Segrera SA, Lawler L, Opotowsky AR, Systrom D, Waxman AB.

Pulm Circ. 2017 Apr-Jun;7(2):531-538. doi: 10.1177/2045893217709024. Epub 2017
May 12.

A growing body of evidence suggests that exercise pulmonary hypertension (ePH) is
an early form of pulmonary arterial hypertension (PAH). Identifying the disease
at an early, potentially more responsive phase, and initiating treatment may
improve functional status and prevent progression to severe forms of PAH.
This was a single-center, open-label six-month treatment trial to evaluate the effect
of ambrisentan on pulmonary hemodynamics and exercise capacity in ePH utilizing
invasive cardiopulmonary exercise testing (iCPET). After six months of treatment
with ambrisentan, patients repeated iCPET; exercise capacity, symptoms, and
pulmonary hemodynamics were reassessed. Twenty-two of 30 patients completed the
treatment phase and repeat iCPET. After six months of treatment there was a
significant decline in peak exercise mPAP (-5.2 ± 5.6 mmHg, P = 0.001), TPG
(-7.1 ± 8.0 mmHg, P = 0.001), PVR (-0.9 ± 0.7 Woods units, P = 0.0002), and
Ca-vO2 (-1.8 ± 2.3 mL/dL, P = 0.0002), with significant increases in peak PCWP
(+2.9 ± 5.6 mmHg, P = 0.02), PVC (+0.8 ± 1.4 mL/mmHg, P = 0.03), and CO
(+2.3 ± 1.4 L/min, P = 0.0001). A trend toward increased VO2max (+4.4 ± 2.6%
predicted, P = 0.07) was observed. In addition, there were improvements in 6MWD
and WHO FC after 24 weeks.
Our findings suggest that treatment of ePH with
ambrisentan results in improved pulmonary hemodynamics and functional status over
a six-month period. Treatment of ePH may prevent the progression of vascular
remodeling and development of established PAH.

Ward SA; Human Bio-Energetics Research Centre, Crickhowell, United Kingdom of Great Britain and Northern Ireland ; saward@dsl.pipex.com.
Grocott MP; University of Southampton, 7423, Anaesthesia and Critical Care Research Unit, Faculty of Medicine, Southampton, Hampshire, United Kingdom of Great Britain and Northern Ireland ; m.grocott@soton.ac.uk.
Levett DZ; University of Southampton, Anaesthesia and Critical Care Research Unit, Faculty of Medicine, Southampton, Hampshire, United Kingdom of Great Britain and Northern Ireland ; d.levett@soton.ac.uk.

Annals Of The American Thoracic Society [Ann Am Thorac Soc] 2017 Jun 07. Date of Electronic Publication: 2017 Jun 07.

Cardiopulmonary exercise testing (CPET) in hyperoxia and hypoxia has several applications, stemming from characterization of abnormal physiological response profiles associated with exercise intolerance. As altered oxygenation can impact on the performance of gas-concentration and flow sensors and pulmonary gas exchange algorithms, integrated CPET system function requires validation under these conditions. Also, as oxygenation status can influence peak O2 uptake, care should be taken in the selection of work-rate incrementation rates when CPET performance is to be compared with sea-level. CPET has been used to evaluate the effects of supplemental O2 on exercise intolerance in chronic obstructive pulmonary disease, interstitial pulmonary fibrosis and cystic fibrosis at sea-level. However, identification of those CPET indices likely to be predictive of supplemental O2 outcomes for exercise tolerance at altitude in such patients is lacking. CPET performance with supplemental O2 in respiratory patients residing at high altitudes is poorly studied. Finally, CPET has the potential to give physiological and clinical information about acute and chronic mountain sickness, high-altitude pulmonary edema, and high-altitude cerebral edema. It can translate high-altitude acclimatization and adaptive processes in healthy individuals into intensive care medical practice.

Riley MS; Belfast City Hospital, Regional Respiratory Centre, Belfast, United Kingdom of Great Britain and Northern Ireland ; marshall.riley@belfasttrust.hscni.net.
Nicholls DP; Royal Victoria Hospital, Department of Medicine, Belfast, United Kingdom of Great Britain and Northern Ireland ; paul.nicholls@belfasttrust.hscni.net.
Cooper CB; Harbor-UCLA Medical Center , Div of Respiratory/Physiology & Medicine , 1000 W Carson Street , Torrance, California, United States , 90509 ; ccooper@mednet.ucla.edu.

Annals Of The American Thoracic Society [Ann Am Thorac Soc] 2017 Jun 07. Date of Electronic Publication: 2017 Jun 07.

Skeletal muscle requires a large increase in its adenosine triphosphate production to meet the energy needs of exercise. Normally, most of this increase in energy is supplied by the aerobic process of oxidative phosphorylation. The main defects in muscle metabolism that interfere with production of adenosine triphosphate are a) disorders of glycogenolysis and glycolysis, which prevent both carbohydrate entering the tricarboxylic acid cycle and the production of lactic acid, b) mitochondrial myopathies where the defect is usually within the electron transport chain, reducing the rate of oxidative phosphorylation and c) disorders of lipid metabolism. Gas exchange measurements derived from exhaled gas analysis during cardiopulmonary exercise testing can identify defects in muscle metabolism because oxygen consumption and carbon dioxide production are abnormal at the level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely diagnosis and guide additional investigation. Defects in glycogenolysis and glycolysis are identified by a low peak oxygen uptake and absence of excess carbon dioxide production from buffering of lactic acid by bicarbonate. Defects in the electron transport chain also result in low peak oxygen uptake, but because there is an over-reliance on anaerobic processes, lactic acid accumulation and excess carbon dioxide from buffering occur early during exercise. Defects in lipid metabolism result in only minor abnormalities during cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and in mitochondrial myopathies other features may include an exaggerated cardiovascular response to exercise, a low oxygen-pulse and excessive ammonia release.

• Lais Helena Camacho NavarroEmail author,
• Joshua A Bloomstone,
• Jose Otavio Costa AulerJr,
• Maxime Cannesson,
• Giorgio Della Rocca,
• Tong J Gan,
• Michael Kinsky,
• Sheldon Magder,
• Timothy E Miller,
• Monty Mythen,
• Azriel Perel,
• Daniel A Reuter,
• Michael R Pinsky and
• George C Kramer

• Matthew Weston
• Kathryn L Weston,
• James M. Prentis and
• Chris P Snowden

DOI: 10.1186/s13741-015-0026-8

The advancement of perioperative medicine is leading to greater diversity in development of pre-surgical interventions, implemented to reduce patient surgical risk and enhance post-surgical recovery. Of these interventions, the prescription of pre-operative exercise training is gathering momentum as a realistic means for enhancing patient surgical outcome. Indeed, the general benefits of exercise training have the potential to pre-operatively optimise several pre-surgical risks factors, including cardiorespiratory function, frailty and cognitive function.

Any exercise programme incorporated into the pre-operative pathway of care needs to be effective and time efficient in that any fitness gains are achievable in the limited period between the decision for surgery and operation (e.g. 4 weeks). Fortunately, there is a large volume of research describing effective and time-efficient exercise training programmes within the discipline of sports science. Accordingly, the objective of our commentary is to synthesise contemporary exercise training research, both from non-clinical and clinical populations, with the overarching aim of informing the development of effective and time-efficient pre-surgical exercise training programmes.

The development of such exercise training programmes requires the careful consideration of several key principles, namely frequency, intensity, time, type and progression of exercise. Therefore, in light of more recent evidence demonstrating the effectiveness and time efficiency of high-intensity interval training—which involves brief bouts of intense exercise interspersed with longer recovery periods—the principles of exercise training programme design will be discussed mainly in the context of such high-intensity interval training programmes. Other issues pertinent to the development, implementation and evaluation of pre-operative exercise training programmes, such as individual exercise prescription, training session monitoring and potential barriers and risks to high-intensity exercise are also discussed. The evidence presented suggests that individually prescribed and supervised high-intensity interval training programmes, encompassing a variety of exercise modes represent an effective and safe means of exercise therapy prior to surgery.

Villareal DT, Aguirre L, Gurney AB, et al.

N Engl J Med. 2017;376(20):1943-1955

BACKGROUND: Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia.
METHODS: In this clinical trial involving 160 obese older adults, we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss. Participants were randomly assigned to a weight-management program plus one of three exercise programs – aerobic training, resistance training, or combined aerobic and resistance training – or to a control group (no weight-management or exercise program). The primary outcome was the change in Physical Performance Test score from baseline to 6 months (scores range from 0 to 36 points; higher scores indicate better performance). Secondary outcomes included changes in other frailty measures, body composition, bone mineral density, and physical functions.
RESULTS: A total of 141 participants completed the study. The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups (27.9 to 33.4 points [21% increase] vs. 29.3 to 33.2 points [14% increase] and 28.8 to 32.7 points [14% increase], respectively; P=0.01 and P=0.02 after Bonferroni correction); the scores increased more in all exercise groups than in the control group (P<0.001 for between-group comparisons). Peak oxygen consumption (milliliters per kilogram of body weight per minute) increased more in the combination and aerobic groups (17.2 to 20.3 [17% increase] and 17.6 to 20.9 [18% increase], respectively) than in the resistance group (17.0 to 18.3 [8% increase]) (P<0.001 for both comparisons). Strength increased more in the combination and resistance groups (272 to 320 kg [18% increase] and 288 to 337 kg [19% increase], respectively) than in the aerobic group (265 to 270 kg [4% increase]) (P<0.001 for both comparisons). Body weight decreased by 9% in all exercise groups but did not change significantly in the control group. Lean mass decreased less in the combination and resistance groups than in the aerobic group (56.5 to 54.8 kg [3% decrease] and 58.1 to 57.1 kg [2% decrease], respectively, vs. 55.0 to 52.3 kg [5% decrease]), as did bone mineral density at the total hip (grams per square centimeter; 1.010 to 0.996 [1% decrease] and 1.047 to 1.041 [0.5% decrease], respectively, vs. 1.018 to 0.991 [3% decrease]) (P<0.05 for all comparisons). Exercise-related adverse events included musculoskeletal injuries.
CONCLUSIONS: Of the methods tested, weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults. (Funded by the National Institutes of Health; LITOE ClinicalTrials.gov number, NCT01065636 .).

Dumitrescu D, Rosenkranz S

Ann Am Thorac Soc. 2017 May 25. doi: 10.1513/AnnalsATS.201612-955FR. [Epub ahead
of print]

Cardiopulmonary exercise testing is a well-known, valuable tool in the clinical
evaluation of patients with different causes of exercise limitation, and
unexplained dyspnea. A wealth of data is generated by each individual test. This
may be challenging with regard to a comprehensive and reliable interpretation of
an exercise study in a timely manner. An optimized graphical display of exercise
data may substantially help to improve the efficacy and reliability of the
interpretation process. However, there are limited and heterogeneous
recommendations on standardized graphical display in current exercise testing
guidelines. To date, a widely used three-by-three array of specifically arranged
graphical panels known as “Nine Panel Plot” is probably the most common method of
plotting exercise gas exchange data in a standardized way. Furthermore, optimized
scaling of the plots, the use of colours and style elements as well as suitable
averaging methods have to be considered in order to achieve a high level of
quality and reproducibility of the results. Specific plots of key parameters may
allow a fast and reliable visual determination of important diagnostic and
prognostic markers in cardiac and pulmonary diseases.

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

British Journal Of Anaesthesia [Br J Anaesth] 2017 May 01; Vol. 118 (5), pp. 747-754.

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 determined.
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.

Mezzani A; Spa SB,

Annals Of The American Thoracic Society [Ann Am Thorac Soc] 2017 May 16. Date of Electronic Publication: 2017 May 16.

Cardiopulmonary exercise testing adds measurement of ventilation and volume of oxygen uptake and exhaled carbon dioxide to routine physiological and performance parameters obtainable from conventional exercise testing, furnishing an all-round vision of the systems involved in both oxygen transport from air to mitochondria and its utilization during exercise. Peculiarities of cardiopulmonary exercise testing methodology are the use of ramp protocols and calibration procedures for flow meters and gas analyzers. Among the several parameters provided by this technique, peak oxygen uptake, first and second ventilatory thresholds, respiratory exchange ratio, oxygen pulse, slope of ventilation divided by exhaled carbon dioxide relationship, exercise oscillatory ventilation, circulatory power and partial pressure of end-tidal carbon dioxide are among the most relevant in the clinical setting. The choice of parameters to be considered will depend on the indication to cardiopulmonary exercise testing in the individual subject or patient, namely, exercise tolerance assessment, prognostic stratification, training prescription, treatment efficacy evaluation, diagnosis of causes of unexplained exercise tolerance reduction or exercise (patho)physiology evaluation for research purposes. Overall, cardiopulmonary exercise testing is a methodology now widely available and supported by a sound scientific evidence. Despite this, its potential still remains largely underused. Strong efforts and future investigations are needed to address these issues and further promote the use of cardiopulmonary exercise testing in the clinical and research setting.

Liu HJ, Guo J, Zhao QH, Wang L, Yang WL, He J, Gong SG, Liu
JM

Am J Med Sci. 2017 Mar;353(3):216-223. doi: 10.1016/j.amjms.2016.12.015. Epub
2016 Dec 21.

BACKGROUND: To study the relationship between chronotropic incompetence (CI) and
disease severity and to assess the effect of CI on exercise capacity in patients
with chronic obstructive pulmonary disease (COPD).
MATERIALS AND METHODS: Arterial blood gas analysis, pulmonary function test and
cardiopulmonary exercise testing were conducted in 60 patients with stable COPD
and 45 healthy volunteers. CI was defined using the chronotropic response index
(CRI = (peak heart rate-resting heart rate) / (220-age-resting heart rate). Based
on CRI, patients with COPD were divided into the normal chronotropic group (n =
23) and CI group (n = 37).
RESULTS: CI was present in 61.7% of the patients with COPD. Exercise capacity
(peak oxygen uptake as percentage of predicted value, peak VO2%pred), peak heart
rate and CRI were significantly lower in patients with COPD than in controls.
However, resting heart rate was significantly higher than in controls. FEV1%pred
and exercise capacity were significantly decreased in the CI group when compared
with those in the normotropic group. There was significant association between
CRI with FEV1%pred and peak VO2%pred. Multivariate regression analysis showed
that CRI and FEV1%pred were independent predictors of exercise capacity in
patients with COPD. A cutoff of 0.74 for the CRI showed a specificity of 94.1% in
predicting patients with a peak VO2%pred < 60%. CONCLUSIONS: CRI was associated with disease severity in patients with COPD. CI may be an important parameter to reflect exercise capacity in patients with COPD.