To investigate the prevalence and significance of increased left ventricular (LV) trabeculation in highly trained athletes.
Cross sectional echocardiographic study.
Sports cardiology institutions in ...the UK and France.
1146 athletes aged 14-35 years (63.3% male), participating in 27 sporting disciplines, and 415 healthy controls of similar age. The results of athletes fulfilling conventional criteria for LV non-compaction (LVNC) were compared with 75 patients with LVNC.
Number of athletes with increased LV trabeculation and the number fulfilling criteria for LVNC.
Athletes displayed a higher prevalence of increased LV trabeculation compared with controls (18.3% vs 7.0%; p ≤ 0.0001) and 8.1% athletes fulfilled conventional criteria for LVNC. Increased LV trabeculation were more common in athletes of African/Afro-Caribbean origin. A small proportion of athletes (n = 10; 0.9%) revealed reduced systolic function and marked repolarisation changes in association with echocardiographic criteria for LVNC raising the possibility of an underlying cardiomyopathy. Follow-up during the ensuing 48.6 ± 14.6 months did not reveal adverse events.
A high proportion of young athletes exhibit conventional criteria for LVNC highlighting the non-specific nature of current diagnostic criteria if applied to elite athletic populations. Further assessment of such athletes should be confined to the small minority that demonstrate low indices of systolic function and marked repolarisation changes.
Long-term effects of Coronavirus Disease of 2019 (COVID-19) are of utmost relevance.
We aimed to determine: 1) the functional capacity of COVID-19 survivors by cardiopulmonary exercise testing ...(CPET); 2) the characteristics associated with cardiopulmonary exercise testing (CPET) performance; 3) the safety and tolerability of CPET.
We prospectively enrolled consecutive patients with laboratory-confirmed COVID-19 from Azienda Sanitaria Locale 3, Genoa. Three months after hospital discharge a complete clinical evaluation, trans-thoracic echocardiography, CPET, pulmonary function tests, and dominant leg extension (DLE) maximal strength measurement were performed.
From the 225 patients discharged alive from March to November 2020, we excluded 12 incomplete/missing cases and 13 unable to perform CPET, leading to a final cohort of 200. Median percent-predicted peak oxygen uptake (%pVO2) was 88% (78.3–103.1).
Ninety-nine (49.5%) patients had %pVO2 below, whereas 101 (50.5%) above the 85% predicted value.
Among the 99 patients with reduced %pVO2, 61 (61%) had a normal anaerobic threshold: of these, 9(14.8%) had respiratory, 21(34.4%) cardiac, and 31(50.8%) non-cardiopulmonary reasons for exercise limitation. Inerestingly, 80% of patients experienced at least one disabling symtpom, not related to %pVO2 or functional capacity.
Multivariate linear regression showed percent-predicted forced expiratory volume in one-second(β = 5.29,p = 0.023), percent-predicted diffusing capacity of lungs for carbon monoxide(β = 6.31,p = 0.001), and DLE maximal strength(β = 14.09,p = 0.008) to be independently associated with pVO2.
No adverse event was reported during or after CPET, and no involved health professional developed COVID-19.
At three months after discharge, about 1/3rd of COVID-19 survivors show functional limitations, mainly explained by muscular impairment, calling for future research to identify patients at higher risk of long-term effects that may benefit from careful surveillance and targeted rehabilitation.
•Long-term effects of COVID-19 are of utmost relevance.•At 3 months half of COVID-19 patients previously discharged home have significant reduction in peak oxygen consumption at cardiopulmonary exercise test.•One third of them has no cardio-pulmonary cause as the principal mechanism of CPET impairment.•Four out of five experience at least one disabling symptom at 3-month evaluation.•Symptoms are not related with abnormal peak oxygen consumption or functional capacity.
Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by ...conventional investigative studies.
What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome in patients without cardiopulmonary disease?
This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19.
The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption VO
) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO
was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency VE/VCO
slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation.
Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO
from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.
Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent ...recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.
Abstract Background Sit-to-stand tests (STST) have recently been developed as easy-to-use field tests to evaluate exercise tolerance in COPD patients. As several modalities of the test exist, this ...review presents a synthesis of the advantages and limitations of these tools with the objective of helping health professionals to identify the STST modality most appropriate for their patients. Method Seventeen original articles dealing with STST in COPD patients have been identified and analysed including eleven on 1min-STST and four other versions of the test (ranging from 5 to 10 repetitions and from 30 s to 3 min). In these studies the results obtained in sit-to-stand tests and the recorded physiological variables have been correlated with the results reported in other functional tests. Results A good set of correlations was achieved between STST performances and the results reported in other functional tests, as well as quality of life scores and prognostic index. According to the different STST versions the processes involved in performance are different and consistent with more or less pronounced associations with various physical qualities. These tests are easy to use in a home environment, with excellent metrological properties and responsiveness to pulmonary rehabilitation, even though repetition of the same movement remains a fragmented and restrictive approach to overall physical evaluation. Conclusions The STST appears to be a relevant and valid tool to assess functional status in COPD patients. While all versions of STST have been tested in COPD patients, they should not be considered as equivalent or interchangeable.
Exercise limitation is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF) but is not consistently improved by any of the current guideline-directed medical therapies.
To ...determine whether omecamtiv mecarbil, a novel direct myosin activator that improves cardiac performance and reduces the risk for cardiovascular death or first HF event in HFrEF, can improve peak exercise capacity in patients with chronic HFrEF.
Phase 3, double-blind, placebo-controlled randomized trial of patients with HFrEF (left ventricular ejection fraction ≤35%), New York Heart Association class II-III symptoms, N-terminal pro-B-type natriuretic peptide level of 200 pg/mL or greater, and baseline peak oxygen uptake (V̇o2) of 75% or less of predicted. Patients were randomized in a 2:1 ratio (omecamtiv mecarbil to placebo) between March 2019 and May 2021 at 63 sites in North America and Europe, with the last patient visit occurring on November 29, 2021.
Omecamtiv mecarbil (n = 185) or matching placebo (n = 91), given orally twice daily at a dose of 25 mg, 37.5 mg, or 50 mg based on target plasma levels, for 20 weeks.
The primary end point was a change in exercise capacity (peak V̇o2) from baseline to week 20. Secondary end points included total workload, ventilatory efficiency, and daily physical activity as determined by accelerometry.
Among 276 patients who were randomized (median age, 64 years; IQR, 55-70 years; 42 women 15%), 249 (90%) completed the trial. The median left ventricular ejection fraction was 28% (IQR, 21-33) and the median baseline peak V̇o2 was 14.2 mL/kg/min (IQR, 11.6-17.4) in the omecamtiv mecarbil group and 15.0 mL/kg/min (IQR, 12.0-17.2) in the placebo group. Mean change in peak V̇o2 did not differ significantly between the omecamtiv mecarbil and placebo groups (mean, -0.24 mL/kg/min vs 0.21 mL/kg/min; least square mean difference, -0.45 mL/kg/min 95% CI, -1.02 to 0.13; P = .13). Adverse events included dizziness (omecamtiv mecarbil: 4.9%, placebo: 5.5%), fatigue (omecamtiv mecarbil: 4.9%, placebo: 4.4%), heart failure events (omecamtiv mecarbil: 4.9%, placebo: 4.4%), death (omecamtiv mecarbil: 1.6%, placebo: 1.1%), stroke (omecamtiv mecarbil: 0.5%, placebo: 1.1%), and myocardial infarction (omecamtiv mecarbil: 0%, placebo: 1.1%).
In patients with chronic HFrEF, omecamtiv mecarbil did not significantly improve exercise capacity over 20 weeks compared with placebo. These findings do not support the use of omecamtiv mecarbil for treatment of HFrEF for improvement of exercise capacity.
ClinicalTrials.gov Identifier: NCT03759392.
IL-1 family member interleukin 37 (IL-37) has broad antiinflammatory properties and functions as a natural suppressor of innate inflammation. In this study, we demonstrate that treatment with ...recombinant human IL-37 reverses the decrease in exercise performance observed during systemic inflammation. This effect was associated with a decrease in the levels of plasma and muscle cytokines, comparable in extent to that obtained upon IL-1 receptor blockade. Exogenous administration of IL-37 to healthy mice, not subjected to an inflammatory challenge, also improved exercise performance by 82% compared with vehicle-treated mice (P = 0.01). Treatment with eight daily doses of IL-37 resulted in a further 326% increase in endurance running time compared with the performance level of mice receiving vehicle (P = 0.001). These properties required the engagement of the IL-1 decoy receptor 8 (IL-1R8) and the activation of AMP-activated protein kinase (AMPK), because both inhibition of AMPK and IL-1R8 deficiency abrogated the positive effects of IL-37 on exercise performance. Mechanistically, treatment with IL-37 induced marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption, and increased oxidative phosphorylation. Metabolomic analyses of plasma and muscles of mice treated with IL-37 revealed an increase in AMP/ATP ratio, reduced levels of proinflammatory mediator succinate and oxidative stress-related metabolites, as well as changes in amino acid and purine metabolism. These effects of IL-37 to limit the metabolic costs of chronic inflammation and to foster exercise tolerance provide a rationale for therapeutic use of IL-37 in the treatment of inflammation-mediated fatigue.
Several extrapulmonary disorders have been linked to cigarette smoking. Smoking is reported to cause cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in the airway, and is also ...associated with pancreatitis, male infertility, and cachexia, features characteristic of cystic fibrosis and suggestive of an etiological role for CFTR.
To study the effect of cigarette smoke on extrapulmonary CFTR function.
Demographics, spirometry, exercise tolerance, symptom questionnaires, CFTR genetics, and sweat chloride analysis were obtained in smokers with and without chronic obstructive pulmonary disease (COPD). CFTR activity was measured by nasal potential difference in mice and by Ussing chamber electrophysiology in vitro. Serum acrolein levels were estimated with mass spectroscopy.
Healthy smokers (29.45 ± 13.90 mEq), smokers with COPD (31.89 ± 13.9 mEq), and former smokers with COPD (25.07 ± 10.92 mEq) had elevated sweat chloride levels compared with normal control subjects (14.5 ± 7.77 mEq), indicating reduced CFTR activity in a nonrespiratory organ. Intestinal current measurements also demonstrated a 65% decrease in CFTR function in smokers compared with never smokers. CFTR activity was decreased by 68% in normal human bronchial epithelial cells exposed to plasma from smokers, suggesting that one or more circulating agents could confer CFTR dysfunction. Cigarette smoke-exposed mice had decreased CFTR activity in intestinal epithelium (84.3 and 45%, after 5 and 17 wk, respectively). Acrolein, a component of cigarette smoke, was higher in smokers, blocked CFTR by inhibiting channel gating, and was attenuated by antioxidant N-acetylcysteine, a known scavenger of acrolein.
Smoking causes systemic CFTR dysfunction. Acrolein present in cigarette smoke mediates CFTR defects in extrapulmonary tissues in smokers.
Succi, PJ, Dinyer, TK, Byrd, MT, Voskuil, CC, and Bergstrom, HC. Application of V̇ o2 to the critical power model to derive the critical V̇ o2 . J Strength Cond Res 36(12): 3374-3380, 2022-The ...purposes of this study were to (a) determine whether the critical power (CP) model could be applied to V̇ o2 to estimate the critical V̇ o2 (CV̇ o2 ) and (b) to compare the CV̇ o2 with the V̇ o2 at CP (V̇ o2 CP), the ventilatory threshold (VT), respiratory compensation point (RCP), and the CV̇ o2 without the V̇ o2 slow component (CV̇ o2 slow). Nine subjects performed a graded exercise test to exhaustion to determine V̇ o2 peak, VT, and RCP. The subjects performed 4 randomized, constant power output work bouts to exhaustion. The time to exhaustion (T Lim ), the total work (W Lim ), and the total volume of oxygen consumed with (TV̇ o2 ) and without the slow component (TV̇ o2 slow) were recorded during each trial. The linear regressions of the TV̇ o2 vs. T Lim , TV̇ o2 slow vs. T Lim , and W Lim vs. T Lim relationship were performed to derive the CV̇ o2 , CV̇ o2 slow, and CP, respectively. A 1-way repeated-measures analysis of variance ( p ≤ 0.05) with follow-up Sidak-Bonferroni corrected pairwise comparisons indicated that CV̇ o2 (42.49 ± 3.22 ml·kg -1 ·min -1 ) was greater than VT (30.80 ± 4.66 ml·kg -1 ·min -1 ; p < 0.001), RCP (36.74 ± 4.49 ml·kg -1 ·min -1 ; p = 0.001), V̇ o2 CP (36.76 ± 4.31 ml·kg -1 ·min -1 ; p < 0.001), and CV̇ o2 slow (38.26 ± 2.43 ml·kg -1 ·min -1 ; p < 0.001). However, CV̇ o2 slow was not different than V̇ o2 CP ( p = 0.140) or RCP ( p = 0.235). Thus, the CP model can be applied to V̇ o2 to derive the CV̇ o2 and theoretically is the highest metabolic steady state that can be maintained for an extended period without fatigue. Furthermore, the ability of the CV̇ o2 to quantify the metabolic cost of exercise and the inefficiency associated with the V̇ o2 slow component may provide a valuable tool for researchers and coaches to examine endurance exercise.
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