Category Archives: Publications

Peak oxygen uptake and incident coronary heart disease in a healthy population: the HUNT Fitness Study

Letnes JM; Dalen H; Vesterbekkmo EK; Wisløff U; Nes BM;

European Heart Journal [Eur Heart J] 2018 Nov 29. Date of Electronic Publication: 2018 Nov 29.

Aims: The majority of previous research on the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is based on indirect assessment of CRF in clinically referred predominantly male populations. Therefore, our aim was to examine the associations between VO2peak measured by the gold-standard method of cardiopulmonary exercise testing and fatal and non-fatal coronary heart disease (CHD) in a healthy and fit population.
Methods and results: Data on VO2peak from 4527 adults (51% women) with no previous history of cardiovascular or lung disease, cancer, and hypertension or use of antihypertensive medications participating in a large population-based health-study (The HUNT3 Study), were linked to hospital registries and the cause of death registry. Average VO2peak was 36.0 mL/kg/min and 44.4 mL/kg/min among women and men, and 83.5% had low 10-year risk of CVD at baseline. Average follow-up was 8.8 years, and 147 participants reached the primary endpoint. Multi-adjusted Cox-regression showed 15% lower risk for the primary endpoint per one-MET (metabolic equivalent task) higher VO2peak [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77-0.93], with similar results across sex. The highest quartile of VO2peak had 48% lower risk of event compared with the lowest quartile (multi-adjusted HR 0.52, 95% CI 0.33-0.82). Oxygen pulse and ventilatory equivalents of oxygen and carbon dioxide also showed significant predictive value for the primary endpoint.
Conclusion: VO2peak was strongly and inversely associated with CHD across the whole fitness continuum in a low-risk population sample. Increasing VO2peak may have substantial benefits in reducing the burden of CHD.

Influence of Baseline Physical Activity Level on Exercise Training Response and Clinical Outcomes in Heart Failure: The HF-ACTION Trial.

Mediano MFF; Leifer ES; Cooper LS; Keteyian SJ; Kraus WE; Mentz RJ; Fleg JL;

JACC. Heart Failure [JACC Heart Fail] 2018 Dec; Vol. 6 (12), pp. 1011-1019.

Objectives: This study sought to evaluate the influence of baseline physical activity (PA) on responses to aerobic exercise training and clinical events in outpatients with chronic systolic heart failure (HF) from the multicenter HF-ACTION (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure) trial.
Background: The influence of baseline PA on exercise capacity, responses to exercise training and clinical outcomes in patients with chronic HF is unclear.
Methods: Of 2,130 participants who provided consent for this analysis, 1,494 patients (64%) had complete baseline PA data, using a modified version of the International Physical Activity Questionnaire-Short Form questionnaire and were included in the analysis; 742 received usual care and 752 were allocated to the exercise training group. Changes in exercise capacity, all-cause mortality and hospitalization, cardiovascular (CV) mortality and hospitalization, and CV mortality and HF hospitalization were evaluated as a function of baseline PA tertile.
Results: At baseline, the highest PA tertile showed greater peak oxygen uptake, cardiopulmonary exercise test duration, and 6-min walk test distance than the other 2 PA tertiles, as well as lower New York Heart Association functional class, lower Beck depression score, and lower atrial fibrillation prevalence than the lowest PA tertile. Compared to the lowest PA tertile, the middle tertile had 18% lower risk of CV death/CV hospitalizations, and the upper tertile showed 23% lower risk of CV death/HF hospitalizations. Exercise capacity and clinical outcome responses to training were similar and largely nonsignificant across baseline PA tertiles with significant benefit of training on exercise test duration for all tertiles.
Conclusions: In patients with chronic systolic HF, aerobic exercise training significantly improves exercise test duration to a similar extent across baseline PA tertiles. Although higher baseline PA was associated with lower risk of clinical events, no significant differences in event rates within each PA tertile were seen between subgroups randomized to exercise training versus usual care. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure [HF-ACTION]; NCT00047437).

Pulmonary effects on exercise testing in tetralogy of Fallot patients repaired with a transannular patch.

Powell AW, Mays WA, Knecht SK, Chin C;

Cardiol Young. 2018 Nov 26:1-7. doi: 10.1017/S1047951118001920. [Epub ahead of

BACKGROUND: A transannular patch is often used in the contemporary surgical
repair of tetralogy of Fallot. This can lead to significant pulmonary
insufficiency and increased right ventricular volumes and ultimately pulmonary
valve replacement. Cardiopulmonary exercise testing is used to assess exercise
capacity in tetralogy of Fallot patients before pulmonary valve replacement.
There is only few published literatures on how lung function affects functional
capacity in tetralogy of Fallot patients repaired with a transannular patch.
METHODS: A retrospective chart review was done from 2015 to 2017 on patients with
tetralogy of Fallot who underwent maximal effort cardiopulmonary exercise testing
with cycle ergometry and with concurrent pulmonary function testing. Tetralogy of
Fallot patients repaired with a transannular patch without pulmonary valve
replacement were compared with age, gender, and size-matched normal controls.
RESULTS: In the tetralogy of Fallot group, 24 out of 57 patients underwent
primary repair with a transannular patch. When compared to the normal controls,
they demonstrated abnormal predicted forced expiratory volume in one second (79 ±
23.1% versus 90.7 ± 14.1%, p<0.05), predicted maximal voluntary ventilation (74 ±
18% versus 90.5 ± 16.2%, p<0.05) while having low-normal predicted forced vital
capacity (80.5 ± 17.2% versus 90.2 ± 12.4%, p<0.05) and normal breathing reserve
percentage (50.3 ± 11.3% versus 47.5 ± 17.3%, p = 0.52). Cardiopulmonary exercise
testing abnormalities included significantly lower percent predicted oxygen
consumption (63.2 ± 12.2% versus 87 ± 12.1%, p<0.05), maximal heart rate (171.8 ±
18.9 versus 184.6 ± 13.6, p<0.05), and percent predicted maximum workload (61.7 ±
15.9% versus 88.3 ± 21.5%, p<0.05).
CONCLUSIONS: Tetralogy of Fallot patients repaired with a transannular patch can
have abnormal pulmonary function testing with poor exercise capacity in addition
to chronotropic incompetence and impaired muscular power.

Total haemoglobin mass, but not haemoglobin concentration, is associated with preoperative cardiopulmonary exercise testing-derived oxygen-consumption variables.

Otto JM, Plumb JOM, Wakeham D, Clissold E, Loughney L, Schmidt W, Montgomery HE, Grocott MPW, Richards

Br J Anaesth. 2017 May 1;118(5):747-754. doi: 10.1093/bja/aew445.
Comment in Br J Anaesth. 2017 May 1;118(5):655-657.
Comment on Eur J Appl Physiol. 2013 May;113(5):1181-8.

Background: Cardiopulmonary exercise testing (CPET) measures peak exertional
oxygen consumption ( V˙O2peak ) and that at the anaerobic threshold ( V˙O2 at AT,
i.e. the point at which anaerobic metabolism contributes substantially to overall
metabolism). Lower values are associated with excess postoperative morbidity and
mortality. A reduced haemoglobin concentration ([Hb]) results from a reduction in
total haemoglobin mass (tHb-mass) or an increase in plasma volume. Thus, tHb-mass
might be a more useful measure of oxygen-carrying capacity and might correlate
better with CPET-derived fitness measures in preoperative patients than does
circulating [Hb].
Methods: Before major elective surgery, CPET was performed, and both tHb-mass
(optimized carbon monoxide rebreathing method) and circulating [Hb] were
Results: In 42 patients (83% male), [Hb] was unrelated to V˙O2 at AT and V˙O2peak
( r =0.02, P =0.89 and r =0.04, P =0.80, respectively) and explained none of the
variance in either measure. In contrast, tHb-mass was related to both ( r =0.661,
P <0.0001 and r =0.483, P =0.001 for V˙O2 at AT and V˙O2peak , respectively). The
tHb-mass explained 44% of variance in V˙O2 at AT ( P <0.0001) and 23% in V˙O2peak
( P =0.001).
Conclusions: In contrast to [Hb], tHb-mass is an important determinant of
physical fitness before major elective surgery. Further studies should determine
whether low tHb-mass is predictive of poor outcome and whether targeted increases
in tHb-mass might thus improve outcome.

Exercise performance and symptoms in lowlanders with COPD ascending to moderate altitude: randomized trial.

Furian M; Flueck D; Latshang TD; Scheiwiller PM; Segitz SD; Mueller-Mottet S; Murer C; Steiner A; Ulrich S; Rothe T; Kohler M; Bloch KE;

International Journal Of Chronic Obstructive Pulmonary Disease [Int J Chron Obstruct Pulmon Dis] 2018 Oct 26; Vol. 13, pp. 3529-3538. Date of Electronic Publication: 20181026 (Print Publication: 2018).

Objective: To evaluate the effects of altitude travel on exercise performance and symptoms in lowlanders with COPD.
Design: Randomized crossover trial.
Setting: University Hospital Zurich (490 m), research facility in mountain villages, Davos Clavadel (1,650 m) and Davos Jakobshorn (2,590 m).
Participants: Forty COPD patients, Global Initiative for Obstructive Lung Disease (GOLD) grade 2-3, living below 800 m, median (quartiles) age 67 y (60; 69), forced expiratory volume in 1 second 57% predicted (49; 70).
Intervention: Two-day sojourns at 490 m, 1,650 m, and 2,590 m in randomized order.
Outcome measures: Six-minute walk distance (6MWD), cardiopulmonary exercise tests, symptoms, and other health effects.
Results: At 490 m, days 1 and 2, median (quartiles) 6MWD were 558 m (477; 587) and 577 m (531; 629). At 2,590 m, days 1 and 2, mean changes in 6MWD from corresponding day at 490 m were -41 m (95% CI -51 to -31) and -40 m (-53 to -27), n=40, P<0.05, both changes. At 1,650 m, day 1, 6MWD had changed by -22 m (-32 to -13), maximal oxygen uptake during bicycle exercise by -7% (-13 to 0) vs 490 m, P<0.05, both changes. At 490 m, 1,650 m, and 2,590 m, day 1, resting PaO2 were 9.0 (8.4; 9.4), 8.1 (7.5; 8.6), and 6.8 (6.3; 7.4) kPa, respectively, P<0.05 higher altitudes vs 490 m. While staying at higher altitudes, nine patients (24%) experienced symptoms or adverse health effects requiring oxygen therapy or relocation to lower altitude.
Conclusion: During sojourns at 1,650 m and 2,590 m, lowlanders with moderate to severe COPD experienced a mild reduction in exercise performance and nearly one quarter required oxygen therapy or descent to lower altitude because of adverse health effects. The findings may help to counsel COPD patients planning altitude travel.

Echo-derived peak cardiac power output-to-left ventricular mass with cardiopulmonary exercise testing predicts outcome in patients with heart failure and depressed systolic function.

Pugliese NR; Fabiani I; Mandoli GE; Guarini G; Galeotti GG; Miccoli M; Lombardo A; Simioniuc A; Bigalli G;
Pedrinelli R; Cardiac, Dini FL;

European Heart Journal Cardiovascular Imaging [Eur Heart J Cardiovasc Imaging] 2018 Nov 23. Date of Electronic Publication: 2018 Nov 23.

Aims: Peak cardiac power output-to-mass (CPOM) represents a measure of the rate at which cardiac work is delivered respect to the potential energy stored in left ventricular (LV) mass. We studied the value of CPOM and cardiopulmonary exercise test (CPET) in risk stratification of patients with heart failure (HF).
Materials and results: We studied 159 patients with chronic HF (mean rest LV ejection fraction 30%) undergoing CPET and exercise stress echocardiography. CPOM was calculated as the product of a constant (K = 2.22 × 10-1) with cardiac output (CO) and the mean blood pressure (MBP), divided by LV mass (M), and expressed in the unit of W/100 g: CPOM = [K × CO (L/min) × MBP (mmHg)]/LVM(g). Patients were followed-up for the primary endpoint, including all-cause death, ventricular assist device implantation, and heart transplantation, and the secondary endpoint that comprised hospitalization for HF. In multivariate Cox regression analyses, peak CPOM was selected as the most powerful independent predictor of both primary and secondary endpoint [hazard ratio (HR) 0.004, 95% confidence interval (CI) 0.004-0.3; P = 0.002 and HR 0.09, 95% CI 0.02-0.55; P = 0.009]. Sixty-month survival free from the combined endpoint was 85% in those exhibiting oxygen consumption (VO2) > 14 mL/min/kg and peak CPOM > 0.6 W/100 g. Peak VO2 ≤ 14 mL/min/kg provided incremental prognostic value over demographic and clinical variables, brain natriuretic peptide, and resting echocardiographic parameters (χ2 from 58 to 64; P = 0.04), that was further increased by peak CPOM ≤ 0.6 W/100 g (χ2 77; P < 0.001).
Conclusion: Peak CPOM and peak VO2 showed independent and incremental prognostic values in patients with chronic HF.

The Intra-rater and Inter-rater Reliability of measures derived from Cardiopulmonary Exercise Testing (CPET) in patients with Abdominal Aortic Aneurysms (AAA).

Harwood AE; Totty J; Wallace T; Smith GE; Carradice D; Carroll S; Chetter IC;

Annals Of Vascular Surgery [Ann Vasc Surg] 2018 Nov 23. Date of Electronic Publication: 2018 Nov 23.

Introduction: Patients with abdominal aortic aneurysms (AAA) often have low exercise tolerance due to comorbidities and advance age. Cardiopulmonary exercise testing (CPET) is predictive of post-operative morbidity and mortality in patients with AAA. We aimed to assess the intra- and inter-rater reliability of both treadmill and cycle ergometer based CPET variables.
Methods: Patients with a AAA (>3.5cm) were randomised to treadmill or bike CPET. Participants were asked to perform two separate CPET tests seven days apart after a familiarisation protocol. All CPETs were carried out using a ramp cycle or modified Bruce treadmill protocol with breath-by-breath gas analysis.
Results: Twenty-two male and 2 female patients, aged 73.6 ± 6.0, completed the study. Intra-rater analysis (intraclass correlation coefficients) demonstrated high reliability on both the treadmill and bike for VAT (r = 0.834 and r = 0.975, respectively). All other CPET variables demonstrated high intra-rater reliability on both modalities bar the highest point for VE/VO2 on the treadmill (substantial agreement r = 0.755). Further, inter-rater reliability demonstrated high agreement for VAT on both the treadmill and cycle (r = 0.983 and 0.905, respectively). All other CPET variables demonstrated high intra-rater reliability on both modalities, with the exception of VO2PEAK on the cycle ergometer (fair agreement r = 0.400).
Discussion: CPET in AAA patients is reliable on short-term repeat testing patients and between CPET test reviewers for common testing modalities/protocols. These findings provide further support for the use of CPET, especially treadmill walking, as a clinical measure of peri-operative cardiorespiratory fitness in patients with AAA.


Peak Blood Pressure Responses During Maximum Cardiopulmonary Exercise Testing: Reference Standards From FRIEND (Fitness Registry and the Importance of Exercise: A National Database).

Sabbahi A, Arena R, Kaminsky LA, Myers J, Phillips SA

Hypertension. 2018 Feb;71(2):229-236. doi: 10.1161/HYPERTENSIONAHA.117.10116.
Epub 2017 Dec 18.

The objective of this study is to expand on previous efforts in establishing
normative standards of exercising blood pressure (BP) at maximal physical
exertion derived from treadmill cardiopulmonary exercise testing in the United
States. Four experienced laboratories in the United States with established
quality control procedures contributed data from September 1, 1986, to February
1, 2015. A total of 2917 maximal (peak respiratory exchange ratio ≥1.00)
treadmill cardiopulmonary exercise testing responses from apparently healthy men
and women (aged 20-79 years) without cardiovascular disease were submitted to
FRIEND (Fitness Registry and the Importance of Exercise: A National Database).
Percentiles of maximal systolic and diastolic BP were determined for each decade.
Our results show a continued increase in peak systolic BP with age in both men
and women to the sixth decade, followed by a plateau between the sixth and
seventh decades. However, the trajectory of peak diastolic BP with age is
different between men and women. Men showed an increase in peak systolic BP until
the fifth decade, which plateaued by the seventh decade. In contrast, women
showed a continued increase in peak diastolic BP across each decade. Existing
reference data for exercising BP have not been updated for >20 years. Normative
peak exercising BP values from FRIEND can be used to provide a more current
representation of maximal BP during exercise testing in the US population.

Using predicted 30 day mortality to plan postoperative colorectal surgery care: a cohort study.

Swart M, Carlisle JB, Goddard J

Br J Anaesth. 2017 Jan;118(1):100-104. doi: 10.1093/bja/aew402.

BACKGROUND: Preoperative identification of high-risk surgical patients might help
to reduce postoperative morbidity and mortality. Using a patient’s predicted
30 day mortality to plan postoperative high-dependency unit (HDU) care after
elective colorectal surgery might be associated with reduced postoperative
METHODS: The 30 day postoperative mortality was predicted for 504 elective
colorectal surgical patients in a preoperative clinic. The prediction was used to
determine postoperative surgical ward or HDU care. Those with a predicted 30 day
mortality of 1-3% mortality, and thus deemed at intermediate risk, had either
planned HDU care (n=68) or planned ward care (n=139). The main outcome measures
were emergency laparotomy and unplanned critical care admission.
RESULTS: There were more emergency laparotomies and unplanned critical care
admissions in patients with a predicted 30 day mortality of 1-3% who went to an
HDU after surgery compared with patients who went to a ward: 0 vs 14 (10%),
P=0.0056 and 0 vs 22 (16%), P=0.0002, respectively.
CONCLUSIONS: Planned postoperative critical care was associated with a lower rate
of complications after elective colorectal surgery.