Author Archives: Paul Older

Cardiopulmonary exercise testing in the evaluation of liver disease in adults who have had the Fontan operation.

Agarwal A, Cunnington C, Sabanayagam A, Zier L, McCulloch CE,
Harris IS, Foster E, Atkinson D, Bryan A, Jenkins P, Dua J,
Parker MJ, Karunaratne D, Moore JA, Meadows J, Clarke B,
Hoschtitzky JA, Mahadevan VS.

Arch Cardiovasc Dis. 2018 Apr;111(4):276-284.

BACKGROUND: Liver disease (LD) is a long-term complication in patients with a
single ventricle who have had the Fontan operation. A decline in cardiopulmonary
exercise testing (CPET) variables is associated with increased risk of
hospitalization, but its association with LD is unknown.
AIM: To determine the association between CPET variables and LD in adults who
have had the Fontan operation.
METHODS: We retrospectively reviewed the medical records from two tertiary
RESULTS: We identified 114 adults (≥18 years; mean 30.9±7.4 years) who had
undergone the Fontan operation: 56% were women; 63% had total cavopulmonary
connection; 66% had New York Heart Association (NYHA) class I status; 42% had
arrhythmias; 22% had systemic right ventricle; and 35% had ventricular
dysfunction. Of 81 patients with liver-imaging data, 41% had LD (i.e. imaging
evidence of cirrhosis, with or without portal hypertension, splenomegaly or
varices). There were no differences in clinical or echocardiographic variables
between those with and without LD. Among the 58 patients with CPET data, mean
peak oxygen consumption (VO2) was 18.6±5.7mL/kg/min, per-cent-predicted peak VO2
was 53.9±15.5%, peak oxygen pulse was 9.3±2.9mL/beat and per-cent-predicted peak
oxygen pulse was 82.6±21.5%. Of the 44 patients with liver and CPET data, each
standard deviation decrease in per-cent-predicted peak VO2 (16%) and
per-cent-predicted peak oxygen pulse (22%) was associated with a 2.3-fold
increase in the odds of LD, after adjusting for NYHA, institution and Fontan type
(P=0.04). Similarly, each standard deviation decrease in per-cent-predicted peak
VO2 and oxygen pulse was associated with an estimated 5.9-year and 4.9-year
earlier onset of LD, respectively (P>0.05).
CONCLUSIONS: Decline in per-cent-predicted peak VO2 and oxygen pulse was
associated with increased odds of LD in adults who had undergone the Fontan
operation. Our study supports more rapid hepatic evaluation among patients with
abnormal or worsening CPET variables.

Physiological Responses and Prognostic Value of Common Exercise Testing Modalities in Idiopathic Pulmonary Fibrosis.

Vainshelboim B, Myers J, Oliveira J, Izhakian S, Unterman A, Kramer MR

Journal Of Cardiopulmonary Rehabilitation And Prevention [J Cardiopulm Rehabil Prev] 2018 Sep 24. Date of Electronic Publication: 2018 Sep 24.

Purpose: This pilot study aimed to compare physiological responses between cycle cardiopulmonary exercise tests (CPETs) and 6-min walk tests (6MWTs) and to assess their prognostic value among patients with idiopathic pulmonary fibrosis (IPF).
Methods: Thirty-four patients with IPF (68 ± 8 yr) underwent CPETs and 6MWTs and were followed up for 40 mo. Differences, levels of agreement, and relative risks for mortality were analyzed between measured and estimated peak responses for the 2 tests.
Results: Compared with the CPET, oxygen uptake (VO2), heart rate (HR), and the nadir of SpO2 were lower during the 6MWT, whereas work rate (WR) was higher. Mean differences were as follows: VO2 =-1.9 mL/kg/min, 95% CI, -1.1 to -2.7, P < .001; HR =-9 beats/min, 95% CI, -4 to -14, P = .002; SpO2 =-6%, 95% CI, -4 to -7, P < .001; and WR = 9 W/min, 95% CI, 3 to 16, P = .008. Interclass correlations ranged from 0.84 to 0.90 and both tests demonstrated prognostic value for mortality.
Conclusions: Significant differences and variation in peak physiological responses were observed between cycle CPETs and 6MWTs in patients with IPF. However, good agreement was evident, suggesting that both tests provide value for clinical and research settings. Future studies should compare the physiological responses between treadmill CPETs and 6MWTs for prognostic utility in IPF.

Efficient Use of Simple Exercise-Induced Bronchoconstriction Challenge Testing in Pediatric Exercise-Induced Dyspnea.

Bhatia R; Schwendeman E;

Respiratory Care [Respir Care] 2018 Sep 25. Date of Electronic Publication: 2018 Sep 25.

Background: A simple exercise test to evaluate for exercise-induced bronchoconstriction (EIB) is routinely ordered in pediatric patients with exercise-induced dyspnea. However, the utility of this test in establishing the cause of exercise-induced dyspnea is not thoroughly examined in the pediatric population. We sought to assess the efficiency of a simple EIB challenge test in finding the cause of exercise-induced dyspnea in pediatric patients referred to our tertiary center in the last 5 y.
Methods: We performed a retrospective chart review for all of these exercise tests done at Akron Children’s Hospital from March 2011 to March 2016. Patients with chronic conditions (eg, cystic fibrosis, cardiac abnormality) were excluded. Demographics, clinical diagnosis of asthma, a presumptive diagnosis of exercise-induced asthma or EIB by the referring provider, symptoms with and without exercise, albuterol use, spirometry, and simple EIB challenge test results were collected. The chi-square test of independence was utilized in the examination of potential dependent relationships between categorical variables. A P value <.05 was considered to be statistically significant.
Results: Out of 164 enrolled subjects (57 males; age 6-20 y), only 19% showed evidence of EIB. There were no significant associations between EIB status (ie, EIB-positive or EIB-negative) based on exercise testing and gender, typical symptoms of EIB, diagnosis of exercise-induced asthma or EIB, and albuterol use (P > .05). However, a subject without asthma was 2.8 times more likely to have negative exercise test for EIB (odds ratio 2.8, 95% CI 1.3-6.5); in addition, approximately 85% of tests in subjects without asthma were negative.
Conclusion: In a majority of subjects without asthma, a simple EIB challenge testing failed to uncover the cause of exercise-induced dyspnea and thus was inefficient. In these subjects, cardiopulmonary exercise testing may be more useful and cost-effective to explore other causes of dyspnea including EIB.

Cardiorespiratory fitness is impaired and predicts mid-term postoperative survival in patients with abdominal aortic aneurysm disease.

Rose GA; Davies RG; Appadurai IR; Lewis WG; Cho JS; Lewis MH; Williams IM; Bailey DM;

Experimental Physiology [Exp Physiol] 2018 Sep 26. Date of Electronic Publication: 2018 Sep 26.

New Findings: What is the central question of this study? To what extent cardiorespiratory fitness (CRF) is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake < 13.1 mL O2 .kg-1 .min-1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥ 34 are associated with increased risk of post-operative mortality at 2 years. These findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients which may help direct care provision.
Abstract: Preoperative cardiopulmonary exercise testing (PCPET) is a standard assessment used for the assessment of cardiorespiratory fitness (CRF) and risk stratification. However, to what extent CRF is impaired in patients undergoing surgical repair of abdominal aortic aneurysm (AAA) disease and corresponding implications for postoperative outcome requires further investigation. We measured CRF during an incremental exercise test to exhaustion using online respiratory gas analysis in patients with AAA disease (n = 124, aged 72 ± 7 years) and healthy sedentary controls (n = 104, aged 70 ± 7 years). Postoperative survival was examined for association with CRF and threshold values calculated for independent predictors of mortality. Patients who underwent PCPET prior to surgical repair had lower CRF [age-adjusted mean difference of 12.5 mL O2 .kg-1 .min-1 for peak oxygen uptake (V̇O2 peak), P < 0.001 vs. controls]. Following multivariable analysis, both V̇O2 peak and the ventilatory equivalent for carbon dioxide at anaerobic threshold (V̇E /V̇CO2 -AT) were independent predictors of mid-term postoperative survival (2 years). Hazard ratios of 5.27 (95% confidence interval (CI) 1.62 to 17.14, P = 0.006) and 3.26 (95% CI 1.00 – 10.59, P = 0.049) were observed for V̇O2 peak < 13.1 mL O2 .kg-1 .min-1 and V̇E /V̇CO2 -AT ≥ 34 respectively. Thus, CRF is lower in patients with AAA and those with a V̇O2 peak < 13.1 mL O2 .kg-1 .min-1 and V̇E /V̇CO2 -AT ≥ 34 are associated with a markedly increased risk of post-operative mortality. Collectively, our findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients which may help direct care provision.

Validation of the Six-Minute Walk Test for Predicting Peak VO2 in Cancer Survivors.

Schumacher AN, Shackelford DY, Brown JM, Hayward R

2018 Sep 19


To assess the quality of the relationship between VO2peak estimated from patient outcomes on the 6-minute walk test (6-MWT) and the VO2peak calculated from patient outcomes on the University of Northern Colorado Cancer Rehabilitation Institute (UNCCRI) treadmill protocol.


Cancer survivors (N = 187) completed the UNCCRI treadmill protocol and a 6MWT one week apart in randomized order to obtain VO2peak. Values from the UNCCRI treadmill protocol were compared against four common 6MWT VO2peak prediction equations.


All four 6MWT prediction equations significantly (p < 0.001) underestimated VO2peak with predicted values ranging from 8.0 ± 4.1 to 18.6 ± 3.1 mL/kg/min, while the UNCCRI treadmill protocol yielded a significantly higher value of 23.9 ± 7.6 mL/kg/min. A positive strong correlation occurred between estimated VO2peak derived from the UNCCRI treadmill protocol and only one of the VO2peak values derived from the 6MWT prediction equations (r = 0.81), and all four equations consistently underpredicted VO2peak.


These findings suggest that the 6MWT is not a valid test for predicting VO2peak in the cancer population due to its consistent underestimation of VO2peak regardless of the prediction equation. Obtaining an accurate and valid VO2peak value is necessary in order to correctly prescribe an individualized exercise rehabilitation regimen for cancer survivors. It is recommended that clinicians avoid the 6MWT and instead implement treadmill testing to volitional fatigue to quantify VO2peak in cancer survivors.

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.