Project description:Cystic fibrosis (CF) is a debilitating chronic condition, which requires complex and expensive disease management. Exercise has now been recognised as a critical factor in improving health and quality of life in patients with CF. Hence, cardiopulmonary exercise testing (CPET) is used to determine aerobic fitness of young patients as part of the clinical management of CF. However, at present there is a lack of conclusive evidence for one limiting system of aerobic fitness for CF patients at individual patient level. Here, we perform detailed data analysis that allows us to identify important systems-level factors that affect aerobic fitness. We use patients' data and principal component analysis to confirm the dependence of CPET performance on variables associated with ventilation and metabolic rates of oxygen consumption. We find that the time at which participants cross the gas exchange threshold (GET) is well correlated with their overall performance. Furthermore, we propose a predictive modelling framework that captures the relationship between ventilatory dynamics, lung capacity and function and performance in CPET within a group of children and adolescents with CF. Specifically, we show that using Gaussian processes (GP) we can predict GET at the individual patient level with reasonable accuracy given the small sample size of the available group of patients. We conclude by presenting an example and future perspectives for improving and extending the proposed framework. The modelling and analysis have the potential to pave the way to designing personalised exercise programmes that are tailored to specific individual needs relative to patient's treatment therapies.
Project description:Cardiopulmonary exercise testing (CPET) has become an important clinical tool to evaluate exercise capacity and predict outcome in patients with heart failure and other cardiac conditions. It provides assessment of the integrative exercise responses involving the pulmonary, cardiovascular and skeletal muscle systems, which are not adequately reflected through the measurement of individual organ system function. CPET is being used increasingly in a wide spectrum of clinical applications for evaluation of undiagnosed exercise intolerance and for objective determination of functional capacity and impairment. This review focuses on the exercise physiology and physiological basis for functional exercise testing and discusses the methodology, indications, contraindications and interpretation of CPET in normal people and in patients with heart failure.
Project description:BackgroundNew therapies with prognostic benefits have been recently introduced in heart failure with reduced ejection fraction (HFrEF) management. The aim of this study was to evaluate the prognostic power of current listing criteria for heart transplantation (HT) in an HFrEF cohort submitted to cardiopulmonary exercise testing (CPET) between 2009 and 2014 (group A) and between 2015 and 2018 (group B).MethodsConsecutive patients with HFrEF who underwent CPET were followed-up for cardiac death and urgent HT.ResultsCPET was performed in 487 patients. The composite endpoint occurred in 19.4% of group A vs. 7.4% of group B in a 36-month follow-up. Peak VO2 (pVO2) and VE/VCO2 slope were the strongest independent predictors of mortality. International Society for Heart and Lung Transplantation (ISHLT) thresholds of pVO2 ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers) and VE/VCO2 slope > 35 presented a similar and lower Youden index, respectively, in group B compared to group A, and a lower positive predictive value. pVO2 ≤ 10 mL/kg/min and VE/VCO2 slope > 40 outperformed the traditional cut-offs. An ischemic etiology subanalysis showed similar results.ConclusionISHLT thresholds showed a lower overall prognostic effectiveness in a contemporary HFrEF population. Novel parameters may be needed to improve risk stratification.
Project description:Accurate prediction of survival for cystic fibrosis (CF) patients is instrumental in establishing the optimal timing for referring patients with terminal respiratory failure for lung transplantation (LT). Current practice considers referring patients for LT evaluation once the forced expiratory volume (FEV1) drops below 30% of its predicted nominal value. While FEV1 is indeed a strong predictor of CF-related mortality, we hypothesized that the survival behavior of CF patients exhibits a lot more heterogeneity. To this end, we developed an algorithmic framework, which we call AutoPrognosis, that leverages the power of machine learning to automate the process of constructing clinical prognostic models, and used it to build a prognostic model for CF using data from a contemporary cohort that involved 99% of the CF population in the UK. AutoPrognosis uses Bayesian optimization techniques to automate the process of configuring ensembles of machine learning pipelines, which involve imputation, feature processing, classification and calibration algorithms. Because it is automated, it can be used by clinical researchers to build prognostic models without the need for in-depth knowledge of machine learning. Our experiments revealed that the accuracy of the model learned by AutoPrognosis is superior to that of existing guidelines and other competing models.
Project description:BackgroundCardiopulmonary exercise testing is an increasingly common test and is considered the accepted standard for assessing exercise capacity. Quantifying variability is important to assess the instrument for quality control purposes. Though guidelines recommend biologic control testing, there are minimal data on how to do it. We sought to describe variability for oxygen consumption (V̇O2 ), carbon dioxide production (V̇CO2 ), and minute ventilation (V̇E) at various work rates under steady-state conditions in multiple subjects over a 1-y period to provide a practical approach to assess and perform biologic control testing.MethodsWe performed a single-center, prospective study with 4 healthy subjects, 2 men and 2 women. Subjects performed constant work rate exercise tests for 6 min each at 25-100 W intervals on a computer-controlled cycle ergometer. Data were averaged over the last 120 s at each work rate to reflect stepwise steady-state conditions. Descriptive statistics, including the mean, median, range, SD, and coefficient of variation (CoV) are reported for each individual across the 4 work rates and all repetitions. As these data were normative, z-scores were utilized, and a value greater than ± 1.96 z-scores was used to define significant test variability.ResultsSubjects performed 16-39 biocontrol studies over 1-y. The mean CoV for all subjects in V̇O2 was 6.59%, V̇CO2 was 6.41%, and V̇E was 6.32%. The ± 1.96 z-scores corresponded to a 9.4-18.1% change in V̇O2 , a 9.6-18.1% change in V̇CO2 , and a 9-21.5% change in V̇E across the 4 workloads.ConclusionsWe report long-term variability for steady-state measurement of V̇O2 , V̇CO2 , and V̇E obtained during biocontrol testing. Utilizing ± 1.96 z-scores allows one to determine if a result exceeds expected variability, which may warrant investigation of the instrument.
Project description:ImportanceCardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis.ObjectiveTo use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis.Design, setting and participantsThis single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months.Main outcomes and measuresComparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis.ResultsAmong the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]).Conclusions and relevanceIn this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.
Project description:BackgroundBronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients.MethodsCross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2).ConclusionsCPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis.Trial registrationClinicalTrials.gov, registration number: NCT03147651.
Project description:BackgroundCardiovascular disease and physical decline are prevalent and associated with morbidity/mortality in liver transplant (LT) patients. Cardiopulmonary exercise testing (CPX) provides comprehensive cardiopulmonary and exercise response assessments. We investigated cardiorespiratory fitness (CRF) and cardiac stress generated during CPX in LT candidates.MethodsLT candidates at 2 centers underwent CPX. Standard-of-care cardiac stress testing (dobutamine stress echocardiography, DSE) results were recorded. Physical function was assessed with liver frailty index and 6-min walk test. CPX/DSE double products were calculated to quantify cardiac stress. To better study the association of CPX-derived metrics with physical function, the cohort was divided into 2 groups based on 6-min walk test median (372 m).ResultsFifty-four participants (62 ± 8 y; 65% men, Model for End-Stage Liver Disease-Na 14 [10-18]) underwent CPX. Peak oxygen consumption was 14.1 mL/kg/min for an anerobic threshold of 10.2 mL/kg/min, with further CRF decline in the lower 6MWT cohort despite lack of liver frailty index-frailty in 90%. DSE was nondiagnostic in 18% versus 4% of CPX (P = 0.058). All CPX were negative for ischemia. A double product of ≥25 000 was observed in 32% of CPX and 11% of DSE (P = 0.020). Respiratory function testing was normal. No patient presented major cardiovascular events at 30 d post-LT.ConclusionsCPX provided efficient and effective combined cardiopulmonary risk and frailty assessments of LT candidates in a 1-stop test. The CRF was found to be very low despite preserved physical function or lack of frailty.
Project description:Unexplained exertional dyspnoea or fatigue can arise from a number of underlying disorders and shows only a weak correlation with resting functional or imaging tests. Noninvasive cardiopulmonary exercise testing (CPET) offers a unique, but still under-utilised and unrecognised, opportunity to study cardiopulmonary and metabolic changes simultaneously. CPET can distinguish between a normal and an abnormal exercise response and usually identifies which of multiple pathophysiological conditions alone or in combination is the leading cause of exercise intolerance. Therefore, it improves diagnostic accuracy and patient health care by directing more targeted diagnostics and facilitating treatment decisions. Consequently, CPET should be one of the early tests used to assess exercise intolerance. However, this test requires specific knowledge and there is still a major information gap for those physicians primarily interested in learning how to systematically analyse and interpret CPET findings. This article describes the underlying principles of exercise physiology and provides a practical guide to performing CPET and interpreting the results in adults.