Category Archives: Publications

Increased physiological dead space at exercise is a marker of mild pulmonary or cardiovascular disease in dyspneic subjects.

Plantier L; Delclaux C;

European Clinical Respiratory Journal [Eur Clin Respir J] 2018 Jul 05; Vol. 5 (1), pp. 1492842. Date of Electronic Publication: 20180705 (Print Publication: 2018).

Background: The characteristics of cardiopulmonary exercise testing (CPET)-derived parameters for the differential diagnosis of exertional dyspnea are not well known.
Objectives: We hypothesized that increased physiological dead space ventilation (VD/Vt) is a marker for mild pulmonary or cardiovascular disease in patients with exertional dyspnea.
Design: We used receiver operating characteristic analysis to determine the performance of individual CPET parameters for identifying subjects with either mild pulmonary or cardiovascular disease, among 77 subjects with mild-to-moderate exertional dyspnea (modified Medical Research Council scale 1-2).
Results: In comparison with subjects without disease, subjects with pulmonary disease (n = 31) had higher VE/V’CO2 slope, higher VD/Vt, and lower ventilatory reserve. Subjects with cardiovascular disease (n = 14) had lower heart rate and cardiovascular double product and higher VD/Vt at peak exercise. At a threshold of 28%, the sensitivity and specificity of VD/Vt at peak exercise for identifying pulmonary or cardiovascular disease were 89% (95% CI: 64-98%) and 72% (95% CI: 46-89%), respectively.
Conclusions: Increased physiological VD/Vt at exercise is a sensitive and specific marker of mild pulmonary or cardiovascular disease in dyspneic subjects

Predictive Capability of Cardiopulmonary and Exercise Parameters From Day 1 to 6 Months After Acute Pulmonary Embolism.

Habedank D; Opitz C; Karhausen T; Kung T; Steinke I; Ewert R;

Clinical Medicine Insights. Circulatory, Respiratory And Pulmonary Medicine [Clin Med Insights Circ Respir Pulm Med] 2018 Aug 16; Vol. 12, pp. 1179548418794155. Date of Electronic Publication: 20180816 (Print Publication: 2018).

We hypothesized that the slope of relation ventilation to carbon dioxide output (V’E/V’CO2-slope) could be predictive already during the very first days after submassive pulmonary embolism (PE) to right ventricular systolic pressure (RVsys by echocardiography) after 6 months. We evaluated 21 hemodynamically stable patients at admittance, at days 3, 7, 90, and 180 by cardiopulmonary exercise testing and echocardiography. V’E/V’CO2-slope (48.4 ± 10.8) decreased within the first week (43.0 ± 9.8 at day 7) and normalized until follow-up at 6 months (35.0 ± 11.3; P < 10-4), p(a-ET)CO2 remained abnormal between days 1 and 3 (5.0 ± 3.9 to 6.7 ± 5.3 mmHg). RVsys declined from 41.7 ± 14.3 to 26.3±13.1 mmHg (P < 10-4) at 6 months. V’E/V’CO2-slope (r²= 0.27; P < .02) and RVsys (r² = 0.28; P = .03) at day 7 correlated with RVsys at 6 months. p(a-ET)CO2, p(a-ET)O2, V’D/V’T were not related to RVsys after 6 months. RVsys 6 months after acute PE is positively correlated with the V’E/V’CO2-slope at day 7.

C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction.

van Wezenbeek J; Canada JM; Ravindra K; Carbone S; Trankle CR; Kadariya D; Buckley LF; Del Buono M; Billingsley H; Viscusi M; Wohlford GF; Arena R; Van Tassell B; Abbate A;

Frontiers In Cardiovascular Medicine [Front Cardiovasc Med] 2018 Dec 21; Vol. 5, pp. 178. Date of Electronic Publication: 20181221 (Print Publication: 2018).

Background: Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.
Methods: Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log10) and NT-proBNP (logN).
Results: Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5-9.0] mg/L, and NT-proBNP levels were 377 [106-1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16 ± 4 mlO2•kg-1•min-1. CRP levels significantly correlated with peakVO2 in all patients (R = -0.350, p < 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, N = 109) (R = -0.282, p < 0.001) and in those with preserved EF (HFpEF, N = 57) (R = -0.459, p < 0.001). NT-proBNP levels also significantly correlated with peak VO2 in all patients (R = -0.330, p < 0.001) and separately in patients with HFrEF (R = -0.342, p < 0.001) and HFpEF (R = -0.275, p = 0.032). CRP and NT-proBNP did not correlate with each other (R = 0.05, p = 0.426), but independently predicted peak VO2 (R = 0.421, p < 0.001 and p < 0.001, respectively).
Conclusions: Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.

Reproducibility of Inert Gas Rebreathing Method to Estimate Cardiac Output at Rest and During Cardiopulmonary Exercise Stress Testing.

Okwose NC; Zhang J; Chowdhury S; Houghton D; Ninkovic S; Jakovljević S; Jevtic B; Ropret R; Eggett C; Bates M;MacGowan G; Jakovljevic D;

International Journal Of Sports Medicine [Int J Sports Med] 2019 Jan 03. Date of Electronic Publication: 2019 Jan 03.

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p=0.54; 114 (28) vs. 108 (15) ml beat-1, p=0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r=0.95, p<0.01 with coefficient of variation of 6.0%), at rest (r=0.90, p<0.01 with coefficient of variation of 5.1%), and during exercise (r=0.89, p<0.01 with coefficient of variation 3.3%). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands.

Cardiorespiratory fitness data from 18,189 participants who underwent treadmill cardiopulmonary exercise testing in a Brazilian population.

Rossi Neto JM; Tebexreni AS; Alves ANF; Smanio PEP; de Abreu FB; Thomazi MC; Nishio PA; Cuninghant IA;

Plos One [PLoS One] 2019 Jan 09; Vol. 14 (1), pp. e0209897. Date of Electronic Publication: 20190109 (Print Publication: 2019).

Purpose: Cardiorespiratory fitness is inversely associated with a high risk of cardiovascular disease, all-cause mortality, and mortality attributable to various cancers. It is often estimated indirectly using mathematical formulas for estimating oxygen uptake. Cardiopulmonary exercise testing, especially oxygen uptake, represents the “gold standard” for assessing exercise capacity. The purpose of this report was to develop reference standards for exercise capacity by establishing cardiorespiratory fitness values derived from cardiopulmonary exercise testing in a Brazilian population. We focused on oxygen uptake standards and compared the maximal oxygen uptake [mLO2·kg-1·min-1] values with those in the existing literature.
Methods: A database was constructed using reports from cardiopulmonary exercise testing performed at Fleury laboratory. The final cohort included 18,189 individuals considered to be free of structural heart disease. Percentiles of maximal oxygen uptake for men and women were determined for six age groups between 7 and 84 years. We compared the values with existing reference data from patients from Norway and the United States.
Results: There were significant differences in maximal oxygen uptake between sexes and across the age groups. In our cohort, the 50th percentile maximal oxygen uptake values for men and women decreased from 44.7 and 36.3 mLO2·kg-1·min-1 to 28.4 and 22.3 mLO2·kg-1·min-1 for patients aged 20-29 years to patients aged 60-69 years, respectively. For each age group, both Norwegian men and women had greater cardiorespiratory fitness than cohorts in the United States and Brazil.
Conclusion: To our knowledge, our analysis represents the largest reference data for cardiorespiratory fitness based on treadmill cardiopulmonary exercise testing. Our findings provide reference values of maximal oxygen uptake measurements from treadmill tests in Brazilian populations that are more accurate than previous standard values based on workload-derived estimations. This data may also add information to the global data used for the interpretation of cardiorespiratory fitness.

Inter-observer reliability of preoperative cardiopulmonary exercise test interpretation: a cross-sectional study.

Abbott TEF, Gooneratne M, McNeill J, Lee A, Levett DZH, Grocott
MPW, Swart M, MacDonald N; ARCTIC study investigators.

Br J Anaesth. 2018 Mar;120(3):475-483. doi: 10.1016/j.bja.2017.11.071. Epub 2017
Nov 29.

BACKGROUND: Despite the increasing importance of cardiopulmonary exercise testing
(CPET) for preoperative risk assessment, the reliability of CPET interpretation
is unclear. We aimed to assess inter-observer reliability of preoperative CPET.
METHODS: We conducted a prospective, multi-centre, observational study of
preoperative CPET interpretation. Participants were professionals with previous
experience or training in CPET, assessed by a standardized questionnaire. Each
participant interpreted 100 tests using standardized software. The CPET variables
of interest were oxygen consumption at the anaerobic threshold (AT) and peak
oxygen consumption (VO2 peak). Inter-observer reliability was measured using
intra-class correlation coefficient (ICC) with a random effects model. Results
are presented as ICC with 95% confidence interval, where ICC of 1 represents
perfect agreement and ICC of 0 represents no agreement.
RESULTS: Participants included 8/28 (28.6%) clinical physiologists, 10 (35.7%)
junior doctors, and 10 (35.7%) consultant doctors. The median previous experience
was 140 (inter-quartile range 55-700) CPETs. After excluding the first 10 tests
(acclimatization) for each participant and missing data, the primary analysis of
AT and VO2 peak included 2125 and 2414 tests, respectively. Inter-observer
agreement for numerical values of AT [ICC 0.83 (0.75-0.90)] and VO2 peak [ICC
0.88 (0.84-0.92)] was good. In a post hoc analysis, inter-observer agreement for
identification of the presence of a reportable AT was excellent [ICC 0.93
(0.91-0.95)] and a reportable VO2 peak was moderate [0.73 (0.64-0.80)].
CONCLUSIONS: Inter-observer reliability of interpretation of numerical values of
two commonly used CPET variables was good (>80%). However, inter-observer
agreement regarding the presence of a reportable value was less consistent.

Perioperative cardiopulmonary exercise testing (CPET): consensus clinical guidelines on indications, organization, conduct, and physiological interpretation.

Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C,
Riley M, Danjoux G, Ward SA, Older P, Grocott MPW; Perioperative
Exercise Testing and Training Society (POETTS).

Br J Anaesth. 2018 Mar;120(3):484-500. doi: 10.1016/j.bja.2017.10.020. Epub 2017
Nov 24.

The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the
risk of adverse perioperative events and inform the perioperative management of
patients undergoing surgery has increased over the last decade. CPET provides an
objective assessment of exercise capacity preoperatively and identifies the
causes of exercise limitation. This information may be used to assist clinicians
and patients in decisions about the most appropriate surgical and non-surgical
management during the perioperative period. Information gained from CPET can be
used to estimate the likelihood of perioperative morbidity and mortality, to
inform the processes of multidisciplinary collaborative decision making and
consent, to triage patients for perioperative care (ward vs critical care), to
direct preoperative interventions and optimization, to identify new
comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide
prehabilitation and rehabilitation, and to guide intraoperative anaesthetic
practice. With the rapid uptake of CPET, standardization is key to ensure valid,
reproducible results that can inform clinical decision making. Recently, an
international Perioperative Exercise Testing and Training Society has been
established (POETTS promoting the highest standards of care for
patients undergoing exercise testing, training, or both in the perioperative
setting. These clinical cardiopulmonary exercise testing guidelines have been
developed by consensus by the Perioperative Exercise Testing and Training Society
after systematic literature review. The guidelines have been endorsed by the
Association of Respiratory Technology and Physiology (ARTP).

Compensatory Increase in Heart Rate Is Responsible for Exercise Tolerance among Male Patients with Permanent Atrial Fibrillation.

Mori K; Goto T; Yamamoto J; Muto K; Kikuchi S; Wakami K; Fukuta H; Ohte N;

The Tohoku Journal Of Experimental Medicine [Tohoku J Exp Med] 2018 Dec; Vol. 246 (4), pp. 265-274.

Atrial fibrillation (AF) is an exacerbating factor for exercise tolerance due to the loss of atrial kick. However, many patients with permanent AF, which lasts for at least a year without interruption, and preserved left ventricular ejection fraction (LVEF ≥ 50%) are asymptomatic and have good exercise tolerance. In such cases, the possible mechanism that compensates for the decrease in cardiac output accompanying the loss of atrial kick is a sufficient increase in heart rate (HR) during exercise. We investigated the relationship between exercise tolerance and peak HR during exercise using cardiopulmonary exercise testing in 242 male patients with preserved LVEF, 214 with sinus rhythm (SR) and 28 with permanent AF. Peak HR was significantly higher in the AF group than the SR group (148.9 ± 41.9 vs. 132.0 ± 22.0 beats/min, p = 0.001). However, oxygen uptake at peak exercise did not differ between the AF and SR groups (19.4 ± 5.7 vs. 21.6 ± 6.0 mL/kg/min, p = 0.17). In multiple regression analysis, peak HR (β, 0.091; p < 0.001) and the interaction term constructed by peak HR and presence of permanent AF (β, 0.05; p = 0.04) were selected as determinants for peak VO2; however, presence of permanent AF was not selected (β, -0.38; p = 0.31). Therefore, the impact of peak HR on exercise tolerance differed between the AF and SR groups, suggesting that a sufficient increase in HR during exercise is an important factor to preserve exercise tolerance among patients with AF.

Cardiac function in adolescents with obesity: cardiometabolic risk factors and impact on physical fitness.

Franssen WMA; Beyens M; Hatawe TA; Frederix I; Verboven K; Dendale P; Eijnde BO; Massa G; Hansen D;

International Journal Of Obesity (2005) [Int J Obes (Lond)] 2018 Dec 19. Date of Electronic Publication: 2018 Dec 19.

Objective: To gain greater insights in the etiology and clinical consequences of altered cardiac function in obese adolescents. Therefore, we aimed to examine cardiac structure and function in obese adolescents, and to examine associations between altered cardiac function/structure and cardiometabolic disease risk factors or cardiopulmonary exercise capacity.
Methods: In 29 obese (BMI 31.6 ± 4.2 kg/m², age 13.4 ± 1.1 years) and 29 lean (BMI 19.5 ± 2.4 kg/m², age 14.0 ± 1.5 years) adolescents, fasted blood samples were collected to study hematology, biochemistry, liver function, glycemic control, lipid profile, and hormones, followed by a transthoracic echocardiography to assess cardiac structure/function, and a cardiopulmonary exercise test (CPET) to assess cardiopulmonary exercise parameters. Regression analyses were applied to examine relations between altered echocardiographic parameters and blood parameters or CPET parameters in the entire group.
Results: In obese adolescents, left ventricular septum thickness, left atrial diameter, mitral A-wave velocity, E/e’ ratio were significantly elevated (p < 0.05), as opposed to lean controls, while mitral e’-wave velocity was significantly lowered (p < 0.01). Elevated homeostatic model assessment of insulin resistance and blood insulin, c-reactive protein, and uric acid concentrations (all significantly elevated in obese adolescents) were independent risk factors for an altered cardiac diastolic function (p < 0.01). An altered cardiac diastolic function was not related to exercise tolerance but to a delayed heart rate recovery (HRR; p < 0.01).
Conclusions: In obese adolescents, an altered cardiac diastolic function was independently related to hyperinsulinemia and whole-body insulin resistance, and only revealed by a delayed HRR during CPET. This indicates that both hyperinsulinemia, whole-body insulin resistance, and delayed HRR could be regarded as clinically relevant outcome parameters.

The Role of Cardiopulmonary Exercise Testing (CPET) in Pulmonary Rehabilitation (PR) of Chronic Obstructive Pulmonary Disease (COPD) Patients.

Stringer W; Marciniuk D;

COPD [COPD] 2018 Dec 30, pp. 1-11. Date of Electronic Publication: 2018 Dec 30.

Chronic obstructive pulmonary disease (COPD) is a common multisystem inflammatory disease with ramifications involving essentially all organ systems. Pulmonary rehabilitation is a comprehensive program designed to prevent and mitigate these disparate systemic effects and improve patient quality of life, functional status, and social functioning. Although initial patient assessment is a prominent component of any pulmonary rehabilitation (PR) program, cardiopulmonary exercise testing (CPET) is not regularly performed as a screening physiologic test prior to PR in COPD patients. Further, CPET is not often used to assess or document the improvement in exercise capacity related to completion of PR. In this review we will describe the classic physiologic abnormalities related to COPD on CPET parameters, the role of CPET in Risk Stratification/Safety prior to PR, the physiologic changes that occur in CPET parameters with PR, and the literature regarding the use of CPET to assess PR results. Finally, we will compare CPET to 6MW in COPD PR, the common minimal clinically important difference (MCID) is associated with CPET, and the potential future roles of CPET in PR and Research.