Author Archives: Paul Older

Two new Board members

At the recent Board Meeting in Munich two new Board Members were appointed to replace the two outgoing members.

The outgoing members are Professor Franz Kleber and Professor Paolo Palange. We are indebted to both these Board members for their invaluable assistance over some years. They will still remain as members of the Practicum Faculty.

The two new members are Professor Doctor Alfred Hager and Dr Daniel Dumitrescu.Both these people will be known to many of you and we wish them all the best in their new appointment.

Dr Paul Older

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.

Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice

Berry, Natalia
C.; Manyoo, Agarwal; Oldham, William M.; Stephens, Thomas E.;
Goldstein, Ronald H.; Waxman, Aaron B.; Tracy, Julie A.; Leary, Peter
J.; Leopold, Jane A.; Kinlay, Scott; Opotowsky, Alexander R.; Systrom,
David M.; Maron, Bradley A..

Pulmonary Circulation (JSTOR), December 2015, Vol. 5 Issue: Number 4 p610-618, 9p;

Abstract: Invasive cardiopulmonary exercise testing (iCPET) combines full central
hemodynamic assessment with continuous measurements of pulmonary gas
exchange and ventilation to help in understanding the pathophysiology
underpinning unexplained exertional intolerance. There is increasing
evidence to support the use of iCPET as a key methodology for
diagnosing heart failure with preserved ejection fraction and
exercise-induced pulmonary hypertension as occult causes of exercise
limitation, but there is little information available outlining the
methodology to use this diagnostic test in clinical practice. To bridge
this knowledge gap, the operational protocol for iCPET at our
institution is discussed in detail. In turn, a standardized iCPET
protocol may provide a common framework to describe the evolving
understanding of mechanism(s) that limit exercise capacity and to
facilitate research efforts to define novel treatments in these

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF

Jiang, Rong; Wang, Lan; Zhu,
Chang-Tai; Yuan, Ping; Pudasaini, Bigyan; Zhao, Qin-Hua; Gong, Su-Gang;
He, Jing; Liu, Jin-Ming; Hu, Qing-Hua.

Hypertension Research, December 2015, Vol. 38 Issue: Number 12 p829-839, 11p;


There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but
the rationale for using sildenafil to treat pulmonary arterial
hypertension with heart failure with reduced ejection fraction (HFrEF)
has been supported by short-term studies. We performed a meta-analysis
to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A
systematic literature search of PubMed, EMBASE and the Cochrane Central
Register of Controlled Trials was conducted from inception through
October 2014 for randomized trials and for observational studies with
control groups, evaluating the effectiveness of sildenafil to treat
PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial
systolic pressure both at the acute phase and at the 6-month follow-up
(weighted mean difference (WMD): −6.03 mm Hg, P=0.02; WMD:
−11.47 mm Hg, P<0.00001, respectively). Sildenafil was found to reduce
mean pulmonary artery pressure (WMD: −3 mm Hg, P=0.0004) and pulmonary
vascular resistance (WMD: −60.0 dynes cm−5, P=0.01) at the 3-month
follow-up. Oxygen consumption at peak significantly increased to
3.66 ml min−1kg−1(P<0.00001), 3.36 ml min−1kg−1(P<0.00001) and
2.60 ml min−1kg−1(P=0.03) at 3, 6 and 12 months, respectively. There
were significant reductions in ventilation to CO2production slope of
−2.00, −4.68 and −7.12 at 3, 6 and 12 months, respectively (P<0.00001).
Sildenafil was superior to placebo regarding left ventricular ejection
fraction at the 6-month follow-up (WMD: 4.35, P<0.00001), and it
significantly improved quality of life. Sildenafil therapy could
effectively improve pulmonary hemodynamics and cardiopulmonary exercise
testing measurements of PH-LHD with HFrEF, regardless of acute or
chronic treatment.

The 2016 Practicum to be held in Milan 26th to 28th October 2016

European2016 Practicum on Cardiopulmonary Exercise Testing 2016

‘Click’ on this link to see the entire programme for this important event.

Dear colleague,
the 2016 annual CPX International congress “European Practicum on Cardiopulmonary Exercise Testing” will be held in Italy after 10 years since the last Italian edition. The congress will last from 26 to 29 October 2016 and the venue will be Centro Cardiologico Monzino, in Milan.
It is a very important event for all of us who are at the forefront in this field. Wasserman himself may come to Italy, but, since he is more than 90 years old, he could renounce.
I send you attached the official brochure of the congress with the scientific program.
The course is very intensive and gives a wide view across the CPX world.
For the first time we are going to offer three prizes of $1.500 each for the best three abstracts that will be presented on Saturday morning.

Thank you for your participation and advertising that you will give to the event.
Best regards,

Prof. Piergiuseppe Agostoni
CPX International President
Chief of Heart Failure, Clinical Cardiology and Rehabilitation Unit
Centro Cardiologico Monzino
Via C. Parea 4, 20138 Milano



Piazza Wagner, 5-  20145 Milan

Tel.: + 39 02 43 31 92 23 / 02 58 00 28 76 – Fax: + 39 02 48 51 33 53

Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease

Rosenblum, Omer; Katz,
Uriel; Reuveny, Ronen; Williams, Craig; Dubnov-Raz, Gal.

Pediatric Cardiology, December 2015, Vol. 36 Issue: Number 8 p1573-1581, 9p;

Abstract: Few previous studies have addressed exercise capacity in
patients with corrected congenital heart disease (CHD) and significant
anatomical residua. The aim of this study was to determine the aerobic
fitness and peak cardiac function of patients with corrected CHD with
complete or incomplete repairs, as determined by resting
echocardiography. Children, adolescents and young adults (<40 years)
with CHD from both sexes, who had previously undergone biventricular
corrective therapeutic interventions (n= 73), and non-CHD control
participants (n= 76) underwent cardiopulmonary exercise testing. The
CHD group was further divided according to the absence/presence of
significant anatomical residua on a resting echocardiogram
(“complete”/“incomplete” repair groups). Aerobic fitness and cardiac
function were compared between groups using linear regression and
analysis of covariance. Peak oxygen consumption, O2pulse and
ventilatory threshold were significantly lower in CHD patients compared
with controls (all p< 0.01). Compared with the complete repair group,
the incomplete repair group had a significantly lower mean peak work
rate, age-adjusted O2pulse (expressed as % predicted) and a higher
VE/VCO2ratio (all p≤ 0.05). Peak oxygen consumption was comparable
between the subgroups. Patients after corrected CHD have lower peak and
submaximal exercise parameters. Patients with incomplete repair of
their heart defect had decreased aerobic fitness, with evidence of
impaired peak cardiac function and lower pulmonary perfusion. Patients
that had undergone a complete repair had decreased aerobic fitness
attributed only to deconditioning. These newly identified differences
explain why in previous studies, the lowest fitness was seen in
patients with the most hemodynamically significant heart

A Systematic Review of Reference Values in Pediatric Cardiopulmonary Exercise Testing

Blais, Samuel; Berbari, Jade; Counil,
Francois-Pierre; Dallaire, Frederic.

Pediatric Cardiology, December
2015, Vol. 36 Issue: Number 8 p1553-1564, 12p;

Cardiopulmonary exercise testing (CPET) is used for the diagnosis and
prognosis of cardiovascular and pulmonary conditions in children and
adolescents. Several authors have published reference values for
pediatric CPET, but evaluation of their validity is lacking. The aim of
this study was to review pediatric CPET references values published
between 1980 and 2014. We specifically assessed the adequacy of the
normalization methods used to adjust for body size. Articles that
proposed references values were reviewed. We abstracted information on
exercise protocols, CPET measurements and normalization methods. We
then evaluated the studies’ methodological quality and assessed them
for potential biases. Thirty-four studies were included. We found
important heterogeneity in the choice of exercise protocols and in the
approach to adjustment for body size or other relevant confounding
factors. Adjustment for body size was principally done using linear
regression for age or weight. Assessment of potential biases (residual
association, heteroscedasticity and departure from the normal
distribution) was mentioned in only a minority of studies. Our study
shows that contemporary pediatric reference values for CPET have been
developed based on heterogeneous exercise protocols and variable
normalization strategies. Furthermore, assessment of potential bias has
been inconsistent and insufficiently described. High-quality reference
values with adequate adjustment for confounding variables are needed in
order to optimize CPET’s specificity and sensitivity to detect abnormal
cardiopulmonary response to exercise.

The summary of the Munich Practicum and the photo are now on the website ( Many of the talks are on that page in .pdf format. Just ‘click’ on the link.

‘Click’ on Practicum and then ‘Click’ on Munich to view the page.

More talks will be added later.

Dr Paul Older