Category Archives: Publications

Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing.

Singh I; Joseph P; Heerdt PM; Cullinan M; Lutchmansingh DD; Gulati M;
Possick JD; Systrom DM; Waxman AB

Chest. 161(1):54-63, 2022 01.VI 1

BACKGROUND: Some patients with COVID-19 who have recovered from the acute
infection after experiencing only mild symptoms continue to exhibit
persistent exertional limitation that often is unexplained by conventional
investigative studies.
RESEARCH QUESTION: What is the pathophysiologic mechanism of exercise
intolerance that underlies the post-COVID-19 long-haul syndrome in
patients without cardiopulmonary disease?
STUDY DESIGN AND METHODS: This study examined the systemic and pulmonary
hemodynamics, ventilation, and gas exchange in 10 patients who recovered
from COVID-19 and were without cardiopulmonary disease during invasive
cardiopulmonary exercise testing (iCPET) and compared the results with
those from 10 age- and sex-matched control participants. These data then
were used to define potential reasons for exertional limitation in the
cohort of patients who had recovered from COVID-19.
RESULTS: The patients who had recovered from COVID-19 exhibited markedly
reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared
with control participants (70 +/- 11% predicted vs 131 +/- 45% predicted;
P < .0001). This reduction in peak VO2 was associated with impaired
systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen
content difference to arterial oxygen content ratio) compared with control
participants (0.49 +/- 0.1 vs 0.78 +/- 0.1; P < .0001), despite a
preserved peak cardiac index (7.8 +/- 3.1 L/min vs 8.4+/-2.3 L/min; P >
.05). Additionally, patients who had recovered from COVID-19 demonstrated
greater ventilatory inefficiency (ie, abnormal ventilatory efficiency
[VE/VCO2] slope: 35 +/- 5 vs 27 +/- 5; P = .01) compared with control
participants without an increase in dead space ventilation.
INTERPRETATION: Patients who have recovered from COVID-19 without
cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a
peripheral rather than a central cardiac limit, along with an exaggerated
hyperventilatory response during exercise.

A capaciflector provides continuous and accurate respiratory rate monitoring for patients at rest and during exercise.

Hayward N; Shaban M; Badger J; Jones I; Wei Y;  Spencer D; Isichei S; Knight M; Otto J; Rayat G; Levett D; Grocott M; Akerman H; White N;

Journal of clinical monitoring and computing [J Clin Monit Comput] 2022 Jan 18.
Date of Electronic Publication: 2022 Jan 18.

Respiratory rate (RR) is a marker of critical illness, but during hospital care, RR is often inaccurately measured. The capaciflector is a novel sensor that is small, inexpensive, and flexible, thus it has the potential to provide a single-use, real-time RR monitoring device. We evaluated the accuracy of continuous RR measurements by capaciflector hardware both at rest and during exercise. Continuous RR measurements were made with capaciflectors at four chest locations. In healthy subjects (n = 20), RR was compared with strain gauge chest belt recordings during timed breathing and two different body positions at rest. In patients undertaking routine cardiopulmonary exercise testing (CPET, n = 50), RR was compared with pneumotachometer recordings. Comparative RR measurement bias and limits of agreement were calculated and presented in Bland-Altman plots. The capaciflector was shown to provide continuous RR measurements with a bias less than 1 breath per minute (BPM) across four chest locations. Accuracy and continuity of monitoring were upheld even during vigorous CPET exercise, often with narrower limits of agreement than those reported for comparable technologies. We provide a unique clinical demonstration of the capaciflector as an accurate breathing monitor, which may have the potential to become a simple and affordable medical device.

Influence of extracellular volume fraction on peak exercise oxygen pulse following thoracic radiotherapy.

Canada JM; Weiss E; Grizzard JD; Trankle CR; Gharai LR; Dana F; Buckley LF; Carbone S; Kadariya D; Ricco A; JH; Evans RK; Garten RS; Van Tassell BW; Hundley WG;Abbate A;

Cardio-oncology (London, England) [Cardiooncology] 2022 Jan 18; Vol. 8 (1), pp. 1.
Date of Electronic Publication: 2022 Jan 18.

Background: Radiation-induced myocardial fibrosis increases heart failure (HF) risk and is associated with a restrictive cardiomyopathy phenotype. The myocardial extracellular volume fraction (ECVF) using contrast-enhanced cardiac magnetic resonance (CMR) quantifies the extent of fibrosis which, in severe cases, results in a noncompliant left ventricle (LV) with an inability to augment exercise stroke volume (SV). The peak exercise oxygen pulse (O 2 Pulse), a noninvasive surrogate for exercise SV, may provide mechanistic insight into cardiac reserve. The relationship between LV ECVF and O 2 Pulse following thoracic radiotherapy has not been explored.
Methods: Patients who underwent thoracic radiotherapy for chest malignancies with significant incidental heart dose (≥5 Gray (Gy), ≥10% heart) without a pre-cancer treatment history of HF underwent cardiopulmonary exercise testing to determine O 2 Pulse, contrast-enhanced CMR, and N-terminal pro-brain natriuretic peptide (NTproBNP) measurement. Multivariable-analyses were performed to identify factors associated with O 2 Pulse normalized for age/gender/anthropometrics.
Results: Thirty patients (median [IQR] age 63 [57-67] years, 18 [60%] female, 2.0 [0.6-3.8] years post-radiotherapy) were included. The peak VO 2 was 1376 [1057-1552] mL·min - 1 , peak HR = 150 [122-164] bpm, resulting in an O 2 Pulse of 9.2 [7.5-10.7] mL/beat or 82 (66-96) % of predicted. The ECVF, LV ejection fraction, heart volume receiving ≥10 Gy, and NTproBNP were independently associated with %O 2 Pulse (P < .001).
Conclusions: In patients with prior radiotherapy heart exposure, %-predicted O 2 Pulse is inversely associated markers of diffuse fibrosis (ECVF), ventricular wall stress (NTproBNP), radiotherapy heart dose, and positively related to LV function. Increased LV ECVF may reflect a potential etiology of impaired LV SV reserve in patients receiving thoracic radiotherapy for chest malignancies.

Impact of continuous vs. interval training on oxygen extraction and cardiac function during exercise in type 2 diabetes mellitus.

Van Ryckeghem L, Keytsman C, De Brandt J, Verboven K, Verbaanderd E, Marinus N, Franssen WMA, Frederix I, Bakelants E, Petit T, Jogani S, Stroobants S, Dendale P, Bito V, Verwerft J, Hansen D

Eur J Appl Physiol. 2022 Jan 17. doi: 10.1007/s00421-022-04884-9. Online ahead of print.

PURPOSE: Exercise training improves exercise capacity in type 2 diabetes mellitus (T2DM). It remains to be elucidated whether such improvements result from cardiac or peripheral muscular adaptations, and whether these are intensity dependent.
METHODS: 27 patients with T2DM [without known cardiovascular disease (CVD)] were randomized to high-intensity interval training (HIIT, n = 15) or moderate-intensity endurance training (MIT, n = 12) for 24 weeks (3 sessions/week). Exercise echocardiography was applied to investigate cardiac output (CO) and oxygen (O2) extraction during exercise, while exercise capacity [([Formula: see text] (mL/kg/min)] was examined via cardiopulmonary exercise testing at baseline and after 12 and 24 weeks of exercise training, respectively. Changes in glycaemic control (HbA1c and glucose tolerance), lipid profile and body composition were also evaluated.
RESULTS: 19 patients completed 24 weeks of HIIT (n = 10, 66 ± 11 years) or MIT (n = 9, 61 ± 5 years). HIIT and MIT similarly improved glucose tolerance (pTime = 0.001, pInteraction > 0.05), [Formula: see text] (mL/kg/min) (pTime = 0.001, pInteraction > 0.05), and exercise performance (Wpeak) (pTime < 0.001, pInteraction > 0.05). O2 extraction increased to a greater extent after 24 weeks of MIT (56.5%, p1 = 0.009, pTime = 0.001, pInteraction = 0.007). CO and left ventricular longitudinal strain (LS) during exercise remained unchanged (pTime > 0.05). A reduction in HbA1c was correlated with absolute changes in LS after 12 weeks of MIT (r = - 0.792, p = 0.019, LS at rest) or HIIT (r = - 0.782, p = 0.038, LS at peak exercise).
CONCLUSION: In patients with well-controlled T2DM, MIT and HIIT improved exercise capacity, mainly resulting from increments in O2 extraction capacity, rather than changes in cardiac output. In particular, MIT seemed highly effective to generate these peripheral adaptations.

Performance of Heart Failure Patients with Severely Reduced Ejection Fraction during Cardiopulmonary Exercise Testing on Treadmill and Cycle Ergometer; Similarities and Differences.

Mazaheri R; Sadeghian M; Nazarieh M; Niederseer D; Schmied C

International Journal of Environmental Research & Public Health
[Electronic Resource]. 18(24), 2021 12 08.

BACKGROUND: Peak oxygen consumption (VO2) measured by cardiopulmonary
exercise testing (CPET) is a significant predictor of mortality and future
transplantation in heart failure patients with severely reduced ejection
fraction (HFrEF). The present study evaluated the differences in peak VO2
and other prognostic variables between treadmill and cycle CPETs in these
patients.
METHODS: In this cross-over study design, thirty males with severe HFrEF
underwent CPET on both a treadmill and a cycle ergometer within 2-5 days
apart, and important CPET parameters between two exercise test modalities
were compared.
RESULTS: Peak VO2 was 23.12% higher on the treadmill than on cycle (20.55
+/- 3.3 vs. 16.69 +/- 3.01, p < 0.001, respectively). Minute ventilation
to carbon dioxide production (VE/VCO2) slope was not different between the
two CPET modes (p = 0.32). There was a strong positive correlation between
the VE/VCO2 slopes during treadmill and cycle testing (r = 0.79; p <
0.001). VE/VCO2 slope was not related to peak respiratory exchange ratio
(RER) in either modality (treadmill, r = 0.13, p = 0.48; cycle, r = 0.25,
p = 0.17). The RER level was significantly higher on the cycle ergometer
(p < 0.001).
CONCLUSION: Peak VO2 is higher on treadmill than on cycle ergometer in
severe HFrEF patients. In addition, VE/VCO2 slope is not a modality
dependent parameter and is not related to the patients’ effort during
CPET.

 

Comparison of V˙O2-Kinetic Parameters for the Management of Heart Failure

Jonathan Wagner, Max Niemeyer, Denis Infanger, Otmar Pfister, Jonathan Myers; Arno Schmidt-Trucksäss and Raphael Knaier

Frontiers in Physiology | www.frontiersin.org
November 2021 | Volume 12 | Article 775601

Objective: The aim of this study was to analyze whether V˙ O2-kinetics during
cardiopulmonary exercise testing (CPET) is a useful marker for the diagnosis of
heart failure (HF) and to determine which V˙ O2-kinetic parameter distinguishes healthy
participants and patients with HF.
Methods: A total of 526 healthy participants and 79 patients with HF between 20 and
90 years of age performed a CPET. The CPET was preceded by a 3-min low-intensity
warm-up and followed by a 3-min recovery bout. V˙ O2-kinetics was calculated from
the rest to exercise transition of the warm-up bout (on-kinetics), from the exercise to
recovery transition following ramp test termination (off-kinetics) and from the initial delay
of V˙ O2 during the warm-up to ramp test transition (ramp-kinetics).
Results: V˙ O2 off-kinetics showed the highest z-score differences between healthy
participants and patients with HF. Furthermore, off-kinetics was strongly associated
with V˙ O2peak. In contrast, ramp-kinetics and on-kinetics showed only minimal z-score
differences between healthy participants and patients with HF. The best on- and
off-kinetic parameters significantly improved a model to predict the disease severity.
However, there was no relevant additional value of V˙ O2-kinetics when V˙ O2peak was
part of the model.
Conclusion: V˙ O2 off-kinetics appears to be superior for distinguishing patients with HF
and healthy participants compared with V˙ O2 on-kinetics and ramp-kinetics. If V˙ O2peak
cannot be determined, V˙ O2 off-kinetics provides an acceptable substitute. However, the
additional value beyond that of V˙ O2peak cannot be provided by V˙ O2-kinetics.

Is BMI Associated with Cardiorespiratory Fitness? A Cross-Sectional Analysis Among 8470 Apparently Healthy Subjects Aged 18–94 Years from the Low-Lands Fitness Registry

T. Takken;  H. J. Hulzebos;

ObjectiveThe purpose of the present study was to investigate the association between cardiorespiratory fitness (CRF) measured as peak oxygen uptake (VO2peak, expressed in mL/min) and body mass index (BMI) in a large cohort of apparently healthy subjects.
MethodsBMI and VO2peak were measured in a cross-sectional study of 8470 apparently healthy adults. VO2peak (mL/min) was determined by an incremental cycle ergometer test to exhaustion. Linear regression analyses were performed to identify predictors of CRF.
ResultsThere was no difference in CRF between adults with a normal weight (BMI between 18.5–24.9 kg/m2) and those who were overweight (BMI 25.0–29.9 kg/m2). Subjects who were underweight (BMI < 18.5 kg/m2) as well as females who were obese (BMI ≥ 30.0 kg/m2) showed a reduced CRF compared to the normal and overweight groups. Age, height, and gender were significant predictors of CRF (R2 = 0.467, P < 0.0001); BMI did not add significantly to this relationship.
ConclusionOur findings indicate that BMI was not associated with CRF in addition to age, height, and gender. In subjects with a BMI < 18.5 kg/m2, CRF was lower compared to subjects with a BMI between 18.5 and 29.9 kg/m2. In obese subjects, CRF was only lower in females compared to females with a BMI between 18.5 and 29.9 kg/m2. Correcting CRF for BMI may be beneficial for subjects with a low BMI, and females with a BMI ≥ 30.0 kg/m2. The outcome of this study might help to improve the interpretation of exercise testing results in individuals with a low or high BMI.

Is BMI Associated with Cardiorespiratory Fitness? A Cross‑Sectional Analysis Among 8470 Apparently Healthy Subjects Aged 18–94 Years from the Low‑Lands Fitness Registry

T. Takken · H. J. Hulzebos

Journal of Science in Sport and Exercise https://doi.org/10.1007/s42978-021-00143-z

ObjectiveThe purpose of the present study was to investigate the association between cardiorespiratory fitness (CRF) measured as peak oxygen uptake (VO2peak, expressed in mL/min) and body mass index (BMI) in a large cohort of apparently healthy subjects.
MethodsBMI and VO2peak were measured in a cross-sectional study of 8470 apparently healthy adults. VO2peak (mL/min) was determined by an incremental cycle ergometer test to exhaustion. Linear regression analyses were performed to identify predictors of CRF.
ResultsThere was no difference in CRF between adults with a normal weight (BMI between 18.5–24.9 kg/m2) and those who were overweight (BMI 25.0–29.9 kg/m2). Subjects who were underweight (BMI < 18.5 kg/m2) as well as females who were obese (BMI ≥ 30.0 kg/m2) showed a reduced CRF compared to the normal and overweight groups. Age, height, and gender were significant predictors of CRF (R2 = 0.467, P < 0.0001); BMI did not add significantly to this relationship.
ConclusionOur findings indicate that BMI was not associated with CRF in addition to age, height, and gender. In subjects with a BMI < 18.5 kg/m2, CRF was lower compared to subjects with a BMI between 18.5 and 29.9 kg/m2. In obese subjects, CRF was only lower in females compared to females with a BMI between 18.5 and 29.9 kg/m2. Correcting CRF for BMI may be beneficial for subjects with a low BMI, and females with a BMI ≥ 30.0 kg/m2. The outcome of this study might help to improve the interpretation of exercise testing results in individuals with a low or high BMI.

The Impact of beta blockade on the cardio-respiratory system and symptoms during exercise.

Priel E; Wahab M; Mondal T; Freitag A; O’Byrne PM; Killian KJ; Satia I;

Current research in physiology [Curr Res Physiol] 2021 Oct 28; Vol. 4, pp. 235-242.
Date of Electronic Publication: 2021 Oct 28 (Print Publication: 2021).

Background: Beta blockers prolong life in patients with cardiovascular diseases. Negative chronotropic and inotropic effects carry the potential to adversely effect peripheral skeletal and airway smooth muscle contributing to further fatigue, dyspnea and exercise intolerance.
Research Questions: Do beta-blockers reduce maximal power output (MPO), VO2 max, cardiorespiratory responses, increase the perceived effort required to cycle and breath during cardiopulmonary exercise tests (CPET) and limit the capacity to exercise?
Methods: Retrospective observational study of subjects performing CPET to capacity from 1988 to 2012. Subjects with and without beta-blockers were compared: baseline physiological characteristics, MPO, VO 2 max, heart rate max, ventilation responses and perceived exertion required to cycle and breathe (modified Borg scale). Forward stepwise linear additive regression was performed with MPO as the dependent factor with height, age, gender, muscle strength, FEV1 and DLCO as independent contributors.
Results: 42,771 subjects were included 7,787 were receiving beta-blocker [mean age 61 yrs, BMI 28.40 kg/m 2 , 9% airflow obstruction (FEV1/FVC<0.7)] and 34,984 were not [mean age 51yrs, BMI 27.40 kg/m 2 , 11% airflow obstruction]. Heart rate was lower by 18.2% (95% C.I. 18.15-18.38) (p<0.0001) while Oxygen pulse (VO 2 /HR) was higher by 19.5% (95% C.I. 19.3-19.7) in those receiving beta blockers. Maximum power output (MPO) was 3.3% lower in those taking beta-blockers. The perceived effort required to cycle and breathe (mBorg) was 8% lower in those taking beta-blockers.
Interpretation: Increases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.

Predictors of Prolonged Cardiopulmonary Exercise Impairment After COVID-19 Infection: A Prospective Observational Study.

Vonbank K; Lehmann A; Bernitzky D; Gysan MR; Simon S; Schrott A;Burtscher M; Idzko M; Gompelmann D;

Frontiers in medicine [Front Med (Lausanne)] 2021 Dec 24; Vol. 8, pp. 773788.
Date of Electronic Publication: 2021 Dec 24 (Print Publication: 2021).

Objectives: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting individuals to varying degrees. There is emerging evidence that even patients with mild symptoms will suffer from prolonged physical impairment. Methods: In this prospective observational study, lung function, and cardiopulmonary exercise testing have been performed in 100 patients for 3-6 months after COVID-19 diagnosis (post-CoVG). Depending on the severity of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, patients were divided into asymptomatic, or mild to moderate (mild post-CoVG), and severe post-CoVG [hospitalization with or without intensive care unit/non-invasive ventilation (ICU/NIV)]. Results have been compared with age, sex, and body mass index (BMI) matched control group (CG, N = 50).
Results: Both lung function (resting) and exercise capacity (peak workload, Wpeak and peak oxygen uptake, VO 2 peak – % predicted) were considerably affected in patients with severe post-CoV (81.7 ± 27.6 and 86.1 ± 20.6%), compared to the mild post-CoVG (104.8 ± 24.0%, p = 0.001 and 100.4 ± 24.8; p = 0.003). In addition, also the submaximal exercise performance was significantly reduced in the severe post-CoVG (predicted VT1/VO 2 peak; p = 0.013 and VT2/VO 2 peak; p = 0.001). Multiple linear regression analyses revealed that 74 % (adjusted R2 ) of the variance in relative VO 2 peak of patients who had CoV could be explained by the following variables: lower age, male sex, lower BMI, higher DLCO, higher predicted heart rate (HR) peak, lower breathing reserve (BR), and lower SaO 2 peak, which were related to higher relative VO 2 peak values. Higher NT-proBNP and lower creatinine kinase (CK) values were seen in severe cases compared to patients who experienced mild CoV.
Discussion: Maximal and submaximal exercise performance in patients recovering from severe COVID-19 remain negatively affected for 3-6 months after COVID-19 diagnosis. The presented findings reveal that impaired pulmonary, cardiac, and skeletal muscle function contributed to the limitation of VO 2 peak in those patients, which may have important implications on rehabilitation programs.