Author Archives: Paul Older

Scaling the Oxygen Uptake Efficiency Slope for Body Size in Cystic Fibrosis.

Tomlinson OW, Barker AR, Oades PJ, Williams CA.

Med Sci Sports Exerc. 2017 May 9. doi: 10.1249/MSS.0000000000001314. [Epub ahead
of print]

PURPOSE: The aim of this study was to describe the relationship between body size
and the oxygen uptake efficiency slope (OUES) in paediatric patients with cystic
fibrosis (CF) and healthy controls (CON), in order to identify appropriate
scaling procedures to adjust the influence of body size upon OUES.
METHODS: The OUES was derived using maximal and submaximal points from
cardiopulmonary exercise testing in 72 children (36 CF and 36 CON). OUES was
subsequently scaled for stature, body mass (BM) and body surface area (BSA) using
ratio-standard (Y/X) and allometric (Y/X) methods. Pearson’s correlation
coefficients were utilised to determine the relationship between body size and
the OUES.
RESULTS: When scaled using the ratio-standard method, OUES had a significant
positive relationship with stature (r = 0.54, P < 0.001) and BSA (r = 0.25, P = 0.031) and significant negative relationship with BM (r = -0.38, P = 0.016) in the CF group. Combined allometric exponents (b) for CF and CON were: stature 3.00, BM 0.86, BSA 1.40. A significant negative correlation was found between OUES and stature in the CF group when scaled allometrically (r = -0.37, P = 0.027). Non-significant (P > 0.05) correlations for the whole group were found
between OUES and allometrically scaled BM (CF: r = -0.25, CON: r = 0.15) and BSA
(CF r = -0.27, CON r = 0.13).
CONCLUSIONS: Only allometric scaling of either BM or BSA, and not ratio-standard
scaling, successfully eliminates the influence of body size upon OUES. Therefore
this enables a more direct comparison of the oxygen uptake slope between patients
with CF and healthy controls.

Measuring Cardiac Output during Cardiopulmonary Exercise Testing

Vignati C, Cattadori G

Ann Am Thorac Soc. 2017 Apr 25. doi: 10.1513/AnnalsATS.201611-852FR. [Epub ahead
of print]

Cardiac output is a key parameter in the assessment of cardiac function, and its
measurement is fundamental to the diagnosis, treatment, and prognostic evaluation
of all heart diseases. Until recently, cardiac output determination during
exercise had been only possible through invasive methods, which were not
practical in the clinical setting. Since oxygen uptake (V.O2) is cardiac output
times arteriovenous content difference [C(a-v)O2)], evaluation of cardiac output
is usually included its measurement. Because of the difficulty of directly
measuring peak exercise cardiac output, indirect surrogate parameters have been
proposed, but with only modest clinical usefulness. Direct measurement of cardiac
output can now be made by several noninvasive measurements, such as rebreathing
inert gases, impedance cardiology, thoracic bioreactance, estimated continuous
cardiac output (EsCCO) technology, and transthoracic echocardiography coupled to
cardiopulmonary exercise testing allow more definitive results and better
understanding of the underlying physiopathology.

Periodic Breathing during Incremental Exercise.

Agostoni P, Corrà U, Emdin M.

Ann Am Thorac Soc. 2017 Apr 26. doi: 10.1513/AnnalsATS.201701-003FR. [Epub ahead
of print]

Periodic breathing during incremental cardiopulmonary exercise testing is a
regularly recurring waxing and waning of tidal volume due to oscillations in
central respiratory drive. Periodic breathing is a sign of respiratory control
system instability, which may occur at rest or during exercise. The possible
mechanisms responsible of exertional periodic breathing might be related to any
instability of the ventilatory regulation caused by: 1) increased circulatory
delay (i.e., circulation time from the lung to the brain and chemoreceptors, due
to reduced cardiac index leading to delay in information transfer), 2) increase
in controller gain (i.e., increased central and peripheral chemoreceptor
sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or 3)
reduction in system damping (i.e., baroreflex impairment). Periodic breathing
during exercise is observed in several cardiovascular disease populations, but it
is a particularly frequent phenomenon in heart failure due to systolic
dysfunction. The detection of exertional periodic breathing is linked to outcome
and heralds worst prognosis in heart failure, independently of the criteria
adopted for its definition. In small heart failure cohorts, exertional periodic
breathing has been abolished with more than a few dedicated interventions, but
results have not been confirmed, yet. Accordingly, further studies are needed to
define the role of visceral feed-backs in determining periodic breathing during
exercise, as well as to look for specific tools for preventing/treat its
occurrence in heart failure.

Cardiopulmonary exercise factors predict survival in patients with advanced interstitial lung disease referred for lung transplantation.

Layton AM, Armstrong HF, Kim HP, Meza KS, D’Ovidio F, Arcasoy SM.

Respir Med. 2017 May;126:59-67. doi: 10.1016/j.rmed.2017.03.022. Epub 2017 Mar

BACKGROUND: The purpose of this work was to determine if parameters assessed
during Cardiopulmonary Exercise Testing (CPET) while using supplemental oxygen
can independently predict one-year transplant-free survival in patients with
Interstitial Lung Disease (ILD) referred for lung transplant evaluation.
METHODS: We performed a chart review of patients with ILD who completed CPET with
30% FiO2 and gathered spirometry, pulmonary hemodynamic, six-minute walk, and
CPET data. The primary end-point was death or lung transplantation within
one-year of CPET.
RESULTS: The final data set included 192 patients. 79 patients died/underwent
transplant, 113 survived transplant-free. Multivariable Cox regression revealed
peak workload % predicted, nadir CPET SpO2, and FVC% predicted as independent
predictors of one-year transplant-free survival. Of the independent predictors of
survival, receiver operating characteristics analysis revealed peak workload
%predicted cutoff of 35% to be highly discriminatory, more so than nadir CPET
SpO2 or FVC % predicted in identifying patients at risk for one-year mortality or
transplant (peak workload % predicted < 35% HR = 4.71, 95% CI = 2.64-8.38 and area under the curve (AUC) = 0.740, nadir CPET SpO2 < 86% HR = 2.27, 95%CI = 1.41-3.68, AUC = 0.645, FVC %predicted <45% HR = 1.82, 95% CI = 1.15-2.87, AUC = 0.624). CONCLUSION: Peak workload % predicted, nadir CPET SpO2, and FVC% predicted in ILD patients referred for lung transplant evaluation are independently predictive of one-year mortality or need for transplant.

Effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD.

Key A; Parry M; West MA; Asher R; Jack S; Duffy N; Torella F; Walker PP;

Liverpool and Southampton

[BMJ Open Respir Res] 2017 Apr 05; Vol. 4 (1), pp. e000164. Date of Electronic Publication: 20170405 (Print Publication: 2017)

Introduction: β Blockers are important treatment for ischaemic heart disease and heart failure; however, there has long been concern about their use in people with chronic obstructive pulmonary disease (COPD) due to fear of symptomatic worsening of breathlessness. Despite growing evidence of safety and efficacy, they remain underused. We examined the effect of β-blockade on lung function, exercise performance and dynamic hyperinflation in a group of vascular surgical patients, a high proportion of who were expected to have COPD.
Methods: People undergoing routine abdominal aortic aneurysm (AAA) surveillance were sequentially recruited from vascular surgery clinic. They completed plethysmographically measured lung function and incremental cardiopulmonary exercise testing with dynamic measurement of inspiratory capacity while taking and not taking β blocker.
Results: 48 participants completed tests while taking and not taking β blockers with 38 completing all assessments successfully. 15 participants (39%) were found to have, predominantly mild and undiagnosed, COPD. People with COPD had airflow obstruction, increased airway resistance (Raw) and specific conductance (sGaw), static hyperinflation and dynamically hyperinflated during exercise. In the whole group, β-blockade led to a small fall in FEV1 (0.1 L/2.8% predicted) but did not affect Raw, sGaw, static or dynamic hyperinflation. No difference in response to β-blockade was seen in those with and without COPD.
Conclusions: In people with AAA, β-blockade has little effect on lung function and dynamic hyperinflation in those with and without COPD. In this population, the prevalence of COPD is high and consideration should be given to case finding with spirometry.

Short-term preoperative exercise therapy does not improve long-term outcome after lung cancer surgery: a randomized controlled study

Karenovics W; Licker M; Ellenberger C; Christodoulou M; Diaper J; Bhatia C; Robert J; Bridevaux PO; Triponez F;

University Hospitals of Geneva, Geneva, Switzerland.

[Eur J Cardiothorac Surg] 2017 Apr 17

Objectives: Poor aerobic fitness is a potential modifiable risk factor for long-term survival and quality of life in patients with lung cancer. This randomized trial evaluates the impact of adding rehabilitation (Rehab) with high-intensity interval training (HIIT) before lung cancer surgery to enhance cardiorespiratory fitness and improve long-term postoperative outcome.
Methods: Patients with operable lung cancer were randomly assigned to usual care (UC, n  = 77) or to intervention group (Rehab, n  = 74) that entailed HIIT that was implemented only preoperatively. Cardiopulmonary exercise testing (CPET) and pulmonary functional tests (PFTs) including forced vital capacity (FVC), forced expiratory volume (FEV 1 ) and carbon monoxide transfer factor (KCO) were performed before and 1 year after surgery.
Results: During the preoperative waiting time (median 25 days), Rehab patients participated to a median of 8 HIIT sessions (interquartile [IQ] 25-75%, 7-10). At 1 year follow-up, 91% UC patients and 93% Rehab patients were still alive ( P  = 0.506). Pulmonary functional changes were non-significant and comparable in both groups (FEV 1 mean -7.5%, 95% CI, -3.6 to -12.9 and in KCO mean 5.8% 95% CI 0.8-11.8) Compared with preoperative CPET results, both groups demonstrated similar reduction in peak oxygen uptake (mean -12.2% 95% CI -4.8 to -18.2) and in peak work rate (mean -11.1% 95% CI -4.2 to -17.4).
Conclusions: Short-term preoperative rehabilitation with HIIT does not improve pulmonary function and aerobic capacity measured at 1 year after lung cancer resection.

A comparison of methods for determining the ventilatory threshold: implications for surgical risk stratification.

Vainshelboim B; Rao S; Chan K; Lima RM; Ashley EA; Myers J

Canadian Journal Of Anaesthesia [Can J Anaesth] 2017 Apr 05. Date of Electronic Publication: 2017 Apr 05.

Purpose: The ventilatory threshold (VT) is an objective physiological marker of the capacity of aerobic endurance that has good prognostic applications in preoperative settings. Nevertheless, determining the VT can be challenging due to physiological and methodological issues, especially in evaluating surgical risk. The purpose of the current study was to compare different methods of determining VT and to highlight the implications for assessing perioperative risk.
Methods: Our study entailed analysis of 445 treadmill cardiopulmonary exercise tests from 140 presurgical candidates with an aortic abdominal aneurysm (≥3.0 to ≤5.0 cm) and a mean (standard deviation [SD]) age of 72 (8) yr. We used three methods to determine the VT in 328 comparable tests, namely, self-detected metabolic system (MS), experts’ visual (V) readings, and software using a log-log transformation (LLT) of ventilation vs oxygen uptake. Differences and agreement between the three methods were assessed using analysis of variance (ANOVA), coefficient of variation (CV), typical error limits of agreement (LoA), and interclass correlation coefficients (ICC).
Results: Overall, ANOVA revealed significant differences between the methods [MS = 14.1 (4.3) mLO2·kg-1·min-1; V = 14.6 (4.4) mLO2·kg-1·min-1; and LLT = 12.3 (3.3) mLO2·kg-1·min-1; P < 0.001]. The assessment of agreement between methods provided the following results: ICC = 0.85; 95% confidence interval (CI), 0.82 to 0.87; P < 0.001; typical error, 2.1-2.8 mLO2·kg-1·min-1; and, 95% LoA and CV ranged from 43 to 55% and 15.9 to 19.6%, respectively. Conclusions: The results show clinically significant variations between the methods and underscore the challenges of determining VT for perioperative risk stratification. The findings highlight the importance of meticulous evaluation of VT for predicting surgical outcomes. Future studies should address the prognostic perioperative utility of computed mathematical models combined with an expert's review. This trial was registered at, identifier: NCT00349947.

Maximal heart rate declines linearly with age independent of cardiorespiratory fitness levels.

Ozemek C; Whaley MH; Finch WH;Kaminsky LA;

European Journal Of Sport Science [Eur J Sport Sci] 2017 Jun; Vol. 17 (5), pp. 563-570. Date of Electronic Publication: 2017 Jan 18

There have been many conflicting observations between the linear or curvilinear decline in maximal heart rate (HRmax) with age. The aim of this study was to determine if linear or curvilinear equations would better describe the decline in HRmax with age in individuals of differing cardiorespiratory fitness (CRF) levels. Treadmill cardiopulmonary exercise test (CPX) results from participants (1510 men and 1134 women; 18-76 years) free of overt cardiovascular disease were retrospectively examined using cross-sectional and longitudinal study designs. Participants completing ≥2 CPX with ≥1 year between test dates were included in the longitudinal analysis (325 men and 150 women). Linear and quadratic regressions were applied to age and HRmax for the whole cohort and respective CRF groups (high, moderate, and low, relative to age and gender normative values). To test for differences among linear, quadratic, and polynomial equations, the change in R2 (cross-sectional analysis) and Bayesian information criterion (BIC) (longitudinal analysis) from the linear to the more complex models were calculated. The quadratic or polynomial regression in the cross-sectional analysis, marginally improved the variance in HRmax explained by age compared to the linear regression for the whole cohort (0.2%), moderate fit group (0.3%), and low fit group (0.8%). With no improvements in the high fit group. BIC did not improve for any CRF category in the longitudinal analysis. In conclusion, the minimal differences among linear, quadratic, and polynomial equations in the respective CRF groups, emphasizes the use of linear prediction equations to estimate HRmax.

Three-Dimensional Left Ventricular Torsion in Patients With Dilated Cardiomyopathy - A Marker of Disease Severity.

Sveric KM, Ulbrich S, Rady M, Ruf T, Kvakan H, Strasser RH, Jellinghaus S

Circ J. 2017 Mar 24;81(4):529-536. doi: 10.1253/circj.CJ-16-0965. Epub 2017 Jan
24. (Article from Dresden)

BACKGROUND: LV twist has a key role in maintaining left ventricular (LV)
contractility during exercise. The purpose of this study was to investigate LV
torsion instead of twist as a surrogate marker of peak oxygen uptake (peak V̇O2)
assessed by cardiopulmonary exercise testing (CPET) in patients with non-ischemic
dilated cardiomyopathy (DCM).Methods and Results:We evaluated 45 outpatients with
DCM (50±12 years, 24% females) with 3D speckle-tracking electrocardiography prior
to CPET. LV torsion, LV ejection fraction (EF), LV diastolic function, LV global
longitudinal (GLS) and circumferential (GCS) strain were quantified. A reduced
functional capacity (FC) was defined as a peak V̇O2<20 mL/kg/min. LV torsion correlated most strongly with peak V̇O2(r=0.76, P<0.001). LV torsion instead of twist was an independent predictor of peak V̇O2(B: 0.59 to 0.71, P<0.001) in multivariable analyses. Impaired LV torsion <0.61 degrees/cm was able to predict a reduced FC with higher sensitivity and specificity (0.91 and 0.81; area under the curve (AUC): 0.88, P<0.001) than LV EF, GLS or GCS (AUC 0.64, 0.63 and 0.66; P<0.05 for differences in AUC). CONCLUSIONS: Peak V̇O2 correlated more strongly with LV torsion than with LV diastolic function, LV EF, GLS or GCS. LV torsion had high accuracy in identifying patients with a reduced FC.

Cardiopulmonary Exercise Testing in Pediatrics.

Takken T, Bongers BC, van Brussel M, Haapala EA, Hulzebos EH

Ann Am Thorac Soc. 2017 Apr 11. doi: 10.1513/AnnalsATS.201611-912FR. [Epub ahead
of print] (Article from Netherlands)

Aerobic fitness is an important determinant of overall health. Higher aerobic
fitness has been associated with many health benefits. Because myocardial
ischemia is rare in children, indications for exercise testing differ in children
compared to adults. Pediatric exercise testing is imperative to unravel the
physiological mechanisms of a reduced aerobic fitness and to evaluate
intervention effects in children and adolescents with a chronic disease or
disability. Cardiopulmonary exercise testing includes the measurement of
respiratory gas exchange and is the gold standard for determining aerobic
fitness, as well as for examining the integrated physiological responses to
exercise in pediatric medicine. As the physiological responses to exercise change
during growth and development, appropriate pediatric reference values are
essential for an adequate interpretation of the cardiopulmonary exercise test.