Category Archives: Publications

Cardiorespiratory fitness in long-term juvenile dermatomyositis: a controlled, cross-sectional study of active/inactive disease.

Berntsen KS; Edvardsen E; Hansen BH; Flato B; Sjaastad I; Sanner H.

Rheumatology. 58(3):492-501, 2019 03 01.

OBJECTIVES: To compare cardiorespiratory fitness (CRF) expressed as
maximal oxygen uptake (VO2max) between patients with long-term JDM and
controls and between patients with active and inactive disease, as well as
to explore exercise limiting factors and associations between CRF and
disease variables.

METHODS: JDM patients (n = 45) and age- and gender-matched controls (n =
45) performed a cardiopulmonary exercise test (CPET) on a treadmill until
exhaustion. Physical activity was measured by accelerometers. Disease
activity, damage and muscle strength/function were assessed by validated
tools. Clinically inactive disease was defined according to PRINTO

RESULTS: The mean disease duration was 20.8 (s.d. 11.9) years and 29/45
(64%) patients had inactive disease. A low VO2max was found in 27% of
patients vs 4% of controls (P = 0.006). The mean VO2max and maximal
ventilation (VEmax) were lower in patients with active and inactive
disease compared with controls. Patients with active disease also had
lower maximal voluntary ventilation (MVV) compared with controls and lower
VEmax and MVV compared with those with inactive disease. Patients with
inactive disease had lower physical activity levels compared with
controls. VO2max correlated negatively with disease damage in patients
with inactive disease and positively with muscle strength/function in
patients with active disease.

CONCLUSION: CRF was lower in JDM patients, both with active and inactive
disease, compared with controls after a mean 20 years disease duration.
Cardiopulmonary exercise test results suggested different limiting factors
contributing to the reduced CRF according to disease activity, including
deconditioning in inactive disease and reduced ventilatory capacity in
active disease. Further research is needed to verify this.

Aerobic capacity attainment and reasons for cardiopulmonary exercise test termination in people with cancer: a descriptive, retrospective analysis from a single laboratory.

Santa Mina D, Au D, Papadopoulos E, O’Neill M, Diniz C, Dolan L, Lipton J, Chang E, Jones JM.

2020 Jan 4. doi: 10.1007/s00520-019-05094-4. [Epub ahead of print]


Aerobic exercise prescriptions in clinical populations commonly involve target intensities based on cardiopulmonary exercise tests (CPET). CPETs are often discontinued prior to a patient achieving true maximum oxygen consumption (VO2 max) which can adversely affect exercise dose and efficacy monitoring; however, reasons for early discontinuation are poorly reported. Accordingly, we explored the CPET termination reasons in persons with cancer participating in exercise intervention studies.


This study comprised of an exploratory, descriptive analysis of retrospective CPET data (VO2 and anaerobic threshold) and termination reasons in a convenience sample of people with cancer participating in exercise intervention studies in a single laboratory. CPETs were standardized using the modified Bruce treadmill protocol with expired gas collection and analysis using a metabolic cart. VO2 max was considered “met” when participants demonstrated (a) oxygen consumption plateau or (b) two of the following criteria: rating of perceived exertion ≥ 9/10, respiratory exchange ratio ≥ 1.15, and/or heart rate of 95% of age-predicted maximum. The frequency and distribution of reasons for test termination relative to the number of CPET exposures for the participants were reported.


Forty-four participants engaged in exercise studies between February 2016 and March 2018 provided data for the analysis. Participants completed up to three CPETs during this period (total of 78 CPETs in the current analysis). Eighty-six percent of all CPETs were terminated prior to achieving VO2 max verification criteria and no tests resulted in an oxygen consumption plateau. For those that did not demonstrate achievement of VO2 max verification criteria, reasons for discontinuation were distributed as follows: equipment discomfort-49%, volitional peak-36%, and physical discomfort-14.9%. For those who met VO2 max criteria, volitional peak was the most common reason for test termination (45.5%), followed by physical discomfort (36.4%), and equipment discomfort (18.2%).


In our sample of cancer survivors, VO2 max criteria were infrequently met with equipment discomfort being a primary reason for participant-driven test termination. Protocol and equipment considerations are necessary for interpretation and application of CPET findings in clinical practice.

Ventilatory and sensory responses to incremental exercise in adults with a Fontan circulation.

Guenette JA; Ramsook AH; Dhillon SS; Puyat JH; Riahi M; Opotowsky AR;
Grewal J.

American Journal of Physiology – Heart & Circulatory Physiology.
316(2):H335-H344, 2019 02 01.

Many adults with single-ventricle congenital heart disease who have
undergone a Fontan procedure have abnormal pulmonary function resembling
restrictive lung disease. Whether this contributes to ventilatory
limitations and increased dyspnea has not been comprehensively studied. We
recruited 17 Fontan participants and 17 healthy age- and sex-matched
sedentary controls. All participants underwent complete pulmonary function
testing followed by a symptom-limited incremental cardiopulmonary cycle
exercise test with detailed assessments of dyspnea and operating lung
volumes. Fontan participants and controls were well matched for age, sex,
body mass index, height, and self-reported physical activity levels (all P
> 0.05), although Fontan participants had markedly reduced
cardiorespiratory fitness and peak work rates ( P < 0.001). Fontan
participants had lower values for most pulmonary function measurements
relative to controls with 65% of Fontan participants showing evidence of a
restrictive ventilatory defect. Relative to controls, Fontan participants
had significantly higher breathing frequency, end-inspiratory lung volume
(% total lung capacity), ventilatory inefficiency (high ventilatory
equivalent for CO2), and dyspnea intensity ratings at standardized
absolute submaximal work rates. There were no between-group differences in
qualitative descriptors of dyspnea. The restrictive ventilatory defect in
Fontan participants likely contributes to their increased breathing
frequency and end-inspiratory lung volume during exercise. This abnormal
ventilatory response coupled with greater ventilatory inefficiency may
explain the increased dyspnea intensity ratings in those with a Fontan
circulation. Interventions that enhance the ventilatory response to
exercise in Fontan patients may help optimize exercise rehabilitation
interventions, resulting in improved exercise tolerance and exertional
NEW & NOTEWORTHY This is the first study to comprehensively
characterize both ventilatory and sensory responses to exercise in adults
that have undergone the Fontan procedure. The majority of Fontan
participants had a restrictive ventilatory defect. Compared with
well-matched controls, Fontan participants had increased breathing
frequency, end-inspiratory lung volume, and ventilatory inefficiency.
These abnormal ventilatory responses likely form the mechanistic basis for
the increased dyspnea intensity ratings observed in our Fontan
participants during exercise.

The association between preoperative cardiopulmonary exercise-test variables and short-term morbidity after esophagectomy: A hospital-based cohort study.

Lam S; Alexandre L; Hardwick G; Hart AR.

Surgery. 166(1):28-33, 2019 07.

BACKGROUND: Postoperative complications after esophagectomy are thought to
be associated with reduced fitness. This observational study explored the
associations between aerobic fitness, as determined objectively by
preoperative cardiopulmonary exercise testing (CPEX), and 30-day morbidity
after esophagectomy.

METHODS: We retrospectively identified 254 consecutive patients who
underwent esophagectomy at a single academic teaching hospital between
September 2011 and March 2017. Postoperative complication data were
measured using the Esophageal Complications Consensus Group definitions
and graded using the Clavien-Dindo classification system of severity
(blinded to cardiopulmonary exercise testing values). Associations between
preoperative cardiopulmonary exercise testing variables and postoperative
outcomes were estimated using logistic regression.

RESULTS: A total of 206 patients (77% male) were included in the
analyses, with a mean age of 67 years (SD 9). The mean values for the
maximal oxygen consumed at the peak of exercise (VO2peak) and the
anaerobic threshold were 21.1 mL/kg/min (SD 4.5) and 12.4 mL/kg/min (SD
2.8), respectively. The vast majority of patients (98.5%) had malignant
disease-predominantly adenocarcinoma (84.5%), for which most received
neoadjuvant chemotherapy (79%) and underwent minimally invasive Ivor Lewis
esophagectomy (53%). Complications at postoperative day 30 occurred in 111
patients (54%), the majority of which were cardiopulmonary (72%). No
associations were found between preoperative cardiopulmonary exercise
testing variables and morbidity for either VO2peak (OR 1.00, 95% CI
0.94-1.07) or anaerobic threshold (OR 0.98, 95% CI 0.89-1.09).

CONCLUSION: Preoperative cardiopulmonary exercise testing variables were
not associated with 30-day complications after esophagectomy. The findings
do not support the use of cardiopulmonary exercise testing as an isolated
preoperative screening tool to predict short-term morbidity after
esophagectomy. This modestly sized observational work highlights the need
for larger studies examining associations between preoperative
cardiopulmonary exercise testing and outcomes after esophagectomy to look
for consistency in our findings.

Low income as a determinant of exercise capacity in COPD.

Porta AS; Lam N; Novotny P; Benzo R;

Chronic Respiratory Disease [Chron Respir Dis] 2019 Jan-Dec; Vol. 16, pp. 1479972318809491.

Exercise capacity (EC) is a critical outcome in chronic obstructive lung disease (chronic obstructive pulmonary disease (COPD)). It measures the impact of the disease and the effect of specific interventions like pulmonary rehabilitation (PR). EC determines COPD prognosis and is associated with health-care utilization and quality of life. Field walking tests and cardiopulmonary exercise test (CPET) are two ways to measure EC. The 6-minute walking test (6MWT) is the commonest and easiest field test. CPET has the advantage of assessing maximal aerobic capacity. Determinants of EC include age, gender, breathlessness, and lung function. Previous research suggests that socioeconomic status (SES), a meaningful factor in COPD, may also be associated with EC. However, those findings have not been replicated. We aimed to determine whether SES is an independent factor associated with EC in COPD. For this analysis, we used the National Emphysema Treatment Trial (NETT) database. NETT was a multicenter clinical trial where severe COPD patients were randomized to lung volume reduction surgery or medical therapy. Measures used were taken at baseline, postrehabilitation. Patients self-reported their income and were divided in two groups whether it was less or above US$30,000. Patients with a lower income had worse results in 6MWT ( p < 0.0001). We found an independent association between income and the 6MWT in patients with severe COPD after adjusting for age, gender, lung function, dyspnea, and living conditions ( p < 0.0007). One previous publication stated the relationship between income and EC. Our research confirms and extends previous publications associating EC with income by studying a large and well characterized cohort of severe COPD patients, also addressing EC by two different methods (maximal watts and 6MWT). Our results highlight the importance of addressing social determinants of health such as income when assessing COPD patients.

Prognostic value of cardiopulmonary exercise testing in cardiac patients with atrial fibrillation.

Tsuneoka H; Koike A; Nagayama O; Sakurada K; Kato J; Sato A; Yamashita T;
Aonuma K.

International Heart Journal. 53(2):102-7, 2012.

Parameters obtained from cardiopulmonary exercise testing (CPX) are
recognized for their high prognostic value in predicting future cardiac
events in cardiac patients. Our group compared the prognostic value of CPX
parameters between patients with sinus rhythm (SR) and patients with
atrial fibrillation (AF).Peak O2 uptake (VO2), the ratio of the increase
in VO2 to the increase in work rate (DELTAVO2/DELTAWR), and the slope of
the increase in ventilation to the increase in CO2 output (VE-VCO2 slope)
were obtained from CPX in 72 AF patients and 478 SR patients. The
prognostic values of these indices were compared between the two
groups.Six cardiac deaths and 25 cardiac events were observed in the AF
group and 9 cardiac deaths and 96 cardiac events were observed in the SR
group, over a prospective follow-up period of 1,192 days. The percentages
of cardiac deaths and cardiac events were higher in the AF group than in
the SR group. In a multivariate Cox proportional hazards analysis, peak
VO2 was identified as a sole significant predictor of cardiac death and
cardiac events in SR patients and VE-VCO2 slope was identified as a sole
significant predictor of cardiac death and cardiac events in AF
Our results suggest that the VE-VCO2 slope is strongly predictive
of future cardiac events in patients with AF and that peak VO2 is strongly
predictive of future cardiac events in SR patients.

Distinct prognostic factors in patients with chronic heart failure and chronic kidney disease.

Sato T; Yamauchi H; Suzuki S; Yoshihisa A; Yamaki T; Sugimoto K; Kunii H;
Nakazato K; Suzuki H; Saitoh S; Takeishi Y.

International Heart Journal. 54(5):311-7, 2013.

Impaired renal function is a strong predictor of mortality in chronic
heart failure (CHF). However, the impact of chronic kidney disease (CKD)
on prognostic factors has not been rigorously examined in CHF. The purpose
of this study was to compare prognostic factors between CHF patients with
and without CKD. Consecutive 505 patients with CHF, who performed
cardiopulmonary exercise testing before discharge, were enrolled. Patients
were divided into two groups: CKD group (eGFR < 60 mL/minute/1.73 m2, n =
213) and non-CKD group (eGFR >= 60 mL/minute/1.73 m2, n = 292). The
patients were followed up to register cardiac events including cardiac
death and re-hospitalization due to worsening heart failure. There were
115 events during the follow-up period (746 +/- 238 days), and the cardiac
event rate was higher in the CKD group than in the non-CKD group (34%
versus 14%, P < 0.001). Multivariate Cox hazard analysis demonstrated that
body mass index (P < 0.001), log BNP (P < 0.001), peak VO2 (P < 0.05), and
left atrial dimension (P < 0.05) were independent parameters to predict
cardiac events after discharge in the non-CKD group. In contrast, peak VO2
(P < 0.01), log BNP (P < 0.01), and the concentrations of hemoglobin (P <
0.05) and uric acid (P < 0.05) were independent prognostic factors in the
CKD group. Prognostic factors were different between CHF patients with and
without CKD, and this should be considered when managing CHF patients with

Exercise intolerance in heart failure: update on exercise parameters for diagnosis, prognosis and therapeutic interventions. [Review]

Pardaens S; Calders P; Derom E; De Sutter J.

Acta Cardiologica. 68(5):495-504, 2013 Oct.

Exercise intolerance is a hallmark feature of chronic heart failure and is
associated with poor prognosis. This review provides an update on
cardiopulmonary exercise variables, proven to be prognostically important
in heart failure. Besides the widely accepted peak oxygen consumption
(peak VO2) and VEN/VCO2 slope, other exercise variables – exercise
oscillatory ventilation (EOV) and partial pressure of end-tidal CO2,
(PETCO2) – should gain attention in the interpretation of cardiopulmonary
exercise testing. In addition to prognosis, the pathophysiological origin
is also discussed. Different mechanisms underlie these exercise variables
with an important contribution of haemodynamic, pulmonary and peripheral
abnormalities. Given the different pathophysiological origin, a
multivariate assessment with the inclusion of all the aforementioned
parameters should be encouraged, not only for diagnostic and prognostic
purposes but also for evaluating the effect of interventions.

Impact of lifestyle modification on left ventricular function and cardiopulmonary exercise capacity in patients with heart failure with normal ejection fraction and cardiometabolic syndrome: a prospective interventional study.

Ritzel A; Otto F; Bell M; Sabin G; Wieneke H.

Acta Cardiologica. 70(1):43-50, 2015 Feb.

BACKGROUND: Heart failure with normal left ventricular ejection fraction
(HFNEF) accounts for about one third of all heart failure patients with
considerable mortality. The metabolic syndrome (MS) is a risk factor for
diastolic dysfunction and HFNEF. We hypothesized that modifying metabolic
burden by exercise training and weight loss might improve left ventricular
diastolic function, heart failure symptoms and rehospitalization rate.

METHODS AND RESULTS: Forty patients with HFNEF, MS and prediabetes were
enrolled in this prospective study. Echocardiography and cardiopulmonary
exercise testing (CPET) were done at baseline and after 3 months lifestyle
modification (LSM). NT-pro BNP and adiponectin were determined at baseline
as both peptidehormones play a crucial role in MS and heart failure. After
discharge a 3-month LSM program with the aim of weight reduction by diet
and exercise was started. After the intervention period a weight reduction
of >= 2% was defined as successful LSM (group A = 23 patients), while a
weight reduction < 2% was classified as unsuccessful LSM (group B = 17
patients). At baseline NT-pro BNP (424 +/- 381 versus 121 +/- 99 pg/ml, P
< 0.01) and adiponectin (10.1 +/- 6.2 versus 4.6-2.0 micro&#32;g/ml, P <
0.01) were higher in group A than in group B. After 3 months of LSM, CPET
showed a significant improve- ment of VO2 peak (P < 0.01), EqCO2 (P <
0.001), O2-pulse (P = 0.02) and VE / VCO2 slope (P = 0.01) in group A.
After one year of follow-up a modest but significant reduction of left
atrial size and mitral flow to mitral annulus velocity ratio E/E’ was seen
in group A. LSM resulted in significant improvement of NYHA status (P =
0.03) and higher freedom of rehospitalization (P = 0.04) in group A.

CONCLUSION: Successful lifestyle modification in obese, prediabetic
patients with HFNEF improves diastolic left ventricular function and
cardiopulmonary exercise capacity. As these measures result in improved
NYHA status and less hospitalization, LSM might be a promising approach to
prevent chronic diastolic heart failure.

IMproved exercise tolerance in patients with PReserved Ejection fraction by Spironolactone on myocardial fibrosiS in Atrial Fibrillation rationale and design of the IMPRESS-AF randomised controlled trial.

Shantsila E; Haynes R; Calvert M; Fisher J; Kirchhof P; Gill PS; Lip GY.

BMJ Open. 6(10):e012241, 2016 10 05.

INTRODUCTION: Patients with atrial fibrillation frequently suffer from
heart failure with preserved ejection fraction. At present there is no
proven therapy to improve physical capacity and quality of life in
participants with permanent atrial fibrillation with preserved left
ventricular contractility.

OBJECTIVE: The single-centre IMproved exercise tolerance In heart failure
With PReserved Ejection fraction by Spironolactone On myocardial fibrosiS
In Atrial Fibrillation (IMPRESS-AF) trial aims to establish whether
treatment with spironolactone as compared with placebo improves exercise
tolerance (cardiopulmonary exercise testing), quality of life and
diastolic function in patients with permanent atrial fibrillation.

METHODS AND ANALYSIS: A total of 250 patients have been randomised in
this double-blinded trial for 2-year treatment with 25 mg daily dose of
spironolactone or matched placebo. Included participants are 50 years old
or older, have permanent atrial fibrillation and ejection fraction >55%.
Exclusion criteria include contraindications to spironolactone, poorly
controlled hypertension and presence of severe comorbidities with life
expectancy <2 years. The primary outcome is improvement in exercise
tolerance at 2 years and key secondary outcomes include quality of life
(assessed using the EuroQol EQ-5D-5L (EQ-5D) and Minnesota Living with
Heart Failure (MLWHF) questionnaires), diastolic function and all-cause

ETHICS AND DISSEMINATION: The study has been approved by the National
Research and Ethics Committee West Midlands-Coventry and Warwickshire (REC
reference number 14/WM/1211). The results of the trial will be published
in an international peer-reviewed journal.