Bar-Yoseph R; Mandel H; Mainzer G; Gur M; Tal G; Shalloufeh G; Bentur L.

Pediatric Pulmonology. 53(3):366-373, 2018 03.

INTRODUCTION: Enzyme replacement therapy (ERT) with Myozyme improved the
prospect of Pompe disease patients. Our aim was to evaluate ERT acute
effect on exercise capacity in pediatric Pompe patients.

METHODS: Five Pompe patients (10-19 years, 4 infantile-onset and 1
diagnosed at 5 years) were evaluated before and 2 days after ERT using
cardiopulmonary exercise testing (CPET), 6 min walking test (6MWT) and
motor function test (GMFM-88).

RESULTS: Preserved normal peak oxygen uptake, 6MWT and motor function
were observed in the relative mild disease and impairment of these
parameters in the more advanced disease. Two days following ERT, three
patients demonstrated changes; one patient (relative mild disease)
increased both oxygen uptake (11%) and walking distance (38%). Second
patient (advanced disease) increased oxygen uptake (11%) while a small
decrease in walking distance in the 6MWT (8%) was observed. Third patient
(advanced disease) decreased oxygen uptake (39%) but increased walking
distance (42%) and motor function score (27%).

CONCLUSIONS: CPET is safe for pediatric Pompe patients. ERT may benefit
exercise capacity in patients with less advanced disease. Individualized
assessment by CPET, 6MWT, and motor function may help ERT adjustment by
providing precise quantification of the response to treatment. Additional
studies are needed to clarify the benefit of this assessment protocol.

Onofre T; Oliver N; Carlos R; Felismino A; Corte RC; Silva E; Bruno S.

PLoS ONE [Electronic Resource]. 12(4):e0172894, 2017.

Cardiopulmonary assessment through oxygen uptake efficiency slope (OUES)
data has shown encouraging results, revealing that we can obtain important
clinical information about functional status. Until now, the use of OUES
has not been established as a measure of cardiorespiratory capacity in an
obese adult population, only in cardiac and pulmonary diseases or
pediatric patients. The aim of this study was to characterize submaximal
and maximal levels of OUES in a sample of morbidly obese women and analyze
its relationship with traditional measures of cardiorespiratory fitness,
anthropometry and pulmonary function.
Thirty-three morbidly obese women
(age 39.1 +/- 9.2 years) performed Cardiopulmonary Exercise Testing (CPX)
on a treadmill using the ramp protocol. In addition, anthropometric
measurements and pulmonary function were also evaluated. Maximal and
submaximal OUES were measured, being calculated from data obtained in the
first 50% (OUES50%) and 75% (OUES75%) of total CPX duration. In one-way
ANOVA analysis, OUES did not significantly differ between the three
different exercise intensities, as observed through a Bland-Altman
concordance of 58.9 mL/min/log(L/min) between OUES75% and OUES100%, and
0.49 mL/kg/min/log(l/min) between OUES/kg75% and OUES/kg100%. A strong
positive correlation between the maximal (r = 0.79) and submaximal (r =
0.81) OUES/kg with oxygen consumption at peak exercise (VO2peak) and
ventilatory anaerobic threshold (VO2VAT) was observed, and a moderate
negative correlation with hip circumference (r = -0.46) and body adiposity
index (r = -0.50) was also verified. There was no significant difference
between maximal and submaximal OUES, showing strong correlations with each
other and oxygen consumption (peak and VAT).
These results indicate that
OUES can be a useful parameter which could be used as a cardiopulmonary
fitness index in subjects with severe limitations to perform CPX, as for
morbidly obese women.

Dirou S; Chambellan A; Chevallier P; Germaud P; Lamirault G; Gourraud PA;
Perrot B; Delasalle B; Forestier B; Guillaume T; Peterlin P; Garnier A;
Magnan A; Blanc FX; Lemarchand P.

Bone Marrow Transplantation. 53(3):281-290, 2018 03.

Long-term survivors after allogeneic hematopoietic stem cell
transplantation (allo-HSCT) are at high risk for treatment-related adverse
events, that may worsen physical capacity and may induce fatigue and
disability. The aims of this prospective study were to evaluate exercise
capacity in allotransplant survivors and its relationship with fatigue and
disability. Patient-reported outcomes and exercise capacity were evaluated
in 71 non-relapse patients 1 year after allo-HSCT, using validated
questionnaires, cardiopulmonary exercise testing (CPET) with measure of
peak oxygen uptake (peakVO2) and deconditioning, pulmonary function
testing, echocardiography and 6-min walk test. A high proportion (75.4%)
of allo-HSCT survivors showed abnormal cardiopulmonary exercise testing
parameters as compared to predicted normal values, including 49.3%
patients who exhibited moderate to severe impairment in exercise capacity
and 37.7% patients with physical deconditioning. PeakVO2 values were not
accurately predicted by 6-min walk distances (r = 0.53). Disability and
fatigue were strongly associated with decreased peakVO2 values (p = 0.002
and p = 0.008, respectively). Exercise capacity was reduced in most
allo-HSCT long-term survivors. Because reduced exercise capacity was
associated with fatigue, disability and a decrease in quality of life,
cardiopulmonary exercise testing should be performed in every patient who
reports fatigue and disability.

Chaudhry S; Arena R; Bhatt DL; Verma S; Kumar N.

Current Opinion in Cardiology. 33(2):168-177, 2018 03.

PURPOSE OF REVIEW: There is growing clinical interest for the use of
cardiopulmonary exercise testing (CPET) to evaluate patients with or
suspected coronary artery disease (CAD). With mounting evidence, this
concise review with relevant teaching cases helps to illustrate how to
integrate CPET data into real world patient care.
RECENT FINDINGS: CPET provides a novel and purely physiological basis to
identify cardiac dysfunction in symptomatic patients with both
obstructive-CAD and nonobstructive-CAD (NO-CAD). In many cases, abnormal
cardiac response on CPET may be the only objective evidence of potentially
undertreated ischemic heart disease. When symptomatic patients have NO-CAD
on coronary angiogram, they are still at increased risk for cardiovascular
events. This problem appears to be more common in women than men and may
warrant more aggressive risk factor modification. As the main intervention
is lifestyle (diet, smoking cessation, exercise) and medical therapy
(statins, angiotensin-converting enzyme inhibitors, beta-blockers), serial
CPET testing enables close surveillance of cardiovascular function and is
responsive to clinical status.
SUMMARY: CPET can enhance outpatient evaluation and management of CAD.
Diagnostically, it can help to identify physiologically significant
obstructive-CAD and NO-CAD in patients with normal routine cardiac
testing. CPET may be of particular value in symptomatic women with NO-CAD.
Prognostically, precise quantification of improvements in exercise
capacity may help to improve long-term lifestyle and medication adherence
for this chronic condition.

Ascha M; Bhattacharyya A; Ramos JA; Tonelli AR.

Medicine & Science in Sports & Exercise. 50(10):1992-1997, 2018 Oct.
VI 1

INTRODUCTION/PURPOSE: Peripheral capillary oxygen saturation (SpO2) is
used as surrogate for arterial blood oxygen saturation. We studied the
degree of discrepancy between SpO2 and arterial oxygen (SaO2) and
identified parameters that may explain this difference.
METHODS: We included patients who underwent cardiopulmonary exercise
testing at Cleveland Clinic. Pulse oximeters with forehead probes measured
SpO2 and arterial blood gas samples provided the SaO2 both at rest and
peak exercise.
RESULTS: We included 751 patients, 54 +/- 16 yr old with 53% of female
gender. Bland-Altman analysis revealed a bias of 3.8% with limits of
agreement of 0.3% to 7.9% between SpO2 and SaO2 at rest. A total of 174
(23%) patients had SpO2 >= 5% of SaO2, and these individuals were older,
current smokers with lower forced expiratory volume in the first second
and higher partial pressure of carbon dioxide and carboxyhemoglobin. At
peak exercise (n = 631), 75 (12%) SpO2 values were lower than the SaO2
determinations reflecting difficulties in the SpO2 measurement in some
patients. The bias between SpO2 and SaO2 was 2.6% with limits of agreement
between -2.9% and 8.1%. Values of SpO2 >= 5% of SaO2 (n = 78, 12%) were
associated with the significant resting variables plus lower heart rate,
oxygen consumption, and oxygen pulse. In multivariate analyses,
carboxyhemoglobin remained significantly associated with the difference
between SpO2 and SaO2 both at rest and peak exercise.
CONCLUSIONS: In the present study, pulse oximetry commonly overestimated
the SaO2. Increased carboxyhemoglobin levels are independently associated
with the difference between SpO2 and SaO2, a finding particularly relevant
in smokers.

Wagner J; Agostoni P; Arena R; Belardinelli R; Dumitrescu D; Hager A;
Myers J; Rauramaa R; Riley M; Takken T; Schmidt-Trucksass A.

American Heart Journal. 202:116-126, 2018 08.
VI 1

Heart failure with reduced ejection fraction (HFrEF) is common in the
developed world and results in significant morbidity and mortality.
Accurate risk assessment methods and prognostic variables are therefore
needed to guide clinical decision making for medical therapy and surgical
interventions with the ultimate goal of decreasing risk and improving
health outcomes. The purpose of this review is to examine the role of
cardiopulmonary exercise testing (CPET) and its most commonly used
ventilatory gas exchange variables for the purpose of risk stratification
and management of HFrEF. We evaluated five widely studied gas exchange
variables from CPET in HFrEF patients based on nine previously used
systematic criteria for biomarkers. This paper provides clinicians with a
comprehensive and critical overview, class recommendations and evidence
levels. Although some CPET variables met more criteria than others,
evidence supporting the clinical assessment of variables beyond peak VO2
is well-established. A multi-variable approach also including the VE-VCO2
slope and EOV is therefore recommended.

DeCato TW; Bradley SM; Wilson EL; Harlan NP; Villela MA; Weaver LK; Hegewald MJ;

Undersea & Hyperbaric Medicine: Journal Of The Undersea And Hyperbaric Medical Society, Inc [Undersea Hyperb Med] 2019 Mar-Apr-May; Vol. 46, pp. 117-124.

Objectives: Hyperbaric oxygen (HBO2) exposure may enhance cardiorespiratory fitness. Exercise training and HBO2 exposure stimulate mitochondrial biogenesis, increase capillary density, and induce adaptive antioxidant mechanisms. We hypothesized that an exercise regimen of sprint interval training (SIT) while breathing HBO2 would lead to a greater improvement in exercise performance compared to the same training breathing ambient air.
Methods: Healthy long-term intermediate-altitude residents, ages 20-39 years, with normal spirometry and cardiorespiratory fitness were randomized to two groups: one performing six sessions of a SIT regimen over two weeks in a hyperbaric chamber (1.4 ATA [141.9 kPa], FiO2=1.0); the other performing under ambient pressure conditions (0.85 ATA [86.1 kPa], FiO2=0.21). Training effect was evaluated by comparing incremental cycle ergometry cardiopulmonary exercise testing before and after the training regimen. The primary outcome measure was peak oxygen consumption (V̇O2), while secondary outcomes included additional exercise parameters. The effect of study group on exercise parameters was assessed using two-factor repeated measures ANOVA.
Results: Of 58 participants randomized, 49 completed the training program and all cardiopulmonary exercise tests (n=23 HBO2, n=26 ambient). Both groups experienced an increase in peak V̇O2: 8.1% HBO2 and 7.1% ambient; the differences were not significant (p=0.50). Secondary parameters of peak work rate and peak V̇E experienced a significantly higher change in the HBO2 group compared to the ambient group (p=0.05 and p=0.03, respectively).
Conclusion: Cardiorespiratory fitness improved after a two-week SIT regimen, but improvement in peak V̇O2 was not significantly different between ambient and HBO2 groups.

Vukomanovic V; Suzic-Lazic J; Celic V; Cuspidi C; Petrovic T;Grassi G; Tadic M;

Journal Of Hypertension [J Hypertens] 2019 Apr 29. Date of Electronic Publication: 2019 Apr 29.

Objective: We aimed to evaluate the association between functional capacity and left ventricular (LV) mechanics in the patients with uncomplicated type 2 diabetes.
Methods: The present cross-sectional study included 80 controls and 70 uncomplicated diabetic patients. These participants underwent laboratory analysis, comprehensive echocardiographic examination and cardiopulmonary exercise testing.
Results: Global longitudinal (-21.6 ± 2.8 vs. -18.4 ± 2.3%, P < 0.001) and circumferential (-22.0 ± 2.9 vs. -19.5 ± 2.6%, P < 0.001) strains were significantly reduced in diabetic participants. The same was found for longitudinal and circumferential endocardial, mid-myocardial and epicardial strains. Peak oxygen uptake (27.0 ± 4.3 vs. 20.7 ± 4.0 ml/kg/min, P < 0.001) and oxygen pulse (14.1 ± 3.0 vs. 11.6 ± 3.2 ml/beat, P < 0.001) were significantly lower in the diabetic group, while ventilation/carbon dioxide slope was significantly higher in these patients. In the whole study population glycosylated hemoglobin, as well as LV endocardial longitudinal and circumferential strains were independently of other clinical and echocardiographic parameters of LV structure, systolic and diastolic function associated with peak oxygen consumption and oxygen pulse.
Conclusion: Our investigation showed that diabetes equally affected all LV myocardial layers. Endocardial LV longitudinal and circumferential strains, as well as glycosylated hemoglobin – main parameter of glucose regulation, were independently associated with functional capacity in the whole study population. These findings indicate that determination of LV strain and functional capacity could detect subclinical target organ damage and prevent development of further complications in uncomplicated diabetes mellitus patients.

Roberts TJ; Burns AT; MacIsaac RJ; MacIsaac AI; Prior DL; La Gerche A;

Journal Of Applied Physiology (Bethesda, Md.: 1985) [J Appl Physiol (1985)] 2019 May 02. Date of Electronic Publication: 2019 May 02.

Exercise capacity is frequently reduced in people with diabetes mellitus (DM) and the contribution of pulmonary microvascular dysfunction remains undefined. We hypothesized that pulmonary microvascular disease, measured by a novel exercise echocardiography technique termed pulmonary transit of agitated contrast (PTAC), would be greater in subjects with DM, and that the use of pulmonary vasodilator agent sildenafil would improve exercise performance by reducing right ventricular afterload. Forty subjects with DM and 20 matched controls performed cardiopulmonary exercise testing and semi-supine exercise echocardiography one hour after placebo or sildenafil ingestion in a double-blind randomized cross-over design. The primary efficacy end-point was exercise capacity (VO2peak) whilst secondary measures included pulmonary vascular resistance, cardiac output and change in PTAC. DM subjects were aged 44 ± 13 years, 73% male, with 16 ± 10 years’ DM history. Sildenafil caused marginal improvements in echocardiographic measures of biventricular systolic function in DM subjects. Exercise-induced increases in pulmonary artery systolic pressure and pulmonary vascular resistance were attenuated with sildenafil, while heart rate (+2.4 ±1.2bpm P=0.04) and cardiac output (+322 ±21 ml, P=0.03) improved. However, the degree of PTAC did not change (P=0.93) and VO2max did not increase following sildenafil as compared to placebo (VO2peak 31.8 ±9.7 vs. 32.1 ±9.5 ml/min/kg, P=0.42). We conclude that sildenafil administration causes modest acute improvements in central hemodynamics but does not improve exercise capacity. This may be due to the mismatch in action of sildenafil on the pulmonary arteries rather than the distal pulmonary microvasculature and potential adverse effects on peripheral oxygen extraction.

Agostoni P; Dumitrescu D;

International Journal Of Cardiology [Int J Cardiol] 2019 Apr 18. Date of Electronic Publication: 2019 Apr 18.

In the present practice review, we will explain how to perform and interpret a cardiopulmonary exercise test (CPET) in heart failure patients. Specifically, we will explain why cycle ergometer should be preferred to treadmill, the type of protocol needed, and the ideal exercise duration. Thereafter, we will discuss how to interpret CPET findings and determine the parameters that should be included. We will focus specifically on: peak VO2 (absolute value and a percentage of its predicted value), exercise duration, respiratory exchange ratio, peak work rate, heart rate, O2 pulse, end-tidal carbon dioxide pressure (PetCO2), PetO2, and -if blood gas samples are obtained-dead space to tidal volume ratio. Moreover, we will discuss the physiological and clinical value of anaerobic threshold, respiratory compensation point, ventilation vs. VCO2 and VO2 vs. work relationships. Finally, attention will be dedicated to exercise-induced periodic breathing. We will also discuss when and why CPET should be integrated with other measurements in the so-called complex CPET. Specifically: a) when and how to use a complex non-invasive CPET, which integrates CPET measurements with non-invasive cardiac output determination, working muscle near-infrared spectroscopy, transthoracic echocardiography, thoracic ultrasound, and lung diffusion analysis; b) when and how to use a complex minimally invasive CPET, in which CPET is combined with esophageal balloon recordings or with serial arterial blood sampling for blood gas analysis; c) when and how to use a complex invasive CPET, which usually implies the presence of a Swan Ganz catheter in the pulmonary artery and an arterial line.