Author Archives: Paul Older

Exercise Testing, Supplemental Oxygen, and Hypoxia.

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.

The role of cardiopulmonary exercise tests in pulmonary arterial hypertension.

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.

Gender differences in outcomes after aortic aneurysm surgery should foster further research to improve screening and prevention programmes.

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.

Right ventriculo-arterial uncoupling and impaired contractile reserve in obese patients with unexplained exercise intolerance.

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.

Correlation of the New York Heart Association classification and the cardiopulmonary exercise test: A systematic review.

Lim FY; Yap J; Gao F;Teo LL; Lam CSP;Yeo KK

International Journal Of Cardiology [Int J Cardiol] 2018 Apr 07. Date of Electronic Publication: 2018 Apr 07.

Aims: The New York Heart Association (NYHA) classification is frequently used in the management of heart failure but may be limited by patient and physician subjectivity. Cardiopulmonary exercise testing (CPET) provides a potentially more objective measurement of functional status. We aim to study the correlation between NYHA classification and peak oxygen consumption (pVO2) on Cardiopulmonary Exercise Testing (CPET) within and across published studies.
Methods and Results: A systematic literature review on all studies reporting both NYHA class and CPET data was performed, and pVO2 from CPET was correlated to reported NYHA class within and across eligible studies. 38 studies involving 2645 patients were eligible. Heterogenity was assessed by the Q statistic, which is a χ2 test and marker of systematic differences between studies. Within each NYHA class, significant heterogeneity in pVO2 was seen across studies: NYHA I (n = 17, Q = 486.7, p < 0.0001), II (n = 24, Q = 381.0, p < 0.0001), III (n = 32, Q = 761.3, p < 0.0001) and IV (n = 5, Q = 12.8, p = 0.012). Significant differences in mean pVO2 were observed between NYHA I and II (23.8 vs 17.6 mL/(kg·min), p < 0.0001) and II and III (17.6 vs 13.3 mL/(kg·min), p < 0.0001); but not between NYHA III and IV (13.3 vs 12.5 mL/(kg·min), p = 0.45). These differences remained significant after adjusting for age, gender, ejection fraction and region of study.
Conclusion: There was a general inverse correlation between NYHA class and pVO2. However, significant heterogeneity in pVO2 exists across studies within each NYHA class. While the NYHA classification holds clinical value in heart failure management, direct comparison across studies may have its limitations.

Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

Higashi A, Dohi Y, Yamabe S, Kinoshita H, Sada Y, Kitagawa T,
Hidaka T, Kurisu S, Yamamoto H, Yasunobu Y, Kihara Y

Heart Vessels. 2017 Nov;32(11):1350-1357. doi: 10.1007/s00380-017-0999-y. Epub
2017 May 30.

Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients
with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide
pressure (PETCO2) during exercise is reduced with elevated pulmonary artery
pressure. However, the utility of ventilatory parameters such as CPET for
detecting PH remains unclear. We conducted a review in 155 patients who underwent
right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary
arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between
PETCO2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple
regression analysis showed that PETCO2 at the AT was independently associated
with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH
were 80 and 86%, respectively, when the cut-off value identified by receiver
operating characteristic curve analysis for PETCO2 at the AT was ≤34.7 mmHg. A
combination of echocardiography and CPET improved the sensitivity in detecting PH
without markedly reducing specificity (sensitivity 87%, specificity 85%).
Evaluation of PETCO2 at the AT is useful for estimating pulmonary pressure. A
combination of CPET and previous screening algorithms for PH may enhance the
diagnostic ability of PH.

Routine pre- and post-neoadjuvant chemotherapy fitness testing is not indicated for oesophagogastric cancer surgery.

Drummond RJ, Vass D, Wadhawan H, Craig CF, MacKay CK, Fullarton
GM, Forshaw MJ

Ann R Coll Surg Engl. 2018 Apr 25:1-5. doi: 10.1308/rcsann.2018.0067. [Epub ahead
of print

Introduction There is a known correlation between anaerobic threshold (AT) during
cardiopulmonary exercise testing and development of cardiopulmonary complications
in high-risk patients undergoing oesophagogastric cancer surgery. This study
aimed to assess the value of routine retesting following neoadjuvant
chemotherapy.

Methods Patients undergoing neoadjuvant chemotherapy with
subsequent oesophagogastric cancer surgery with pre- and post-neoadjuvant
chemotherapy cardiopulmonary exercise data were identified from a prospectively
maintained database. Measured cardiopulmonary exercise variables included AT and
maximum oxygen uptake at peak exercise (VO2 peak). Anaerobic threshold values
within 1 ml/kg/minute were considered static. Patients were grouped into AT
ranges of less than 9 ml/kg/minute, 9-11 ml/kg/minute and greater than 11
ml/kg/minute. Outcome measures were unplanned intensive care stay, postoperative
cardiovascular morbidity and mortality.

Results Between May 2008 and August 2017,
42 patients from 675 total resections were identified, with a mean age of 65
years (range 49-84 years). Mean pre-neoadjuvant chemotherapy AT was 11.07
ml/kg/minute (standard deviation, SD, 3.24 ml/kg/minute, range 4.6-19.3
ml/kg/minute) while post-neoadjuvant chemotherapy AT was 11.19 ml/kg/minute (SD
3.05 ml/kg/minute, range 5.2-18.1 ml/kg/minute). Mean pre-neoadjuvant
chemotherapy VO2 peak was 17.13 ml/kg/minute, while post-chemotherapy this mean
fell to 16.59 ml/kg/minute. Some 44.4% of patients with a pre-chemotherapy AT
less than 9 ml/kg/minute developed cardiorespiratory complications compared with
42.2% of those whose AT was greater than 9 ml/kg/minute (P = 0.914); 63.6% of
patients in the post-neoadjuvant chemotherapy group with an AT less than 9
ml/kg/minute developed cardiorespiratory complications. There was no correlation
between direction of change in AT and outcome.

Conclusion In our patient
population, neoadjuvant chemotherapy does not appear to result in a significant
mean reduction in cardiorespiratory fitness. Routine pre- and post-neoadjuvant
chemotherapy cardiopulmonary exercise testing is currently not indicated;
however, larger studies are required to demonstrate this conclusively.

Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer.

Navidi M, Phillips AW, Griffin SM, Duffield KE, Greystoke A, Sumpter K, Sinclair RCF

The British Journal Of Surgery [Br J Surg] 2018 Mar 30. Date of Electronic Publication: 2018 Mar 30.

Background: Neoadjuvant chemotherapy may have a detrimental impact on cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic threshold by cardiopulmonary exercise testing (CPET) provides an objective measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict perioperative risk. A low anaerobic threshold is associated with increased morbidity after oesophagogastrectomy. The aim of this study was to establish whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether there is recovery of fitness before surgery for oesophageal and gastric adenocarcinoma.
Methods: CPET was completed before, immediately after (week 0), and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were compared before and after neoadjuvant chemotherapy, and at the three time intervals.
Results: Some 31 patients were recruited. The mean anaerobic threshold was lower following neoadjuvant treatment: 15·3 ml per kg per min before chemotherapy versus 11·8, 12·1 and 12·6 ml per kg per min at week 0, 2 and 4 respectively (P < 0·010). Measurements were also significantly different at each time point (P < 0·010). The same pattern was noted for Vo2 peak between values before chemotherapy (21·7 ml per kg per min) and at weeks 0, 2 and 4 (17·5, 18·6 and 19·3 ml per kg per min respectively) (P < 0·010). The reduction in anaerobic threshold and Vo2 peak did not improve during the time between completion of neoadjuvant chemotherapy and surgery.
Conclusion: There was a decrease in cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was sustained up to the point of surgery at 4 weeks after chemotherapy.

Cardiopulmonary Exercise Testing in Aortic Stenosis

Le VDT

Dan Med J. 2017 May;64(5). pii: B5352.

Patients with moderate to severe aortic stenosis (AVA <1.3 cm2) who were judged,
by a referring cardiologist, as asymptomatic or equivocal symptomatic from the
aortic stenosis were included in the study. Patients with left ventricular
ejection fraction <50% were not included. Twenty-nine percent of the referred
patients were judged asymptomatic and 71% equivocal symptomatic from their valve
disease. The mean age was 72 years and 90% of the patients had an AVA-index <0.6
cm2/m2. By clinical evaluation in the outpatient clinic, 48% were judged as
having functional limitation corresponding to NYHA≥II. The study participants had
cardiopulmonary exercise testing (CPX) at inclusion, and, if relevant, pre- and
nine months post-aortic valve replacement (AVR). CPX was feasible in 130 of 131
study participants recruited across 19 months. The coefficient of variability by
test-retest was 5.4% and 4.6% for peak oxygen consumption (pVO2) and peak oxygen
pulse (pO2pulse= pVO2/peak heart rate), respectively. The stroke volume generally
increased with exercise, also in those with peak flow velocity across the aortic
valve (Vmax) >5 m/s, >4 m/s, and <4 m/s but with high valvuloarterial impedance
(Zva >5.5 mm Hg/(mL·m2 )). This was found both when assessed by inert gas
rebreathing and by the pO2pulse/hemoglobin index. Both resting and exercise
stroke volume were lower for the latter group, with Vmax <4 m/s but high
valvuloarterial impedance. A pVO2 <83% of the predicted, which corresponds to the
lower 95% percentile found in the healthy sedentary population, was predicted
independently by lower stroke volume during exercise, lower heart rate during
exercise, lower FEV1, and by higher ventilation/carbon dioxide exhaustion rate
(VE/VCO2), but not by the severity of the aortic stenosis as determined by
echocardiography. According to the CPX results, the patients were prospectively
grouped into 3 groups, as follows: 1) normal pVO2 (>83% of predicted) and
pO2pulse (>95% of predicted); 2) subnormal pVO2 or pO2pulse that according to CPX
could be explained by causes other than hemodynamic compromise; 3) subnormal pVO2
and pO2pulse. Groups 1 and 2 followed an initial conservative strategy, whereas
Group 3 was referred for angiogram and Heart Team evaluation for AVR. The
patients were followed for an average of 24 months and, in Groups 1 and 2, one
patient (0.9%) suffered cardiac death and seven were hospitalized with heart
failure (6.7%). The patient who died and another patient with heart failure had
both previously, during the study, declined AVR. For Groups 1 and 2, the rate of
the combined endpoint progression to cardiac death, hospitalization with heart
failure, or AVR was 37.5%, which seems lower than what was reported in the
literature by conventional assessment and strategy for younger asymptomatic
patients with comparable echocardiographic severity of aortic stenosis. The
endpoint progression to cardiac death, hospitalization with heart failure, or AVR
with improvement in pVO2 or in the Physical Component Score of the SF-36
health-related quality of life score was reached in 25.6% in Groups 1+2 and in
62.5% in Group 3 (p=0.003). A decreased pO2pulse, which expresses stroke volume
at peak exercise, predicted this endpoint. In 73 operated patients without left
ventricular dysfunction and no coronary stenosis, including 37 patients from the
above-mentioned study, a CPX 9 months post-AVR showed that the pVO2, on average,
was less than that predicted (mean 89% of the predicted ) and 35% of the patients
had a subnormal pVO2 (<83% of that predicted). A preoperative mean gradient <40
mm Hg across the aortic valve, the presence of atrial fibrillation, and a
permanent pacemaker post-AVR all predicted a post-AVR pVO2 <83% of that
predicted. For the 37 patients with a pre-AVR CPX, a postoperative decrease >10%
in the absolute pVO2 was noted in 30% and an increase >10% in 24% of patients. A
decrease >10% in pVO2 was predicted by preoperative mean gradient <40 mm Hg and
an increase in pVO2 was predicted by preoperative AVAI <0.4 cm2/m2 and
preoperative pO2pulse <the median in the study population (<98% of that
predicted).

CONCLUSIONS: In this group of patients, where clinical assessment is
difficult and conventional exercise testing is regarded as less useful, CPX
showed high feasibility and reproducibility. CPX therefore has potential as a
useful tool for serial monitoring. In general, the stroke volume increased during
exercise, including in patients with severe aortic stenosis or decreased resting
stroke volume. CPX gives information on hemodynamics and the physiologic
components that determine decreased pVO2. CPX seems useful to identify 1)
patients with a low risk of cardiac death and low risk of progression to symptoms
from the aortic stenosis, and 2) patients with hemodynamic compromise who improve
in functional capacity after AVR. Patients with a preoperative mean gradient <40
mm Hg across the aortic valve, with the presence of atrial fibrillation or who
have a permanent pacemaker, postoperatively seem to benefit less from AVR,
whereas the benefit seems larger in those with more severe aortic stenosis and a
decreased pO2pulse. These findings may be of importance for decisions and
information of patients before AVR.

Oxygen consumption trajectory flattening-yet another cardiopulmonary exercise testing parameter in chronic heart failure.

Kleber FX; Köln PJ

European Journal Of Heart Failure [Eur J Heart Fail], ISSN: 1879-0844, 2018 Apr 14;

This article refers to ‘A flattening oxygen consumption
trajectory phenotypes disease severity and poor prognosis
in patients with heart failure with reduced,mid-range, and
preserved ejection fraction’ by D. Popovic et al., published
in this issue on pages xxx.
Cardiopulmonary exercise testing (CPET) has gained major importance
in heart failure (HF) units and in the evaluation of patients for
heart transplantation (HTx) or left ventricular assist device (LVAD)
implantation. While oxygen consumption at maximal effort (peak
VO2) has been accepted even far beyond the field of cardiology,
other parameters such as ventilatory efficiency,1 end-tidal partial
pressure of carbon dioxide (PETCO2)2 and exercise oscillatory
ventilation (EOV),3 have broadened the spectrum of understanding
and measurements of HF symptoms and helped in evaluation
of prognosis. Most data are derived from patients with systolic HF
and none of these parameters have conclusively helped to specifically
characterize diastolic HF, which is currently in the focus of
efforts to understand the HF epidemic.