistency regularization, and pseudolabeling and train four cardiac magnetic resonance (MR) segmentation networks. We evaluate the models on multiinstitutional, multiscanner, multidisease cardiac MR datasets using five cardiac functional biomarkers, which are compared to an expert’s measurements using Lin’s concordance correlation coefficient (CCC), the within-subject coefficient of variation (CV), and the Dice coefficient. RESULTS: The semi-supervised networks achieve strong agreement using Lin’s CCC (>0.8), CV similar to an expert, and strong generalization performance. We compare the error modes of the semi-supervised networks against fully supervised networks. We evaluate semi-supervised model performance as a function of labeled training data and with different types of model supervision, showing that a model trained with 100 labeled image slices can achieve a Dice coefficient within 1.10% of a network trained with 16,000+ labeled image slices. CONCLUSION: We evaluate semi-supervision for medical image segmentation using heterogeneous datasets and clinical metrics. As methods for training models with little labeled data become more common, knowledge about how they perform on clinical tasks, how they fail, and how they perform with different amounts of labeled data is useful to model developers and users

Measurement of T1 Mapping in Patients With Cardiac Devices: Off-Resonance Error Extends Beyond Visual Artifact but Can Be Quantified and Corrected

Background: Measurement of myocardial T1 is increasingly incorporated into standard cardiovascular magnetic resonance (CMR) protocols, however accuracy may be reduced in patients with metallic cardiovascular implants. Measurement is feasible in segments free from visual artifact, but there may still be off-resonance induced error. Aim: To quantify off-resonance induced T1 error in patients with metallic cardiovascular implants, and validate a method for error correction for a conventional MOLLI pulse sequence. Methods: Twenty-four patients with cardiac implantable electronic devices (CIEDs: 46% permanent pacemakers, PPMs; 33% implantable loop recorders, ILRs; and 21% implantable cardioverter-defibrillators, ICDs); and 31 patients with aortic valve replacement (AVR) (45% metallic) were studied. Paired mid-myocardial short-axis MOLLI and single breath-hold off-resonance field maps were acquired at 1.5 T. T1 values were measured by AHA segment, and segments with visual artifact were excluded. T1 correction was applied using a published relationship between off-resonance and T1. The accuracy of the correction was assessed in 10 healthy volunteers by measuring T1 before and after external placement of an ICD generator next to the chest to generate off-resonance. Results: T1 values in healthy volunteers with an ICD were underestimated compared to without (967 ± 52 vs. 997 ± 26 ms respectively, p = 0.0001), but were similar after correction (p = 0.57, residual difference 2 ± 27 ms). Artifact was visible in 4 ± 12, 42 ± 31, and 53 ± 27% of AHA segments in patients with ILRs, PPMs, and ICDs, respectively. In segments without artifact, T1 was underestimated by 63 ms (interquartile range: 7–143) per patient. The greatest error for patients with ILRs, PPMs and ICDs were 79, 146, and 191 ms, respectively. The presence of an AVR did not generate T1 error. Conclusion: Even when there is no visual artifact, there is error in T1 in patients with CIEDs, but not AVRs. Off-resonance field map acquisition can detect error in measured T1, and a correction can be applied to quantify T1 MOLLI accurately

Direct in-vivo assessment of global and regional mechano-electric feedback in the intact human heart

BACKGROUND: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechano-electric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in-vivo human heart is unclear. OBJECTIVE: The aim of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. METHODS: In ten patients undergoing open-heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transoesophageal echocardiography. Parameters were matched to six AHA LV model segments. The association between changes in regional myocardial segment length and in the activation-recovery interval (ARI, a conventional surrogate for action potential duration) was studied using mixed-effect models. RESULTS: Increased ventricular loading reduced longitudinal shortening (P=0.01) and shortened the ARI (P=0.02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20, 0.01 - 0.38, ms/% P=0.04) and increased local ARI dispersion (effect size -0.13, -0.23 - -0.03) ms/%, P=0.04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient, r=0.81, P=0.01). CONCLUSIONS: Mechano-electric feedback can establish a potentially pro-arrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias

Impact of microvascular obstruction on semiautomated techniques for quantifying acute and chronic myocardial infarction by cardiovascular magnetic resonance

AIMS: The four most promising semiautomated techniques (5-SD, 6-SD, Otsu and the full width half maximum (FWHM)) were compared in paired acute and follow-up cardiovascular magnetic resonance (CMR), taking into account the impact of microvascular obstruction (MVO) and using automated extracellular volume fraction (ECV) maps for reference. Furthermore, their performances on the acute scan were compared against manual myocardial infarct (MI) size to predict adverse left ventricular (LV) remodelling (≥20% increase in end-diastolic volume). METHODS: 40 patients with reperfused ST segment elevation myocardial infarction (STEMI) with a paired acute (4±2 days) and follow-up CMR scan (5±2 months) were recruited prospectively. All CMR analysis was performed on CVI42. RESULTS: Using manual MI size as the reference standard, 6-SD accurately quantified acute (24.9±14.0%LV, p=0.81, no bias) and chronic MI size (17.2±9.7%LV, p=0.88, no bias). The performance of FWHM for acute MI size was affected by the acquisition sequence used. Furthermore, FWHM underestimated chronic MI size in those with previous MVO due to the significantly higher ECV in the MI core on the follow-up scans previously occupied by MVO (82 (75-88)% vs 62 (51-68)%, p<0.001). 5-SD and Otsu were precise but overestimated acute and chronic MI size. All techniques were performed with high diagnostic accuracy and equally well to predict adverse LV remodelling. CONCLUSIONS: 6-SD was the most accurate for acute and chronic MI size and should be the preferred semiautomatic technique in randomised controlled trials. However, 5-SD, FWHM and Otsu could also be used when precise MI size quantification may be adequate (eg, observational studies)

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis

Pulsatile and resistive systolic loads as determinants of left ventricular remodelling after physical training

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Barts Cardiovascular Biomedical Research Centre onbehalf The Marathon Study Consortium Introduction Cardiovascular function depends on the inter-relation between heart and vasculature. The contribution of aorta and peripheral vessels to the total systolic load of the left ventricle (LV) can be represented respectively by a "pulsatile" and a "resistive" component. We sought to understand their interrelation by exploring how LV remodelling occurred with altered load associated with an external stimulus (training). Methods: 237 untrained healthy male and female subjects volunteering for their first-time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided into 4 groups according to the variation (positive versus null or negative) in Total Arterial Compliance Index (TACi), representing the pulsatile component of the LV load, and in Systemic Vascular Resistance Index (SVRI), representing the resistive component of the LV load. Results: 138runners (age 21-69 years; F: 51%) completed the race. Data are reported for each variable as Δ mean [95% Confidence Interval]. In the whole cohort, training was associated with a small increase in LV mass index (+3g/m2, [0, 6 g/m2]), indexed LV end-diastolic volume (EDVi) (+3ml/m2, [-2, 5 3ml/m2]), in LV mass/LVEDV ratio (+0.02g/ml, [0.00, 0.04 g/ml]) and in TACi (+0.02ml/m2, [0.02, 0.38 ml/m2]). SVRi mildly fell (-43dyn·s/cm2[-103, 17dyn·s/cm2]). TACi increase was associated with LVEDVi increase and no change in LV mass/EDV (eccentric remodelling). On the other hand, both TACi reduction and SVRi increase were associated with increase in LV mass/EDV and no significant change in LVEDVi (concentric remodelling). A similar increase in LV mass was observed in all groups. See Table. Conclusion: Cardiac remodelling observed after mild, medium term, unsupervised training seems to be related to the modifications of aorta and peripheral vessels. In particular, a reduction in pulsatile load seems associated with eccentric LV remodelling, while an increase in both pulsatile and resistive with concentric LV remodelling. Further research is needed to understand the interaction between TACi and SVRi. Table 1 LV EDVi (ml/m2) LV mass index (g/m2) LV mass/EDV TACi increase (n = 75) +4 [0, 9] +3 [0, 7] 0 [-0.03, 0.03] TACi decrease (n = 62) -1 [-6, 4] +3 [0, 8] 0.04 [0.01, 0.07] SVRi increase (n = 63) 0 [-4,4] +3 [0, 7] +0.03 [0, 0.06] SVRi decrease (n = 73) +3 [-3, 7] +3 [-1, 6] +0.01 [-0.02, 0.04

Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

BACKGROUND: Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). OBJECTIVES: This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. METHODS: Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm2/m2) were assessed pre-aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 - ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. RESULTS: At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p < 0.001), and indexed LV mass had regressed by 19% (88 ± 26 g/m2to 71 ± 19 g/m2; p < 0.001). Focal fibrosis by CMR late gadolinium enhancement did not change, but ECV increased (28.2 ± 2.9% to 29.9 ± 4.0%; p < 0.001): this was the result of a 16% reduction in matrix volume (25 ± 9 ml/m2to 21 ± 7 ml/m2; p < 0.001) but a proportionally greater 22% reduction in cell volume (64 ± 18 ml/m2to 50 ± 13 ml/m2; p < 0.001). These changes were accompanied by improvement in diastolic function, N-terminal pro-B-type natriuretic peptide, 6-min walk test results, and New York Heart Association functional class. CONCLUSIONS: Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)