Category Archives: Publications

Exercise efficiency impairment in metabolic myopathies.

Noury JB; Zagnoli F; Petit F; Marcorelles P; Rannou F;

Scientific reports [Sci Rep] 2020 May 29; Vol. 10 (1), pp. 8765. Date of Electronic Publication: 2020 May 29.

Metabolic myopathies are muscle disorders caused by a biochemical defect of the skeletal muscle energy system resulting in exercise intolerance. The primary aim of this research was to evaluate the oxygen cost (∆V’O 2 /∆Work-Rate) during incremental exercise in patients with metabolic myopathies as compared with patients with non-metabolic myalgia and healthy subjects. The study groups consisted of eight patients with muscle glycogenoses (one Tarui and seven McArdle diseases), seven patients with a complete and twenty-two patients with a partial myoadenylate deaminase (MAD) deficiency in muscle biopsy, five patients with a respiratory chain deficiency, seventy-three patients with exercise intolerance and normal muscle biopsy (non-metabolic myalgia), and twenty-eight healthy controls. The subjects underwent a cardiopulmonary exercise test (CPX Medgraphics) performed on a bicycle ergometer. Pulmonary V’O 2 was measured breath-by-breath throughout the incremental test. The ∆V’O 2 /∆Work-Rate slope for exercise was determined by linear regression analysis. Lower oxygen consumption (peak percent of predicted, mean ± SD; p < 0.04, one-way ANOVA) was seen in patients with glycogenoses (62.8 ± 10.2%) and respiratory chain defects (70.8 ± 23.3%) compared to patients with non-metabolic myalgia (100.0 ± 15.9%) and control subjects (106.4 ± 23.5%). ∆V’O 2 /∆Work-Rate slope (mLO 2 .min -1 .W -1 ) was increased in patients with MAD absent (12.6 ± 1.5), MAD decreased (11.3 ± 1.1), glycogenoses (14.0 ± 2.5), respiratory chain defects (13.1 ± 1.2), and patients with non-metabolic myalgia (11.3 ± 1.3) compared with control subjects (10.2 ± 0.7; p < 0.001, one-way ANOVA). In conclusion, patients with metabolic myopathies display an increased oxygen cost during exercise and therefore can perform less work for a given VO 2 consumption during daily life-submaximal exercises.

The Role of Cardiopulmonary Exercise Testing as a Risk Assessment Tool in Patients Undergoing Oesophagectomy: A Systematic Review and Meta-analysis.

Sivakumar J; Sivakumar H; Read M; Snowden CP; Hii MW;

Annals of surgical oncology [Ann Surg Oncol] 2020 Jun 02. Date of Electronic Publication: 2020 Jun 02.

Introduction: Cardiopulmonary exercise testing (CPET) is an objective method of assessing functional capacity to meet the metabolic demands of surgery and has been adopted as a preoperative risk-stratification tool for patients undergoing major procedures. The two main measures are the peak rate of oxygen uptake during exercise ([Formula: see text]O 2 peak) and anaerobic threshold (AT), the point at which anaerobic metabolism exceeds aerobic metabolism during exercise. This systematic review and meta-analysis evaluates the predictive value of CPET for patients undergoing oesophagectomy.
Methods: A systematic literature search was conducted in databases of CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and Scopus to identify studies that examined associations between preoperative CPET variables and postoperative outcomes following oesophagectomy. Results were presented as standardised mean difference (SMD) with 95% confidence interval.
Results: Seven studies were included in this review. Preoperative [Formula: see text]O 2 peak moderately correlated with cardiopulmonary complications [SMD = - 0.43; 95% confidence interval (CI) - 0.77 to - 0.09; p = 0.013; I 2  = 80.4%], unplanned ICU admissions (SMD = - 0.34; 95% CI - 0.60 to - 0.08; p = 0.011; I 2  = 0.0%), and 1-year survival (SMD = 0.31; 95% CI 0.02-0.61; p = 0.045; I 2  = 0.0%). Preoperative AT values moderately correlated with unplanned ICU admissions (SMD = - 0.34; 95% CI - 0.61 to - 0.07; p = 0.014; I 2  = 0.0%), and 1-year survival (SMD = 0.34; 95% CI 0.00-0.68; p = 0.049; I 2  = 7.4%). Neither [Formula: see text]O 2 peak nor AT demonstrated prognostic value for noncardiopulmonary complications.
Conclusions: [Formula: see text]O 2 peak and AT, where measured by preoperative CPET testing, are inversely associated with postoperative cardiopulmonary complications, unplanned ICU admissions, and 1-year survival following oesophagectomy. This meta-analysis was not able to identify an absolute cutoff value for CPET variables to discriminate between patients of varying levels of operative risk.

Relationship between echocardiographic and functional parameters in patients with heart failure undergoing cardiopulmonary exercise test.

Pucci G; Alessio S; Russo A; Cerasari A; Dominioni I; Sanesi L; Filippucci L; Vaudo G;

Minerva cardioangiologica [Minerva Cardioangiol] 2020 Apr; Vol. 68 (2), pp. 72-80.

Background: HF patients typically show effort intolerance due to a reduction in peak exercise oxygen (peak VO2) consumption, which is related to inability to adapt systolic function to increased demand. Left ventricular ejection fraction (EF) is a surrogate marker of cardiac contractility and a powerful predictor of adverse prognosis in chronic heart failure (HF). The aim of the study was to explore the relationship between EF and other echocardiographic findings with peak VO2 in a population of HF individuals undergoing cardiopulmonary exercise testing (CPX).
Methods: We evaluated 101 patients (61% hypertensives, 74% with documented coronary artery disease) undergoing both resting echocardiography and symptom-limited CPX.
Results: Mean age was 58±13 years, 83% were males. Mean EF was 55±12%; 20% of the patients showed EF<40%. Mean test duration was 9.4±2.2 min. Average peak VO2 was 21±6 mL/kg/min. Peak VO2 showed a robust positive correlation with EF (R=0.42, P<0.001). Other independent predictors of peak VO2 were age, male sex, height and tricuspidal anular plane systolic excursion (TAPSE), this latter reflecting right ventricular dysfunction. When subjects were dichotomized according to predicted peak VO2values, those with higher-than-predicted peak VO2 showed significantly lower VE/VCO2 slope, and higher values of both oxygen pulse and VO2/WR slope.
Conclusions: EF and TAPSE are associated with peak VO2 in HF patients independently from age, sex and height. The evaluation of potentially relevant mechanisms affecting exercise capacity in HF patients requires further investigation.


Magrì D; Piepoli M; Corrà U;  et al, MECKI score Research Group

Journal of cardiac failure [J Card Fail] 2020 May 16. Date of Electronic Publication: 2020 May 16

Background: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains still debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing (CPET).
Methods and Results: We analyzed data of 4,535 HF with reduced EF (HFrEF) and 1,176 rec-HFmrEF outpatients from the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database. The end-point was cardiovascular death at 5 years. The median follow-up was 1,343 days (25th-75th range, 627-2,403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score’s variables in HFrEF (C-index=0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO 2 ) remained associated to the end-point (C-index=0.745). A pVO 2 ≤55% of predicted and a ventilatory efficiency ≥31 resulted as the most accurate cut-off values in the outcome prediction.
Conclusions: Present data support the CPET and, particularly, the pVO 2 , as a useful tool in the rec-HFmrEF prognostic assessment. Peak VO 2 ≤55% predicted and ventilatory efficiency ≥31 might help to identify a high risk rec-HFmrEF subgroup.

Long-Term Cardiac Function After Peripartum Cardiomyopathy and Preeclampsia: A Danish Nationwide, Clinical Follow-Up Study Using Maximal Exercise Testing and Cardiac Magnetic Resonance Imaging.

Ersboll AS; Bojer AS; Hauge MG; Johansen M; Damm P; Gustafsson F;
Vejlstrup NG.

Journal of the American Heart Association. 7(20):e008991, 2018 10 16.
VI 1

Background Long-term clinical studies of peripartum cardiomyopathy ( PPCM)
are few. We aimed to measure the long-term effect of PPCM on cardiac
function in comparison with the long-term effects of severe preeclampsia
and uncomplicated pregnancy.
Methods and Results A nationwide Danish
cohort of women diagnosed with PPCM from 2005 to 2014 ( PPCM group) were
invited to participate in a clinical follow-up study including maximal
cardiopulmonary exercise testing and cardiac magnetic resonance imaging.
Matched women with previous severe preeclampsia (preeclampsia group) and
previous uncomplicated pregnancies (uncomplicated pregnancies group)
served as comparison groups. A total of 84 women with 28 in each group
participated. Median time to follow-up after PPCM was 91 months. Most
women (85%) in the PPCM group reported no symptoms of heart failure. Mean
left ventricular ejection fraction in the PPCM group was normal at 62%,
but significantly lower than in the preeclampsia group and the
uncomplicated pregnancies group where mean left ventricular ejection
fraction was 69% and 67%, respectively ( P<0.0001). Women in the PPCM
group also had impaired diastolic function with reduced left ventricular
peak filling rate, left atrial passive emptying volume, and left atrial
passive emptying fraction. Maximal exercise capacity (peak VO2) was also
reduced in the PPCM group compared with the preeclampsia group and the
uncomplicated pregnancies group, and PPCM , high body mass index, and low
left ventricular ejection fraction independently predicted reduced peak VO2.
Only 1 woman with PPCM had late gadolinium enhancement.
Conclusions Women generally recovered left ventricular ejection fraction and were
asymptomatic 7 years after PPCM , but had subtle diastolic dysfunction on
cardiac magnetic resonance imaging and reduced peak VO2. Focal myocardial
fibrosis assessed with late gadolinium enhancement was, however, uncommon.

Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study.

Wijeysundera DN; Pearse RM; Shulman MA; Abbott TEF; Torres E; Ambosta A;
Croal BL; Granton JT; Thorpe KE; Grocott MPW; Farrington C; Myles PS;
Cuthbertson BH; METS study investigators.

Lancet. 391(10140):2631-2640, 2018 06 30.
VI 1

BACKGROUND: Functional capacity is an important component of risk
assessment for major surgery. Doctors’ clinical subjective assessment of
patients’ functional capacity has uncertain accuracy. We did a study to
compare preoperative subjective assessment with alternative markers of
fitness (cardiopulmonary exercise testing [CPET], scores on the Duke
Activity Status Index [DASI] questionnaire, and serum N-terminal
pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting
death or complications after major elective non-cardiac surgery.

METHODS: We did a multicentre, international, prospective cohort study at
25 hospitals: five in Canada, seven in the UK, ten in Australia, and three
in New Zealand. We recruited adults aged at least 40 years who were
scheduled for major non-cardiac surgery and deemed to have one or more
risk factors for cardiac complications (eg, a history of heart failure,
stroke, or diabetes) or coronary artery disease. Functional capacity was
subjectively assessed in units of metabolic equivalents of tasks by the
responsible anaesthesiologists in the preoperative assessment clinic,
graded as poor (<4), moderate (4-10), or good (>10). All participants also
completed the DASI questionnaire, underwent CPET to measure peak oxygen
consumption, and had blood tests for measurement of NT pro-BNP
concentrations. After surgery, patients had daily electrocardiograms and
blood tests to measure troponin and creatinine concentrations until the
third postoperative day or hospital discharge. The primary outcome was
death or myocardial infarction within 30 days after surgery, assessed in
all participants who underwent both CPET and surgery. Prognostic accuracy
was assessed using logistic regression, receiver-operating-characteristic
curves, and net risk reclassification.

FINDINGS: Between March 1, 2013, and March 25, 2016, we included 1401
patients in the study. 28 (2%) of 1401 patients died or had a myocardial
infarction within 30 days of surgery. Subjective assessment had 19.2%
sensitivity (95% CI 14.2-25) and 94.7% specificity (93.2-95.9) for
identifying the inability to attain four metabolic equivalents during
CPET. Only DASI scores were associated with predicting the primary outcome
(adjusted odds ratio 0.96, 95% CI 0.83-0.99; p=0.03).

INTERPRETATION: Subjectively assessed functional capacity should not be
used for preoperative risk evaluation. Clinicians could instead consider a
measure such as DASI for cardiac risk assessment.

A new approach to estimate aerobic fitness using the NHANES dataset.

Lu KD; Bar-Yoseph R; Radom-Aizik S; Cooper DM.

Scandinavian Journal of Medicine & Science in Sports. 29(9):1392-1401,
2019 Sep.

INTRODUCTION: Physical activity and fitness are essential for healthy
growth in children. The National Health and Nutrition Examination Survey
(NHANES) evaluated fitness by estimating VO2 max from submaximal
measurements of heart rate (HR) during graded treadmill exercise. Our aims
were (a) to examine how well NHANES methodology used to estimate VO2 max
correlated with actual VO2 max and (b) to evaluate a novel fitness metric
using actual data collected during exercise and its relationship to
physical activity and sedentary time, lipid profiles, and body

METHODS: Fifty-three adolescents completed NHANES submaximal exercise
protocol and maximal graded cardiopulmonary exercise testing. We used a
novel approach to quantifying fitness (DELTAvelocity x incline x body mass
(VIM)/DELTAHR slopes) and evaluated its relationship to physical activity
and sedentary time using NHANES data (n = 4498). In a subset (n = 740), we
compared DELTAVIM/DELTAHR slopes to NHANES estimated VO2 max and examined
their relationship to cardiovascular risk factors (BMI percentiles and
lipid levels).

RESULTS: Measured VO2 peak was moderately correlated with NHANES
estimated VO2 max (r = 0.53, P < 0.01). Significantly higher
DELTAVIM/DELTAHR slopes were associated with increased physical activity
and decreased sedentary time. DELTAVIM/DELTAHR slopes were negatively
associated with LDL, triglycerides, and BMI percentiles (P < 0.01). In
general, the two fitness models were similar; however, DELTAVIM/DELTAHR
was more discriminating than NHANES in quantifying the relationship
between fitness and LDL levels.

CONCLUSION: We found that the NHANES estimated VO2 max accounted for
approximately 28% of the variability in the measured VO2 peak. Our
approach to estimating fitness (DELTAVIM/DELTAHR slopes) using actual data
provided similar relationships to lipid levels. We suggest that fitness
measurements based on actually measured data may produce more accurate
assessments of fitness and, ultimately, better approaches linking exercise
to health in children.

Echocardiography and MRI parameters associated with exercise capacity in patients after the arterial switch operation.

Warmerdam EG, Magni F, Leiner T, Doevendans PA, Sieswerda GT, van
Wijk SW, Breur HM, Driesen BW, Grotenhuis HB, Takken T.

J Cardiol. 2020 May 10. pii: S0914-5087(20)30105-2. doi:
10.1016/j.jjcc.2020.02.025. [Epub ahead of print]

BACKGROUND: The arterial switch operation (ASO) for transposition of the great
arteries has excellent survival, but a substantial number of patients suffer from
a reduced exercise capacity. The goal of this study was to identify imaging
parameters associated with a reduced exercise capacity in patients after ASO.
METHODS: A retrospective analysis was performed of ASO patients who underwent
cardiopulmonary exercise testing (CPET) between 2007 and 2017. Reduced exercise
performance was defined as a reduced workload peak (Wpeak) with Z-score <-2 or a
peak oxygen uptake indexed for weight (VO2peak/kg) with Z-score <-2. Data on
echocardiography and cardiac magnetic resonance performed within 1 year of the
CPET were collected for comparison.
RESULTS: A total of 81 ASO patients (age 17±7 years) were included. Reduced
exercise performance was found in 22 patients (27%) as expressed by either a
reduced Wpeak and/or a reduced VO2peak/kg. Main pulmonary artery gradient and
tricuspid regurgitation gradient by echocardiography were found to be associated
with reduced Wpeak (p=0.031; p=0.020, respectively). The main pulmonary artery
gradient and tricuspid regurgitation gradient by echocardiography were found to
be associated with reduced VO2peak/kg (p=0.009; p=0.019, respectively). No left
ventricular parameters were found to be associated with abnormal exercise
CONCLUSION: This study demonstrates that ASO patients frequently experience
reduced exercise capacity. Echocardiographic evidence of main pulmonary artery
stenosis and increased right ventricular pressure were associated with reduced
exercise capacity, and are therefore key to monitor during serial follow-up of
ASO patients.

Exercise Field Testing in Children: A New Approach for Age-Appropriate Evaluation of Cardiopulmonary Function


Schoffl I, Ehrlich B, Stanger S, Rottermann K, Dittrich S, Schoffl V.

Pediatr Cardiol. 2020 May 9. pii: 10.1007/s00246-020-02359-2.

Based on the wide range of problems to effectively perform cardiopulmonary testing in young children, this study strives to develop a new cardiopulmonary exercise test for children using a mobile testing device worn in a backpack in order to test children during their natural movement habits, namely, running outdoors. A standard cardiopulmonary exercise ramp test on a cycle ergometer was performed by a group of twenty 7-10-year-old children. The results were compared with a self-paced incremental running test performed using a mobile cardiopulmonary exercise measuring device in an outdoor park. The children were able to reach significantly higher values for most of the cardiopulmonary exercise variables during the outdoor test and higher. Whereas a plateau in [Formula: see text] was reached by 25% of the children during the outdoor test, only 75% were able to reach a reasonable VT2, let alone [Formula: see text], during the bicycle test. The heart rate at VT1, the O2-pulse, and the OUES were comparable between both tests. OUES was also positively correlated with [Formula: see text] in both tests. Testing children outdoors using a mobile cardiopulmonary exercise unit represents an alternative to standard exercise testing, but without the added problems of exercise equipment like treadmills or bicycles. It allows for individualized exercise testing with the aim of standardized testing durations instead of standardized testing protocols. The running speeds determined during the outdoor tests may then be used to develop age-adapted testing protocols for treadmill testing.


Exercise induced myocardial dysfunction detected by cardiopulmonary exercise testing is associated with increased risk of mortality in major oncological colorectal surgery

Mann J, Williams M, Wilson J, Yates D, Harrison A

BJA, 124 (4): 473-479 (2020)

BACKGROUND: Cardiopulmonary exercise testing (CPET) identifies high-risk patients before major surgery. In addition to using oxygen uptake and ventilatory efficiency to assess functional capacity, CPET can be used to identify underlying myocardial dysfunction through the assessment of the oxygen uptake to heart rate response (oxygen pulse response). We examined the relationship of oxygen pulse response, in combination with other CPET variables and known cardiac risk factors, with mortality after colorectal cancer surgery.
METHODS: This work focused on a retrospective cohort study of patients who had CPET and underwent colorectal cancer surgery. The primary outcome was a composite of in-hospital and 30-day mortality. Ventilatory inefficiency (Ve/Vco2>34) and exercise-induced myocardial dysfunction (abnormal oxygen pulse response) were investigated for an association with mortality using bivariable analysis and multivariable Cox regression.
RESULTS: A total of 1214 patients who underwent colorectal cancer surgery were included, and the primary outcome occurred in 26 patients (2.1%). Multivariable Cox regression showed abnormal oxygen pulse response was independently associated with the primary outcome (odds ratio [OR]=2.75; 95% confidence interval [CI], 1.17-6.47). Bivariable analysis showed that Ve/Vco2 >34 was associated with the primary outcome (OR=3.43; 95% CI, 1.47-8.01). Combining Ve/Vco2 >34 and abnormal oxygen pulse response conferred an increased risk for the primary outcome (OR=4.47; 95% CI, 1.62-12.34), compared with Ve/Vco2 >34 and normal oxygen pulse response. CONCLUSION: Ventilatory inefficiency and an abnormal oxygen pulse response were independently associated with short- (30-day) and long-term (2-yr) mortality. Oxygen pulse response may provide additional information when considering perioperative risk stratification.