Predicted Peak VO2 Research Articles

ASSESSING VO2 PEAK PREDICTION ACCURACY IN OLDER ADULTS IN CARDIOPULMONARY REHAB

https://youtu.be/OC7ttYm1LLU BACKGROUND Peak oxygen uptake (VO2 peak) is an important measure in cardiopulmonary rehabilitation (CR), reflecting cardiovascular health and guiding treatment. Clinical exercise tests predict VO2 using the ACSM model, which may overestimate VO2 peak for older adults in CR. Age-related changes and handrail support during exercise are not considered in most equations. Foster developed a prediction equation for older adults with handrail support, but it hasn’t been tested on CR patients. This study aims to evaluate the accuracy of VO2 peak prediction equations, including the ACSM equation and Foster equations (with and without handrail support), in older adults undergoing CR. METHODS CR patients (n=11, age: 69.5 ± 10.4 yrs) underwent a treadmill test measuring VO2 peak via gas exchange analysis. Predicted VO2 peak was calculated using the ACSM equation (modified Bruce protocol) and the Foster equation (Pepper protocol, with and without handrail support). Paired t-tests compared actual and predicted VO2 peak, and effect sizes were calculated. RESULTS The Foster model with handrail support provided the most accurate estimate of VO2 peak, but still overestimated it (Foster handrail: 18.06 ± 5.38 ml/kg/min vs. actual: 15.8 ± 6.4 ml/kg/min, p = 0.047). The ACSM model had the greatest discrepancy (ACSM: 21.27 ± 7.75 ml/kg/min vs. actual: 15.8 ± 6.4 ml/kg/min, p = 0.001), with a large effect size (Cohen’s d = -1.37). CONCLUSION The ACSM model significantly overestimated VO2 peak in CR patients, while the Foster handrail model provided the most accurate estimates, though still with some overestimation. These results emphasize the need for improved VO2 prediction models for clinical stress testing.

Natural shear wave elastography reveals hidden cardiac dysfunction in adult survivors of childhood cancer during cardiopulmonary stress testing

Abstract Background Hidden cardiotoxicity in adult survivors of childhood cancer may carry significant prognostic implications. Many of these survivors are asymptomatic at rest but show impaired cardiorespiratory fitness during exercise. Stress echocardiography combined with cardiopulmonary exercise testing (CPET) can reveal hidden diastolic dysfunction, although it presents major challenges. High frame rate (HFR) natural shear wave (SW) imaging is emerging as an innovative method for assessing myocardial stiffness, a key determinant of diastolic function. Purpose We investigated the relationship between natural SW measured at rest as a marker of myocardial stiffness and patient performance during CPET as markers of cardiorespiratory fitness. Methods A total of 115 subjects; 72 cancer survivors (mean age 20 ±4 years) and 43 matched healthy volunteers (HV) were recruited. We acquired both conventional as well as high frame rate echocardiographic images (ca. 1200 frames/second) at rest. During an incremental, symptom-limited cardiopulmonary exercise test on a treadmill, both peak and efficiency of oxygen consumption (VO2 peak and VO2/work slope) were recorded. All HFR data were analysed offline by drawing an anatomical M-mode along the ventricular septum in the parasternal long axis view, colour coded for tissue acceleration. SW after mitral valve closure (MVC) appeared as green bands and their velocities were measured by estimating the slope semi-automatically. Results In our survivors’ cohort, the prevalence of cardiac dysfunction based on reduced global longitudinal strain was 9.7%. In a univariate regression model, predictors of peak VO2 were age, body mass index (BMI), systolic blood pressure (SBP), left ventricular end-diastolic diameter (LVEDD), left atrial volume indexed (LAVi), mitral inflow to mitral relaxation velocity ratio (E/e’) and SW velocities after MVC. In the multivariate model, SW velocities remained as the strongest predictor for peak VO2, followed by LVEDD, BMI and SBP (Figure 1). Moreover, natural SWs correlate significantly with both peak VO2 and VO2/work slope (r= -0.65; p <0.001, and r=-0.31; p =0.002 respectively) (Figure 2A&B). Interestingly, SW velocities were on average significantly higher in survivors with reduced peak VO2 (non-fit survivors) compared to both survivors with normal peak VO2 (fit survivors) and HV (4.2 ±0.6 m/s vs 3.5 ±0.5 m/s & 3.2 ±0.3 m/s respectively; p <0.001) (Figure 2C). Conclusions Our preliminary data indicate that natural SW velocities measured at rest are related to cardiorespiratory fitness and can identify hidden cardiac dysfunction among childhood cancer survivors. Natural SW elastography appears as promising and innovative echocardiographic parameter for early detection of cardiac dysfunction in follow-up of adult survivors of childhood cancer. Figure 1 Figure 2

Effect of obesity on cardiovascular remodeling, and aerobic capacity in adults with coarctation of aorta.

We hypothesized that patients with coarctation of aorta (COA) and obesity would have more advanced cardiovascular remodeling and impaired aerobic capacity compared to COA patients without obesity. The purpose of this study was to assess the relationship between obesity, cardiovascular remodeling, and aerobic capacity in adults with repaired COA. The study comprised of 3 groups: (1) Obese COA group (n=177) (COA patients with body mass index [BMI] >30 kg/m2); (2) Non-obese COA group (n=572) (COA patients with BMI ≤30 kg/m2); (3) Control group (n=59) (subjects without structural heart disease and BMI ≤30 kg/m2). Cardiovascular remodeling was assessed using the following indices: (1) Arterial stiffness - total arterial compliance index (TACI). (2) Left ventricular hypertrophy - LV mass (LVM) and relative wall thickness (RWT). (3) LV diastolic function - Doppler-derived estimated LV end-diastolic pressure (LVEDP) and Tau. (4) Right ventricular (RV)-pulmonary artery coupling - RV free wall strain and RV systolic pressure (RVFW/RVSP). Aerobic capacity was assessed using predicted peak oxygen consumption (VO2). The obese COA group had higher LVM, RWT, LVEDP, and Tau, as well as lower RVFWS/RVSP, TACI and peak VO2 compared to non-obese COA group and controls. There was a correlation between BMI and LVM (r=0.39, p<0.001), RWT (r=0.47, p<0.001), LVEDP (r=0.43, p<0.001), tau (r=0.22, p=0.008), RVFWS/RVSP (r=- 0.24, p<0.001), and predicted peak VO2 (r=-0.48, p<0.001). These findings underscore the cardiovascular implications of obesity in the setting of COA, and provide opportunities for interventions to address obesity, and improve outcomes in this population.

Aerobic Capacity of Adults With Fontan Palliation: Disease-Specific Reference Values and Relationship to Outcomes.

Patients with Fontan palliation have reduced aerobic capacity because of impaired cardiac, pulmonary, and skeletal muscle function. However, the assessment of aerobic capacity in this population still relies on comparisons with people without cardiovascular disease rather than comparison with the expected aerobic capacity of other Fontan patients. The purpose of this study was to determine the expected aerobic capacity of adults with Fontan palliation. Adults with Fontan palliation who underwent a cardiopulmonary exercise test at Mayo Clinic (2003-2023) were stratified into quartiles based on the predicted peak oxygen consumption (VO2). We assessed the correlates of predicted peak VO2 and the relationship between predicted peak VO2 quartiles and cardiovascular outcomes (death/transplant). Of 323 patients (age, 29±9 years; 177 [55%] men), the median peak VO2 was 19.1 (15.2-23.9) mL/kg per minute, and this corresponds to a predicted peak VO2 of 51% (range, 19-88; interquartile range, 41-62). After multivariable adjustments, the correlates of predicted peak VO2 were body mass index (β±SE, -2.61±0.95; 2.61% decrease in predicted peak VO2 per 5 kg/m2 increase in body mass index; P=0.009), systemic saturation (β±SE, 3.65±0.85; 3.65% increase in predicted peak VO2 per 5% increase in oxygen saturation; P<0.001), and Fontan pressure (β±SE, -1.24±0.22; 1.24% decrease in predicted peak VO2 per 1 mm Hg increase in Fontan pressures; P<0.001). There was a 47% increase in the risk for death/transplant from a higher predicted peak VO2 quartile to the next lower quartile (adjusted hazard ratio, 1.47 [95% CI, 1.09-2.05]; P=0.01). The results of the current study would help calibrate the interpretation of exercise test data in adults with Fontan palliation and improve risk stratification in this population. It also underscores the need to maintain normal Fontan hemodynamics and body weight, which are important determinants of aerobic capacity.

Association of Step Count with Cardiorespiratory Fitness: Results from the Virtual 2-Minute Step Test.

To test the hypothesis that step count based on a virtual 2-minute step test (2MST) predicts cardiorespiratory fitness (CRF). Cross-sectional study. Veteran Affairs Medical Centers participating in a randomized trial of functional exercise training delivered by videoconferencing. People with human immunodeficiency virus (HIV) (PWH) who were aged ≥50 years and clinically stable on antiretroviral therapy were eligible for the trial. Consecutive male participants who were enrolled prior to November 9, 2023 and completed a baseline 2MST and cardiopulmonary exercise test (CPET) were included in the cross-sectional study (N=74). None. Step count was measured by a 2MST performed by live videoconferencing using the Rikli and Jones protocol. CRF was measured by peak oxygen utilization (VO2peak) during a modified Bruce cardiopulmonary exercise testing. Most participants (62.2%) were ≥60 years of age. The mean (SD) VO2peak was 23.6 (5.7) mL/kg/min, which represented 72.4% (SD, 14.1) of expected VO2peak. Step count correlated with VO2peak (r=0.47, P<.001). Multivariable linear regression showed that step count was significantly associated with VO2peak independently of age and body mass index. Based on this model, the prediction of VO2peak based on step count explained 60% of the variance in VO2peak. A Bland-Altman plot showed good agreement between predicated and measured VO2peak without heteroscedasticity. The virtual 2MST predicted VO2peak independently of age and body mass index in men with well-controlled HIV. In ambulatory populations with known impaired cardiorespiratory fitness, the virtual 2MST may be a feasible and valid estimate of VO2peak that can be used in the telerehabilitation setting. Future work is required in more demographically diverse individuals with various chronic conditions.

Abstract 4138282: Effect of cardiopulmonary exercise testing parameters and global longitudinal strain on survival after surgery for severe primary mitral regurgitation

Background: Optimum timing of surgery for severe primary mitral regurgitation (MR) particularly in the absence of significant symptoms or echo evidence of LV impairment remains unclear. Other modalities of assessment include cardiopulmonary exercise testing (CPET) and novel echo measurements, such as LV global longitudinal strain (LVGLS). We sought to evaluate whether pre-op CPET or LVGLS are associated with survival after surgery. Methods: We identified consecutive patients who had surgery for severe primary MR between 2007 and 2017 and had pre-op CPET. Clinical and mortality data were collected from chart review and our institutional database. LVGLS was retrospectively collected by a single person blinded to patient outcomes. Primary outcome was post surgery all cause death, and we used univariable analysis to identify variables associated with all cause death. Results: We included 176 patients with median age 63 (IQR 51, 71) years, 63 patients (35.8%) were female and 31 patients (14.8%) had a history of atrial fibrillation. 165 patients (93.8%) had mitral repair, 18 (10.2%) had concomitant CABG, 22 (12.5%) had concomitant ablation procedure and 14 (8.0%) had concomitant tricuspid procedure. 114 patients (64.8%) were in NYHA Class I and 56 (31.8%) were in NYHA Class II. There was no operative mortality. Median % predicted peak VO2 (ppVO2) was 89 (74, 101), median ventilatory equivalent of carbon dioxide (VE/VCO2) was 28.0 (25.7, 31.0) l/min/l/min and median respiratory exchange ratio was 1.2 (1.1, 1.2). 73 patients (41.5%) had abnormal CPET (defined as ppVO2&lt;85%). Median LVEF was 65 (60, 68) %, median LVESD was 35 (32, 38) mm and median LVGLS was 18.5 (16.6, 20.3) %. 45 patients (25.9%) had abnormal LVEF (defined as ≤ 60%), 11 patients (6.7%) had abnormal LVESD (defined as ≥45mm) and 35 patients (20.8%) had abnormal LVGLS (defined as &lt;16%). At a median follow up of 10.2 (6.8, 13.2) years, there were 19 (10.8%) deaths. In the univariate analysis, age at surgery (HR 1.12, p&lt;0.001), LVESD (HR 1.11, p=0.009), LVGLS (HR 1.11, p=0.013) and VE/VCO2 (HR 1.08, p=0.044) were associated with all cause mortality. Conclusion: A significant proportion of patients with no or mild symptoms exhibit echocardiographic evidence of LV impairment when having surgery for severe primary MR. CPET parameters such as VE/VCO2 and novel echocardiographic measurements such as LVGLS may predict risk of long term mortality and potentially inform timing of surgery in these patients.

Comparative study of the effects of preferential left ventricular and biventricular pacing on echocardiographic and cardiorespiratory indices and clinical status of heart failure patients: preliminary

Abstract Introduction Nonresponse to cardiac resynchronization therapy (CRT) has been related with right ventricular dysfunction. Preferential left ventricular pacing (pLV-P) can achieve left ventricle resynchronization allowing for intrinsic activation of the right side, and benefit cardiac output while reducing atrial fibrillation occurrence. Moreover, the AdaptivCRT® algorithm also automatically adjusts interventricular (V-V) delay every minute. Methods We evaluated the effects of a pLVP algorithm on 100 systolic heart failure patients ( all Caucasians, 49% male; 67 +/- 8 years old; 51% ischemic cardiomyopathy; 44% diabetics; NYHA II-III) following randomization to standard biventricular pacing and pLVP, on echocardiographic and cardiopulmonary exercise test indices of functional status. Device programming was based on echocardiography-evaluated maximization of stroke volume and subsequent interventricular and atrioventricular delay adjustments delegated to the device. The follow-up consisted of 6 and 12-months visits; after the 1rst month of optimizing maximum CRT response. Results Significant comparative effects of pLV-P over optimized CRT were noted regarding right ventricle systolic velocity in TDI at 12-months from baseline (mean (SE); 4.5(0.8), p=0.035); decrease in end-diastolic volume of left ventricle (mean (SE); 11.33(7), p=0.035); decrease in right ventricle strain mean ((SE); 9.2(2.1), p=0.03). According to other echocardiographic indices, again taking into account baseline levels, patients in pLV-P group exhibited lower E/e value at 6-months (mean (SE); 8.390(4,3), p=0.04), and at 12 -months (mean (SE); 7.45(3.9), p=0.035); improved values in left atrium contractility strain at 12-months (mean (SE); 8.390(0.8), p=0.04); a borderline improvement in left ventricular ejection fraction (mean (SE); 8.7(433), p=0.05) at 12-months; and borderline improvement in left ventricular longitudinal strain at 6-months (mean (SE); 4.9(2.6), p=0.035), compared to optimized CRT. In CPET, taking into account baseline levels, patients in the pLVP group showed higher METs at 12-months (mean (SE); 1,16(0.8), p=0.03) compared to opt CRT group; higher predicted Ventilation rate (%) even from 6-months (mean (SE); 8.167(5,7), p=0.03) and higher predicted peak VO2 (%) at 6 months (mean (SE); 34,13(14), p=0.03) and borderline significance at 12 months (mean (SE); 4.88(3), p=0.08), compared to opt CRT. Conclusions In the preliminary findings of READAPT study, it seems that pLVP optimized by a standardized echocardiographic protocol in patients with preserved AV conduction and LBBB, can achieve improvement in parameters of right ventricular and left atrium structure and function, as well as in survival-predictive parameters of CPET compared to optimized CRT during the 12-months of follow-up.

Coronary microvascular dysfunction as assessed by cardiac MRI and its association with aerobic exercise capacity in dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) has a poor prognosis. Aerobic exercise capacity (peak VO2) is an independent predictor of mortality but the central mechanisms contributing to exercise intolerance in DCM are unknown. Purpose To characterise myocardial perfusion reserve (MPR) and determine if cardiovascular magnetic resonance (CMR) measures of structure, function and microvascular function are associated with aerobic exercise capacity in DCM. Methods Single centre, prospective, case-control comparison of adults with DCM and matched controls. Adenosine-stress perfusion CMR to assess cardiac structure, function and quantitative perfusion, and cardiopulmonary exercise testing (CPET) to determine peak VO2, was performed. Controls were propensity matched based on age, sex, body mass index and diabetes status, and between group comparison was adjusted for other key clinical characteristics (CMR: ethnicity and systolic blood pressure; CPET: ethnicity, systolic blood pressure, smoking history and lung disease). Comparison of perfusion in segments with and without late gadolinium enhancement was performed using mixed effects linear regression taking into account individual patient segmental perfusion. Pre-specified multivariable linear regression, including key clinical and cardiac variables, was undertaken in patients with DCM to identify independent associations with percentage predicted peak VO2, which incorporates age, sex, height and weight. Results Sixty-six patients with DCM (median age 61 years, 71% male) were matched to 66 controls (median age 59 years, 71% male). The DCM group had greater left ventricular (LV) end-diastolic and end-systolic volumes, lower systolic and diastolic function, and had more focal and diffuse fibrosis compared to controls (Table 1). There was lower rest (0.58±0.14 versus 0.65±0.17 mL/min/g; P=0.033) and stress (1.53±0.49 versus 2.01±0.60 mL/g/min; P&amp;lt;0.001) myocardial blood flow, and lower MPR (2.69±0.84 versus 3.15±0.84 mL/g/min; P=0.002) in the DCM group. In DCM patients, mixed effects linear regression demonstrated lower rest (adjusted mean 0.54(95% CI 0.50-0.57) versus 0.58(0.55-0.62) mL/g/min; P&amp;lt;0.001) and stress MBF (1.38(1.25-1.51) versus 1.55(1.43-1.67) mL/g/min; P&amp;lt;0.001) in segments with LGE compared to segments without LGE, but there was no difference in MPR (2.71(2.47-2.96) versus 2.76(2.55-2.97) mL/g/min; P=0.496). DCM patients had markedly lower peak VO2 (19.8±5.5 versus 25.2±7.3 mL/kg/min; P&amp;lt;0.001). Multivariable linear regression demonstrated that LV ejection fraction, extracellular volume fraction and MPR, but not LV mass, were independently associated with percentage predicted peak VO2 in DCM (R squared=0.531, P&amp;lt;0.001; Table 2). Conclusions DCM patients have lower rest and stress myocardial blood flow and lower MPR compared to controls. In DCM, MPR, LV ejection fraction and fibrosis are independently associated with aerobic exercise capacity.

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope &amp;gt;3mmHg/L/min) was recently associated with worse outcome in &amp;gt;moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with &amp;gt;moderate PMR, no/discordant symptoms, preserved LV function and without &amp;gt;moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs &amp;lt;80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with &amp;gt;moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

Cardiopulmonary exercise testing predicts risk of progressive heart failure and long term mortality in ambulatory patients awaiting isolated heart transplant

Abstract Introduction Cardiopulmonary exercise testing (CPET) parameters such as peak VO2 ≤ 14ml/kg/min, percentage predicted peak VO2 (ppVO2) ≤ 50% and ventilation equivalent of carbon dioxide (Ve/VCO2) &amp;gt;35 l/min/l/min are recommended thresholds to list for isolated heart transplant. There is minimal data on clinical events after listing to guide clinical management or priority in organ allocation. Purpose To assess the effect of peak VO2, ppVO2, Ve/VCO2 on clinical events after listing for isolated heart transplant. Methods In a single centre retrospective study, we identified patients who were status 6 or status 2 prior to 2018 at time of listing for isolated heart transplant between 2007 and 2021. Clinical data were collected by chart review. Primary outcome of progressive heart failure was defined as death or upgrade in transplant priority status (new inotropes or mechanical circulatory support). Comparison was made between peak VO2 strata (&amp;gt; 14 vs ≤ 14 ml/kg/min), ppVO2 strata (&amp;gt; 50% vs 40-50% vs &amp;lt;40%) and Ve/VCO2 strata (&amp;lt;35 vs &amp;gt;35 l/min/l/min). Secondary outcome was time dependent survival after listing for heart transplant. Results We identified 141 patients of which 133 underwent CPET and follow up was available for 130 who were included in the analysis. Median age was 53 years (interquartile range 41-59 years), 29.1% of patients were female. Median peak VO2 was 14.0 ml/kg/min (11.2-15.7), ppVO2 was 44% (36-52), Ve/VCO2 slope was 34.0 (31.0-37.0) and RER was 1.1 (1.1-1.2). 87 patients had progressive heart failure consisting of 34 deaths and 83 patients having upgrade in priority status. There was a significant difference in risk of progressive heart failure comparing peak VO2 strata (Figure 1) (freedom from event at one year 71.4% with peak VO2 &amp;gt; 14 vs 46.5% with peak VO2 ≤ 14, p=0.00061) and ppVO2 strata (Figure 2) (freedom from event at one year 75.0% with ppVO2 &amp;gt;50% vs 61.2% with ppVO2 40-50% vs 42.6% with ppVO2 &amp;lt;40%, p=0.0015). There was no significant difference with Ve/VCO2 strata (freedom from event at one year 59.8% with Ve/VCO2 &amp;lt;34 vs 54.9% with Ve/VCO2 &amp;gt;34, p=0.52). There were 34 deaths before transplant and 23 deaths after transplant. 87 patients underwent transplant. In a time dependent survival analysis, age, gender and ppVO2&amp;lt;50% (HR 1.65 (0.87-3.12)) were not significant predictors of mortality. Both early transplant (defined as &amp;lt; 1 year after listing, HR 0.14 (0.06-0.34) and late transplant (defined as &amp;gt; 1 year after listing, HR 0.16 (0.08-0.32)) were significant predictors of lower mortality whilst Ve/VCO2&amp;gt;35 (HR 2.09 (1.19-3.68)) was a significant predictor of higher mortality. Conclusions Peak VO2 and ppVO2 stratify risk of progressive heart failure in ambulatory patients awaiting isolated heart transplant. However, Ve/VCO2 is a predictor of significantly higher mortality. These findings should affect clinical management and transplant priority status; and influence revision of future guidelines.Freedom from event by peak VO2 strataFreedom from event by ppVO2 strata

Cardio-pulmonary exercise testing in adult congenital heart patients: a new data-focused approach to predict mortality

Abstract Background/Introduction The cardio-pulmonary exercise test (CPET) has been a pivotal tool for functional and prognostic evaluation in adults with congenital heart disease (ACHD). During a routine CPET test, a myriad of variables are collected reflecting the cardiovascular, pulmonary, and skeletal muscle systems. However, clinicians typically use only a few easily and accessible variables to establish prognosis, which can come at an accuracy cost. Machine learning algorithms have undergone significant development in recent years and have found applications in the medical field. One of their main advantages is the ability to handle a large number of variables and extract information from their various combinations, while excluding redundant data, thus offering a higher level of prediction accuracy. Purpose Our objective was to develop a machine learning model to predict death during follow-up in a large population of ACHD patients who have undergone routine CPET in a large-volume single specialist centre. Methods All available CPET studies for adult ACHD patients (age &amp;gt; 15 years) performed from December 1999 to December 2021 at our centre were included, and all standard available variables were extracted. The primary outcome was all-cause mortality since the CPET, collected up to November 2023. Data exploration, data cleaning, and feature engineering steps were conducted using Python (v3.8). Continuous variables were standardised. The supervised machine learning algorithm XGBoost was used for classification (all-cause mortality), with the best hyperparameters selected through cross-validation. For the final model, a feature importance analysis based on permutation techniques was used to explore the variables with more impact on model accuracy. Results A total of 6361 studies were included, with median age of 31 years (IQR 23-43), 56% male. During follow-up, a total of 491 deaths were recorded. Of available demographic, clinical and exercise parameters (n=129 variables), 21 were deemed sufficient in terms of completeness, absence of significant correlation and clinically relevant for the subsequent analysis. These included demographic variables (age and sex) and CPET variables (peak VO2, FEV1, peak heart rate, exercise time, etc.) and were used to train the model. The accuracy of the model in predicting death after CPET in the test set had an accuracy of 93.5% and an area under the ROC curve (AUC) of 85.0% (Figure1). The parameters with the highest relative feature importance were FEV1, body mass index and percent predicted peak VO2 (Figure 2). Conclusions Machine learning models can be effectively employed in specialised cardiac populations, such as ACHD, potentially providing a high level of prediction accuracy by efficiently harnessing the potential of available data. However, its applicability to mortality prediction for ACHD patients requires further external validation.ROC curve AUC for the model predictionsFeature importance using permutation

The home-based breathing and chest mobility exercise improves cardiorespiratory functional capacity in long COVID with cardiovascular comorbidities: a randomized study

BackgroundBeyond the acute phase, a considerable proportion of patients recovering from the coronavirus disease 2019 (COVID-19) experience long-term sequelae that profoundly impact their quality of life, particularly their physical fitness. This study aims to assess the effect of home-based breathing and chest mobility exercise on the cardiorespiratory functional capacity of long COVID with cardiovascular comorbidity.MethodsIn this randomized, controlled, single-blind clinical trial, 46 long COVID with cardiovascular comorbidities were randomly assigned to either intervention or control group. The intervention group (n = 23) received additional home-based breathing and chest mobility exercise 3x/week for 12 weeks supervised by attending physicians, whereas the control group only received a home-based cardiac rehabilitation program. Baseline and post-intervention assessments consisted of laboratory (D-Dimer and CRP levels) and functional capacity, assessed through 6-minute walking test (6-MWT), exercise stress test’s metabolic equivalents (METS), and predicted peak oxygen consumption (VO2 peak), peak expiratory flow rate (PEFR), peak cough flow (PCF), chest expansion, and EuroQoL’s quality of life. Intention to treat analysis was performed.ResultsAt the 12th week, intervention subjects had significantly greater functional capacity with higher mean PEFR (p = .031) and PCF (p = .016). Similarly, 6-MWT was higher in the group receiving home-based breathing and chest mobility training (p = .032). The bottom part of the chest circumference was statistically different between the two groups (p = .01). METS and predicted VO2 peak were also higher in the intervention group. However, laboratory parameters and quality of life did not differ markedly (p > .05).ConclusionsHome-based respiratory and chest mobility exercise could be an adjunct to cardiac rehabilitation in long COVID with cardiovascular comorbidities for improving cardiorespiratory functional capacity.Trial registrationThe study protocol was registered at http://ClinicalTrial.gov.id NCT05077943 (14/10/2021).

High-Performing Fontan Patients: A Fontan Outcome Registry by Cardiac Magnetic Resonance Imaging Study

BackgroundFontan patients exhibit decreased exercise capacity. However, there is a subset of high-performing Fontan (HPF) patients with excellent exercise capacity. ObjectivesThis study aims to: 1) create a Fontan-specific percent predicted peak VO2 tool using exercise data; 2) examine clinical factors associated with HPF patients; and 3) examine late outcomes in HPF patients. MethodsPatients in the multi-institutional Fontan Outcomes Registry Using CMR Examination above the age of 8 years who had a maximal exercise test were included. An HPF patient was defined as a patient in the upper Fontan-specific percent predicted peak VO2 quartile. Multivariable logistic regression was employed to investigate factors associated with the HPF and Cox regression was used to examine the association between HPF patients and late outcomes (composite of death or listing for cardiac transplant). ResultsThe study included 813 patients (mean age: 20.2 ± 8.7 years). An HPF patient was associated with left ventricular morphology (OR: 1.50, P = 0.04), mixed morphology (OR: 2.23, P < 0.001), and a higher ejection fraction (OR: 1.31 for 10% increase, P = 0.01). Patients with at least moderate atrioventricular valve regurgitation, protein-losing enteropathy, or who were using psychiatric medications, were less likely to be an HPF patient. After a mean follow-up of 3.7 years, 46 (5.7%) patients developed a composite endpoint. HPF had a lower risk of death or listing for cardiac transplant (HR: 0.06 [95% CI: 0.01–0.25]). ConclusionsPatients with HPF have more favorable outcomes when compared to patients with lower exercise capacity. This large registry data highlights the role of exercise testing in providing personalized care and surveillance post-Fontan.

Functional Capacity Assessment in Adults After Fontan Palliation: A Cardiopulmonary Exercise Test–Invasive Exercise Hemodynamics Correlation Study

While cardiopulmonary exercise testing (CPET) parameters have known prognostic value in adults post-Fontan, there is limited data correlating treadmill CPET with invasive exercise hemodynamics. Furthermore, the invasive hemodynamic underpinnings of exercise limitations have not been thoroughly investigated. This is retrospective analysis of 55 adults (≥18 years) post-Fontan who underwent treadmill CPET prior to invasive exercise hemodynamic testing via supine cycle protocol between November 2018 and April 2023. Median age was 32.2 (24.1; 37.2) years. Peak heart rate (HR) was 139.7±28.1 bpm and peak oxygen consumption (VO2) was 19.1±5.7 ml/kg/min (47.4±13.5% predicted). VO2/HR was directly related to exercise stroke volume index (Svi) (r=0.50; p=0.0002), while no association was seen with exercise arterio-mixed venous O2 content difference (r=0.14; p=0.32). Peak HR was inversely related to exercise pulmonary artery (PA) pressures (r=-0 61; p<0.0001) and PA wedge pressures (PAWP) (r=-0.61; p<0.0001). Moreover, % predicted VO2 was inversely related to exercise PA pressures (r=-0.50; p<0.0001) and PAWP (r=-0.55; p<0.0001). Peak VO2 ≤19.1 ml/kg/min had a sensitivity of 81% and specificity of 76% (AUC 0.82) for predicting a ΔPAWP/ΔQs ratio >2 mmHg/l/min and/or a ΔPA/ΔQp ratio >3 mmHg/l/min, while a predicted peak VO2 ≤48% had a sensitivity of 74% and specificity of 81% (AUC 0.79) for the same parameters. In summary, lower peak HR and lower peak VO2 were associated with higher exercise PAWP and PA pressure. Peak VO2 ≤48% predicted provided the optimal cut-off for predicting elevated indexed exercise PAWP or PA pressures, thus low peak VO2 should alert clinicians of abnormal underlying hemodynamics.

Comparison of Cardiopulmonary Exercise Test Variables to Predict Adverse Events in Patients with Heart Failure.

Given the rising burden of heart failure (HF), stratification of patients at increased risk for adverse events is critical. We aim to compare the predictive value of various maximal and submaximal cardiopulmonary exercise test (CPET) variables for adverse events in patients with HF. 237 patients with HF (66 [58-73] years, 30% women, 70% HF with reduced ejection fraction) completed a CPET and had five years of follow-up. Baseline characteristics and clinical outcomes (all-cause mortality, major adverse cardiovascular events, and cardiovascular-related hospitalization) were extracted from electronic patient files. Receiver operating characteristics curves for maximal (e.g. peak VO2) and submaximal CPET variables (e.g. VE/VCO2 slope, cardiorespiratory optimal point (COP), VO2 at anaerobic threshold) were compared using the Akaike Information Criterion (AIC) method, whereas their calibration was assessed. 103 participants (43%) reached the composite endpoint, and 55 (23%) died. Percent predicted peak VO2 was the best predictor for adverse outcomes (AIC: 302.6) followed by COP (AIC: 304.3), and relative peak VO2 (mL/(kg·min), AIC: 304.4). Relative peak VO2 (AIC: 217.1) and COP (AIC: 224.4) were also among the three best predictors for mortality, together with absolute peak VO2 (ml/min, AIC: 220.5). A good calibration between observed and predicted event rate was observed for these variables. Percent predicated and relative peak VO2 had the best predictive accuracy for adverse events and mortality, but the submaximal COP had a non-inferior predictive accuracy for adverse events in patients with HF. These findings highlight the potential of submaximal exercise testing in patients with HF.

Exercise testing in clinical context: Reference ranges for interpreting anaerobic threshold as an outcome for congenital heart disease patients

BackgroundChange in the oxygen consumption (VO2) at the ventilatory anaerobic threshold (VAT) is an important outcome in research studies of children with congenital heart disease (CHD). The range of values reported by different raters for any given VAT is needed to contextualize a change in VAT in intervention studies. MethodsSixty maximal cardiopulmonary exercise tests (CPET) for CHD patients 8–21 years old were independently reviewed by six exercise physiologists and four pediatric cardiologists. For each of the unique rater pairs for the 60 CPETs, the absolute difference in VAT was calculated and displayed on a histogram to demonstrate the distribution of inter-rater variability. This method was repeated for subgroups of test modality (cycle/treadmill), patient factors (diagnoses, exercise capacity), and rater factors (cardiologist/physiologist, years of experience). ResultsRater agreement was good with an intraclass correlation coefficient of 0.79–0.91 but the distribution of differences was broad. The median difference was 2.7 % predicted peak VO2 (60 mL/min, 1.0 mL/kg/min), the 75th percentile was 6.4 % (140 mL/min, 2.5 mL/kg/min), and the 95th percentile was 16.3 % (421 mL/min, 6.5 mL/kg/min). Distributions were similar for CPET modality and years of rater experience, but differed for other factors. ConclusionsThe baseline distribution of reported VAT is relatively broad, varied by units, and was not explained by differences in rater experience or test modality, but varies by patient factors. When evaluating clinical relevance, a change in the VO2 at VAT in response to an intervention of <6.5 % predicted falls within the majority (75th percentile) of expected variability and should be interpreted with caution.

Association of Smartwatch-Based Heart Rate and Physical Activity With Cardiorespiratory Fitness Measures in the Community: Cohort Study.

Resting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. This study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. Electronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. We included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)-adjusted P values <.001 for all. Reductions of 2.4 beats per minute in nonactive HR, or increases of nearly 1000 daily steps, corresponded to a 1.3 mL/kg/min higher peak VO2. In addition, ventilatory efficiency (VE/VCO2; FDR-adjusted P=.009), % predicted maximum HR (FDR-adjusted P<.001), and systolic blood pressure-to-workload slope (FDR-adjusted P=.01) were associated with nonactive HR but not associated with daily steps. Our findings suggest that smartwatch-based assessments are associated with a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise. Metrics captured by wearable devices offer a valuable opportunity to use extensive data on health factors and behaviors to provide a window into individual cardiovascular fitness levels.

Assessment of non-communicable disease risk factors, functional performance, and health-related quality of life in adults: a comparative analysis in low-resourced urban and rural areas of South Africa

BackgroundGlobally, disparities between non-communicable disease (NCD) risk factors, functional performance, and health-related quality of life (HRQoL) exist in people living in rural and low-resourced urban settings. Evidence of these health differences determined with objective NCD risk factors and functional performance measurements in South Africa, is scarce. Therefore, the study aimed to determine the differences in NCD risk factors, functional performance and HRQoL between rural and low-resourced urban areas.MethodsThe study recruited 311 adults (35–80 years) presenting with at least one NCD risk factor from low-resourced urban- (n = 183) and rural (n = 128) communities. Objective measurements of physical activity (PA) by means of combined heart rate and accelerometery, body composition employing skinfolds, peripheral lipid and glucose concentrations, blood pressure, functional performance indicators (handgrip, single leg stand, sit-to-stand, timed-up-and-go speed, predicted peak VO2 max); and HRQoL were measured according to standard procedures. Independent t-tests, Mann-Whitney U, and chi-square tests were performed to determine differences between the variables of low-resourced urban and rural settings.ResultsThe participants from the low-resourced urban setting were significantly older than the rural residents (59.1 ± 10.7 years vs. 52.8 ± 11.3 years; p = 0.001). NCD risk factors were significantly more prevalent in the low-resourced urban participants compared to rural participants, in particular for elevated systolic (85.8% vs. 62.5%; p = 0.001), and diastolic blood pressure (88.5% vs. 65.6%; p = 0.001), physical inactivity (95.9% vs. 87.7%; p = 0.026), increased cholesterol concentrations (22.1% vs. 8.7%; p = 0.002), and increased waist circumference (61.9% vs. 49.2%; p = 0.027). Low-resourced urban residents presented with a higher average body fat percentage (27.69% ± 7.65% vs. 12.23% ± 4.67%; p < 0.001), and lower moderate to vigorous PA levels (37.19 ± 49.55 [95% CI = 29.12–45.27] vs. 62.92 ± 60.43 min/week [95% CI = 47.95–77.90]; p = 0.003) compared to rural residents. Rural residents showed significantly better functional performance, including peak VO2 (23.99 ± 9.89 vs. 16.95 ± 7.64 ml/min/kg; p = 0.001) and single leg stand (right leg: 44.96 ± 18.47 vs. 20.87 ± 19.18 s; p = 0.001) as well as higher HRQoL for the physical (51.06 ± 8.14% vs. 45.62 ± 11.13%; p < 0.001) and mental (54.75 ± 8.24% vs. 48.91 ± 12.27%; p < 0.001) component scores compared to participants from the low-resourced urban areas.ConclusionNCD risk factors, functional performance, and HRQoL significantly differ in rural communities compared to low-resourced urban communities in South Africa. Urban areas’ most prevalent risk factors were elevated blood pressure, physical inactivity, and increased waist circumference. Participants from rural areas demonstrated significantly better functional performance, such as fitness and balance. HRQoL was better in rural settings than in urban settings. Future intervention programmes should be tailored for specific settings.

Exercise Capacity Following Pulmonary Embolism in Children and Adolescents

BackgroundSelf-reported physical activity following pediatric pulmonary embolism(PE) is reduced after diagnosis. However, objectively measured exercise capacity and mechanisms of exercise pathophysiology following PE are unknown. Research QuestionDoes exercise capacity one year after acute PE in children differ from controls? Study Design and MethodsOur case-control study compared exercise capacity and responses to maximal exercise in PE survivors with controls. We also investigated the association of low exercise capacity following PE with prespecified clinical/radiological features at PE diagnosis and elucidated the cause of functional limitations. The primary study outcome was exercise capacity defined by peak oxygen uptake (peak VO2) as a percent of predicted on cardiopulmonary exercise testing (CPET), with <80% predicted peak VO2 considered abnormal/low. Ventilatory inefficiency was defined as VE/VCO2 slope >30 and abnormal stroke volume augmentation as oxygen pulse <10 mL O2.min -1 at peak exercise. Logistic regression was performed to assess the association of prespecified variables with low peak VO2. ResultsWe compared 25 consecutive pediatric PE survivors who completed CPET one-year post-diagnosis with 25 controls who underwent CPET within the same period and were otherwise healthy. Exercise capacity was reduced in 8 of the 25 PE survivors (32%) at one-year post-diagnosis vs. 2 of the 25 control participants (8%) (p:0.034). PE survivors with low exercise capacity demonstrated elevated VE/VCO2 slope (p: 0.01) and a decreased oxygen pulse at peak exercise (p:0.001) consistent with cardiovascular limitation. In univariable analysis, PE category, pulmonary vascular obstruction by Qanadli index, or RV dysfunction at diagnosis was not associated with low exercise capacity. InterpretationAbnormal exercise capacity of cardiopulmonary origin occurred in 1 of 3 pediatric PE survivors despite anticoagulation and irrespective of PE severity, degree of pulmonary vascular obstruction, or RV dysfunction at diagnosis. Cardiorespiratory fitness should be formally considered to develop rehabilitation interventions following pediatric PE.

Risk profiles for ventricular arrhythmias in hypertrophic cardiomyopathy through clustering analysis including left ventricular strain.

AimsThe prediction of ventricular arrhythmia (VA) in hypertrophic cardiomyopathy (HCM) remains challenging. We sought to characterize the VA risk profile in HCM patients through clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis (LV-LS). MethodsA total of 434 HCM patients (65% men, mean age 56 years) were included from two referral centers and followed longitudinally (mean duration 6 years). Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The principal endpoint was VA. Results4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively). These 4 clusters differed mainly by LV-mechanics with a severe and homogeneous decrease of myocardial deformation for cluster 4, a small decrease for clusters 2 and 3 and a marked deformation delay and temporal dispersion for cluster 1 associated with a moderate decrease of the GLS (p < 0.0001 for GLS comparison between clusters). Patients from cluster 4 had the most severe phenotype (mean LV mass index 123 vs. 112 g/m2; p = 0.0003) with LV and left atrium (LA) remodeling (LA-volume index (LAVI) 46.6 vs. 41.5 ml/m2, p = 0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak VO2 58.6 vs. 69.5%; p = 0.025). ConclusionProcessing LV-LS parameters in HCM patients 4 clusters with specific LV-strain patterns and different rhythmic risk levels are identified. Automatic extraction and analysis of LV strain parameters improves the risk stratification for VA in HCM patients.