Category Archives: Publications

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.

Operative and Functional Outcome After Pulmonary Endarterectomy for Advanced Thromboembolic Pulmonary Hypertension

Leung Wai Sang,
Stephane; Morin, Jean‐Francois; Hirsch, Andrew.

Journal of Cardiac
Surgery, January 2016, Vol. 31 Issue: Number 1 p3-8, 6p;


To  evaluate the midterm hemodynamic and functional outcome of pulmonary
endarterectomy (PEA) for patients with advanced chronic thromboembolic
pulmonary hypertension (CTEPH). Thirty‐eight consecutive patients
underwent PEA for CTEPH from May 2004 to March 2012. All patients were
followed prospectively at six months postoperatively and annually
thereafter. Each patient underwent serial cardiopulmonary exercise
testing (CPET) and transthoracic echocardiography, and were followed
for up to four years. Overall, 31.5% (12/38) of patients had Jamieson
class II disease while 65.8% (25/38) had class III disease. There were
three in‐hospital mortalities (7.9%), all of which had baseline
pulmonary vasculature resistance (PVR) greater than
1400 dynes‐sec‐cm−5. Preoperative PVR and mean pulmonary artery
pressure were 1209 ± 723 dynes‐sec‐cm−5and 50 ± 14 mmHg, respectively,
signifying a high‐risk operative group. Ninety‐seven percent of
patients were in NYHA class III or IV preoperatively. At median
follow‐up of 29 months 89.5% (17/19) of patients were in NYHA class I
or II. CPET revealed a progressive increase in peak oxygen consumption
from 16.5 ± 4.1 ml/kg/min at first follow‐up, to a plateau of
20.2 ± 5.6 ml/kg/min (p = 0.032) at two years. CPET can be used to
quantify progress in functional capacity post‐CTEPH, although
improvements in peak oxygen consumption plateau at two years.

Oxygen uptake is more efficient in idiopathic pulmonary arterial hypertension than in chronic thromboembolic pulmonary hypertension

Shi, Xiaofang; Guo, Jian; Gong, Sugang; Sapkota, Rikesh; Yang, Wenlan;
Liu, Hui; Xiang, Wenjing; Wang, Lan; Sun, Xingguo; Liu, Jinming.

Respirology, January 2016, Vol. 21 Issue: Number 1 p149-156, 8p;
Abstract: The responses of oxygen uptake efficiency (OUE) during
cardiopulmonary exercise training (CPET) have not been reported in
patients with pulmonary hypertension. We aimed to investigate the
differences in OUE between patients with idiopathic pulmonary arterial
hypertension (IPAH) and chronic thromboembolic pulmonary hypertension
(CTEPH). Forty‐four patients with IPAHand 29 patients with CTEPH were
retrospectively enrolled into our study. All patients underwent
right‐heart catheterization, pulmonary function test and performed the
6‐min walk test and CPET. We found that oxygen uptake efficiency
plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold
(OUE@AT) was significantly higher in IPAH than that in CTEPH (both
P= 0.002). However, patients with CTEPH had lower mean pulmonary artery
pressure, pulmonary vascular resistance and transpulmonary gradient
(all P< 0.05). The correlation between OUEP and heart rate at anaerobic
threshold (HR_AT) was significant (r = 0.376, P< 0.05); however, no
statistically significant correlation was found with ventilation at
anaerobic threshold (VE_AT) (r = −0.074, P> 0.05) in patients with
IPAH. In patients with CTEPH, both anaerobic threshold (r = 0.307,
P> 0.05) and VE_AT (r = −0.709, P< 0.0001) were reduced. OUEP were
higher in WHO functional class I/IIpatients than in WHO functional class
III/IVpatients (all P< 0.05). OUEP and OUE@ATare higher in IPAHthan that
in CTEPH not in proportion to haemodynamics, probably due to differences
in cardiac function and pulmonary vascular occlusion. OUEP correlates
well with the exercise capacity and the severity of the disease.
Responses of oxygen uptake efficiency during cardiopulmonary exercise
testing in patients with pulmonary hypertension are reported. We
observed a higher oxygen uptake efficiency in patients with idiopathic
pulmonary arterial hypertension compared to patients with chronic
thromboembolic pulmonary hypertension. The oxygen uptake efficiency
plateau correlates with exercise capacity and disease severity.

Cardiopulmonary Exercise Testing in Patients with Asymptomatic or Equivocal Symptomatic Aortic Stenosis: Feasibility, Reproducibility, Safety and Information Obtained on Exercise Physiology

van Le,
Douet; Jensen, Gunnar Vagn Hagemann; Carstensen, Steen; Kjøller-Hansen,

Cardiology, November 2015, Vol. 133 Issue: Number 3 p147-156,

Objective:The aim of this study was to determine the
feasibility, reproducibility, safety and information obtained on
exercise physiology from cardiopulmonary exercise testing (CPX) in
patients with aortic stenosis.
Methods:Patients with an aortic valve
area (AVA) <1.3 cm2who were judged asymptomatic or equivocal
symptomatic underwent CPX and an inert gas rebreathing test. Only those
where comprehensive evaluation of CPX results indicated haemodynamic
compromise from aortic stenosis were referred for valve replacement.
Results:The mean patient age was 72 (±9) years; an AVA index <0.6
cm2/m2and equivocal symptomatic status were found in 90 and 70%,
respectively. CPX was feasible in 130 of the 131 patients. The
coefficients of repeatability by test-retest were 5.4% (pVO2) and 4.6%
(peak O2pulse). A pVO2<83% of the expected was predicted by a lower
stroke volume at exercise, lower peak heart rate and FEV1, and higher
VE/VCO2, but not by AVA index. Equivocal symptomatic status and a low
gradient but high valvulo-arterial impedance were associated with a
lower pVO2, but not with an inability to increase stroke volume. In
total, 18 patients were referred for valve replacement. At 1 year, no
cardiovascular deaths had occurred.
Conclusions:CPX was feasible and
reproducible and provided comprehensive data on exercise physiology. A
CPX-guided treatment strategy was safe up to 1 year.

Cardiopulmonary exercise testing versus spirometry as predictors of cardiopulmonary complications after colorectal surgery

Nikolopoulos,  I.; Ellwood, M.; George, M.; Carapeti, E.; Williams, A..

European Surgery (Acta Chirurgica Austriaca), December 2015, Vol. 47 Issue:
Number 6 p324-330, 7p;

Abstract: To determine the predictive value of
spirometry and cardiopulmonary exercise testing (CPET) preoperatively
in patients scheduled to undergo elective colorectal surgery. We
compared the preoperative results with the incidence of postoperative
cardiopulmonary complications.  A total of 103   patients were scheduled
to undergo preoperative CPET and spirometry; 14
patients did not attend their appointments and another 20 were unable
to perform the test. In all, 69 patients (median age 60 years (range
25–85), 35 males) successfully completed cycle ergometry and lung
function tests. Forced expiratory volume in 1 s (FEV1), percent forced
expiratory volume in 1 s (FEV1/forced vital capacity (FVC)) and
anaerobic threshold (AT) were measured. Patients were divided
postoperatively according to whether cardiopulmonary complications were
absent (group A) or present (group B).  Postoperative
cardiopulmonary complications developed in 8 of the 69 patients (12 %).
Thirty day mortality was 3 %. AT was significantly higher in group A
(mean AT = 13.8; SD ± 3.0; range = 8.1–20.8) than in group B
(mean = 10.91; SD ± 3.0; Range = 7.9–12), (p= 0.0006). Spirometric
pulmonary function tests (FEV1, p= 0.09) and (FEV1/FVC, p= 0.08) showed
no intergroup differences. The median hospital length of stay (HLOS)
was significantly higher in the group of patients that suffered
cardiopulmonary complications (p= 0.0282).     CPET
allows the prediction of postoperative cardiopulmonary complications
which cannot be anticipated by spirometry. Early detection of high risk
patients facilitates the planning of patient specific management
strategies which are likely to improve outcome through invasive
monitoring and optimisation of cardio-respiratory function.

Usefulness of C-Reactive Protein Plasma Levels to Predict Exercise Intolerance in Patients With Chronic Systolic Heart Failure

Justin McNair; Fronk, Daniel Taylor; Cei, Laura Freeman; Carbone,
Salvatore; Erdle, Claudia Oddi; Abouzaki, Nayef Antar; Melchior, Ryan
David; Thomas, Christopher Scott; Christopher, Sanah; Turlington,
Jeremy Shane; Trankle, Cory Ross; Thurber, Clinton Joseph; Evans,
Ronald Kenneth; Dixon, Dave L.; Van Tassell, Benjamin Wallace; Arena,
Ross; Abbate, Antonio.

The American Journal of Cardiology, January
2016, Vol. 117 Issue: Number 1 p116-120, 5p;

Abstract: Patients with
heart failure (HF) have evidence of chronic systemic inflammation.
Whether inflammation contributes to the exercise intolerance in
patients with HF is, however, not well established. We hypothesized
that the levels of C-reactive protein (CRP), an established
inflammatory biomarker, predict impaired cardiopulmonary exercise
performance, in patients with chronic systolic HF. We measured CRP
using high-sensitivity particle-enhanced immunonephelometry in 16
patients with ischemic heart disease (previous myocardial infarction)
and chronic systolic HF, defined as a left ventricular ejection
fraction ≤50% and New York Heart Association class II-III symptoms. All
subjects with CRP >2 mg/L, reflecting systemic inflammation, underwent
cardiopulmonary exercise testing using a symptom-limited ramp protocol.
CRP levels predicted shorter exercise times (R = −0.65, p = 0.006),
lower oxygen consumption (VO2) at the anaerobic threshold (R = −0.66,
p = 0.005), and lower peak VO2(R = −0.70, p = 0.002), reflecting worse
cardiovascular performance. CRP levels also significantly correlated
with an elevated ventilation/carbon dioxide production slope
(R = +0.64, p = 0.008), a reduced oxygen uptake efficiency slope
(R = −0.55, p = 0.026), and reduced end-tidal CO2level at rest and with
exercise (R = −0.759, p = 0.001 and R = −0.739, p = 0.001,
respectively), reflecting impaired gas exchange. In conclusion, the
intensity of systemic inflammation, measured as CRP plasma levels, is
associated with cardiopulmonary exercise performance, in patients with
ischemic heart disease and chronic systolic HF. These data provide the
rationale for targeted anti-inflammatory treatments in HF.

Rationale and Design of a Randomized Controlled Trial Evaluating Whole Muscle Exercise Training Effects in Outpatients with Pulmonary Arterial Hypertension

Sanchis-Gomar, Fabian;  González-Saiz, Laura; Sanz-Ayan, Paz; Fiuza-Luces, Carmen;
Quezada-Loaiza, Carlos; Flox-Camacho, Angela; Santalla, Alfredo;
Munguía-Izquierdo, Diego; Santos-Lozano, Alejandro; Pareja-Galeano,
Helios; Ara, Ignacio; Escribano-Subías, Pilar; Lucia, Alejandro.
Cardiovascular Drugs and Therapy, December 2015, Vol. 29 Issue: Number
6 p543-550, 8p;

Abstract: Physical exercise is an important component
in the management of pulmonary artery hypertension (PAH). The aim of
this randomized controlled trial (RCT) is to determine the effects of
an 8-week intervention combining muscle resistance, aerobic and
inspiratory pressure load exercises in PAH outpatients.
The RCT will be conducted from September 2015 to September 2016
following the recommendations of the Consolidated Standards of Reported
Trials (CONSORT), with a total sample size of n ≥ 48 (≥24
participants/group). We will determine the effects of the intervention
on: (i) skeletal-muscle power and mass (primary end points); and (ii)
NT-proBNP, cardiopulmonary exercise testing variables (VO2peak,
ventilatory equivalent for CO2at the anaerobic threshold (VE/VCO2at the
AT), end-tidal pressure of CO2at the anaerobic threshold (PETCO2at the
AT), 6-min walking distance (6MWD), maximal inspiratory pressure
(PImax), health-related quality of life (HRQoL), objectively-assessed
spontaneous levels of physical activity, and safety (secondary end
points).                   This trial will provide insight into
biological mechanisms of the disease and indicate the potential
benefits of exercise in PAH outpatients, particularly on muscle power.