Vignati C, Cattadori G

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S48-S52. doi:
10.1513/AnnalsATS.201611-852FR.

Cardiac output is a key parameter in the assessment of cardiac function, and its
measurement is fundamental to the diagnosis, treatment, and prognostic evaluation
of all heart diseases. Until recently, cardiac output determination during
exercise had been only possible through invasive methods, which were not
practical in the clinical setting. Because [Formula: see text]o2 is cardiac
output times arteriovenous content difference, evaluation of cardiac output is
usually included in its measurement. Because of the difficulty of directly
measuring peak exercise cardiac output, indirect surrogate parameters have been
proposed, but with only modest clinical usefulness. Direct measurement of cardiac
output can now be made by several noninvasive techniques, such as rebreathing
inert gases, impedance cardiology, thoracic bioreactance, estimated continuous
cardiac output technology, and transthoracic echocardiography coupled to
cardiopulmonary exercise testing, which allow more definitive results and better
understanding of the underlying physiopathology.

Agostoni P, Corrà U, Emdin M

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S116-S122. doi:
10.1513/AnnalsATS.201701-003FR.

Periodic breathing during incremental cardiopulmonary exercise testing is a
regularly recurring waxing and waning of tidal volume due to oscillations in
central respiratory drive. Periodic breathing is a sign of respiratory control
system instability, which may occur at rest or during exercise. The possible
mechanisms responsible for exertional periodic breathing might be related to any
instability of the ventilatory regulation caused by: (1) increased circulatory
delay (i.e., circulation time from the lung to the brain and chemoreceptors due
to reduced cardiac index leading to delay in information transfer), (2) increase
in controller gain (i.e., increased central and peripheral chemoreceptor
sensitivity to arterial partial pressure of oxygen and of carbon dioxide), or (3)
reduction in system damping (i.e., baroreflex impairment). Periodic breathing
during exercise is observed in several cardiovascular disease populations, but it
is a particularly frequent phenomenon in heart failure due to systolic
dysfunction. The detection of exertional periodic breathing is linked to outcome
and heralds worse prognosis in heart failure, independently of the criteria
adopted for its definition. In small heart failure cohorts, exertional periodic
breathing has been abolished with several dedicated interventions, but results
have not yet been confirmed. Accordingly, further studies are needed to define
the role of visceral feedbacks in determining periodic breathing during exercise
as well as to look for specific tools for preventing/treating its occurrence in
heart failure.

Mezzani A

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S3-S11. doi:
10.1513/AnnalsATS.201612-997FR

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-around vision of the systems involved in both oxygen transport from air to
mitochondria and its use 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 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.

Older PO, Levett DZH

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S74-S83. doi:
10.1513/AnnalsATS.201610-780FR

The surgical patient population is increasingly elderly and comorbid and poses
challenges to perioperative physicians. Accurate preoperative risk stratification
is important to direct perioperative care. Reduced aerobic fitness is associated
with increased postoperative morbidity and mortality. Cardiopulmonary exercise
testing is an integrated and dynamic test that gives an objective measure of
aerobic fitness or functional capacity and identifies the cause of exercise
intolerance. Cardiopulmonary exercise testing provides an individualized estimate
of patient risk that can be used to predict postoperative morbidity and
mortality. This technology can therefore be used to inform collaborative
decision-making and patient consent, to triage the patient to an appropriate
perioperative care environment, to diagnose unexpected comorbidity, to optimize
medical comorbidities preoperatively, and to direct individualized preoperative
exercise programs. Functional capacity, evaluated as the anaerobic threshold and
peak oxygen uptake ([Formula: see text]o2peak) predicts postoperative morbidity
and mortality in the majority of surgical cohort studies. The ventilatory
equivalents for carbon dioxide (an index of gas exchange efficiency), is
predictive of surgical outcome in some cohorts. Prospective cohort studies are
needed to improve the precision of risk estimates for different patient groups
and to clarify the best combination of variables to predict outcome. Early data
suggest that preoperative exercise training improves fitness, reduces the
debilitating effects of neoadjuvant chemotherapy, and may improve clinical
outcomes. Further research is required to identify the most effective type of
training and the minimum duration required for a positive effect.

Dumitrescu D, Rosenkranz S.

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S12-S21. doi:
10.1513/AnnalsATS.201612-955FR

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 regarding 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 the “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 colors and style elements, as well as
suitable averaging methods have to be considered 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.

Riley MS, Nicholls DP, Cooper CB

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S129-S139. doi:
10.1513/AnnalsATS.201701-014FR

Skeletal muscle requires a large increase in its ATP production to meet the
energy needs of exercise. Normally, most of this increase in ATP is supplied by
the aerobic process of oxidative phosphorylation. The main defects in muscle
metabolism that interfere with production of ATP are (1) disorders of
glycogenolysis and glycolysis, which prevent both carbohydrate entering the
tricarboxylic acid cycle and the production of lactic acid; (2) mitochondrial
myopathies where the defect is usually within the electron transport chain,
reducing the rate of oxidative phosphorylation; and (3) disorders of lipid
metabolism. Gas exchange measurements derived from exhaled gas analysis during
cardiopulmonary exercise testing can identify defects in muscle metabolism
because [Formula: see text]o2 and [Formula: see text]co2 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 [Formula: see text]o2 and absence of
excess [Formula: see text]co2 from buffering of lactic acid by bicarbonate.
Defects in the electron transport chain also result in low peak [Formula: see
text]o2, but because there is an overreliance 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.

Ward SA, Grocott MPW, Levett DZH.

Ann Am Thorac Soc. 2017 Jul;14(Supplement_1):S140-S148. doi:
10.1513/AnnalsATS.201701-043OT.

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
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 [Formula: see text]o2,
care should be taken in the selection of work-rate incrementation rates when CPET
performance is to be compared with normobaria at 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 also 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 may also translate high-altitude acclimatization and adaptive processes
in healthy individuals into intensive care medical practice.

Farina S; Correale M; Bruno N; Paolillo S; Salvioni E; Badagliacca R; Agostoni P;

European Respiratory Review: An Official Journal Of The European Respiratory Society [Eur Respir Rev] 2018 May 02; Vol. 27 (148). Date of Electronic Publication: 20180502 (Print Publication: 2018).

Despite recent advances in the therapeutic management of patients affected by pulmonary arterial hypertension (PAH), survival remains poor. Prompt identification of the disease, especially in subjects at increased risk of developing PAH, and prognostic stratification of patients are a necessary target of clinical practice but remain challenging. Cardiopulmonary exercise test (CPET) parameters, particularly peak oxygen uptake, end-tidal carbon dioxide tension and the minute ventilation/carbon dioxide production relationship, emerged as new prognostic tools for PAH patients. Moreover, CPET provides a comprehensive pathophysiological evaluation of patients’ exercise limitation and dyspnoea, which are the main and early symptoms of the disease. This review focuses on the role of CPET in the management of PAH patients, reporting guideline recommendations for CPET and discussing the pathophysiology of exercise limitation and the most recent use of CPET in the diagnosis, prognosis and therapeutic targeting of PAH.

Nicolini F; Vezzani A; Corradi F; Gherli R; Benassi F; Manca T; Gherli T;

European Journal Of Preventive Cardiology [Eur J Prev Cardiol] 2018 Jun; Vol. 25 (1_suppl), pp. 32-41.

Background
Gender-related biases in outcomes after thoracic aortic surgery are an important factor to consider in the prevention of potential complications related to aortic diseases and in the analysis of surgical results. Methods The aim of this study is to provide an up-to-date review of gender-related differences in the epidemiology, specific risk factors, outcome, and screening and prevention programmes in aortic aneurysms.
Results
Female patients affected by aortic disease still have worse outcomes and higher early and late mortality than men. It is difficult to plan new specific strategies to improve outcomes in women undergoing major aortic surgery, given that the true explanations for their poorer outcomes are as yet not clearly identified. Some authors recommend further investigation of hormonal or molecular explanations for the sex differences in aortic disease. Others stress the need for quality improvement projects to quantify the preoperative risk in high-risk populations using non-invasive tests such as cardiopulmonary exercise testing.
Conclusions
The treatment of patients classified as high risk could thus be optimised before surgery becomes necessary by means of numerous strategies, such as the administration of high-dose statin therapy, antiplatelet treatment, optimal control of hypertension, lifestyle improvement with smoking cessation, weight loss and careful control of diabetes. Future efforts are needed to understand better the gender differences in the diagnosis, management and outcome of aortic aneurysm disease, and for appropriate and modern management of female patients.

McCabe C;  Oliveira RKF; Rahaghi F; Faria-Urbina M; Howard L; Axell RG; Priest AN; Waxman AB; Systrom DM;

European Journal Of Applied Physiology [Eur J Appl Physiol] 2018 Apr 30. Date of Electronic Publication: 2018 Apr 30.

Background: Right ventricular (RV) dysfunction and heart failure with preserved ejection fraction may contribute to exercise intolerance in obesity. To further define RV exercise responses, we investigated RV-arterial coupling in obesity with and without development of exercise pulmonary venous hypertension (ePVH).
Methods: RV-arterial coupling defined as RV end-systolic elastance/pulmonary artery elastance (Ees/Ea) was calculated from invasive cardiopulmonary exercise test data in 6 controls, 8 obese patients without ePVH (Obese-ePVH) and 8 obese patients with ePVH (Obese+ePVH) within a larger series. ePVH was defined as a resting pulmonary arterial wedge pressure < 15 mmHg but ≥ 20 mmHg on exercise. Exercise haemodynamics were further evaluated in 18 controls, 20 Obese-ePVH and 17 Obese+ePVH patients.
Results: Both Obese-ePVH and Obese+ePVH groups developed exercise RV-arterial uncoupling (peak Ees/Ea = 1.45 ± 0.26 vs 0.67 ± 0.18 vs 0.56 ± 0.11, p < 0.001, controls vs Obese-ePVH vs Obese+ePVH respectively) with higher peak afterload (peak Ea = 0.31 ± 0.07 vs 0.75 ± 0.32 vs 0.88 ± 0.62 mL/mmHg, p = 0.043) and similar peak contractility (peak Ees = 0.50 ± 0.16 vs 0.45 ± 0.22 vs 0.48 ± 0.17 mL/mmHg, p = 0.89). RV contractile reserve was highest in controls (ΔEes = 224 ± 80 vs 154 ± 39 vs 141 ± 34% of baseline respectively, p < 0.001). Peak Ees/Ea correlated with peak pulmonary vascular compliance (PVC, r = 0.53, p = 0.02) but not peak pulmonary vascular resistance (PVR, r = - 0.20, p = 0.46). In the larger cohort, Obese+ePVH patients on exercise demonstrated higher right atrial pressure, lower cardiac output and steeper pressure-flow responses. BMI correlated with peak PVC (r = - 0.35, p = 0.04) but not with peak PVR (r = 0.24, p = 0.25).
Conclusions: Exercise RV-arterial uncoupling and reduced RV contractile reserve further characterise obesity-related exercise intolerance. RV dysfunction in obesity may develop independent of exercise LV filling pressures.