Category Archives: Publications

Minute ventilation/carbon dioxide production in patients with dysfunctional breathing.

Watson M; Ionescu MF; Sylvester K; Fuld J;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Apr 13; Vol. 30 (160). Date of Electronic Publication: 2021 Apr 13 (Print Publication: 2021).

Dysfunctional breathing refers to a multi-dimensional condition that is characterised by pathological changes in an individual’s breathing. These changes lead to a feeling of breathlessness and include alterations in the biomechanical, psychological and physiological aspects of breathing. This makes dysfunctional breathing a hard condition to diagnose, given the diversity of aspects that contribute to the feeling of breathlessness. The disorder can debilitate individuals without any health problems, but may also be present in those with underlying cardiopulmonary co-morbidities. The ventilatory equivalent for CO 2 ( V eqCO 2 ) is a physiological parameter that can be measured using cardiopulmonary exercise testing. This review will explore how this single measurement can be used to aid the diagnosis of dysfunctional breathing. A background discussion about dysfunctional breathing will allow readers to comprehend its multidimensional aspects. This will then allow readers to understand how V eqCO 2 can be used in the wider diagnosis of dysfunctional breathing. Whilst V eqCO 2 cannot be used as a singular parameter in the diagnosis of dysfunctional breathing, this review supports its use within a broader algorithm to detect physiological abnormalities in patients with dysfunctional breathing. This will allow for more individuals to be accurately diagnosed and appropriately managed.

Ventilation/carbon dioxide output relationships during exercise in health.

Ward SA;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Apr 13; Vol. 30 (160). Date of Electronic Publication: 2021 Apr 13 (Print Publication: 2021).

“Ventilatory efficiency” is widely used in cardiopulmonary exercise testing to make inferences regarding the normality (or otherwise) of the arterial CO 2 tension ( P aCO 2 ) and physiological dead-space fraction of the breath ( V D / V T ) responses to rapid-incremental (or ramp) exercise. It is quantified as: 1) the slope of the linear region of the relationship between ventilation ( VE ) and pulmonary CO 2 output ( VCO 2 ); and/or 2) the ventilatory equivalent for CO 2 at the lactate threshold ( VE / VCO 2 [Formula: see text]) or its minimum value ( VE / VCO 2 min), which occurs soon after [Formula: see text] but before respiratory compensation. Although these indices are normally numerically similar, they are not equally robust. That is, high values for VE / VCO 2 [Formula: see text] and VE / VCO 2 min provide a rigorous index of an elevated V D / V T when P aCO 2 is known (or can be assumed) to be regulated. In contrast, a high VEVCO 2 slope on its own does not, as account has also to be taken of the associated normally positive and small VE intercept. Interpretation is complicated by factors such as: the extent to which P aCO 2 is actually regulated during rapid-incremental exercise (as is the case for steady-state moderate exercise); and whether VE / VCO 2 [Formula: see text] or VE / VCO 2 min provide accurate reflections of the true asymptotic value of VE / VCO 2 , to which the VEVCO 2 slope approximates at very high work rates.

Cardiopulmonary Exercise Testing in Athletes: Pearls and Pitfalls

Emery MS

American College of Cardiology. April 13:2021

Cardiopulmonary exercise testing (CPET) has been a valuable tool in medicine and sports performance for decades. However, the intercept of the fields, particularly in consideration of the utility of CPET, is relatively new with the growth of sports cardiology. CPET in medicine is generally indicated in the evaluation of unexplained dyspnea and/or for stratification of patients for heart or lung transplants. In sports performance, CPET has been used to provide details and parameters for the athlete to improve training and human performance. With the promotion of CPET in sports cardiology, it is now not uncommon to see an athlete performing exercise testing in the same lab as those patients undergoing heart transplant evaluations. With some athletes capable of achieving maximal oxygen uptake (VO2max) in excess of 60 ml/kg/min or greater than 140% of predicted, clinicians need to be aware of some fundamental differences in athletes that reflect normal physiology rather than a pathological response as would be encountered in patients with heart and lung disease.



Pulmonary function and COVID-19.

Thomas M; Price OJ; Hull JH;

Current opinion in physiology [Curr Opin Physiol] 2021 Mar 26. Date of Electronic Publication: 2021 Mar 26.

In people recovering from COVID-19, there is concern regarding potential long-term pulmonary sequelae and associated impairment of functional capacity. Data published thus far indicate that spirometric indices appear to be generally well preserved, but that a defect in diffusing capacity (DLco) is a prevalent abnormality identified on follow-up lung function; present in 20-30% of those with mild to moderate disease and 60% in those with severe disease. Reductions in total lung capacity were commonly reported. Functional capacity is also often impaired, with data now starting to emerge detailing walk test and cardiopulmonary exercise test outcome at follow-up. In this review, we evaluate the published evidence in this area, to summarise the impact of COVID-19 infection on pulmonary function and relate this to the clinico-radiological findings and disease severity.

Clinical Interpretation of Cardiopulmonary Exercise Testing: Current Pitfalls and Limitations.

Neder JA; Phillips DB; Marillier M; Bernard AC; Berton DC; O’Donnell DE;

Frontiers in physiology [Front Physiol] 2021 Mar 18; Vol. 12, pp. 552000. Date of Electronic Publication: 2021 Mar 18 (Print Publication: 2021).

Several shortcomings on cardiopulmonary exercise testing (CPET) interpretation have shed a negative light on the test as a clinically useful tool. For instance, the reader should recognize patterns of dysfunction based on clusters of variables rather than relying on rigid interpretative algorithms. Correct display of key graphical data is of foremost relevance: prolixity and redundancy should be avoided. Submaximal dyspnea ratings should be plotted as a function of work rate (WR) and ventilatory demand. Increased work of breathing and/or obesity may normalize peak oxygen uptake (V̇O 2 ) despite a low peak WR. Among the determinants of V̇O 2 , only heart rate is measured during non-invasive CPET. It follows that in the absence of findings suggestive of severe impairment in O 2 delivery, the boundaries between inactivity and early cardiovascular disease are blurred in individual subjects. A preserved breathing reserve should not be viewed as evidence that “the lungs” are not limiting the subject. In this context, measurements of dynamic inspiratory capacity are key to uncover abnormalities germane to exertional dyspnea. A low end-tidal partial pressure for carbon dioxide may indicate either increased “wasted” ventilation or alveolar hyperventilation; thus, direct measurements of arterial (or arterialized) PO 2 might be warranted. Differentiating a chaotic breathing pattern from the normal breath-by-breath noise might be complex if the plotted data are not adequately smoothed. A sober recognition of these limitations, associated with an interpretation report free from technicalities and convoluted terminology, is crucial to enhance the credibility of CPET in the eyes of the practicing physician.

Gut related inflammation and cardiorespiratory fitness in patients with CAD and type 2 diabetes: a sub-study of a randomized controlled trial on exercise training.

Aune SK; Byrkjeland R;  Solheim S; Arnesen H; Trøseid M; Awoyemi A; Seljeflot I; Helseth R;

Diabetology & metabolic syndrome [Diabetol Metab Syndr] 2021 Apr 01; Vol. 13 (1), pp. 36. Date of Electronic Publication: 2021 Apr 01.

Aim: Gut leakage has been shown to associate with low-grade inflammation and lower cardiorespiratory fitness in diabetic subjects. We aimed to investigate whether gut leakage markers related to cardiorespiratory fitness in patients with both coronary artery disease and type 2 diabetes, and whether these were affected by long-term exercise training.
Methods: Patients with angiographically verified coronary artery disease and type 2 diabetes mellitus (n = 137) were randomized to either 12 months exercise intervention or conventional follow-up. A cardiopulmonary exercise test and fasting blood samples were obtained before and after intervention to assess VO 2 peak and the biomarkers soluble CD14, lipopolysaccharide-binding protein and intestinal fatty-acid binding protein as markers of gut leakage.
Results: 114 patients completed the intervention satisfactory. VO 2 peak correlated inversely to sCD14 (r = - 0.248, p = 0.004) at baseline. Dividing sCD14 into quartiles (Q), VO 2 peak was significantly higher in Q1 vs. Q2-4 (p = 0.001), and patients in Q2-4 (sCD14 > 1300 ng/mL) had an OR of 2.9 (95% CI 1.2-7.0) of having VO 2 peak below median (< 23.8 ml/kg/min) at baseline. There were no statistically significant differences in changes in gut leakage markers between the two randomized groups (all p > 0.05) after 12 months.
Conclusions: Cardiorespiratory fitness related inversely to sCD14, suggesting physical capacity to be associated with gut leakage in patients with CAD and T2DM. Long-term exercise training did not affect circulating gut leakage markers in our population. Trial registration NCT01232608,

Comparison of non-exercise cardiorespiratory fitness prediction equations in apparently healthy adults.

Peterman JE; Whaley MH; Harber MP; Fleenor BS; Imboden MT; Myers J; Arena R; Kaminsky LA;

European journal of preventive cardiology [Eur J Prev Cardiol] 2021 Apr 10; Vol. 28 (2), pp. 142-148.

Aims: A recent scientific statement suggests clinicians should routinely assess cardiorespiratory fitness using at least non-exercise prediction equations. However, no study has comprehensively compared the many non-exercise cardiorespiratory fitness prediction equations to directly-measured cardiorespiratory fitness using data from a single cohort. Our purpose was to compare the accuracy of non-exercise prediction equations to directly-measured cardiorespiratory fitness and evaluate their ability to classify an individual’s cardiorespiratory fitness.
Methods: The sample included 2529 tests from apparently healthy adults (42% female, aged 45.4 ± 13.1 years (mean±standard deviation). Estimated cardiorespiratory fitness from 28 distinct non-exercise prediction equations was compared with directly-measured cardiorespiratory fitness, determined from a cardiopulmonary exercise test. Analysis included the Benjamini-Hochberg procedure to compare estimated cardiorespiratory fitness with directly-measured cardiorespiratory fitness, Pearson product moment correlations, standard error of estimate values, and the percentage of participants correctly placed into three fitness categories.
Results: All of the estimated cardiorespiratory fitness values from the equations were correlated to directly measured cardiorespiratory fitness (p < 0.001) although the R2 values ranged from 0.25-0.70 and the estimated cardiorespiratory fitness values from 27 out of 28 equations were statistically different compared with directly-measured cardiorespiratory fitness. The range of standard error of estimate values was 4.1-6.2 ml·kg-1·min-1. On average, only 52% of participants were correctly classified into the three fitness categories when using estimated cardiorespiratory fitness.
Conclusion: Differences exist between non-exercise prediction equations, which influences the accuracy of estimated cardiorespiratory fitness. The present analysis can assist researchers and clinicians with choosing a non-exercise prediction equation appropriate for epidemiological or population research. However, the error and misclassification associated with estimated cardiorespiratory fitness suggests future research is needed on the clinical utility of estimated cardiorespiratory fitness.

Heart rate recovery is useful for evaluating the recovery of exercise tolerance in patients with heart failure and atrial fibrillation.

Tanaka S; Miyamoto T; Mori Y; Harada T; Tasaki H;

Heart and vessels [Heart Vessels] 2021 Mar 30. Date of Electronic Publication: 2021 Mar 30.

This study aimed to examine the factors that contribute to improvement of exercise tolerance in patients with heart failure (HF) and atrial fibrillation (AF) following cardiac rehabilitation. Our hypothesis is that parasympathetic values are important for recovering exercise tolerance in those patients. We included 84 consecutive patients with HF and AF (mean age: 69 ± 15 years, 80% men). All of the patients underwent a cardiopulmonary exercise test and had pre and post 5 month cardiac rehabilitation assessed. After 155 ± 11 days and 44 ± 8 sessions, 73 patients (86%) showed an increase in peak oxygen uptake (VO 2 ) and VO 2 at the anaerobic threshold. In univariate linear regression analysis, the % change in heart rate recovery, plasma B-type natriuretic peptide levels, resting heart rate, and the minute ventilation /carbon dioxide output slope were significantly related to that of peak VO 2 (p < 0.01, p = 0.03, p = 0.02, p < 0.01, respectively). Stepwise multivariate linear regression analysis showed that the % change in heart rate recovery was independently related to that of peak VO 2 (p < 0.05). Our results suggest that heart rate recovery is closely associated with recovery of exercise tolerance in patients with HF and AF after CR.

Dyspnea in Chronic Low Ventricular Preload States.

Tooba R; Mayuga KA; Wilson R; Tonelli AR;

Annals of the American Thoracic Society [Ann Am Thorac Soc] 2021 Apr; Vol. 18 (4), pp. 573-581.

Dyspnea in low-preload states is an underrecognized but growing diagnosis in patients with unexplained dyspnea. Patients can often experience debilitating symptoms at rest and with exertion, as low measured preload often leads to decreased cardiac output and ultimately dyspnea. In the present article, we performed a review of the literature and a multidisciplinary evaluation to understand the pathophysiology, diagnosis, and treatment of dyspnea in low-preload states. We explored selected etiologies and suggested an algorithm to approach unexplained dyspnea. The mainstay of diagnosis remains as invasive cardiopulmonary exercise testing. We concluded with a variety of nonpharmacological and pharmacological therapies, highlighting that a multifactorial approach may lead to the best results.

VE/VCO2 slope predicts RV dysfunction and mortality after left ventricular assist device: a fresh look at cardiopulmonary stress testing for prognostication.

Grinstein J; Sawalha Y; Medvedofsky DA; Ahmad S;Hofmeyer M;  Rodrigo M; Kadakkal A; Barnett C; Kalantari S; Talati I; Zaghol R; Molina EJ; Sheikh FH; Najjar SS;

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs [J Artif Organs] 2021 Apr 01. Date of Electronic Publication: 2021 Apr 01.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO 2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.