Category Archives: Publications

Non-invasive estimation of stroke volume during exercise from oxygen in heart failure patients.

Accalai E; Vignati C; Salvioni E; Pezzuto B; Contini M; Cadeddu C; Meloni L; Agostoni P;

European journal of preventive cardiology [Eur J Prev Cardiol] 2020 Apr 28, pp. 2047487320920755. Date of Electronic Publication: 2020 Apr 28.

Aims: In heart failure, oxygen uptake and cardiac output measurements at peak and during exercise are important in defining heart failure severity and prognosis. Several cardiopulmonary exercise test-derived parameters have been proposed to estimate stroke volume during exercise, including the oxygen pulse (oxygen uptake/heart rate). Data comparing measured stroke volume and the oxygen pulse or stroke volume estimates from the oxygen pulse at different stages of exercise in a sizeable population of healthy individuals and heart failure patients are lacking.
Methods: We analysed 1007 subjects, including 500 healthy and 507 heart failure patients, who underwent cardiopulmonary exercise testing with stroke volume determination by the inert gas rebreathing technique. Stroke volume measurements were made at rest, submaximal (∼50% of exercise) and peak exercise. At each stage of exercise, stroke volume estimates were obtained considering measured haemoglobin at rest, predicted exercise-induced haemoconcentration and peripheral oxygen extraction according to heart failure severity.
Results: A strong relationship between oxygen pulse and measured stroke volume was observed in healthy and heart failure subjects at submaximal (R 2  = 0.6437 and R 2  = 0.6723, respectively), and peak exercise (R 2  = 0.6614 and R 2  = 0.5662) but not at rest. In healthy and heart failure subjects, agreement between estimated and measured stroke volume was observed at submaximal (-3 ± 37 and -11  ±  72 ml, respectively) and peak exercise (1 ± 31 and 6 ± 29 ml, respectively) but not at rest.
Conclusion: In heart failure patients, stroke volume estimation and oxygen pulse during exercise represent stroke volume, albeit with a relevant individual data dispersion so that both can be used for population studies but cannot be reliably applied to a single subject. Accordingly, whenever needed stroke volume must be measured directly.

Cardiopulmonary exercise capacity and quality of life of patients with heart failure undergoing a functional training program: study protocol for a randomized clinical trial.

do Nascimento DM, Machado KC, Bock PM, Saffi MAL, Goldraich LA, Silveira AD, Clausell N, Schaan BD

BMC Cardiovasc Disord. 2020 Apr 25;20(1):200. doi: 10.1186/s12872-020-01481-6.

BACKGROUND: Exercise intolerance is a common finding in heart failure that
generates a vicious cycle in which the individual starts to limit his activities
even more due to progressive fatigue. Regular physical exercise can increase the
cardiopulmonary exercise capacity of these individuals. A new approach to
physical exercise, known as functional training, could improve the oxygen
consumption and quality of life of patients with heart failure; however, there is
no information about the effect of this modality of exercise in this patient
population. This randomized trial will compare the effects of 36 sessions of
functional training versus strength training in heart failure patients.
METHODS: This randomized parallel-design examiner-blinded clinical trial includes
individuals of both sexes aged ≥40 years receiving regular follow-up at a single
academic hospital. Subjects will be randomly allocated to an intervention group
(for 12-week functional training) or an active comparator group (for 12-week
strength training). The primary outcomes will be the difference from baseline to
the 3-month time point in peak oxygen consumption on cardiopulmonary exercise
testing and quality of life assessed by the Minnesota Living with Heart Failure
Questionnaire. Secondary outcome measures will include functionality assessed by
the Duke Activity Status Index and gait speed test; peripheral and inspiratory
muscular strength, assessed by hand grip and manovacuometry testing,
respectively; endothelial function by brachial artery flow-mediated dilation;
lean body mass by arm muscle circumference; and participant adherence to the
exercise programs classified as a percentage of the prescribed exercise dose.
DISCUSSION: The functional training program aims to improve the functional
capacity of the individual using exercises that relate to his specific physical
activity transferring gains effectively to one’s daily life. In this context, we
believe that that functional training can increase the cardiopulmonary exercise
capacity and quality of life of patients with heart failure. The trial has been
recruiting patients since October 2017.

Peak Oxygen Uptake Recovery Delay After Maximal Exercise in Patients With Heart Failure.

Kadariya D;  Canada JM; Del Buono MG; van Wezenbeek; J Tchoukina;  Arena R; Van Tassell B; Abbate A

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2020 Apr 16. Date of Electronic Publication: 2020 Apr 16.

Purpose: Peak oxygen uptake recovery delay (VO2peakRD), measured as the time until post-exercise oxygen uptake (VO2) decreases below VO2peak following maximal cardiopulmonary exercise testing (CPX), has been recognized as an abnormal response, associated with reduced cardiac output reserve during exercise in patients with heart failure (HF). In the current study we examined the association of VO2peakRD during routine CPX testing of patients with symptomatic HF across a wide range of left ventricular ejection fraction (LVEF) values with clinical biomarkers.
Methods: In this retrospective study, 80 clinically stable symptomatic HF patients across a wide range of LVEF at our institution were evaluated that put forth a minimally acceptable effort during CPX testing (respiratory exchange ratio ≥ 1.00). The VO2peakRD was measured in 10-sec intervals following maximal CPX testing. Markers of elevated cardiac filling pressures (N-terminal pro-brain natriuretic peptide [NTproBNP] and echocardio-Doppler E/e’) and other key CPX parameters were explored for their association with VO2peakRD.
Results: The mean VO2peakRD and VO2peak were 10 (interquartile range 10, 40) sec and 13.9 (11.6, 16.4) mL·kg. min, respectively. VO2peakRD demonstrated a positive linear trend with serum NTproBNP levels and E/e’ (TJT = 1239.500, z = 2.634, P < .01; TJT = 1081.000, z = 2.046, P = .04, respectively).
Conclusion: Prolonged VO2peakRD following exercise is associated with markers of greater disease severity in patients with HF.

The early repolarization pattern: Echocardiographic characteristics in elite athletes.

Reinhard W; Trenkwalder T;Haller B; Meindl C;Schoenfeld J; Kaess BM; Hengstenberg C; Schunkert H; Pressler A; Halle M; Scherr J;

Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc [Ann Noninvasive Electrocardiol] 2019 Mar; Vol. 24 (2), pp. e12617. Date of Electronic Publication: 2018 Nov 14.

Background: The electrocardiographic early repolarization (ER) pattern is associated with idiopathic ventricular fibrillation and increased long-term cardiovascular mortality. Whether structural cardiac aberrations influence the phenotype is unclear. Since ER is particularly common in athletes, we evaluated its prevalence and investigated predisposing echocardiographic characteristics and cardiopulmonary exercise capacity in a cohort of elite athletes.
Methods: A total of 623 elite athletes (age 21 ± 5 years) were examined during annual preparticipation screening from 2006 until 2012 including electrocardiography, echocardiography, and exercise testing. ECGs were analyzed with focus on ER. All athletes participated in a clinical follow-up.
Results: The prevalence of ER was 17% (108/623). ER-positive athletes were predominantly male (71%, 77/108), showed a lower heart rate (57.1 ± 9.3 bpm versus 60.0 ± 11.2 bpm; p = 0.015) and a higher lean body mass compared to ER-negative participants (88.1% ± 5.6% versus 86.5% ± 6.3%; p = 0.015). Echocardiographic measurements and cardiopulmonary exercise capacity in male and female athletes with and without ER largely showed similar results. Only the notching ER subtype (n = 15) was associated with an increased left atrial diameter (OR 7.01, 95%CI 1.65-29.83; p = 0.008), a higher left ventricular mass (OR 1.02, 95%CI 1.00-1.03; p = 0.038) and larger relative heart volume (OR 1.01, 95%CI 1.00-1.01; p = 0.01). During a follow-up of 7.4 ± 1.5 years, no severe cardiovascular event occurred in the study sample.
Conclusions: In elite athletes presence of ER is not associated with distinct alterations in echocardiography and cardiopulmonary exercise. Athletes presenting with ER are rather male, lean with a low heart rate.

Cardiopulmonary exercise testing in patients with asthma: What is its clinical value?

Boutou AK; Daniil Z; Pitsiou G; Papakosta D; Kioumis I; Stanopoulos I;

Respiratory medicine [Respir Med] 2020 Apr 02; Vol. 167, pp. 105953. Date of Electronic Publication: 2020 Apr 02.

Asthma is one of the most common respiratory disorders, characterized by fully or largely reversible airflow limitation. Asthma symptoms can be triggered or magnified during exertion, while physical activity limitation is often present among asthmatic patients. Cardiopulmonary exercise testing (CPET) is a dynamic, non-invasive technique which provides a thorough assessment of exercise physiology, involving the integrative assessment of cardiopulmonary, neuromuscular and metabolic responses during exercise. This review summarizes current evidence regarding the utility of CPET in the diagnostic work-up, functional evaluation and therapeutic intervention among patients with asthma, highlighting its potential role for thorough patient assessment and physician clinical desicion-making.

Appropriate heart rate during exercise in Fontan patients.

Hedlund ER; Söderström L; Lundell B;

Cardiology in the young [Cardiol Young] 2020 Apr 17, pp. 1-7. Date of Electronic Publication: 2020 Apr 17.

Objective: To evaluate heart rate against workload and oxygen consumption during exercise in Fontan patients.
Method: Fontan patients (n = 27) and healthy controls (n = 25) underwent cardiopulmonary exercise testing with linear increase of load. Heart rate and oxygen uptake were measured during tests. Heart rate recovery was recorded for 10 minutes.
Results: Heart rate at midpoint (140 ± 14 versus 153 ± 11, p < 0.001) and at maximal effort (171 ± 14 versus 191 ± 10 beats per minute, p < 0.001) of test was lower for patients than controls. Heart rate recovery was similar between groups. Heart rate in relation to workload was higher for patients than controls both at midpoint and maximal effort. Heart rate in relation to oxygen uptake was similar between groups throughout test. Oxygen pulse, an indirect surrogate measure of stroke volume, was reduced at maximal effort in patients compared to controls (6.6 ± 1.1 versus 7.5 ± 1.4 ml·beat-1·m-2, p < 0.05) and increased significantly less from midpoint to maximal effort for patients than controls (p < 0.05).
Conclusions: Heart rate is increased in relation to workload in Fontan patients compared with controls. At higher loads, Fontan patients seem to have reduced heart rate and smaller increase in oxygen pulse, which may be explained by inability to further increase stroke volume and cardiac output. Reduced ability to increase or maintain stroke volume at higher heart rates may be an important limiting factor for maximal cardiac output, oxygen uptake, and physical performance.

Ventilatory compensation during the incremental exercise test is inversely correlated with air trapping in COPD.

Kuint R; Berkman N; Nusair S;

F1000Research [F1000Res] 2019 Sep 19; Vol. 8, pp. 1661. Date of Electronic Publication: 2019 Sep 19 (Print Publication: 2019).

Background: Air trapping and gas exchange abnormalities are major causes of exercise limitation in chronic obstructive pulmonary disease (COPD). During incremental cardiopulmonary exercise testing, ventilatory equivalents for carbon dioxide (V E /VCO 2 ) and oxygen (V E /VO 2 ) may be difficult to identify in COPD patients because of limited ventilatory compensation capacity. Therefore, we aimed to detect a possible correlation between the magnitude of ventilation augmentation, as manifested by increments in ventilatory equivalents from nadir to peak effort values and air trapping, detected with static testing.
Methods: In this observational study, we studied data obtained previously from 20 COPD patients who, during routine follow-up, underwent a symptom-limited incremental exercise test and in whom a plethysmography was obtained concurrently. Air trapping at rest was assessed by measurement of the residual volume (RV) to total lung capacity (TLC) ratio (RV/TLC). Gas exchange data collected during the symptom-limited incremental cardiopulmonary exercise test allowed determination of the nadir and peak effort values of V E /VCO 2 and V E /VO 2 , thus enabling calculation of the difference between peak effort value and nadir values of  V E /VCO 2 and V E /VO 2 , designated ΔV E /VCO 2 and ΔV E /VO 2 , respectively.
Results: We found a statistically significant inverse correlation between both ΔV E /VCO 2 (r = -0. 5058, 95% CI -0.7750 to -0.08149, p = 0.0234) and ΔV E /VO 2 (r = -0.5588, 95% CI -0.8029 to -0.1545, p = 0.0104) and the degree of air trapping (RV/TLC). There was no correlation between                ΔV E /VCO 2 and peak oxygen consumption, forced expiratory volume in the first second, or body mass index.
Conclusions: The ventilatory equivalents increment to compensate for acidosis during incremental exercise testing was inversely correlated with air trapping (RV/TLC) and may be a candidate prognostic biomarker.

Clinical recommendations for cardiopulmonary exercise testing in children with respiratory diseases.

Powell AW; Veldtman G;

The Canadian Journal of Cardiology [Can J Cardiol] 2019 Nov 15. Date of Electronic Publication: 2019 Nov 15.

Background: Patients with univentricular physiology palliated with the Fontan operation have multiple late cardiovascular and extracardiac complications, including autonomic dysfunction. Despite the observation, little is known about autonomic function driving exercise-related heart rate responses in Fontan patients and whether dominant ventricle subtype or underlying cardiac anatomy affects heart rate responses during exercise.
Methods: We performed a retrospective chart review of all single ventricle patients palliated with a Fontan operation who underwent a maximal effort cardiopulmonary exercise test at Cincinnati Children’s Hospital Medical Center from 2013 to 2018.
Results: One hundred and three Fontan patients aged 16.7 ± 5.5 years were included in this study. Although both the systemic right (n = 38) and systemic left (n = 65) ventricle groups demonstrated chronotropic incompetence, there were no differences between the groups in maximal heart rate (167.5 ± 17.4 vs 169.6 ± 20.9 bpm, P = 0.59), heart rate reserve (87.3 ± 22.6 vs 96.8 ± 25.7, P = 0.06) nor chronotropic index (70 ± 13% vs 74 ± 20%, P = 0.19). In addition, there were no differences between the groups in heart rate recovery at 1, 3, 5, and 10 minutes. Interestingly, patients with hypoplastic left heart syndrome (n = 34) had lower heart rate reserve (84.76 ± 22.8 vs 96.38 ± 26.75, P = 0.04) and chronotropic index (70.5 ± 12.5% vs 76.3 ± 13.2%, P = 0.04) compared with patients with tricuspid atresia (n = 42).
Conclusions: Fontan patients commonly have chronotropic incompetence, diminished heart rate reserve but with preserved heart rate recovery. Although there is overall no difference in chronotropy in Fontan patients based on dominant systemic ventricle, there is a difference between patients with hypoplastic left heart syndrome and those with tricuspid atresia.

Knee extensor muscle strength as a predictor of peak oxygen uptake in patients with heart disease.

Yokote T; Koga H; Eriguchi K; Imamura Y;

Journal of physical therapy science [J Phys Ther Sci] 2020 Apr; Vol. 32 (4), pp. 265-268. Date of Electronic Publication: 2020 Apr 02.

[Purpose] The mortality rate increases when peak oxygen uptake is less than 5 metabolic equivalents, and peak oxygen uptake correlates with knee extensor muscle strength. This study aimed to determine the knee extensor muscle strength at peak oxygen uptake corresponding to 5 metabolic equivalents.
[Participants and Methods] We enrolled 45 consecutive patients (29 males and 16 females; average age, 63.6 ± 13.7 years) with heart disease receiving outpatient rehabilitation with us. We performed cardiopulmonary exercise testing with a bicycle ergometer to measure peak oxygen uptake. We investigated the relationship between peak oxygen uptake and isometric knee extensor muscle strength divided by the body weight (kgf/kg). The cutoff value for knee extensor muscle strength with peak oxygen uptake corresponding to 5 metabolic equivalents was calculated.
[Results] Knee extensor muscle strength was significantly positively associated with peak oxygen uptake. The cutoff value for knee extensor muscle strength at peak oxygen uptake corresponding to 5 metabolic equivalents was 0.46 kgf/kg.
[Conclusion] In this study, the cutoff value for knee extensor muscle strength for achieving peak oxygen uptake corresponding to 5 metabolic equivalents in patients with heart disease was 0.46kgf/kg.

Clinical recommendations for cardiopulmonary exercise testing in children with respiratory diseases.

Takken T; Sonbahar Ulu H; Hulzebos EH;

Expert review of respiratory medicine [Expert Rev Respir Med] 2020 Apr 07. Date of Electronic Publication: 2020 Apr 07.

Introduction : Cardiopulmonary exercise testing (CPET) quantitates and qualitates the integrated physiological response of a person to incremental exercise and provides additional information compared to static lung function tests alone.
Areas covered : This review covers rationale for the use of CPET parameters beyond the usual parameters like peak oxygen uptake and peak minute ventilation in children with respiratory disease.
Expert opinion : CPET provides a wealth of data from rest, submaximal and maximal exercise and data during recovery from exercise. In this review an interpretative approach is described for analyzing CPET data in children with respiratory disease.