Category Archives: Publications

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

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

Lancet (London, England) [Lancet] 2018 Jun 30; Vol. 391 (10140), pp. 2631-2640.

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.
Funding: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.



Causer AJ; Shute JK; Cummings MH; Shepherd AI; Bright V; Connett G; Allenby MI; Carroll MP; Daniels T; Saynor ZL;

Journal Of Applied Physiology (Bethesda, Md.: 1985) [J Appl Physiol (1985)] 2018 Aug 02. Date of Electronic Publication: 2018 Aug 02.

Introduction: The validity and safety of using supramaximal verification (Smax) to confirm a maximal effort during cardiopulmonary exercise testing (CPET) in people with cystic fibrosis (CF) and/or those with severe disease has been questioned. Therefore, this study aimed to investigate these concerns in children, adolescents and adults with mild-to-severe CF lung disease.
Methods: Retrospective analysis of 17 pediatric and 28 adult participants with CF (age range: 9.2-62.9 y; forced expiratory volume in 1 s: 66.7% [range: 29.9-102.3%]; 30 males) who completed a routine ramp incremental cycling test to determine peak oxygen uptake (V̇O2peak). Maximal oxygen uptake (V̇O2max) was subsequently confirmed by Smax at 110% of peak power output.
Results: All participants satisfied the criteria to verify a maximal effort during CPET. However, Smax-V̇O2peak exceeded ramp-V̇O2peak in 3/14 (21.4%) of pediatric and 6/28 (21.4%) adult exercise tests. A valid measurement of V̇O2max was attained in 85.7% of pediatric and 96.4% of adult exercise tests, as Smax-V̇O2peak did not exceed ramp-V̇O2peak by > 9%. Nine adults experienced a {greater than or equal to} 5% reduction in arterial O2 saturation during CPET; 4 during both the ramp and Smax, 3 during only the ramp and 2 during Smax only. Smax did not significantly worsen perceived breathing effort, chest tightness, throat narrowing or exertion compared with ramp incremental testing.
Conclusions: Given the clinical importance of aerobic fitness in people with CF, incorporating Smax is recommended to provide a safe and valid measure of V̇O2max in children, adolescents and adults who span the spectrum of CF disease severity.

Low skeletal muscle mass is associated with low aerobic capacity and increased mortality risk in patients with coronary heart disease – a CARE CR study.

Nichols S; O’Doherty AF; Taylor C; Clark AL; Carroll S; Ingle L;

Clinical Physiology And Functional Imaging [Clin Physiol Funct Imaging] 2018 Aug 30. Date of Electronic Publication: 2018 Aug 30.

Background: In patients with chronic heart failure, there is a positive linear relationship between skeletal muscle mass (SMM) and peak oxygen consumption (V˙O2peak ); an independent predictor of all-cause mortality. We investigated the association between SMM and V˙O2peak in patients with coronary heart disease (CHD) without a diagnosis of heart failure.
Methods: Male patients with CHD underwent maximal cardiopulmonary exercise testing and dual X-ray absorptiometry assessment. V˙O2peak, the ventilatory anaerobic threshold and peak oxygen pulse were calculated. SMM was expressed as appendicular lean mass (lean mass in both arms and legs) and reported as skeletal muscle index (SMI; kg m-2 ), and as a proportion of total body mass (appendicular skeletal mass [ASM%]). Low SMM was defined as a SMI <7·26 kg m-2 , or ASM% <25·72%. Five-year all-cause mortality risk was calculated using the Calibre 5-year all-cause mortality risk score.
Results: Sixty patients were assessed. Thirteen (21·7%) had low SMM. SMI and ASM% correlated positively with V˙O2peak (r = 0·431 and 0·473, respectively; P<0·001 for both). SMI and ASM% predicted 16·3% and 12·9% of the variance in V˙O2peak , respectively. SMI correlated most closely with peak oxygen pulse (r = 0·58; P<0·001). SMI predicted 40·3% of peak V˙O2 /HR variance. ASM% was inversely associated with 5-year all-cause mortality risk (r = -0·365; P = 0·006).
Conclusion: Skeletal muscle mass was positively correlated with V˙O2peak in patients with CHD. Peak oxygen pulse had the strongest association with SMM. Low ASM% was associated with a higher risk of all-cause mortality. The effects of exercise and nutritional strategies aimed at improving SMM and function in CHD patients should be investigated.

Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure.

Kakutani N; Fukushima A; Yokota T; Katayama T; Nambu H; Shirakawa R; Maekawa S; Abe T; Takada S; Furihata T;Ono K; Okita K; Kinugawa S; Anzai T;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2018 Aug 31. Date of Electronic Publication: 2018 Aug 31.

Background: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown.

Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01).
Conclusions: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.

Peripheral endothelial function is positively associated with maximal aerobic capacity in patients with chronic obstructive pulmonary disease.

Vaes AW; Spruit MA; Theunis J; Wouters EFM; De Boever P;

Respiratory Medicine [Respir Med] 2018 Sep; Vol. 142, pp. 41-47. Date of Electronic Publication: 2018 Jul 21.

Background: Patients with COPD are frequently diagnosed with cardiovascular disease. Peripheral endothelial dysfunction is an underlying mechanism and can be used as an early marker of cardiovascular impairment. To date, little is known on the association between peripheral endothelial dysfunction, cardiovascular risk factors and measurements of exercise capacity in patients with COPD. Therefore, we aimed to determine the relation between endothelial function and patient characteristics, cardiovascular risk factors and (micro)vascular and functional performance in patient with CODP.
Methods: Clinical and demographic data of patients with COPD were measured during routine pre-rehabilitation assessment. Cardiovascular risk factors, including blood pressure, ankle brachial index, arterial stiffness and retinal vessel widths were obtained. Peripheral endothelial function was measured using the EndoPAT-2000. Functional performance was assessed using cardiopulmonary exercise test, constant work rate test and six-minute walk test.
Results: 40 patients with COPD completed the study protocol (65% males; mean age: 62.8 ± 7.3 years; mean FEV1: 45.8 ± 17.5 %pred). Peripheral endothelial dysfunction was observed in 55% of the patients. Patients with peripheral endothelial dysfunction had significantly worse aerobic exercise capacity and higher prevalence of cardiovascular risk factors. Stepwise multivariate regression models identified sex, systolic blood pressure and maximal aerobic capacity as independent correlates of peripheral endothelial function. After correction for sex, age and systolic blood pressure, there was a significant partial correlation between peripheral endothelial function and maximal aerobic capacity (R = 0.51, p = 0.004).
Conclusion: Peripheral endothelial function was positively associated with maximal aerobic capacity, when correcting for sex, age and systolic blood pressure. Establishing peripheral endothelial dysfunction as a determinant of impaired aerobic capacity in COPD can be valuable for developing interventions aiming to improve aerobic capacity, and in turn cardiovascular health.

The importance of right ventricular function in patients with pulmonary arterial hypertension.

Badagliacca R; Papa S; Poscia R; Pezzuto B; Manzi G; Torre R; Fedele F; Vizza CD;

Expert Review Of Respiratory Medicine [Expert Rev Respir Med] 2018 Sep 06, pp. 1-7. Date of Electronic Publication: 2018 Sep 06.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, life-threatening, and incurable disease. Its prognosis is based on right ventricular (RV) function. Therefore, adequate assessment of RV function is mandatory. Areas covered: This article presents the case of a patient with PAH in which the traditional diagnostic approach did not provide a complete assessment of RV function. The authors show how the analysis of other parameters yielded additional information that improved the management of this patient. Expert commentary: Despite current treatments, PAH often worsens due to progressive RV dysfunction. Appropriate assessment of RV function may facilitate the early identification of patients at risk of RV function impairment. More aggressive treatment of PAH might delay progression of the disease. Traditional risk stratification, which is based on New York Heart Association/World Health Organization (NYHA/WHO) functional class evaluation, the 6-minute walk test, and right heart catheterization, proves insufficient in many PAH patients, as it does not provide complete information about RV function. Thus, further parameters are required. Analysis of RV function, in addition to echocardiography and cardiopulmonary exercise testing, may add relevant prognostic information and improve therapy.

Step oximetry test: a validation study.

Fox BD; Sheffy N; Vainshelboim B; Fuks L; Kramer MR;

BMJ Open Respiratory Research [BMJ Open Respir Res] 2018 Aug 03; Vol. 5 (1), pp. e000320. Date of Electronic Publication: 20180803 (Print Publication: 2018).

Introduction: Step climbing is a potentially useful modality for testing exercise capacity. However, there are significant variations between test protocols and lack of consistent validation against gold standard cycle ergometry cardiopulmonary exercise testing (CPET). The purpose of the study was to validate a novel technique of exercise testing using a dedicated device.
Methods: We built a step oximetry device from an adapted aerobics step and pulse oximeter connected to a computer. Subjects performed lung function tests, a standard incremental cycle CPET and also a CPET while stepping on and off the step oximetry device to maximal exertion. Data from the step oximetry device were processed and correlated with standard measurements of pulmonary function and cycle CPET.
Results: We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9 mL/kg/min (95% CI -3.6 to 5.4) higher in the step test compared with the gold standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated negatively with diffusion capacity for carbon monoxide (r=-0.43, p<0.005). No adverse events occurred.
Conclusions: The step oximetry test was a maximal test of exertion in the subjects studied, achieving slightly higher VO2 than during the standard test. The test was safe to perform and well tolerated by the patients. Parameters derived from the step oximetry device correlated well with gold standard measurements. The step oximetry test could become a useful and standardisable exercise test for clinical settings where advanced testing is not available or appropriate.

Feasibility of a home-based exercise intervention with remote guidance for patients with stable grade II and III gliomas: a pilot randomized controlled trial.

Gehring K, Kloek CJ, Aaronson NK, Janssen KW, Jones LW,
Sitskoorn MM, Stuiver MM

Clin Rehabil. 2018 Mar;32(3):352-366. doi: 10.1177/0269215517728326. Epub 2017
Sep 8.

OBJECTIVE: In this pilot study, we investigated the feasibility of a home-based,
remotely guided exercise intervention for patients with gliomas.
DESIGN: Pilot randomized controlled trial (RCT) with randomization (2:1) to
exercise or control group.
SUBJECTS: Patients with stable grade II and III gliomas.
INTERVENTION: The six-month intervention included three home-based exercise
sessions per week at 60%-85% of maximum heart rate. Participants wore heart rate
monitors connected to an online platform to record activities that were monitored
weekly by the physiotherapist.
MAIN MEASURES: Accrual, attrition, adherence, safety, satisfaction,
patient-reported physical activity, VO2 peak (by maximal cardiopulmonary exercise
testing) and body mass index (BMI) at baseline and at six-month follow-up.
RESULTS: In all, 34 of 136 eligible patients (25%) were randomized to exercise
training ( N = 23) or the control group ( N = 11), of whom 19 and 9,
respectively, underwent follow-up. Mean adherence to prescribed sessions was 79%.
Patients’ experiences were positive. There were no adverse events. Compared to
the control group, the exercise group showed larger improvements in absolute VO2
peak (+158.9 mL/min; 95% CI: -44.8 to 362.5) and BMI (-0.3 kg/m²; 95% CI: -0.9 to
0.2). The median increase in physical activity was 1489 metabolic equivalent of
task (MET) minutes higher in the exercise group. The most reported reasons for
non-participation were lack of motivation or time.
CONCLUSION: This innovative and intensive home-based exercise intervention was
feasible in a small subset of patients with stable gliomas who were interested in
exercising. The observed effects suggest that the programme may improve
cardiorespiratory fitness. These results support the need for large-scale trials
of exercise interventions in brain tumour patients.

The Impact of Bariatric Surgery on Cardiopulmonary Function: Analyzing VO2 Recovery Kinetics.

Remígio MI; Santa Cruz F; Ferraz Á; Remígio MC; Parente G; Nascimento I; Brandão D; Dornelas de Andrade AF;
de Moraes Neto F; Campos J;

Obesity Surgery [Obes Surg] 2018 Aug 15. Date of Electronic Publication: 2018 Aug 15.

Purpose: To assess cardiopulmonary capacity, autonomic heart function, and oxygen recovery kinetics during exercise testing before and after bariatric surgery.
Methods: This is a prospective cohort study. Symptom-limited cardiopulmonary exercise testing was performed with 24 patients, 1 week before and 4 months after bariatric surgery. The main variables were maximum oxygen uptake (VO2 max), the time elapsed until the appearance of the first ventilatory threshold (TLV1), and VO2 oxygen kinetics during recovery with a 50% reduction in peak oxygen uptake in the recovery period after exercise (50%VO2RP).
Results: The study demonstrated that the peak VO2\kg increased significantly after bariatric surgery. When analyzed without adjusting for weight, the peak VO2 paradoxically and significantly decreased after the surgical procedure (p = 0.007). The exercise time until the anaerobic threshold was longer after surgical procedure than before it (p = 0.001). Regarding post-exercise oxygen recovery kinetics, there was a faster reduction in the peak oxygen uptake after bariatric surgery than before the procedure (p < 0.001).
Conclusions: There was an obvious cardiac autonomic improvement after surgery. Despite the improvement in exercise tolerance, patients undergoing bariatric surgery had lower maximum oxygen consumption in the analysis not corrected for body weight. The mean VO2RP before bariatric surgery was 141 s and was 111 s after the surgical procedure (p < 0.001). These results suggest an improvement in the recovery kinetics of oxygen consumption, a novel index of cardiac reserve capacity, on patients undergoing bariatric surgery.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

Lai S, Mastroluca D, Matino S, Panebianco V, Vitarelli A,
Capotosto L, Turinese I, Marinelli P, Rossetti M, Galani A,
Baiocchi P, D’Angelo AR, Palange P.

Kidney Blood Press Res. 2017;42(6):1290-1302. doi: 10.1159/000486011. Epub 2017
Dec 15.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity
and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients,
often before the onset of renal failure, and the pathogenetic mechanism is not
yet well elucidated. The aim of the study was to identify early and noninvasive
markers of cardiovascular risk in young ADPKD patients, in the early stages of
METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age
and sex, were enrolled, and we have assessed inflammatory indexes, mineral
metabolism, metabolic state and markers of atherosclerosis and endothelial
dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI),
flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass
index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake
(V’O2max), and O2 uptake at lactic acid threshold (V’O2@LT).
RESULTS: The ADPKD patients compared to control group, showed a significant
higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model
Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT
(cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001,
p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and
25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of
exercise tolerance, as V’O2max, V’O2max/Kg and V’O2max (% predicted) (p<0.001,
p<0.001, p=0.018; respectively), and metabolic response indexes (V’O2@LT, V’O2
@LT%, V’O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover,
inflammatory indexes were significantly higher in ADPKD patients, and we found a
positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507,
p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585,
CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed
a greater insulin resistance, endothelial dysfunction, inflammation and mineral
metabolism disorders, respect to control group. Moreover, these patients
presented reduced tolerance to stress, and decreased anaerobic threshold to CPET.
Our results indicate a major and early cardiovascular risk in ADPKD patients.
Therefore early and noninvasive markers of cardiovascular risk and CPET should be
carried out, in ADPKD patients, in the early stages of disease, despite the cost