Category Archives: Publications

Correlation between myocardial deformation on three-dimensional speckle tracking echocardiography and cardiopulmonary exercise testing.

Li M, Lu Y, Fang C, Zhang X

Echocardiography. 2017 Nov;34(11):1640-1648. doi: 10.1111/echo.13675. Epub 2017
Sep 19.

PURPOSE: Heart failure (HF) is a multifactorial entity that combines derangements
in both systolic and diastolic function. The relationship between systolic and
diastolic function and exercise capacity is not fully understood. We sought to
determine the mechanisms linking cardiac function and exercise tolerance in
patients with HF.
METHODS: One hundred fifty-six subjects with different cardiac function levels
were included in the study. Subjects’ 2D echocardiographic, 3D speckle tracking
echocardiographic, and cardiopulmonary exercise testing (CPET) data were
RESULT: The amount of untwisting at 25% of the untwist duration (25%Untwist) and
global longitudinal peak systolic strain (GLS) showed the best positive
correlations with peak oxygen uptake (peakVO2 ) (r = .41; P < .001 and r = .32;
P < .001, respectively), while the left ventricular ejection fraction (EF) was
weakly correlated with peakVO2 . The 25%Untwist value was negatively correlated
with the carbon dioxide equivalent slope (VE/VCO2 ) (r = -.49; P < .001). Both
E/e and the left atrium volume index (LA index) exhibited good positive
correlations with VE/VCO2 (r = .39; P < .01 and r = .32; P < .001). In the
multiple regression analysis, the best predictive model for the peakVO2 included
the 25%Untwist, GLS, and E/e, explained 64% of the variation in peakVO2 , with
25%Untwist explaining 17.6% of the variation. Including EF in the model explained
only 3.1% of the variation in peakVO2 . In a multivariable model for VE/VCO2 ,
25%Untwist was the strongest independent predictor, explaining 23% of the
variance in VE/VCO2 .
CONCLUSION: Left ventricular early diastolic function is a modest independent
predictor of aerobic exercise capacity. The 25%Untwist value is a good indicator
of cardiac diastolic function.

Fit for surgery? Perspectives on preoperative exercise testing and training

K. Richardson, D.Z.H. Levett, S. Jack, M.P.W. Grocott

BJA 2017, Volume 119, Supplement 1, Pages i34–i43

There is a consistent relationship between physical activity, physical fitness, and health across almost all clinical contexts, including the perioperative setting. Physiological measurements obtained during physical exercise may be used to infer the risk of adverse outcome after major surgery. In particular, data obtained from perioperative cardiopulmonary exercise testing have an expanding role in perioperative care. Such information may be used to inform a variety of changes in clinical practice, including interventions that may reduce the risk of perioperative adverse events. Specifically, for patients undergoing major cancer surgery there is a complex interplay between different cancer treatments, including neoadjuvant therapies (chemo- and chemo- plus radiotherapy), surgery, and physical fitness, and the modulation of these relationships by perioperative exercise interventions. Preoperative cardiopulmonary exercise testing provides an objective evaluation of physical fitness and has been used to provide an individualized risk profile in order to guide collaborative decision-making, inform the consent process, characterize and optimize co-morbidities, and to triage patients to perioperative care. Furthermore, studies evaluating exercise interventions aimed at increasing preoperative exercise capacity have established that training improves physical fitness. However, to date, this literature is largely composed of feasibility and pilot studies with small sample sizes, which are in general underpowered to assess clinical outcomes. Adequately powered prospective multicentre studies are needed to characterize the most effective means of improving patient fitness before surgery and to evaluate the impact of such improvements on surgical and disease-specific (e.g. cancer) outcomes.

Cardiopulmonary exercise testing and survival after elective abdominal aortic aneurysm repair†

S.W. Grant, G.L. Hickey, N.A. Wisely, E.D. Carlson, R.A. Hartley, A.C. Pichel, D. Atkinson, C.N. McCollum
BJA, Volume 114, Issue 3, Pages 430–436


Cardiopulmonary exercise testing (CPET) is increasingly used in the preoperative assessment of patients undergoing major surgery. The objective of this study was to investigate whether CPET can identify patients at risk of reduced survival after abdominal aortic aneurysm (AAA) repair.


Prospectively collected data from consecutive patients who underwent CPET before elective open or endovascular AAA repair (EVAR) at two tertiary vascular centres between January 2007 and October 2012 were analysed. A symptom-limited maximal CPET was performed on each patient. Multivariable Cox proportional hazards regression modelling was used to identify risk factors associated with reduced survival.


The study included 506 patients with a mean age of 73.4 (range 44–90). The majority (82.6%) were men and most (64.6%) underwent EVAR. The in-hospital mortality was 2.6%. The median follow-up was 26 months. The 3-year survival for patients with zero or one sub-threshold CPET value ( Math Eq at AT<10.2 ml kg−1 min−1, peak Math Eq<15 ml kg−1 min−1 or Math Eq at AT>42) was 86.4% compared with 59.9% for patients with three sub-threshold CPET values. Risk factors independently associated with survival were female sex [hazard ratio (HR)=0.44, 95% confidence interval (CI) 0.22–0.85, P=0.015], diabetes (HR=1.95, 95% CI 1.04–3.69, P=0.039), preoperative statins (HR=0.58, 95% CI 0.38–0.90, P=0.016), haemoglobin g dl−1 (HR=0.84, 95% CI 0.74–0.95, P=0.006), peak Math Eq<15 ml kg−1 min−1 (HR=1.63, 95% CI 1.01–2.63, P=0.046), and Math Eq at AT>42 (HR=1.68, 95% CI 1.00–2.80, P=0.049).


CPET variables are independent predictors of reduced survival after elective AAA repair and can identify a cohort of patients with reduced survival at 3 years post-procedure. CPET is a potentially useful adjunct for clinical decision-making in patients with AAA.

Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation

D.Z.H. Levett, S. Jack, M. Swart, J. Carlisle, J. Wilson, C. Snowden, M. Riley, G. Danjoux, S.A. Ward, P. Older, M.P.W. Grocott  For the Perioperative Exercise Testing and Training Society (POETTS)
BJA Volume 120, Issue 3, Pages 484–500

The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative events and inform the perioperative management of patients undergoing surgery has increased over the last decade. CPET provides an objective assessment of exercise capacity preoperatively and identifies the causes of exercise limitation. This information may be used to assist clinicians and patients in decisions about the most appropriate surgical and non-surgical management during the perioperative period. Information gained from CPET can be used to estimate the likelihood of perioperative morbidity and mortality, to inform the processes of multidisciplinary collaborative decision making and consent, to triage patients for perioperative care (ward vs critical care), to direct preoperative interventions and optimization, to identify new comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide prehabilitation and rehabilitation, and to guide intraoperative anaesthetic practice. With the rapid uptake of CPET, standardization is key to ensure valid, reproducible results that can inform clinical decision making. Recently, an international Perioperative Exercise Testing and Training Society has been established (POETTS promoting the highest standards of care for patients undergoing exercise testing, training, or both in the perioperative setting. These clinical cardiopulmonary exercise testing guidelines have been developed by consensus by the Perioperative Exercise Testing and Training Society after systematic literature review. The guidelines have been endorsed by the Association of Respiratory Technology and Physiology (ARTP).

The cardiopulmonary exercise test grey zone; optimising fitness stratification by application of critical difference

Rose GA, Davies RG, Davison GW, et al.

Br J Anaesth. 2018;120(6):1187-1194.

BACKGROUND: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification.
METHODS: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V O2-AT): 11 ml O2 kg(-1) min(-1), peak oxygen uptake (V O2 peak): 16 ml O2 kg(-1) min(-1), and ventilatory equivalent for carbon dioxide at AT (VE/VCO2-AT): 36].
RESULTS: The critical difference for V O2-AT, V O2 peak, and V E/V CO2-AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and >/=13.6 ml O2 kg(-1) min(-1), V O2 peak <14.2 and >/=18.3 ml kg(-1) min(-1), V E/V CO2-AT >/=40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness.
CONCLUSIONS: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for.

Dead-space ventilation is linked to exercise capacity and survival in distal chronic thromboembolic pulmonary hypertension.

Godinas L, Sattler C, Lau EM, Jaïs X, Taniguchi Y, Jevnikar M,
Weatherald J, Sitbon O, Savale L, Montani D, Simonneau G, Humbert
M, Laveneziana P, Garcia G.

J Heart Lung Transplant. 2017 Nov;36(11):1234-1242. doi:
10.1016/j.healun.2017.05.024. Epub 2017 May 22.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is frequently used for the
evaluation of patients with pulmonary hypertension (PH). Non-operable distal
chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique
subgroup of PH where microvascular disease resembling pulmonary arterial
hypertension (PAH) may predominate and efficacious medical therapy is now
available. However, little is known regarding the detailed CPET profile of
patients with distal CTEPH, and whether ventilation and gas exchange responses
are different from PAH.
METHODS: Forty-nine consecutive patients with non-operable distal CTEPH according
to multidisciplinary team assessment and 45 PAH patients underwent CPET and right
heart catheterization. Patients were followed up for a median of 3.2 years
(interquartile range: 1.8 to 4.4).
RESULTS: Pulmonary hemodynamics were similar in distal CTEPH and PAH groups, but
patients with distal CTEPH achieved a lower percent predicted peak oxygen
consumption (59 ± 13% vs 66 ± 14%, p < 0.05). At peak exercise, higher
physiologic dead-space fraction (VD/VT) (0.45 ± 0.07 vs 0.35 ± 0.07, p < 0.0001)
and higher arterial-to-end-tidal carbon dioxide gradient (9 ± 3 vs 5 ± 3 mm Hg, p
< 0.0001) were observed in distal CTEPH compared with PAH. Ventilatory
efficiency, expressed as VE/VCO2 slope, was also more impaired in distal CTEPH
(52.2 ± 10.1 vs 43.8 ± 8.4 liters/min, p < 0.0001). In the distal CTEPH group
only, higher VD/VT was associated with lower peak oxygen consumption (r = -0.46,
p = 0.003) and worse survival.
CONCLUSIONS: Compared with PAH, a distinct pattern of response to exercise was
observed in distal CTEPH, characterized by increased dead-space ventilation that
resulted in worse ventilatory efficiency and greater impairment of exercise
capacity. In distal CTEPH, dead-space ventilation correlated with exercise
capacity and was associated with survival.

Cardiopulmonary exercise testing as prognostic indicators: Comparisons among heart failure patients with reduced, mid-range and preserved ejection fraction.

Sato T, Yoshihisa A, Kanno Y, Suzuki S, Yamaki T, Sugimoto K,
Kunii H, Nakazato K, Suzuki H, Saitoh SI, Ishida T, Takeishi Y

Eur J Prev Cardiol. 2017 Dec;24(18):1979-1987.

We aimed to determine the differences of impact of cardiopulmonary exercise
testing (CPX) parameters on prognosis of heart failure with reduced left
ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and
mid-range ejection fraction (HFmrEF).
We compared clinical
characteristics and CPX parameters among the three groups, and the value of each
CPX parameter to predict adverse cardiac events (cardiac deaths and
re-hospitalizations for heart failure), cardiac deaths and all-cause deaths.
Of 1190 patients, 41.9% had HFrEF, 36.8% had HFpEF and 21.3% had HFmrEF.
The patients in HFrEF group had higher rates of adverse cardiac events, cardiac
death and all-cause death than those of HFpEF and HFmrEF groups. In HFrEF, the
independent predictors of adverse cardiac events were peak oxygen consumption and
oxygen uptake efficiency slope, predictors of cardiac death were peak oxygen
consumption and oxygen uptake efficiency slope, and the predictor of all-cause
death was peak oxygen consumption. In HFpEF, the predictor of adverse cardiac
events was peak oxygen consumption, predictors of cardiac deaths and all-cause
deaths were peak oxygen consumption and exertional oscillatory ventilation. In
HFmrEF, predictors of adverse cardiac events were peak oxygen consumption and
oxygen uptake efficiency slope, and the predictor of cardiac deaths and all-cause
deaths was peak oxygen consumption.
Peak oxygen consumption is the
strong predictor for adverse events in all groups. Oxygen uptake efficiency slope
predicts adverse prognosis in HFrEF, but not in HFpEF. In contrast, exertional
oscillatory ventilation is the predictor only in HFpEF. Thus, different CPX
parameters may be able to differentially predict prognosis in HFrEF and HFpEF.
Those for predicting prognosis in HFmrEF may be intermediate between HFrEF and

Prognostic Value of Cardiopulmonary Exercise Testing in Heart Failure With Reduced, Midrange, and Preserved Ejection Fraction.

Nadruz W Jr, West E, Sengeløv M, Santos M, Groarke JD, Forman
DE, Claggett B, Skali H, Shah AM

J Am Heart Assoc. 2017 Oct 31;6(11)

BACKGROUND: This study aimed to compare the independent and incremental
prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon
dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF),
midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF).
METHODS AND RESULTS: In 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40-49%), and 630
HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary
exercise testing variables with the composite outcome of death, left ventricular
assist device implantation, or heart transplantation (256 events; median
follow-up of 4.2 years), and 2-year incident HF hospitalization (244 events). In
multivariable Cox regression analysis, greater association with outcomes in HFpEF
than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76
[0.67-0.87] versus 0.87 [0.83-0.90] for the composite outcome,
Pinteraction=0.052; 0.77 [0.69-0.86] versus 0.92 [0.88-0.95], respectively for HF
hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06-1.17] versus
1.04 [1.03-1.06], respectively for the composite outcome, Pinteraction=0.012;
1.10 [1.05-1.15] versus 1.04 [1.03-1.06], respectively for HF hospitalization,
Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with
the composite outcome (0.79 [0.70-0.90] and 1.12 [1.05-1.19], respectively),
while only peak VO2 was related to HF hospitalization (0.81 [0.72-0.92]). In
HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value
beyond clinical variables based on the C-statistic, net reclassification
improvement, and integrated diagnostic improvement, with models containing both
measures demonstrating the greatest incremental value.
CONCLUSIONS: Both peak VO2 and VE/VCO2 slope provided incremental value beyond
clinical characteristics and LVEF for predicting outcomes in HFpEF.
Cardiopulmonary exercise testing variables provided greater risk discrimination
in HFpEF than HFrEF.

An official European Respiratory Society statement: pulmonary haemodynamics during exercise.

Kovacs G, Herve P, Barbera JA, Chaouat A, Chemla D, Condliffe R, Garcia G, Grünig E, Howard L, Humbert M, Lau E,
Laveneziana P, Lewis GD, Naeije R, Peacock A, Rosenkranz S, Saggar R, Ulrich S, Vizza D, Vonk Noordegraaf A,
Olschewski H.

Eur Respir J. 2017 Nov 22;50(5)
Erratum in
Eur Respir J. 2018 Jan 18;51(1):.

There is growing recognition of the clinical importance of pulmonary
haemodynamics during exercise, but several questions remain to be elucidated. The
goal of this statement is to assess the scientific evidence in this field in
order to provide a basis for future recommendations.Right heart catheterisation
is the gold standard method to assess pulmonary haemodynamics at rest and during
exercise. Exercise echocardiography and cardiopulmonary exercise testing
represent non-invasive tools with evolving clinical applications. The term
“exercise pulmonary hypertension” may be the most adequate to describe an
abnormal pulmonary haemodynamic response characterised by an excessive pulmonary
arterial pressure (PAP) increase in relation to flow during exercise. Exercise
pulmonary hypertension may be defined as the presence of resting mean PAP
<25 mmHg and mean PAP >30 mmHg during exercise with total pulmonary resistance
>3 Wood units. Exercise pulmonary hypertension represents the haemodynamic
appearance of early pulmonary vascular disease, left heart disease, lung disease
or a combination of these conditions. Exercise pulmonary hypertension is
associated with the presence of a modest elevation of resting mean PAP and
requires clinical follow-up, particularly if risk factors for pulmonary
hypertension are present. There is a lack of robust clinical evidence on targeted
medical therapy for exercise pulmonary hypertension.