Category Archives: Publications

Importance of compensatory heart rate increase during myocardial ischemia to preserve appropriate oxygen kinetics.

J Cardiol. 2017 Mar 7. pii: S0914-5087(16)30308-2. [Epub ahead of print]

Yoshida S, Adachi H, Murata M, Tomono J, Oshima S, Kurabayashi

BACKGROUND: Myocardial ischemia induces cardiac dysfunction, resulting in
insufficient oxygen supply to peripheral tissues and mismatched energy production
during exercise. To relieve the insufficient oxygen supply, heart rate (HR)
response is augmented; however, beta-adrenergic receptor blockers (BB) restrict
HR response. Although BB are essential drugs for angina pectoris, the effect of
BB on exercise tolerance in patients with angina has not been studied. The aim of
this study was to clarify the importance of HR augmentation to preserve exercise
tolerance in patients with angina pectoris.
METHODS: Forty-two subjects who underwent cardiopulmonary exercise testing (CPX)
to detect myocardial ischemia were enrolled. CPX was performed until exhaustion
or onset of significant myocardial ischemia using a ramp protocol. Subjects were
assigned to three groups (Group A: with ST depression during CPX with significant
coronary stenosis and taking BB; Group B: with ST depression and not taking BB;
Group C: without ST depression and not taking BB). HR response to exercise was
evaluated during the following two periods: below and above ischemic threshold
(IT). In Group C, it was evaluated during the first 2min and the last 2min of a
ramp exercise.
RESULTS: No significant differences were observed among the three groups with
regard to patients’ basic characteristics. Below IT, there were no differences in
oxygen pulse/watt (O2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and ΔV˙O2/ΔWR.
Above IT, O2 pulse increasing rate was greater in Group A than in Group B.
ΔHR/ΔWR was smaller in Group A than in Group B. ΔV˙O2/ΔWR became smaller in Group
A than in Group B. There was no difference in anaerobic threshold, and peak V˙O2
was smaller in Group A than in Group B.
CONCLUSIONS: Restriction of HR response by a BB is shown to be one of the
important factors in diminished exercise tolerance.

CORP: Measurement of the Maximum Oxygen Uptake (VO2max): VO2peak is no longer acceptable.

J Appl Physiol (1985). 2017 Feb 2: [Epub ahead of print]

Poole DC
, Jones AM.

The maximum rate of VO2 uptake (i.e., VO2max), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard measurement of integrated cardiopulmonary-muscle oxidative function. The development of rapid-response gas analyzers, enabling measurement of breath-by-breath pulmonary gas exchange, has led to replacement of the discontinuous progressive maximal exercise test (that produced an unambiguous VO2-work rate plateau definitive for VO2max) with the rapidly-incremented or ramp testing protocol. Whilst this expedient is more suitable for clinical and experimental investigations and enables measurement of the gas exchange threshold, exercise efficiency, and VO2 kinetics, a VO2-work rate plateau is not an obligatory outcome. This shortcoming has led to investigators resorting to so-called secondary criteria such as respiratory exchange ratio, maximal heart rate and/or maximal blood lactate concentration, the acceptable values of which may be selected arbitrarily and result in grossly inaccurate VO2max determination. Whereas this may not be an overriding concern in young, healthy subjects with experience of performing exercise to volitional exhaustion, exercise test naïve subjects, patient populations and less motivated subjects may stop exercising before their VO2max is reached. When VO2max is a or the criterion outcome of the investigation this represents a major experimental design issue. This CORP presents the rationale for incorporation of a second, constant-work rate test performed at 105-110% of the work rate achieved on the initial ramp test to resolve the classic VO2-work rate plateau that is the unambiguous validation of VO2max. The broad utility of this procedure has been established for children, adults of varying fitness, obese individuals and patient populations.

Cardiopulmonary exercise testing: A contemporary and versatile clinical tool.

Cleve Clin J Med. 2017 Feb;84(2):161-168. doi: 10.3949/ccjm.84a.15013.

Leclerc K1.


Cardiopulmonary exercise testing (CPET) helps in detecting disorders of the cardiovascular, pulmonary, and skeletal muscle systems. It has a class I (indicated) recommendation from the American College of Cardiology and American Heart Association for evaluating exertional dyspnea of uncertain cause and for evaluating cardiac patients being considered for heart transplant. Advances in hardware and software and ease of use have brought its application into the clinical arena to the point that providers should become familiar with it and consider it earlier in the evaluation of their patients.

Cardiac rehabilitation after acute coronary syndrome: Do all patients derive the same benefit?

Rev Port Cardiol. 2017 Feb 23

Aguiar Rosa S(1), Abreu A(2), Marques Soares R(2), Rio P(2), Filipe C(3),
Rodrigues I(2), Monteiro A(2), Soares C(2), Ferreira V(2), Silva S(2), Alves
S(2), Cruz Ferreira R(2).

INTRODUCTION: Cardiac rehabilitation (CR) has been demonstrated to improve
exercise capacity in acute coronary syndrome (ACS), but not all patients derive
the same benefit. Careful patient selection is crucial to maximize resources.
OBJECTIVE: To identify in a heterogeneous ACS population which patients would
benefit the most with CR, in terms of functional capacity (FC), by using
cardiopulmonary exercise testing (CPET).
METHODS: A retrospective analysis of consecutive ACS patients who underwent CR
and CPET was undertaken. CPET was performed at baseline and after 36 sessions of
exercise. Peak oxygen uptake (pVO2), percentage of predicted pVO2, minute
ventilation/CO2 production (VE/VCO2) slope, VE/VCO2 slope/pVO2 and peak
circulatory power (PCP) (pVO2 times peak systolic blood pressure) were assessed
in two moments. The differences in pVO2 (ΔpVO2), %pVO2, PCP and exercise test
duration were calculated. Patients were classified according to baseline pVO2
(group 1, <20 ml/kg/min vs. group 2, ≥20 ml/kg/min) and left ventricular ejection
fraction (group A, <50% vs. group B, ≥50%).
RESULTS: We analyzed 129 patients, 86% male, mean age 56.3±9.8 years. Both group
1 (n=31) and group 2 (n=98) showed significant improvement in FC after CR, with a
more significant increase in pVO2, in group 1 (ΔpVO2 4.4±7.3 vs. 1.6±5.4;
p=0.018). Significant improvement was observed in CPET parameters in group A
(n=34) and group B (n=95), particularly in pVO2 and test duration.
CONCLUSION: Patients with lower baseline pVO2 (<20 ml/kg/min) presented more
significant improvement in FC after CR. CPET which is not routinely used in
assessement before CR in context of ACS, could be a valuable tool to identify
patients who will benefit the most

Cardiopulmonary exercise testing improves diagnostic specificity in patients with echocardiography-suspected pulmonary hypertension.

Clin Cardiol. 2017 Feb;40(2):95-101. doi: 10.1002/clc.22635. Epub 2016 Nov 2.

Zhao QH(1), Wang L(1), Pudasaini B(1), Jiang R(1), Yuan P(1), Gong SG(1), Guo
J(2), Xiao Q(1), Liu H(1), Wu C(3), Jing ZC(4), Liu JM(1,)(2).

(1)Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji
University, School of Medicine, Shanghai, China. (2)Department of Pulmonary
Function, Shanghai Pulmonary Hospital, Tongji University, School of Medicine,
Shanghai, China. (3)Department of Statistics, the Second Military Medical
University, Shanghai, China. (4)State Key Laboratory of Cardiovascular Disease,
Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical
Science, Beijing, China.

BACKGROUND: Doppler echocardiography is usually the first diagnostic
investigation for patients suspected with pulmonary hypertension (PH), but it is
often inaccurate when used alone, especially in mild PH.
HYPOTHESIS: Cardiopulmonary exercise testing (CPET) may serve as a complementary
tool to improve diagnostic accuracy in echocardiography-suspected “PH possible”
METHODS: Eighty-eight consecutive patients with suspected PH (referred to as “PH
possible” hereafter) based on echocardiography were included in the study. CPET
was assessed subsequently and PH was confirmed by right-heart catheterization in
all subjects. We analyzed CPET data from patients and derived a CPET prediction
rule to hemodynamically differentiate PH.
RESULTS: Eighty-eight patients (27 patients with confirmed PH, and PH ruled out
in 61 patients) were included in the study. Compared with non-PH patients, the PH
subjects had lower peak oxygen uptake (VO2 ), aerobic capacity (AT), peak partial
pressure of end-tidal CO2 (PET CO2 ), oxygen uptake efficiency plateau (OUEP),
and oxygen uptake efficiency slope (OUES), along with higher minute ventilation
(VE)/carbon dioxide output (VCO2 ) slope and lowest VE/VCO2 (P < 0.001). VE/VCO2
slope and AT were independent predictors of PH derived from multivariate logistic
regression adjusted for age and body mass index. A score combining VE/VCO2 slope
and AT reached a high area under the curve value of 0.98. A score ≥0.5 had 95%
specificity and 92.6% sensitivity for diagnosis of PH.
CONCLUSIONS: A score combining VE/VCO2 slope and AT provides high specificity in
screening out PH from a pool of echocardiography-suspected PH patients.

Percutaneous Coronary Intervention of Coronary Chronic Total Occlusions Improves Peak Oxygen Uptake During Cardiopulmonary Exercise Testing.

J Invasive Cardiol. 2017 Mar;29(3):83-91.

Abdullah SM(1), Hastings JL, Amsavelu S, Garcia-Morales F, Hendrix F, Karatasakis
A, Danek BA, Karacsonyi J, Rangan BV, Roesle M, Khalili H, Banerjee S, Brilakis

OBJECTIVES: Although coronary chronic total occlusions (CTOs) are treated with
percutaneous coronary intervention (PCI) to improve symptoms, studies
demonstrating symptom improvement have been mostly limited to questionnaire
responses. The current study assessed for changes in peak oxygen uptake during
cardiopulmonary exercise testing after CTO-PCI.
METHODS: Patients with heart failure or angina symptoms referred for CTO-PCI were
prospectively enrolled. The primary outcome of the study was improvement in peak
oxygen uptake during cardiopulmonary exercise (CPX) testing 5 months after
CTO-PCI. Secondary outcomes included improvement in physical capacity, angina,
and self perception of health as assessed by questionnaires, and in plasma brain
natriuretic peptide (BNP) levels.
RESULTS: CTO-PCI was attempted in 32 men (mean age, 62 ± 6 years; CTO vessel: 47%
right coronary, 44% left anterior descending). CTO-PCI was unsuccessful in 1
patient, and 3 patients had restenosis of their CTO vessel at follow-up. In the
28 patients with patent CTO vessel at follow-up, significant improvements were
noted in self-reported physical capacity, angina, and several aspects of health
perception. In the 25 patients who underwent baseline and follow-up CPX testing,
peak oxygen uptake significantly improved from 17.7 ± 4.3 mL/kg/min to 19.1 ± 4.0
mL/kg/min (P=.02). Plasma BNP levels significantly decreased from 143 ± 138 pg/mL
to 102 ± 123 pg/mL (P=.01).
CONCLUSIONS: CTO-PCI in symptomatic patients was associated with improvements in
cardiovascular exercise capacity, as assessed by peak oxygen uptake. These
results suggest that in symptomatic patients with CTOs, PCI appears clinically

Exertional dyspnoea in interstitial lung diseases: the clinical utility of cardiopulmonary exercise testing.

Eur Respir Rev. 2017 Feb 21;26(143).

Bonini M, Fiorenzano G.

Interstitial lung diseases (ILDs) represent a heterogeneous group of pathologies
characterised by alveolar and interstitial damage, pulmonary inflammation
(usually associated with fibrosis), decreased lung function and impaired gas
exchange, which can be attributed to either a known or an unknown aetiology.
Dyspnoea is one of the most common and disabling symptoms in patients with ILD,
significantly impacting quality of life. The mechanisms causing dyspnoea are
complex and not yet fully understood. However, it is recognised that dyspnoea
occurs when there is an imbalance between the central respiratory efferent drive
and the response of the respiratory musculature. The respiratory derangement
observed in ILD patients at rest is even more evident during exercise.
Pathophysiological mechanisms responsible for exertional dyspnoea and reduced
exercise tolerance include altered respiratory mechanics, impaired gas exchange,
cardiovascular abnormalities and peripheral muscle dysfunction.This review
describes the respiratory physiology of ILD, both at rest and during exercise,
and aims to provide comprehensive and updated evidence on the clinical utility of
the cardiopulmonary exercise test in the assessment and management of these
pathological entities. In addition, the role of exercise training and pulmonary
rehabilitation programmes in the ILD population is addressed.

Cardiopulmonary exercise testing: A contemporary and versatile clinical tool.

Cleve Clin J Med. 2017 Feb;84(2):161-168.

Leclerc K.

Cardiopulmonary exercise testing (CPET) helps in detecting disorders of the
cardiovascular, pulmonary, and skeletal muscle systems. It has a class I
(indicated) recommendation from the American College of Cardiology and American
Heart Association for evaluating exertional dyspnea of uncertain cause and for
evaluating cardiac patients being considered for heart transplant. Advances in
hardware and software and ease of use have brought its application into the
clinical arena to the point that providers should become familiar with it and
consider it earlier in the evaluation of their patients.

Associations of cardiovascular and all-cause mortality events with oxygen uptake at ventilatory threshold.

Int J Cardiol. 2017 Feb 10. pii: S0167-5273(16)32158-1.

Kunutsor SK(1), Kurl S(2), Khan H(3), Zaccardi F(4), Laukkanen JA(5).

BACKGROUND: Oxygen uptake (VO2) at ventilatory threshold (VT), is a
cardiopulmonary exercise testing parameter which may be a proxy for peak VO2. We
aimed to assess the associations of VO2 at VT with sudden cardiac death (SCD),
fatal coronary heart disease (CHD) and cardiovascular disease (CVD), and
all-cause mortality.
METHODS AND RESULTS: VO2 at VT was assessed during a submaximal exercise test
using respiratory gas analyzers in the Kuopio Ischemic Heart Disease cohort of
1639 middle-aged men. Hazard ratios (HRs) (95% CIs) were assessed. During a
median follow-up of 25.6years, 121 SCDs, 202 fatal CHDs, 312 fatal CVDs, and 703
all-cause mortality events occurred. VO2 at VT was correlated with peak VO2
(r=0.90) and linearly associated with each outcome. Comparing extreme quartiles
of VO2 at VT, the HRs (95% CIs) for SCD, fatal CHD, fatal CVD, and all-cause
mortality on adjustment for established risk factors were 0.37 (0.18-0.78), 0.32
(0.18-0.57), 0.45 (0.30-0.69), and 0.50 (0.38-0.64) respectively. The HRs were
1.02 (0.36-2.91), 1.43 (0.63-3.25), 1.46 (0.79-2.71), and 1.02 (0.69-1.51)
respectively on further adjustment for peak VO2. Addition of VO2 at VT to a CVD
mortality risk prediction model containing established risk factors significantly
improved risk discrimination and reclassification at 25years.
CONCLUSIONS: There are linear and inverse associations of VO2 at VT with fatal
cardiovascular and all-cause mortality events, which are dependent on peak VO2.
Inclusion of VO2 at VT in the standard established risk factors panel
significantly improves the prediction and classification of long-term CVD
mortality risk.

Validation of preoperative cardiopulmonary exercise testing‐derived variables to predict in‐hospital morbidity after major colorectal surgery

West, M. A.; Asher, R.; Browning, M.; Minto, G.; Swart, M.;
Richardson, K.; McGarrity, L.; Jack, S.; Grocott, M. P. W.; Challand,
C.; wan Lai, C.; Struthers, R.; Sneyd, R.; Psarelli, E..

British Journal of Surgery: BJS, May 2016, Vol. 103 Issue: Number 6 p744-752,

Abstract: In single‐centre studies, postoperative complications are
associated with reduced fitness. This study explored the relationship
between cardiorespiratory fitness variables derived by cardiopulmonary
exercise testing (CPET) and in‐hospital morbidity after major elective
colorectal surgery. Patients underwent preoperative CPETwith recording
of in‐hospital morbidity. Receiver operating characteristic (ROC)
curves and logistic regression were used to assess the relationship
between CPET variables and postoperative morbidity. Seven hundred and
three patients from six centres in the UK were available for analysis
(428 men, 275 women). ROCcurve analysis of oxygen uptake at estimated
lactate threshold (V˙o2at θ^L) and at peak exercise (V˙o2peak) gave an
area under the ROCcurve (AUROC) of 0·79 (95 per cent c.i. 0·76 to 0·83;
P< 0·001; cut‐off 11·1 ml per kg per min) and 0·77 (0·72 to 0·82; P<
0·001; cut‐off 18·2 ml per kg per min) respectively, indicating that
they can identify patients at risk of postoperative morbidity. In a
multivariable logistic regression model, selected CPETvariables and
body mass index (BMI) were associated significantly with increased odds
of in‐hospital morbidity (V˙o2at θ^L11·1 ml per kg per min or less:
odds ratio (OR) 7·56, 95 per cent c.i. 4·44 to 12·86, P< 0·001;
V˙o2peak18·2 ml per kg per min or less: OR2·15, 1·01 to 4·57, P =0·047;
ventilatory equivalents for carbon dioxide at estimated lactate
threshold (V˙E/V˙co2at θ^L) more than 30·9: OR1·38, 1·00 to 1·89, P
=0·047); BMIexceeding 27 kg/m2: OR1·05, 1·03 to 1·08, P< 0·001). A
laparoscopic procedure was associated with a decreased odds of
complications (OR0·30, 0·02 to 0·44; P =0·033). This model was able to
discriminate between patients with, and without in‐hospital morbidity
(AUROC0·83, 95 per cent c.i. 0·79 to 0·87). No adverse clinical events
occurred during CPET across the six centres. These data provide further
evidence that variables derived from preoperative CPETcan be used to
assess risk before elective colorectal surgery. Validated risk
assessment; (AN 38537189)