Category Archives: Publications

Development of a clinical applicable graphical user interface to automatically detect exercise oscillatory ventilation: The VOdEX-tool.

Cornelis J, Denis T, Beckers P, Vrints C, Vissers D, Goossens M

Int J Cardiol. 2017 Aug 1;240:291-296. doi: 10.1016/j.ijcard.2016.12.159. Epub
2016 Dec 29.

BACKGROUND: Cardiopulmonary exercise testing (CPET) gained importance in the
prognostic assessment of especially patients with heart failure (HF). A
meaningful prognostic parameter for early mortality in HF is exercise oscillatory
ventilation (EOV). This abnormal respiratory pattern is recognized by hypo- and
hyperventilation during CPET. Up until now, assessment of EOV is mainly done upon
visual agreement or manual calculation. The purpose of this research was to
automate the interpretation of EOV so this prognostic parameter could be readily
investigated during CPET.
METHODS AND RESULTS: Preliminary, four definitions describing the original
characteristics of EOV, were selected and integrated in the “Ventilatory
Oscillations during Exercise-tool” (VOdEX-tool), a graphical user interface that
allows automate calculation of EOV. A Discrete Meyer Level 2 wavelet
transformation appeared to be the optimal filter to apply on the collected
breath-by-breath minute ventilation CPET data. Divers aspects of the definitions
i.e. cycle length, amplitude, regularity and total duration of EOV were combined
and calculated. The oscillations meeting the criteria were visualised. Filter
methods and cut-off criteria were made adjustable for clinical application and
research. The VOdEX-tool was connected to a database.
CONCLUSIONS: The VOdEX-tool provides the possibility to calculate EOV
automatically and to present the clinician an overview of the presence of EOV at
a glance. The computerized analysis of EOV can be made readily available in
clinical practice by integrating the tool in the manufactures existing CPET
software. The VOdEX-tool enhances assessment of EOV and therefore contributes to
the estimation of prognosis in especially patients with HF.

Very short/short-term benefit of inpatient/outpatient cardiac rehabilitation programs after coronary artery bypass grafting surgery.

Spiroski D, Andjić M, Stojanović OI, Lazović M, Dikić AD,
Ostojić M, Beleslin B, Kostić S, Zdravković M, Lović D

Clin Cardiol. 2017 May;40(5):281-286. doi: 10.1002/clc.22656. Epub 2017 Jan 11.

BACKGROUND: Exercise-based rehabilitation is an important part of treatment
patients following coronary artery bypass graft (CABG) surgery.
HYPOTHESIS: To evaluate effect of very short/short-term exercise training on
cardiopulmonary exercise testing (CPET) parameters.
METHODS: We studied 54 consecutive patients with myocardial infarction (MI)
treated with CABG surgery referred for rehabilitation. The study population
consisted of 50 men and 4 women (age 57.72 ± 7.61 years, left ventricular
ejection fraction 55% ± 5.81%), who participated in a 3-week clinical and 6-month
outpatient cardiac rehabilitation program. The Inpatient program consisted of
cycling 7 times/week and daily walking for 45 minutes. The outpatient program
consisted mainly of walking 5 times/week for 45 minutes and cycling 3 times/week.
All patients performed symptom-limited CPET on a bicycle ergometer with a ramp
protocol of 10 W/minute at the start, for 3 weeks, and for 6 months.
RESULTS: After 3 weeks of an exercise-based cardiac rehabilitation program,
exercise tolerance improved as compared to baseline, as well as peak respiratory
exchange ratio. Most importantly, peak VO2 (16.35 ± 3.83 vs 17.88 ± 4.25
mL/kg/min, respectively, P < 0.05), peak VCO2 (1.48 ± 0.40 vs 1.68 ± 0.43,
respectively, P < 0.05), peak ventilatory exchange (44.52 ± 11.32 vs
52.56 ± 12.37 L/min, respectively, P < 0.05), and peak breathing reserve
(52.00% ± 13.73% vs 45.75% ± 14.84%, respectively, P < 0.05) were also improved.
The same improvement trend continued after 6 months (respectively, P < 0.001 and
P < 0.0001). No major adverse cardiac events were noted during the rehabilitation
CONCLUSIONS: Very short/short-term exercise training in patients with MI treated
with CABG surgery is safe and improves functional capacity.

Right ventricular systolic dysfunction at rest is not related to decreased exercise capacity in patients with a systemic right ventricle.

Helsen F, De Meester P, Van De Bruaene A, Gabriels C, Santens B,
Claeys M, Claessen G, Goetschalckx K, Buys R, Gewillig M, Troost
E, Voigt JU, Claus P, Bogaert J, Budts W

Int J Cardiol. 2018 Mar 8. pii: S0167-5273(17)37403-X. doi:
10.1016/j.ijcard.2018.03.029. [Epub ahead of print]

BACKGROUND: To evaluate the relationship between right ventricular (RV) systolic
dysfunction at rest and reduced exercise capacity in patients with a systemic RV
METHODS: All patients with congenitally corrected transposition of the great
arteries (ccTGA) or complete TGA after atrial switch (TGA-Mustard/Senning)
followed in our institution between July 2011 and September 2017 who underwent
cardiac imaging within a six-month time period of cardiopulmonary exercise
testing (CPET) were analyzed. We assessed sRV systolic function with TAPSE and
fractional area change on echocardiogram and, if possible, with ejection
fraction, global longitudinal and circumferential strain on cardiac magnetic
resonance (CMR) imaging.
RESULTS: We studied 105 patients with an sRV (median age 34 [IQR 28-42] years,
29% ccTGA and 71% TGA-Mustard/Senning) of which 39% had either a pacemaker
(n = 17), Eisenmenger physiology (n = 6), severe systemic atrioventricular valve
regurgitation (n = 14), or peak exercise arterial oxygen saturation < 92%
(n = 17). Most patients were asymptomatic or mildly symptomatic (NYHA class
I/II/III in 71/23/6%). Sixty-four percent had evidence of moderate or severe sRV
dysfunction on cardiac imaging. Mean peak oxygen uptake (pVO2) was
24.1 ± 7.4 mL/kg/min, corresponding to a percentage of predicted pVO2 (%ppVO2) of
69 ± 17%. No parameter of sRV systolic function as evaluated on echocardiography
(n = 105) or CMR (n = 46) was correlated with the %ppVO2, even after adjusting
for associated cardiac defects or pacemakers.
CONCLUSIONS: In adults with an sRV, there is no relation between
echocardiographic or CMR-derived sRV systolic function parameters at rest and
peak oxygen uptake. Exercise imaging may be superior to evaluate whether sRV
contractility limits exercise capacity.

Pulmonary rehabilitation for COPD improves exercise time rather than exercise tolerance: effects and mechanisms.

Miki K, Maekura R, Kitada S, Miki M, Yoshimura K, Yamamoto H,
Kawabe T, Kagawa H, Oshitani Y, Satomi A, Nishida K, Sawa N,
Inoue K

Int J Chron Obstruct Pulmon Dis. 2017 Apr 3;12:1061-1070

BACKGROUND: COPD patients undergoing pulmonary rehabilitation (PR) show various
responses. The purpose of this study was to investigate the possible mechanisms
and predictors of the response to PR in COPD patients.
METHODS: Thirty-six stable COPD patients underwent PR including a 4-week
high-intensity exercise training program, and they were evaluated by
cardiopulmonary exercise testing. All patients (mean age 69 years, severe and
very severe COPD 94%) were classified into four groups by whether the exercise
time (Tex) or the peak oxygen uptake [Formula: see text] increased after PR: two
factors increased (both the Tex and the peak [Formula: see text] increased); two
factors decreased; time only increased (the Tex increased, but the peak [Formula:
see text] economized); and [Formula: see text] only increased (the Tex decreased,
but the peak [Formula: see text] increased). Within all patients, the
relationships between baseline variables and the post-to-pre-change ratio of the
time-slope, Tex/(peak minus resting [Formula: see text]), were investigated.
RESULTS: Compared with the two factors increased group (n=11), in the time only
increased group (n=18), the mean differences from pre-PR at peak exercise in 1)
minute ventilation [Formula: see text] (P=0.004), [Formula: see text] (P<0.0001),
and carbon dioxide output [Formula: see text] (P<0.0001) were lower, 2) [Formula:
see text]/ [Formula: see text] (P=0.034) and [Formula: see text]/ [Formula: see
text] (P=0.006) were higher, and 3) the dead space/tidal volume ratio (VD/VT) and
the dyspnea level were similar. After PR, there was no significant difference in
the ratio of the observed peak heart rate (HR) to the predicted peak HR (220 –
age [years]) between the two groups. A significant negative correlation with the
baseline time-slope (r=-0.496, P=0.002) and a positive correlation with the
baseline body mass index (BMI) (r=0.496, P=0.002) were obtained.
CONCLUSIONS: PR in COPD patients improves Tex rather than exercise tolerance,
economizing oxygen requirements, resulting in reduced ventilatory requirements
without cardiac loads followed by reduced exertional dyspnea. In addition, the
time-slope and BMI could be used to predict PR responses beforehand.

Exercise training improves characteristics of exercise oscillatory ventilation in chronic heart failure.

Panagopoulou N, Karatzanos E, Dimopoulos S, Tasoulis A, Tachliabouris
I, Vakrou S, Sideris A, Gratziou C, Nanas S

Eur J Prev Cardiol. 2017 May;24(8):825-832.
Epub 2017 Jan 1.

Comment in
Eur J Prev Cardiol. 2017 Aug;24(12 ):1283-1284.
Eur J Prev Cardiol. 2017 Aug;24(12 ):1285-1286.

Background Exercise oscillatory ventilation in chronic heart failure has been
suggested as a factor related to adverse cardiac events, aggravated prognosis and
higher mortality. Exercise training is well known to affect exercise capacity and
mechanisms of pathophysiology beneficially in chronic heart failure. Little is
known, however, about the exercise training effects on characteristics of
exercise oscillatory ventilation in chronic heart failure patients. Design and
methods Twenty (out of 38) stable chronic heart failure patients exhibited
exercise oscillatory ventilation (age 54 ± 11 years, peak oxygen uptake
15.0 ± 5.0 ml/kg per minute). Patients attended 36 sessions of high intensity
interval exercise. All patients underwent cardiopulmonary exercise testing before
and after the programme. Assessment of exercise oscillatory ventilation was based
on the amplitude of cyclic fluctuations in breathing during rest and exercise.
All values are mean ± SD. Results Exercise training reduced ( P < 0.05) the
percentage of exercise oscillatory ventilation duration (79.0 ± 13.0 to
50.0 ± 25.0%), while average amplitude (5.2 ± 2.0 to 4.9 ± 1.6 L/minute) and
length (44.0 ± 10.9 to 41.0 ± 6.7 seconds) did not change ( P > 0.05). Exercise
oscillatory ventilation patients also increased exercise capacity ( P < 0.05).
Conclusions A rehabilitation programme based on high intensity interval training
improved exercise oscillatory ventilation observed in chronic heart failure
patients, as well as cardiopulmonary efficiency and functional capacity.

Relation of heart rate recovery after exercise testing to coronary artery calcification.

Jae SY, Kurl S, Laukkanen JA, Yoon ES, Choi YH, Fernhall B,
Franklin BA

Ann Med. 2017 Aug;49(5):404-410.

BACKGROUND: We examined whether slow heart rate recovery (HRR) after exercise
testing as an estimate of impaired autonomic function is related to coronary
artery calcification (CAC), an emerging marker of coronary atherosclerosis.
METHODS: We evaluated 2088 men who participated in a health-screening program
that included measures of CAC and peak or symptom-limited cardiopulmonary
exercise testing. HRR was calculated as the difference between peak heart rate
(HR) during exercise testing and the HR at 2 min of recovery after peak exercise.
We measured CAC using multidetector computed tomography to calculate the Agatston
coronary artery calcium score. Advanced CAC was defined as a mean CAC >75th
percentile for each age group.
RESULTS: HRR was negatively correlated with CAC (r = -.14, p < .01). After
adjusting for conventional risk factors, participants in the lowest quartile of
HRR (<38 bpm) were 1.59 times (95% CI: 1.17-2.18; p < .05) more likely to have
advanced CAC than their counterparts in the highest quartile of HRR (>52 bpm).
Each 1 bpm decrease in HRR was associated with 1% increase in advanced CAC after
adjusting for potential confounders.
CONCLUSIONS: An attenuated HRR after exercise testing is associated with advanced
CAC, independent of coronary risk factors and other related hemodynamic response.
KEY MESSAGES Slow heart rate recovery (HRR) after maximal exercise testing,
indicating decreased autonomic function, is associated with an increased risk of
cardiovascular event and mortality. Slow HRR has been linked with the occurrence
of malignant ventricular arrhythmias, but it remains unclear whether slow HRR is
associated with an increased risk of coronary artery calcification (CAC), an
emerging marker of coronary atherosclerosis. An attenuated HRR after exercise
testing was associated with advanced CAC, independent of coronary risk factors
and other potential hemodynamic confounder, supporting the hypothesis that slow
HRR is related to the burden of atherosclerotic coronary artery disease.

Cardiopulmonary exercise testing and second-line pulmonary function tests to detect obstructive pattern in symptomatic smokers with borderline spirometry.

Di Marco F, Terraneo S, Job S, Rinaldo RF, Sferrazza Papa GF,
Roggi MA, Santus P, Centanni S

Respir Med. 2017 Jun;127:7-13. doi: 10.1016/j.rmed.2017.04.006. Epub 2017 Apr 10.

BACKGROUND: The need for additional research on symptomatic smokers with normal
spirometry has been recently emphasized. Albeit not meeting criteria for Chronic
obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may
experience activity limitation, evidence of airway disease, and exacerbations.
We, therefore, evaluated whether symptomatic smokers with borderline spirometry
(post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted
values) have pulmonary function abnormalities at rest and ventilatory constraints
during exercise.
METHODS: 48 subjects (aged 60 ± 8 years, mean ± SD, 73% males, 16 healthy, and 17
symptomatic smokers) underwent cardiopulmonary exercise testing (CPET), body
plethysmography, nitrogen single-breath washout test (N2SBW), lung diffusion for
carbon monoxide (DLCO), and forced oscillation technique (FOT).
RESULTS: Compared to healthy subjects, symptomatic smokers showed: 1) reduced
breathing reserve (36 ± 17 vs. 49 ± 12%, P = 0.050); 2) exercise induced dynamic
hyperinflation (-0.20 ± 0.17 vs. -0.03 ± 0.21 L, P = 0.043); 3) higher residual
volume (158 ± 22 vs. 112 ± 22%, P < 0.001); 4) phase 3 slope at N2SBW (4.7 ± 2.1
vs. 1.4 ± 0.6%, P < 0.001); 5) no significant differences in DLCO and FOT
CONCLUSIONS: In smokers with borderline spirometry, CPET and second-line
pulmonary function tests may detect obstructive pattern. These subjects should be
referred for second line testing, to obtain a diagnosis, or at least to clarify
the mechanisms underlying symptoms. Whether the natural history of these patients
is similar to COPD, and they deserve a similar therapeutic approach is worth

Inter-observer reliability of preoperative cardiopulmonary exercise test interpretation: a cross-sectional study.

Abbott TEF; William Harvey Research Institute, Queen Mary University of London, London, UK; Barts Health NHS Trust, London, UK. Electronic address:
Gooneratne M; Barts Health NHS Trust, London, UK.
McNeill J; Barts Health NHS Trust, London, UK.
Lee A; William Harvey Research Institute, Queen Mary University of London, London, UK.
Levett DZH; Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton-University of Southampton, Southampton, UK.
Grocott MPW; Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton-University of Southampton, Southampton, UK.
Swart M; South Devon Healthcare NHS Trust, Torbay, UK.
MacDonald N; Barts Health NHS Trust, London, UK.

British Journal Of Anaesthesia [Br J Anaesth] 2018 Mar; Vol. 120 (3), pp. 475-483. Date of Electronic Publication: 2017 Nov 29.

Background: Despite the increasing importance of cardiopulmonary exercise testing (CPET) for preoperative risk assessment, the reliability of CPET interpretation is unclear. We aimed to assess inter-observer reliability of preoperative CPET.
Methods: We conducted a prospective, multi-centre, observational study of preoperative CPET interpretation. Participants were professionals with previous experience or training in CPET, assessed by a standardized questionnaire. Each participant interpreted 100 tests using standardized software. The CPET variables of interest were oxygen consumption at the anaerobic threshold (AT) and peak oxygen consumption (VO2 peak). Inter-observer reliability was measured using intra-class correlation coefficient (ICC) with a random effects model. Results are presented as ICC with 95% confidence interval, where ICC of 1 represents perfect agreement and ICC of 0 represents no agreement.
Results: Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%) junior doctors, and 10 (35.7%) consultant doctors. The median previous experience was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests (acclimatization) for each participant and missing data, the primary analysis of AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC 0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for identification of the presence of a reportable AT was excellent [ICC 0.93 (0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)].
Conclusions: Inter-observer reliability of interpretation of numerical values of two commonly used CPET variables was good (>80%). However, inter-observer agreement regarding the presence of a reportable value was less consistent.

Calculated versus Measured MVV-Surrogate Marker of Ventilatory CPET.

Colwell KL(1), Bhatia R

Med Sci Sports Exerc. 2017 Oct;49(10):1987-1992.

INTRODUCTION: Maximum voluntary ventilation (MVV), a surrogate marker of maximum
ventilatory capacity, allows for measuring ventilatory reserve during
cardiopulmonary exercise testing (CPET), which is necessary to assess ventilatory
limitation. MVV can be measured directly during a patient maneuver or indirectly
by calculating from forced expiratory volume in 1 s (FEV1 × 40). We investigated
for a potential difference between calculated MVV and measured MVV in pediatric
subjects, and which better represents maximum ventilatory capacity during CPET.

METHODS: Data were collected retrospectively from CPET conducted in pediatric
subjects for exercise-induced dyspnea from January 2014 to June 2015 at Akron
Children’s Hospital. Subjects with neuromuscular weakness, morbid obesity, and
suboptimal effort during the testing were excluded from the study.

RESULTS: Thirty-five subjects (mean ± SD, age = 13.8 ± 2.7 yr, range = 7-18 yr)
fulfilled the criteria. Measured MVV was significantly lower than calculated MVV
(89.9 ± 26.4 vs 122.4 ± 34.5 L·min; P < 0.01). The ventilatory reserve based on
measured MVV was also significantly lower than ventilatory reserve based on
calculated MVV (12.4% ± 19.6% vs 36.1% ± 13.2%; P < 0.01). Calculated MVV (as
well as ventilatory reserve based on calculated MVV) was significantly correlated
with ventilatory parameters. By contrast, no significant correlations were found
between measured MVV (or ventilatory reserve based on measured MVV) and
ventilatory parameters except for peak ventilation (peak V˙E).

CONCLUSIONS: The measured MVV was significantly lower than the calculated MVV in
our pediatric subjects. The calculated MVV was a better surrogate of maximum
ventilatory capacity as shown by significant correlation to other ventilatory
parameters during CPET.