Category Archives: Publications

Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation. Source

Armstrong HF; Schulze PC; Bacchetta M; Thirapatarapong W; Bartels MN.

Respirology. 19(5):675-82, 2014 Jul.
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BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a known
complication in patients with interstitial lung disease (ILD).
Cardiopulmonary exercise testing (CPET) is an essential tool for the
assessment of patients with cardiac and pulmonary diseases due to its
prognostic and therapeutic implications. Few studies have evaluated the
relationship between CPET response and mean pulmonary artery pressures
(mPAP) in ILD. The purpose of the present study was to determine and
compare the potential correlations between CPET, 6-min walk test (6MWT),
pulmonary function testing (PFT) and PH in patients with ILD being
evaluated for lung transplantation.

METHODS: The present study reviewed patients with ILD who received lung
transplantations and had CPETs within 2 years before transplantation,
right heart catheterizations, PFTs and 6MWTs within 4 months of CPET.

RESULTS: A total of 72 patients with ILD were analysed; 36% had PH. There
were significant correlations between mPAP and CPET parameters in patients
with PH; but mPAP had no impact on percent of predicted diffusion capacity
of the lung for carbon monoxide or 6-min walk distance (6MWD). CPET
parameters were able to detect differences between levels of severity of
PH through the use of the ratio of minute ventilation to rate of carbon
dioxide production (VE/VCO2) and the partial pressure of end-tidal carbon

CONCLUSIONS: This is the first study that analyses 6MWD, PFT and CPET in
patients with ILD awaiting lung transplantation with and without PH. The
present study demonstrates the significant impact of PH on exercise
capacity and performance in patients with ILD awaiting lung

Efficiency of the home cardiac rehabilitation program for adults with complex congenital heart disease.

Bhasipol A; Sanjaroensuttikul N; Pornsuriyasak P; Yamwong S; Tangcharoen

Congenital Heart Disease. 13(6):952-958, 2018 Nov.

OBJECTIVE: We aimed to study the efficiency and safety of once-a-week
outpatient rehabilitation followed by home program with tele-monitoring in
patients with complex cyanotic congenital heart disease.

DESIGN: Prospective nonrandomized study.

METHOD: Patients who have been diagnosed either Eisenmenger’s syndrome or
inoperable complex cyanotic heart disease and able to attend 12-week
cardiac rehabilitation program were included. Training with treadmill
walking and bicycling under supervision at cardiac rehabilitation unit
once-a-week in the first 6 weeks followed by home-based exercise program
(bicycle and walking) with a target at 40%-70% of maximum heart rate
(HRmax) at pretraining peak exercise for another 6 weeks was performed in
the intervention group. Video and telephone calls were scheduled for
evaluation of compliance and complication. Data from cardiopulmonary
exercise testing (CPET) on cycle ergometry including peak oxygen
consumption (peakVO2 ), oxygen pulse (O2 pulse), ventilatory equivalent
for carbon dioxide (VE/CO2 at anaerobic threshold), constant work-rate
endurance time (CWRET) at 75% of peak VO2 , and 6-minute walk distance
(6MWD) were compared between baseline and after training by paired t test.

RESULT: Of the 400 patients in our adult congenital heart disease clinic,
60 patients met the inclusion criteria. Eleven patients who could follow
program regularly were assigned home program. There was a statistically
significant improvement of CWRET, O2 pulse, and 6MWD after finishing the
program (P = .003, .039, and .001, respectively). The mean difference of
6MWD change in the home-program group was significantly higher than in the
control group (69.3 +/- 47.9 meters vs. 4.1 +/- 43.4 meters, P = .003). No
serious adverse outcomes were reported during home training.

CONCLUSION: Once-a-week outpatient hospital-based exercise program
followed by supervised home-based exercise program showed a significant
benefit in improvement of exercise capacity in adults with complex
cyanotic congenital heart disease without serious adverse

Exercise testing and spirometry as predictors of mortality in congenital heart disease: Contrasting Fontan physiology with repaired tetralogy of Fallot.

Shafer KM; Opotowsky AR; Rhodes J.

Congenital Heart Disease. 13(6):903-910, 2018 Nov.

OBJECTIVE: Risk prediction using cardiopulmonary exercise testing (CPET)
in complex congenital heart disease tends to either focus on single
diagnoses or complete cohorts. We aimed to evaluate patients with two
distinct anatomies cared for at a single institution over the same time
period to determine CPET variables associated with mortality.

DESIGN: All Fontan and tetralogy of Fallot (TOF) subjects with CPET
between November 1, 2002 and December 31, 2014 and subsequently died were
identified (cases). Cases were matched 1:3 to controls with similar age,
underlying anatomy and timing of exercise test.

RESULTS: Of the 42 cases, 27 had a Fontan circulation and 15 with TOF.
All Fontan patients had a low peak VO2 but there was no significant
difference between cases and controls (52.5 +/- 14.7 v. 57.4% +/- 13.5%
predicted, P = .11). Spirometry values were significantly lower in Fontan
cases than controls (eg, FVC 67.4 +/- 19.1 v 77.6% +/- 14.9% predicted, P
= .007). Spirometry values were also lower in TOF cases than controls (%
predicted FVC 62.8 +/- 16.7 v 75 +/- 14, P = .006). In contrast to the
Fontan analysis, both %peak predicted VO2 and VE/VCO2 slope were worse in
TOF cases than controls (50.1 +/- 13.5 v. 68.5% +/- 15.0% predicted VO2 ,
P = .0004; 33.9 +/- 12.9 v 26.6 +/- 4.4, P = .002). Multivariable analysis
also identified different predictors of mortality among the anatomic
subgroups. Spirometric data (FVC) correlated most strongly with mortality
in Fontan patients while the VE/VCO2 slope was most associated with
outcome in TOF patients.

CONCLUSIONS: Variables most predictive of mortality in Fontan and TOF
patients diverge but spirometry was abnormal and associated with mortality
in both groups. When compared with age-matched controls, reduced FEV1 and
FVC correlated most strongly with mortality in Fontan patients while
VE/VCO2 slope correlated with mortality for TOF patients. These findings
further support the importance of lung health in patients with complex
congenital heart disease.


A Pilot Study of Inspiratory Muscle Training to Improve Exercise Capacity in Patients with Fontan Physiology.

Wu FM; Opotowsky AR; Denhoff ER; Gongwer R; Gurvitz MZ; Landzberg MJ;
Shafer KM; Valente AM; Uluer AZ; Rhodes J.

Seminars in Thoracic & Cardiovascular Surgery. 30(4):462-469, 2018 Winter.
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Comment in: Semin Thorac Cardiovasc Surg. 2018 Winter;30(4):470-471; PMID:

While the Fontan procedure has improved life expectancy, patients with
single ventricle physiology have impaired exercise capacity due to limited
increase in pulmonary blood flow during activity. Enhancing the “thoracic
pump” using inspiratory muscle training (IMT) may ameliorate this
impairment. Adult nonsmokers with Fontan physiology were recruited through
Boston Children’s Hospital’s outpatient clinic. Participants underwent
cardiopulmonary exercise testing and pulmonary function testing, followed
by 12 weeks of IMT and then repeat testing. The primary endpoint was
change in % predicted peak oxygen consumption (VO2). Secondary endpoints
were changes in other exercise metrics. Eleven patients (6 male) were
enrolled. Median ages at time of enrollment and Fontan completion were
28.8 years (25.7, 45.5) and 7.8 years (3.9, 16.5), respectively. Average
baseline maximal inspiratory pressure (MIP) was normal; only 2 patients
had MIP <70% predicted. Peak work rate improved significantly from
baseline after 12 weeks of IMT (116.5 +/- 45.0 to 126.8 +/- 47.0 W,
P=0.019). Peak VO2 tended to improve (baseline 68.1 +/- 14.3, change + 5.3
+/- 9.6% predicted, P=0.12), as did VE/VCO2 slope (34.1 +/- 6.7 to 31.4
+/- 3.6, P=0.12). There was no change in peak tidal volume or MIP. In a
small cohort of Fontan patients with mostly normal MIP, IMT was associated
with significant improvement in peak work rate and a trend toward higher
peak VO2 and improved ventilatory efficiency. Larger studies are needed to
determine if this reflects true lack of effect or whether this pilot study
was underpowered for effect size, and whether IMT is more narrowly useful
for patients with impaired MIP.


An Objective Method to Accurately Measure Cardiorespiratory Fitness in Older Adults Who Cannot Satisfy Widely Used Oxygen Consumption Criteria.

Dougherty RJ; Lindheimer JB; Stegner AJ; Van Riper S; Okonkwo OC; Cook DB.

Journal of Alzheimer’s Disease. 61(2):601-611, 2018.

Cardiorespiratory fitness (CRF) is routinely investigated in older adults;
however, the most appropriate CRF measure to use for this population has
received inadequate attention. This study aimed to 1) evaluate the
reliability and validity of the oxygen uptake efficiency slope (OUES) as a
sub-maximal measurement of CRF; 2) examine demographic, risk-factor, and
exercise testing differences in older adults who satisfied standardized
criteria for a peak oxygen consumption (VO2peak) test compared to those
who did not; and 3) determine the difference between directly measured
VO2peak values and OUES-predicted VO2peak values. One hundred ten
enrollees from the Wisconsin Registry for Alzheimer’s Prevention
participated in this study. Participants performed a graded maximal
exercise test and wore an accelerometer for 7 days. For each participant,
the OUES was calculated at 75%, 90%, and 100% of exercise duration.
VO2peak was recorded at peak effort, and one week of physical activity
behavior was measured. OUES values calculated at separate relative
exercise durations displayed excellent reliability (ICC = 0.995; p <
0.001), and were strongly correlated with VO2peak (rrange = 0.801-0.909; p
< 0.001). As hypothesized, participants who did not satisfy VO2peak
criteria were significantly older than those who satisfied criteria (p =
0.049) and attained a directly measured VO2peak that was 2.31
less than the value that was predicted by OUES VO2peak (p = 0.003). Older
adults are less likely to satisfy VO2peak criteria, which results in an
underestimation of their CRF. Without adhering to standardized criteria,
VO2peak measurement error may lead to misinterpretation of CRF and
age-related associations. Here, we conclude that OUES is a reliable, valid
measurement of CRF which does not require achievement of standardized

A randomised controlled trial to assess whether prehabilitation improves fitness in patients undergoing neoadjuvant treatment prior to oesophagogastric cancer surgery: study protocol.

Allen S; Brown V; Prabhu P; Scott M; Rockall T; Preston S; Sultan J;

BMJ Open [BMJ Open] 2018 Dec 22; Vol. 8 (12), pp. e023190. Date of Electronic Publication: 2018 Dec 22.

Introduction: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients’ functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery.
Methods and Analysis: This will be a prospective, randomised, controlled, parallel, single-centre superiority trial comparing a multimodal ‘prehabilitation’ intervention with ‘standard care’ in patients with oesophagogastric malignancy who are treated with neoadjuvant therapy prior to surgical resection. The primary aim is to demonstrate an improvement in baseline cardiopulmonary function as assessed by anaerobic threshold during CPX testing in an interventional (prehab) group following a 15-week preoperative exercise programme, throughout and following neoadjuvant treatment, when compared with those that undergo standard care (control group). Secondary objectives include changes in peak oxygen uptake and work rate (total watts achieved) at CPX testing, insulin resistance, quality of life, chemotherapy-related toxicity and completion, nutritional assessment, postoperative complication rate, length of stay and overall mortality.
Ethics and Dissemination: This study has been approved by the London-Bromley Research Ethics Committee and registered on The results will be disseminated in a peer-reviewed journal.

Cardiorespiratory Fitness and Cardiovascular Disease – the Past, Present, and Future.

Kaminsky LA; Arena R; Ellingsen Ø; Harber MP; Myers J; Ozemek C; Ross R;

Progress In Cardiovascular Diseases [Prog Cardiovasc Dis] 2019 Jan 09. Date of Electronic Publication: 2019 Jan 09.

The importance of cardiorespiratory fitness (CRF) is now well established and it is increasingly being recognized as an essential variable which should be assessed in health screenings. The key findings that have established the clinical significance of CRF are reviewed in this report, along with an overview of the current relevance of exercise as a form of medicine that can provide a number of positive health outcomes, including increasing CRF. Current assessment options for assessing CRF are also reviewed, including the direct measurement via cardiopulmonary exercise testing which now can be interpreted with age and sex-specific reference values. Future directions for the use of CRF and related measures are presented.

Efficacy of Cardiac Rehabilitation in Heart Failure Patients With Low Body Mass Index.

Marume K; Takashio S; Nakanishi M; Kumasaka L; Fukui S; Nakao K; Arakawa T; Yanase M; Noguchi T; Yasuda S; Goto Y;

Circulation Journal: Official Journal Of The Japanese Circulation Society [Circ J] 2019 Jan 16. Date of Electronic Publication: 2019 Jan 16.

Background: Low body mass index (BMI) is a relevant prognostic factor for heart failure (HF), but HF patients with low BMI are reported to be at risk of not receiving optimal drug treatment. We sought to evaluate the efficacy of cardiac rehabilitation (CR) in patients with low vs. normal BMI. Methods and Results: We studied 152 consecutive patients (low BMI, n=32; normal BMI, n=119) who participated in a 3-month CR program. Low BMI was defined as <18.5 kg/m2and normal BMI, as 18.5≤BMI<25 kg/m2. All patients underwent cardiopulmonary exercise testing and muscle strength testing at the beginning and end of the 3-month CR program. After CR, a significantly greater proportion of HF patients with low BMI had a positive change in peak V̇O2than in the normal BMI group (91% vs. 70%; P=0.010). Average percent change in peak V̇O2was significantly greater in patients with low vs. normal BMI (17.1±2.8% vs. 7.8±1.5%; P<0.001). In addition, on multivariable logistic regression, low BMI was an independent predictor of a positive change in peak V̇O2after CR (OR, 3.97; 95% CI: 1.10-14.31; P=0.035).
Conclusions: CR has a greater effect in patients with low than normal BMI, and low BMI is an independent predictor of a positive change in peak V̇O2. Thus, CR should be strongly recommended for HF patients with low BMI.

A survey of UK peri-operative medicine: pre-operative care.

Bougeard AM, Brent A, Swart M, Snowden C

Anaesthesia. 2017 Aug;72(8):1010-1015. doi: 10.1111/anae.13934. Epub 2017 Jun 14.

The majority of UK hospitals now have a Local Lead for Peri-operative Medicine (n
= 115). They were asked to take part in an online survey to identify provision
and practice of pre-operative assessment and optimisation in the UK. We received
86 completed questionnaires (response rate 75%). Our results demonstrate
strengths in provision of shared decision-making clinics. Fifty-seven (65%, 95%CI
55.8-75.4%) had clinics for high-risk surgical patients. However, 80 (93%,
70.2-87.2%) expressed a desire for support and training in shared
decision-making. We asked about management of pre-operative anaemia, and
identified that 69 (80%, 71.5-88.1%) had a screening process for anaemia, with
72% and 68% having access to oral and intravenous iron therapy, respectively. A
need for peri-operative support in managing frailty and cognitive impairment was
identified, as few (24%, 6.5-34.5%) respondents indicated that they had access to
specific interventions. Respondents were asked to rank their ‘top five’ priority
topics in Peri-operative Medicine from a list of 22. These were: shared
decision-making; peri-operative team development; frailty screening and its
management; postoperative morbidity prediction; and primary care collaboration.
We found variation in practice across the UK, and propose to further explore this
variation by examining barriers and facilitators to improvement, and highlighting
examples of good practice.