Category Archives: Publications

Relationship between non‐invasive haemodynamic responses and cardiopulmonary exercise testing in patients with coronary artery disease

Sperling, Milena Pelosi Rizk; Caruso, Flávia Cristina Rossi;
Mendes, Renata Gonçalves; Dutra, Daniela Bassi; Arakelian, Vivian
Maria; Bonjorno, José Carlos; Catai, Aparecida Maria; Arena, Ross;
Borghi‐Silva, Audrey.

Clinical Physiology and Functional Imaging, March
2016, Vol. 36 Issue: Number 2 p92-98, 7p;

Abstract: Non‐invasive
assessment of haemodynamic function by impedance cardiography (IC)
constitutes an interesting approach to monitor cardiac function in
patients with coronary artery disease (CAD). However, such measurements
are most often performed at rest, whereas symptoms are also possible
during exertion, particularly at higher intensities. In addition, the
association between IC during exertion and cardiopulmonary exercise
testing (CPX) is not well understood in these patients, which was the
aim of this study. Nineteen men (age = 62 ± 6 years) with CAD [left
ventricular ejection fraction (LVEF) = 61 ± 10%] underwent a CPX using
an incremental protocol on a cycle ergometer, with simultaneous
measurement of IC. Cardiac output (CO), stroke volume (SV), cardiac
index (CI), peak oxygen consumption (VO2), the oxygen uptake efficiency
slope (OUES), circulatory power and ventilatory power were determined.
Pearson product‐moment correlation analysis revealed peak VO2 (r= 0·46)
was significantly related to CO. Peak oxygen pulse (0·52) was
associated with SV. OUES was associated with resting SV(0·47) and with
peak SV(r= 0·52). These findings suggest that ICindices are associated
with certain, but not all, established CPX measures in patients with
stable CAD.

Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review

Moran, J.; Wilson, F.; Guinan, E.; McCormick, P.; Hussey, J.; Moriarty,

British Journal of Anaesthesia, February 2016, Vol. 116 Issue:
Number 2 p177-177, 1p;

Background. Cardiopulmonary exercise
testing (CPET) is used as a preoperative risk-stratification tool for
patients undergoing non-cardiopulmonary intra-abdominal surgery.
Previous studies indicate that CPET may be beneficial, but research is
needed to quantify CPET values protective against poor postoperative
outcome [mortality, morbidity, and length of stay (LOS)]. Methods. This
systematic review aimed to assess the ability of CPET to predict
postoperative outcome. The following databases were searched: PubMed,
EMBASE, PEDro, The Cochrane Library, Cinahl, and AMED. Thirty-seven
full-text articles were included. Data extraction included the
following: author, patient characteristics, setting, surgery type,
postoperative outcome measure, and CPET outcomes. Results. Surgeries
reviewed were hepatic transplant and resection (n</it>=7), abdominal
aortic aneurysm (AAA) repair (n</it>=5), colorectal (n</it>=6),
pancreatic (n</it>=4), renal transplant (n</it>=2), upper
gastrointestinal (n</it>=4), bariatric (n</it>=2), and general
intra-abdominal surgery (n</it>=12). Cardiopulmonary exercise
testing-derived cut-points, peak oxygen consumption (VO2pk), and
anaerobic threshold (AT) predicted the following postoperative
outcomes: 90 day–3 yr survival (AT 9–11 ml kg−1 min−1) and intensive
care unit admission (AT <9.9–11 ml kg−1 min−1) after hepatic transplant
and resection, 90 day survival after AAA repair
VO2pk 15 ml kg−1 min−1), LOS and morbidity after pancreatic surgery (AT <10–10.1 ml kg−1
min−1), and mortality and morbidity after intra-abdominal surgery (AT
10.9 and <10.1 ml kg−1 min−1, respectively).
Cardiopulmonary exercise testing is a useful preoperative
risk-stratification tool that can predict postoperative outcome.
Further research is needed to justify the ability of CPET to predict
postoperative outcome in renal transplant, colorectal, upper
gastrointestinal, and bariatric surgery.

Cardiopulmonary exercise test and sudden cardiac death risk in hypertrophic cardiomyopathy

Heart doi:10.1136/heartjnl-2015-308453




Background In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification.

Methods A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions.

Results During a median follow-up of 3.7 years (25th–75th centile: 2.2–5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72).

Conclusions Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction

The Henry Ford HospITal
CardioPulmonary EXercise Testing (FIT-CPX) project by Shafiq, Ali;
Brawner, Clinton A.; Aldred, Heather A.; Lewis, Barry; Williams,
Celeste T.; Tita, Christina; Schairer, John R.; Ehrman, Jonathan K.;
Velez, Mauricio; Selektor, Yelena; Lanfear, David E.; Keteyian, Steven

American Heart Journal, 20160101, Issue: Number Preprints;

Abstract: Although cardiopulmonary exercise (CPX) testing in patients
with heart failure and reduced ejection fraction is well established,
there are limited data on the value of CPX variables in patients with
HF and preserved ejection fraction (HFpEF). We sought to determine the
prognostic value of select CPX measures in patients with HFpEF.

Case report: Subjective loss of performance after pulmonary embolism in an athlete– beyond normal values

Dumitrescu, Daniel; Gerhardt,
Felix; Viethen, Thomas; Schmidt, Matthias; Mayer, Eckhard; Rosenkranz,
Stephan. BMC

Pulmonary Medicine, December 2016, Vol. 16 Issue: Number 1
p1-4, 4p;

Abstract: Chronic thromboembolic pulmonary hypertension
(CTEPH) is a progressive disease. For patients with operable CTEPH,
there is a clear recommendation for surgical removal of persistent
thrombi by pulmonary endarterectomy (PEA). However, without the
presence of PH, therapeutic management of chronic thromboembolic
disease (CTED) is challenging – especially in highly trained subjects
exceeding predicted values of maximal exercise capacity.
A 43-year-old male athlete reported with progressive exercise
limitation since 8 months. Six months earlier, pulmonary embolism had
occurred, and was treated since with oral anticoagulation. A pulmonary
ventilation/perfusion scan showed severe ventilation/perfusion
mismatch: chest CT and pulmonary angiography revealed bilateral
wall-adherent thrombotic material, but pulmonary hemodynamics were
completely normal. His peak oxygen uptake exceeded predicted values,
however exercise ventilatory efficiency was abnormal, compared to a
matching athlete. After thoroughly discussing therapeutic options with
the patient, he successfully underwent pulmonary endarterectomy at an
expert center. Five and twelve months after surgery, his maximal
exercise capacity and ventilatory efficiency profoundly improved beyond
preoperative values, and his subjective exercise tolerance had returned
to normal.                   Significant CTED may be present without
relevant pathologic changes in pulmonary hemodynamics at rest. Reaching
normal values of maximal exercise capacity does not exclude pulmonary
vascular disease in highly trained subjects. More data are needed to
evaluate the risk-/benefit ratio of PEA in patients with CTED and
normal pulmonary hemodynamics. A thorough discussion with the patient
as well as shared decision making regarding therapy are mandatory.
Cardiopulmonary exercise testing may add important clinical information
in the non-invasive diagnostic evaluation at baseline and during

Measured by the oxygen uptake in the field, the work of refuse collectors is particularly hard work: Are the limit values for physical endurance workload too low?

Preisser, Alexandra; Zhou, Linfei; Garrido, Marcial; Harth, Volker.

International Archives of Occupational  and Environmental Health, February 2016, Vol. 89 Issue: Number 2
p211-220, 10p;

Abstract: Collecting waste is regarded as a benchmark
for “particularly heavy” work. This study aims to determine and compare
the workload of refuse workers in the field. We examined heart rate
(HR) and oxygen uptake as parameters of workload during their daily
work.   Sixty-five refuse collectors from three  task-specific groups
(residual and organic waste collection, and street
sweeping) of the municipal sanitation department in Hamburg, Germany,
were included. Performance was determined by cardiopulmonary exercise
testing (CPX) under laboratory conditions. Additionally, the oxygen
uptake (VO2) and HR under field conditions (1-h morning shift) were
recorded with a portable spiroergometry system and a pulse belt.
There was a substantial correlation of both absolute HR and
VO2during CPX [HR/VO2 R 0.89 (SD 0.07)] as well as during field
measurement [R0.78 (0.19)]. Compared to reference limits for heavy
work, 44 % of the total sample had shift values above 30 % heart rate
reserve (HRR); 34 % of the individuals had mean HR during work (HRsh)
values that were above the HR corresponding to 30 % of individual
maximum oxygen uptake (VO2,max). All individuals had a mean oxygen
uptake (VO2,1h) above 30 % of VO2,max.
HR as well as the measurement of VO2can be valuable tools for investigating
physiological workload, not only under laboratory conditions but also
under normal working conditions in the field. Both in terms of absolute
and relative HR and oxygen consumption, employment as a refuse
collector should be classified in the upper range of defined heavy
work. The limit of heavy work at about 33 % of the individual maximum
load at continuous work should be reviewed.

Biological quality control for cardiopulmonary exercise testing in multicenter clinical trials

Porszasz, Janos; Blonshine, Susan; Cao,  Robert; Paden, Heather; Casaburi, Richard; Rossiter, Harry. BMC

Pulmonary Medicine, December 2016, Vol. 16 Issue: Number 1 p1-10, 10p;

Abstract: Precision and accuracy assurance in cardiopulmonary exercise
testing (CPET) facilitates multicenter clinical trials by maximizing
statistical power and minimizing participant risk. Current guidelines
recommend quality control that is largely based on precision at
individual testing centers (minimizing test–retest variability). The
aim of this study was to establish a multicenter biological quality
control (BioQC) method that considers both precision and accuracy in
CPET.   BioQC testing was 6-min treadmill walking at 20 W and 70 W
(below the lactate threshold) with healthy non-smoking
laboratory staff (15 centers; ~16 months). Measurements were made twice
within the initial 4 weeks and quarterly thereafter. Quality control
was based on: 1) within-center precision (coefficient of variation [CV]
for oxygen uptake [V̇O2], carbon dioxide output [V̇CO2], and minute
ventilation [V̇E] within ±10 %); and 2) a criterion that V̇O2at 20 W
and 70 W, and ∆V̇O2/∆WR were each within ±10 % predicted. “Failed”
BioQC tests (i.e., those outside the predetermined criterion) prompted
troubleshooting and repeated measurements. An additional retrospective
analysis, using a composite z-score combining both BioQC precision and
accuracy of V̇O2at 70 W and ∆V̇O2/∆WR, was compared with the other
Of 129 tests (5 to 8 per center), 98 (76 %)
were accepted by within-center precision alone. Within-center CV was
<9 %, but between-center CV remained high (9.6 to 12.5 %). Only 43
(33 %) tests had all V̇O2measurements within the ±10 % predicted
criterion. However, a composite z-score of 0.67 identified 67 (52 %)
non-normal outlying tests, exclusion of which coincided with the
minimum CV for CPET variables.
Study-wide BioQC using
a composite z-score can increase study-wide precision and accuracy, and
optimize the design and conduct of multicenter clinical trials
involving CPET.

The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients (The EMPOWER Trial)

Study  protocol for a randomised controlled trial

Loughney, Lisa; West, Malcolm; Kemp, Graham; Rossiter, Harry; Burke, Shaunna; Cox, Trevor;
Barben, Christopher; Mythen, Michael; Calverley, Peter; Palmer, Daniel;
Grocott, Michael; Jack, Sandy.

Trials, December 2016, Vol. 17 Issue: Number 1 p1-13, 13p;

Abstract: The standard treatment pathway for
locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT)
followed by surgery. Neoadjuvant CRT has been shown to decrease
physical fitness, and this decrease is associated with increased
post-operative morbidity. Exercise training can stimulate skeletal
muscle adaptations such as increased mitochondrial content and improved
oxygen uptake capacity, both of which are contributors to physical
fitness. The aims of the EMPOWER trial are to assess the effects of
neoadjuvant CRT and an in-hospital exercise training programme on
physical fitness, health-related quality of life (HRQoL), and physical
activity levels, as well as post-operative morbidity and cancer
staging. The EMPOWER Trial is a randomised controlled
trial with a planned recruitment of 46 patients with locally advanced
rectal cancer and who are undergoing neoadjuvant CRT and surgery.
Following completion of the neoadjuvant CRT (week 0) prior to surgery,
patients are randomised to an in-hospital exercise training programme
(aerobic interval training for 6 to 9 weeks) or a usual care control
group (usual care and no formal exercise training). The primary
endpoint is oxygen uptake at lactate threshold (VO2 at AT)
measured using cardiopulmonary exercise testing assessed over several time points throughout the
study. Secondary endpoints include HRQoL, assessed using
semi-structured interviews and questionnaires, and physical activity
levels assessed using activity monitors. Exploratory endpoints include
post-operative morbidity, assessed using the Post-Operative Morbidity
Survey (POMS), and cancer staging, assessed by using magnetic resonance
tumour regression grading.   The EMPOWER trial is the
first randomised controlled trial comparing an in-hospital exercise
training group with a usual care control group in patients with locally
advanced rectal cancer. This trial will allow us to determine whether
exercise training following neoadjuvant CRT can improve physical
fitness and activity levels, as well as other important clinical
outcome measures such as HRQoL and post-operative morbidity. These
results will aid the design of a large, multi-centre trial to determine
whether an increase in physical fitness improves clinically relevant
post-operative outcomes.

Prevalence and characterization of exercise oscillatory ventilation in apparently healthy individuals at variable risk for cardiovascular disease

A subanalysis of the EURO-EX trial

Guazzi, Marco; Arena, Ross; Pellegrino, Marta; Bandera, Francesco; Generati, Greta; Labate,
Valentina; Alfonzetti, Eleonora; Villani, Simona; Gaeta, Maddalena M;
Halle, Martin; Haslbauer, Robert; Phillips, Shane A; Cahalin, Lawrence

European Journal of Preventive Cardiology,
February 2016, Vol. 23 Issue: Number 3 p328-334, 7p;

Abstract: Introduction  There has been a
greater appreciation of several variables obtained by cardiopulmonary
exercise testing (CPX). Exercise oscillatory ventilation (EOV) is a CPX
pattern that has gained recognition as an ominous marker of poor
prognosis in cardiac patients. The purpose of the present study is to
characterize whether such an abnormal ventilatory pattern may also be
detected in apparently healthy subjects and determine its clinical

Methods  The study involved 510 subjects (mean age 60 ± 14
years; 49% male) with a broad cardiovascular (CV) risk factor profile
who underwent CPX.Results  The population was divided into two groups
according to the presence (17%) or absence of EOV. Subjects with EOV
were significantly older and a higher percentage was female. Risk
factor profile and medication use was significantly different between
subgroups, indicating subjects with EOV had a worse CV risk factor
profile and were prescribed CV-focused preventive medications at a
significantly higher frequency. Subjects with EOV had comparatively
poorer CPX performance and gas exchange phenotype. Multivariate binary
logistic regression analysis found being female was the strongest
predictor of EOV (odds ratio: 2.77, 95% confidence interval (CI):
1.66-4.61, p< 0.001). A diagnosis of diabetes (odds ratio: 2.40, 95%
CI: 1.34–4.15.2, p< 0.001) added significant value for predicting EOV
and was retained in the regression. The likelihood for EOV for subjects
who were female and diagnosed with diabetes was 3.71 (95% CI 1.88–7.30,
p< 0.001).

Conclusions  This is the first study to examine EOV
prevalence and characterization in apparently healthy persons with
results supporting an in-depth definition of abnormal exercise

Pulmonary Sarcoidosis

Valeyre, Dominique; Bernaudin,
Jean-François; Jeny, Florence; Duchemann, Boris; Freynet, Olivia;
Planès, Carole; Kambouchner, Marianne; Nunes, Hilario.

Clinics in Chest  Medicine, December 2015, Vol. 36 Issue: Number 4 p631-641, 11p;
Abstract: Sarcoidosis is a systemic disease, with lung involvement in
almost all cases. Abnormal chest radiography is usually a key step for
considering diagnosis. Lung impact is investigated through imaging;
pulmonary function; and, when required, 6-minute walk test,
cardiopulmonary exercise testing, or right heart catheterization. There
is usually a reduction of lung volumes, and forced vital capacity is
the most accurate parameter to reflect the impact of pulmonary
sarcoidosis with or without pulmonary infiltration at imaging. Various
evolution patterns have been described. Increased risk of death is
associated with advanced pulmonary fibrosis or cor pulmonale,
particularly in African American patients.