Author Archives: Paul Older

The role of a structured exercise training program on cardiac structure and function after acute myocardial infarction

Study protocol for a randomized controlled trial

Fontes-Carvalho, Ricardo;
Sampaio, Francisco; Teixeira, Madalena; Gama, Vasco; Leite-Moreira,

Trials, December 2015, Vol. 16 Issue: Number 1 p1-6, 6p;
Abstract: Exercise training is effective in improving functional
capacity and quality of life in patients with coronary artery disease,
but its effects on left ventricular systolic and diastolic function are
controversial. Diastolic dysfunction is a major determinant of adverse
outcome after myocardial infarction and, contrary to systolic function,
no therapy or intervention has proved to significantly improve
diastolic function. Data from animal studies and from patients with
diastolic heart failure has suggested that exercise training can have a
positive effect on diastolic function parameters.
This trial aims to evaluate if a structured exercise training program
can improve resting left ventricular diastolic and systolic function in
patients who have had an acute myocardial infarction.
This is a phase II, prospective, randomized, open-label,
blinded-endpoint trial that will include at least 96 consecutive
patients who have had an acute myocardial infarction one month
previously. Patients will be randomized (1:1) to an exercise training
program or a control group, receiving standard of care. At enrolment,
and at the end of the follow-up period, patients will be submitted to
an echocardiography (with detailed assessment of diastolic and systolic
function using recent consensus guidelines), cardiopulmonary exercise
testing, an anthropometric assessment, blood testing, and clinical
evaluation. Patients randomized to the intervention group will be
submitted to an eight-week outpatient exercise program, combining
endurance and resistance training, for three sessions per week. The
primary endpoint will be the change in lateral E’ velocity immediately
after the eight-week exercise training program. Secondary endpoints
will include other echocardiographic parameters of left ventricular
diastolic and systolic function, cardiac structure, metabolic and
inflammation biomarkers (high-sensitivity C-reactive protein and
pro-BNP), functional capacity (peak oxygen consumption and anaerobic
threshold) and anthropometric measurements.                   New
strategies that can improve left ventricular diastolic function are
clinically needed. This will be the first trial to evaluate, in
patients who have had an acute myocardial infarction, the effects of a
structured program of exercise training on diastolic and systolic
function, assessed by novel echocardiographic parameters.

Prognostic value of breathing reserve index at anaerobic threshold during cardiopulmonary exercise testing in children with cystic fibrosis

O’Connor, R.; Rand, S.; Grillo, L.; Hebestreit, H.;
Prasad, S.A.; Urquhart, D..

Journal of Cystic Fibrosis, June 2015, Vol.
14 Issue: Number 1, Number 1 Supplement 1 pS40-S40, 1p;

Cardiopulmonary exercise test (CPET) testing is the gold standard
exercise test in CF. Elevated breathing reserve index at anaerobic
threshold (BRIAT) is a prognostic indicator of mortality in CF adults
awaiting transplant, but no data on BRIAT in the paediatric CF
population are reported. The aim of this study was to investigate the
relationship between BRIAT and morbidity (death or transplant) in
children with CF.

Gender differences and exercise performance in adults with cystic fibrosis

Savi, D.; Quattrucci, S.; Di Paolo, M.; Leggieri,
E.; D’Alù, V.; De Biase, R.V.; Cucchiara, S.; Palange, P.; Simmonds,

Journal of Cystic Fibrosis, June 2015, Vol. 14 Issue: Number 1,
Number 1 Supplement 1 pS28-S28, 1p;

Abstract: In cystic fibrosis (CF)
maximal oxygen uptake and maximal work rate measured during
cardiopulmonary exercise testing (CPET) are significant predictors of
mortality. Several previous studies, predominantly of children with CF,
showed gender differences in exercise capacity. To date, it has not
been well established if these observations carry over into adulthood.

The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms – A blinded interventional study

West, M. A.; Parry, M.; Asher, R.; Key, A.; Walker, P.;
Loughney, L.; Pintus, S.; Duffy, N.; Jack, S.; Torella, F..

British Journal of Anaesthesia, June 2015, Vol. 114 Issue: Number 6
p878-878, 1p;

Abstract: <sec><st>Background</st> Perioperative
beta-blockade is widely used, especially before vascular surgery;
however, its impact on exercise performance assessed using
cardiopulmonary exercise testing (CPET) in this group is unknown. We
hypothesized that beta-blocker therapy would significantly improve
CPET-derived physical fitness in this group. </sec>
<sec><st>Methods</st> We recruited patients with abdominal aortic
aneurysms (AAA) of <5.5 cm under surveillance. All patients underwent
CPET on and off beta-blockers. Patients routinely prescribed
beta-blockers underwent a first CPET on medication. Beta-blockers were
stopped for one week before a second CPET. Patients not routinely
taking beta-blockers underwent the first CPET off treatment, then
performed a second CPET after commencement of bisoprolol for at least
48 h. Oxygen uptake (<f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f>) at
estimated lactate threshold (<f>$${\hat{\theta }}_{L}$$</f>) and
<f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f> at peak were primary outcome
variables. A linear mixed-effects model was fitted to investigate any
difference in adjusted CPET variables on and off beta-blockers. </sec>
<sec><st>Results</st> Forty-eight patients completed the study. No
difference was observed in <f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f> at
<f>$${\hat{\theta }}_{L}$$</f> and
<f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f> at peak; however, a significant
decrease in <f>$${\dot{V}}_{E}/{\dot{V}}_{{\mathrm{CO}}_{2}}$$</f> at
<f>$${\hat{\theta }}_{L}$$</f> and peak, an increase in workload at
<f>$${\hat{\theta }}_{L}$$</f>, O<inf>2</inf> pulse and heart rate both
at <f>$${\hat{\theta }}_{L}$$</f> and peak was found with
beta-blockers. Patients taking beta-blockers routinely (chronic group)
had worse exercise performance (lower
<f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f>). </sec>

Conclusions</st>Beta blockade has a significant impact on
CPET-derived exercise performance, albeit without changing
<f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f> at <f>$${\hat{\theta
}}_{L}$$</f> and <f>$${\dot{V}}_{{\mathrm{O}}_{2}}$$</f> at peak. This
supports performance of preoperative CPET on or off beta-blockers
depending on local perioperative practice.

Relationship between daily physical activity and aerobic fitness in adults with cystic fibrosis

Savi, Daniela; Di Paolo, Marcello;
Simmonds, Nicholas; Onorati, Paolo; Internullo, Mattia; Quattrucci,
Serena; Winston, Banya; Laveneziana, Pierantonio; Palange, Paolo.

Pulmonary Medicine, December 2015, Vol. 15 Issue: Number 1 p1-9, 9p;
Abstract: The best clinical practice to investigate aerobic fitness
includes measurements obtained during cardiopulmonary exercise testing
(CPET), however it remains an underutilised clinical measure in cystic
fibrosis (CF). To investigate this further, different methods of
quantifying exercise capacity in CF are required. The possibility that
measuring physical activity (PA) by a portable accelerometer could be
used to assess the CF aerobic state and could be added among the CPET
surrogates has not been investigated. The aim of this study was to
examine the relationship between PA and exercise fitness both at
submaximal and maximal levels in clinically stable adults with CF.
Thirty CF patients (FEV171 ± 19% predicted) and fifteen
healthy controls undertook an incremental CPET on a cycle ergometer.
CPET-related measurements included: oxygen uptake (V’O2), carbon
dioxide production (V’CO2), ventilatory profile, heart rate (HR) and
oxygen pulse (V’O2/HR) throughout exercise and at lactic threshold (LT)
and peak. LT measures represent submaximal exercise related data. PA
was assessed using the accelerometer SenseWear Pro3 Armband.
Moderate (>4.8 metabolic equivalents (METS)) and moderate +
vigorous (>7.2 METS) PA was related to V’O2(p = 0.005 and p = 0.009,
respectively) and work rate (p = 0.004 and p = 0.002, respectively) at
LT. Moderate PA or greater was positively related to peak V’O2(p =
0.005 and p = 0.003, respectively). Daily PA levels were similar in CF
and healthy controls. Except for peak values, V’O2profile and the
V’O2at LT were comparable between CF and healthy controls.
In adult CF patients daily PA positively correlated with aerobic
capacity. PA measurements are a valuable tool in the assessment of
exercise performance in an adult CF population and could be used for
interventional exercise trials to optimize exercise performance and
health status. PA levels and parameters obtained at submaximal exercise
are similar in CF and in healthy controls.;

A 12-month, moderate-intensity exercise training program improves fitness and quality of life in adults with asthma: a controlled trial

Meyer, Andreas; Günther, Sabine; Volmer, Timm; Taube, Karin;
Baumann, Hans.

BMC Pulmonary Medicine, December 2015, Vol. 15 Issue:
Number 1 p1-8, 8p;

Abstract: Physical training has been shown to
improve exercise capabilities in patients with asthma. Most studies
focused on children and younger adults. Previously, the maximum program
duration was six months. It is not known whether the same results may
be obtained with lower intensity programs and sustained for time
periods longer than 6 months. This controlled study was undertaken to
investigate the effects of a moderate intensity outpatient training
program of one year duration on physical fitness and quality of life in
adults with asthma.    21 adult asthmatics (mean age
56 ± 10 years) were allocated to outpatient training (n = 13) or
standard care (n = 8). Exercise consisted of once weekly, 60-minute
sessions of moderate intensity. Assessments at baseline and after one
year included cardiopulmonary exercise testing and Short Form-36 and
Asthma Quality of Life Questionnaires.     Following one
year of exercise, relevant improvements were observed in the training
group for maximum work capacity (p = 0.005), peak oxygen uptake
(p < 0.005), O2pulse (p < 0.05), maximum ventilation (p < 0.005), and
most of the quality of life domains. No changes were observed in the
control group.

A physiotherapist-led, long-term,
moderate-intensity exercise program of one year duration can induce
clinically relevant improvements in exercise capabilities and
health-related quality of life in well-motivated adults with asthma. NCT01097473. Date trial registered:

CPET in the diagnosis of CAD – a new approach: Abstract from ESC CONGRESS 2014

N. Kumar, S. Choudhry

PURPOSE: Prospective study to examine the diagnostic accuracy of a new exercise-based parameter (abrupt steepening of HR response) in late exercise to diagnose macro-vascular CAD.
METHOD: 1000 CPX performed in symptomatic patients & 50 Angiograms in a single centre.
RESULTS: Patients without inducible ischemia have a linear HR response as a function of VO2 throughout exercise (Fig 1). Patients with inducible ischemia  develop mechanical dysfunction and a compensatory steepening of HR response (curvilinear) (Fig 2); this signifies clinically significant global ischemic burden. Fifty consecutive patients with an abnormal response underwent angiography.  The sensitivity and specificity for significant large vessel atherosclerosis (one or more vessels with >50% stenosis) was 92% (Fig 3).
CONCLUSION: In the contracting Ischemic Myocardium, an oxygen supply-demand mismatch results in diastolic dysfunction causing the stroke volume response to deteriorate and HR response to steepen with a progressively increasing work rate past the ischemic threshold.  This methodology is seen far more frequently than ST depression and is highly sensitive to the presence of a physiologically significant ischemic burden

Disordered breathing during sleep and exercise in idiopathic pulmonary fibrosis

Lee, R.N.C.; Kelly,
E.; Nolan, G.; Eigenheer, S.; Boylan, D.; Murphy, D.; Dodd, J.; Keane,
M.P.; McNicholas, W.T

An International Journal of Medicine,
April 2015, Vol. 108 Issue: Number 4 p315-315, 1p

Abstract: Background
and objective: Idiopathic pulmonary fibrosis (IPF) patients report
fatigue, possibly reflecting sleep disturbance, but little is known
about sleep-related changes. We compared ventilation and gas exchange
during sleep and exercise in a cohort of IPF patients, and evaluated
associations with selected biological markers. Methods: Twenty stable
IPF patients (aged 67.9 ± 12.3 [SD]) underwent overnight
polysomnography following an acclimatization night. Cardiopulmonary
exercise testing was performed and inflammatory markers measured
including TNF-α, IL-6, CXCL8, C-C motif ligand 18 (CCL-18) and
C-reactive protein (CRP) Results: Nine patients had sleep-disordered
breathing (SDB) with an apnea–hypopnea frequency (AHI) ≥ 5/h, but only
two had Epworth sleepiness score ≥10, thus having an obstructive sleep
apnea syndrome. Sleep quality was poor. Transcutaneous carbon dioxide
tension (PtcCO<inf>2</inf>) rose by 2.56 ± 1.59 kPa overnight (P</it> =
0.001), suggesting hypoventilation. Oxygen saturation (SaO<inf>2</inf>)
was lower during sleep than exercise (P</it> < 0.01), and exercise
variables correlated with resting pulmonary function. CCL-18 and CRP
levels were elevated and correlated with PtcCO<inf>2</inf> rise during
sleep (P</it> < 0.05). CCL-18 negatively correlated with diffusion
capacity of carbon monoxide (DLCO), arterial oxygen (PaO<inf>2</inf>)
and mean arterial carbon dioxide (PaCO<inf>2</inf>) (P</it> < 0.05) and
CRP negatively correlated with DLCO, PaO<inf>2</inf>, sleep
SaO<inf>2</inf> and oxygen uptake (VO<inf>2</inf>) during exercise
(P</it> < 0.05).
Conclusions: IPF patients desaturate more during sleep
than exercise; thus, nocturnal pulse oxymetry could be included in
clinical assessment. CCL-18 and CRP levels correlate with physiological
markers of fibrosis.

Prediction of organ‐specific complications following abdominal aortic aneurysm repair using cardiopulmonary exercise testing

Barakat, H. M.; Shahin, Y.; McCollum, P. T.; Chetter, I. C.

Anaesthesia, June 2015, Vol. 70 Issue: Number 6 p679-685, 7p

Abstract: This study aimed
at assessing whether measures of aerobic fitness can predict
postoperative cardiac and pulmonary complications, 30‐day mortality and
length of hospital stay following elective abdominal aortic aneurysm
repair. We prospectively collected cardiopulmonary exercise testing
data over two years for 130 patients. Upon multivariate analysis, a
decreased anaerobic threshold (OR (95% CI) 0.55 (0.37–0.84); p = 0.005)
and open repair (OR(95% CI) 6.99 (1.56–31.48); p = 0.011) were
associated with cardiac complications. Similarly, an increased
ventilatory equivalent for carbon dioxide (OR(95% CI) 1.18 (1.05–1.33);
p = 0.005) and open repair (OR (95% CI) 14.29 (3.24–62.90); p < 0.001)
were associated with pulmonary complications. Patients who had an
endovascular repair had shorter hospital and critical care lengths of
stay (p < 0.001). Measures of fitness were not associated with 30‐day
mortality or length of hospital stay. Cardiopulmonary exercise testing
variables, therefore, seem to predict different postoperative
complications following abdominal aortic aneurysm repair, which adds
value to their routine use in risk stratification and optimisation of
peri‐operative care.;

MR augmented cardiopulmonary exercise testing-a novel approach to assessing cardiovascular function

Barber, Nathaniel J; Ako, Emmanuel
O; Kowalik, Grzegorz T; Steeden, Jennifer A; Pandya, Bejal; Muthurangu,

Physiological Measurement, May 2015, Vol. 36 Issue: Number 5
pN85-N94, 10p

Abstract: The purposes of this study were: (1) to
evaluate feasibility and acceptability of MRI augmented cardiopulmonary
exercise testing (MR-CPET) in healthy adults and (2) to test whether
peak values obtained at conventional and MR-CPET correlate and to
demonstrate variation in peak oxygen consumption (VO2) relates to both
peak cardiac output (CO) and peak oxygen extraction (DcO2).

Seventeen  healthy adults underwent CPET and MR-CPET using an MR compatible
ergometer and CPET system customised for MR use. Continuous aortic flow
measurement used a validated UNFOLD-SENSE spiral phase contrast
magnetic resonance (PCMR) sequence.Fifteen of 17 volunteers completed
exercise; exclusions were due to claustrophobia and inability to
effectively master exercise technique. Measures of acceptability were
lower but still satisfactory for MR-CPET.There were strong correlations
between conventional and MR-CPET for peak VO2 (r = 0.94, p < 0.001);
VCO2 (r = 0.87, p < 0.001) and VE (r = 0.88, p < 0.001).Multiple linear
regression analysis demonstrated peak CO and DcO2 were independent
predictors of peak VO2 measured during MR-CPET (b = 0.73 and 0.38 p <
0.0001) and conventional CPET (b = 0.78, 0.28 p < 0.0001).MR-CPET is
feasible, acceptable and demonstrates physiology not apparent with
conventional CPET.
MR-CPET allows differentiation of the contributions
of CO and DcO2 to variation in peak VO2. We believe that this will be
useful in understanding the origin of reduced exercise capacity in
cardiac disease.