Accurate Prediction Equations for Ventilatory Thresholds in Cardiometabolic Disease When Gas Exchange Analysis is Unavailable: Development and Validation.

AIMS: To develop and validate equations predicting heart rate (HR) at the first and second ventilatory thresholds (VTs) and an optimized range-adjusted prescription for patients with cardiometabolic disease (CMD). To compare their performance against guideline-based exercise intensity domains. METHODS: Cross-sectional study involving 2,868 CMD patients from nine countries. HR predictive equations for first and second VTs (VT1, VT2) were developed using multivariate linear regression with 975 cycle-ergometer cardiopulmonary exercise tests (CPET). 'Adjusted' percentages of peak HR (%HRpeak) and HR reserve (%HRR) were derived from this group. External validation with 1,893 CPET (cycle-ergometer or treadmill) assessed accuracy, agreement, and reliability against guideline-based %HRpeak and %HRR prescriptions using mean absolute percentage error (MAPE), Bland-Altman analyses, intraclass correlation coefficients (ICC). RESULTS: HR predictive equations (R²: 0.77 VT1, 0.88 VT2) and adjusted %HRR (VT1: 42%, VT2: 77%) were developed. External validation demonstrated superiority over widely used guideline-directed intensity domains for %HRpeak and %HRR. The new methods showed consistent performance across both VTs with lower MAPE (VT1: 7.1%, VT2: 5.0%), 'good' ICC for VT1 (0.81, 0.82) and 'excellent' for VT2 (0.93). Guideline-based exercise intensity domains had higher MAPE (VT1: 6.8%-21.3%, VT2: 5.1%-16.7%), 'poor' to 'good' ICC for VT1, and 'poor' to 'excellent' for VT2, indicating inconsistencies related to specific VTs across guidelines. CONCLUSION: Developed and validated HR predictive equations and the optimized %HRR for CMD patients for determining VT1 and VT2 outperformed the guideline-based exercise intensity domains and showed ergometer interchangeability. They offer a superior alternative for prescribing moderate intensity exercise when CPET is unavailable.

Equations to predict heart rate at ventilatory thresholds were developed and externally validated, offering a new perspective when a cardiopulmonary exercise test is unavailable to accurately determine the aerobic exercise intensity domains. Additionally, an adjusted range for exercise intensity prescription based on the percentage of heart rate reserve (%HRR) was provided, utilizing a large sample from eight countries. The proposed equations and the range-adjusted %HRR significantly outperformed the guideline-directed methods for determining exercise intensity, exhibiting higher accuracy, agreement, and reliability. Exercise intensity prescription based on the percentage of heart rate peak showed higher errors, raising concerns about its clinical applicability. Our study may enhance the efficacy of exercise training and physical activity advice when gas exchange analysis is unavailable, potentially leading to improved clinical outcomes, even in low-resource settings. Employing these approaches in research could facilitate more tailored and consistent interventions, introducing a contemporary perspective for studies comparing exercise intensity prescriptions.

Peak oxygen uptake after the 80s as a survival predictor.

PURPOSE: Peak oxygen uptake (VO2peak) is a crucial health marker, extensively studied in adults for its prognostic value. However, its significance in the older persons, especially octogenarians, remains underexplored due to limited representation in research. This study aims to assess the predictive power of VO2peak for survival in individuals aged 80 and above. METHODS: We included individuals aged 80 or older who underwent cardiopulmonary exercise tests at a single center. Mortality rates were compared based on VO2peak relative to 80% of predicted values (%VO2peak). We employed three multivariate Cox regression models: Model 1 (unadjusted), Model 2 (adjusted for age) and Model 3 (adjusted for age and stroke). RESULTS: Among 188 participants (mean age 83.3 ± 3 years, 68.9% male), 22 (11.7%) passed away during a median follow-up of 494 days. Non-survivors tended to be older with lower VO2peak and %VO2peak. All models demonstrated associations between %VO2peak ≤ 80% and mortality: HR = 3.19 (95% CI: 1.30-7.86, p = 0.011) for M1; HR = 3.12 (95% CI: 1.26-7.74, p = 0.013) for M2 and HR = 2.80 (95% CI: 1.11-7.06, p = 0.028) for M3. CONCLUSION: In the context of an aging population, this study underscores the enduring significance of VO2peak as a survival predictor among the older person, including octogenarians. These findings carry profound implications for tailoring healthcare strategies to address the evolving demographic landscape.

Longitudinal strain and myocardial work in symptomatic patients having recovered from COVID-19 and possible associations with the severity of the disease.

COVID-19 may have residual consequences in multiple organs, including the cardiovascular system. The purpose of the present investigation is to quantify myocardial function in symptomatic individuals with long COVID and investigate the association between illness severity and myocardial function. A retrospective cross-sectional study was conducted in which symptomatic individuals with previous COVID-19 underwent echocardiographic analysis of left ventricle global longitudinal strain (LVGLS) and myocardial work (MW). Individuals also performed cardiopulmonary testing (CPX) to assess peak oxygen uptake (VO2peak). Differences between illness severity subgroups were analyzed by the Mann-Whitney test. Correlations were calculated using the Spearman correlation test. Multilinear regressions were performed to evaluate the influences of COVID-19 severity, body mass index, age, and sex on MW. Fifty-six individuals were included (critical subgroup: 17; moderate/severe subgroup: 39), 59% females; median age: 56 years (IQR: 43-63). CPX revealed a substantial reduction in VO2peak (median of 53% of predicted values). LVGLS were not statistically different between subgroups. Global wasted work (GWW) was higher in the critical subgroup [146 (104-212) versus 121 (74-163) mmHg%, p = 0.01], and global work efficiency (GWE) was lower in this subgroup [93 (91-95) versus 94 (93-96), p = 0.03]. Illness severity was the only independent predictor of GWW and GWE (GWW: r2 = 0.167; p = 0.009; GWE: r2 = 0.172; p = 0.005) in multilinear regressions. In our study with long COVID-19 individuals, despite having a similar LVGLS, patients had subclinical LV dysfunction, demonstrated only by an increase in GWW and a decrease in GWE.

Exercise intensity domains determined by heart rate at the ventilatory thresholds in patients with cardiovascular disease: new insights and comparisons to cardiovascular rehabilitation prescription recommendations.

Objectives: To compare the elicited exercise responses at ventilatory thresholds (VTs: VT1 and VT2) identified by cardiopulmonary exercise testing (CPET) in patients with cardiovascular disease (CVD) with the guideline-directed exercise intensity domains; to propose equations to predict heart rate (HR) at VTs; and to compare the accuracy of prescription methods. Methods: A cross-sectional study was performed with 972 maximal treadmill CPET on patients with CVD. First, VTs were identified and compared with guideline-directed exercise intensity domains. Second, multivariate linear regression analyses were performed to generate prediction equations for HR at VTs. Finally, the accuracy of prescription methods was assessed by the mean absolute percentage error (MAPE). Results: Significant dispersions of individual responses were found for VTs, with the same relative intensity of exercise corresponding to different guideline-directed exercise intensity domains. A mathematical error inherent to methods based on percentages of peak effort was identified, which may help to explain the dispersions. Tailored multivariable equations yielded r2 of 0.726 for VT1 and 0.901 for VT2. MAPE for the novel VT1 equation was 6.0%, lower than that for guideline-based prescription methods (9.5 to 23.8%). MAPE for the novel VT2 equation was 4.3%, lower than guideline-based methods (5.8%-19.3%). Conclusion: The guideline-based exercise intensity domains for cardiovascular rehabilitation revealed inconsistencies and heterogeneity, which limits the currently used methods. New multivariable equations for patients with CVD were developed and demonstrated better accuracy, indicating that this methodology may be a valid alternative when CPET is unavailable.

Oxygen Uptake Efficiency Slope in South American Healthy Adults: COMPREHENSIVE REFERENCE VALUES AND INTERNATIONAL COMPARISONS.

PURPOSE: The purpose of this study is to provide comprehensive reference values for oxygen uptake efficiency slope (OUES) in healthy adults. International heterogeneity was also explored through published databases. METHODS: A cross-sectional study was conducted with treadmill cardiopulmonary exercise testing (CPX) from a Brazilian healthy adult sample, in which absolute OUES and values normalized by weight and body surface area (BSA) were calculated. Data were stratified by sex and age group. Prediction equations were calculated using age and anthropometric variables. International data were pooled and differences were explored using factorial analysis of variance or the t test, as appropriate. The OUES age-related patterns were calculated using regression analysis. RESULTS: A total of 3544 CPX were included (1970 males and 1574 females) and the age ranged from 20-80 yr. Males had higher values than females for OUES, OUES/kg, and OUES/BSA. Lower values were found with aging and the data followed a quadratic regression curve. Reference value tables and predictive equations were provided for absolute and normalized OUES in both sexes. International comparisons of absolute OUES values among Brazilian, European, and Japanese data revealed substantial heterogeneity. The OUES/BSA measure minimized the discrepancies between Brazilian and European data. CONCLUSIONS: Our study provided comprehensive OUES reference values in a large healthy adult sample from South America with a wide age range and included absolute and normalized values. Differences observed between Brazilian and European data were reduced in the BSA-normalized OUES.

Cardiopulmonary Exercise Testing in Post-COVID-19 Patients: Where Does Exercise Intolerance Come From? / Teste Cardiopulmonar em Pacientes Pós-COVID-19: De Onde vem a Intolerância ao Exercício?

BACKGROUND: Post-COVID-19 exercise intolerance is poorly understood. Cardiopulmonary exercise testing (CPET) can identify the underlying exercise limitations. OBJECTIVES: To evaluate the source and magnitude of exercise intolerance in post-COVID-19 subjects. METHODS: Cohort study assessing subjects with different COVID-19 illness severities and a control group selected by propensity score matching. In a selected sample with CPET prior to viral infection, before and after comparisons were performed. Level of significance was 5% in the entire analysis. RESULTS: One hundred forty-four subjects with COVID-19 were assessed (median age: 43.0 years, 57% male), with different illness severities (60% mild, 21% moderate, 19% severe). CPET was performed 11.5 (7.0, 21.2) weeks after disease onset, with exercise limitations being attributed to the peripheral muscle (92%), and the pulmonary (6%), and cardiovascular (2%) systems. Lower median percent-predicted peak oxygen uptake was observed in the severe subgroup (72.2%) as compared to the controls (91.6%). Oxygen uptake differed among illness severities and controls at peak and ventilatory thresholds. Conversely, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse were similar. Subgroup analysis of 42 subjects with prior CPET revealed significant reduction in only peak treadmill speed in the mild subgroup and in oxygen uptake at peak and ventilatory thresholds in the moderate/severe subgroup. By contrast, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse did not change significantly. CONCLUSIONS: Peripheral muscle fatigue was the most common exercise limitation etiology in post-COVID-19 patients regardless of the illness severity. Data suggest that treatment should emphasize comprehensive rehabilitation programs, including aerobic and muscle strengthening components.

FUNDAMENTO: A intolerância ao exercício pós-COVID-19 não é bem entendida. O teste de esforço cardiopulmonar (TECP) pode identificar as limitações ao exercício subjacentes. OBJETIVOS: Avaliar a etiologia e a magnitude da intolerância ao exercício em sujeitos pós-COVID-19. MÉTODOS: Estudo de coorte que avaliou sujeitos com níveis de gravidades diferentes da doença COVID-19 e um grupo de controle selecionado por pareamento por escores de propensão. Em uma amostra seleta com TECP anterior à infecção viral disponível, foram realizadas comparações antes e depois. O nível de significância foi de 5% em toda a análise. RESULTADOS: Foram avaliados cento e quarenta e dois sujeitos com COVID-19 (idade mediana: 43 anos, 57% do sexo masculino), com níveis de gravidade de doença diferentes (60% leve, 21% moderada, 19% grave). O TECP foi realizado 11,5 (7,0, 21,2) semanas após o aparecimento da doença, com as limitações ao exercício sendo atribuídas aos sistemas muscular periférico (92%), pulmonar (6%), e cardiovascular (2%). Menor valor mediano do consumo de oxigênio pico percentual foi observado no subgrupo com níveis graves de doença (72,2%) em comparação com os controles (91,6%). O consumo de oxigênio foi diferente entre os grupos com diferentes níveis de gravidade de doença e o controle no pico e nos limiares ventilatórios. Inversamente, os equivalentes ventilatórios, a inclinação da eficiência do consumo de oxigênio, e o pico do pulso de oxigênio foram semelhantes. A análise do subgrupo de 42 sujeitos com TECP prévio revelou uma redução significativa no pico de velocidade da esteira no subgrupo com nível leve de doença, e no consumo de oxigênio no pico e nos limiares ventilatórios nos subgrupos com níveis moderado/grave. Por outro lado, os equivalentes ventilatórios, a inclinação da eficiência do consumo de oxigênio e o pico do pulso de oxigênio não apresentaram alterações significativas. CONCLUSÕES: A fadiga do músculo periférico foi a etiologia de limitação de exercício mais comum em pacientes pós-COVID-19 independentemente da gravidade da doença. Os dados sugerem que o tratamento deve enfatizar programas de reabilitação abrangentes, incluindo componentes aeróbicos e de fortalecimento muscular.

Teste Cardiopulmonar em Pacientes Pós-COVID-19: De Onde vem a Intolerância ao Exercício? / Cardiopulmonary Exercise Testing in Post-COVID-19 Patients: Where Does Exercise Intolerance Come From?

Resumo Fundamento A intolerância ao exercício pós-COVID-19 não é bem entendida. O teste de esforço cardiopulmonar (TECP) pode identificar as limitações ao exercício subjacentes. Objetivos Avaliar a etiologia e a magnitude da intolerância ao exercício em sujeitos pós-COVID-19. Métodos Estudo de coorte que avaliou sujeitos com níveis de gravidades diferentes da doença COVID-19 e um grupo de controle selecionado por pareamento por escores de propensão. Em uma amostra seleta com TECP anterior à infecção viral disponível, foram realizadas comparações antes e depois. O nível de significância foi de 5% em toda a análise. Resultados Foram avaliados cento e quarenta e dois sujeitos com COVID-19 (idade mediana: 43 anos, 57% do sexo masculino), com níveis de gravidade de doença diferentes (60% leve, 21% moderada, 19% grave). O TECP foi realizado 11,5 (7,0, 21,2) semanas após o aparecimento da doença, com as limitações ao exercício sendo atribuídas aos sistemas muscular periférico (92%), pulmonar (6%), e cardiovascular (2%). Menor valor mediano do consumo de oxigênio pico percentual foi observado no subgrupo com níveis graves de doença (72,2%) em comparação com os controles (91,6%). O consumo de oxigênio foi diferente entre os grupos com diferentes níveis de gravidade de doença e o controle no pico e nos limiares ventilatórios. Inversamente, os equivalentes ventilatórios, a inclinação da eficiência do consumo de oxigênio, e o pico do pulso de oxigênio foram semelhantes. A análise do subgrupo de 42 sujeitos com TECP prévio revelou uma redução significativa no pico de velocidade da esteira no subgrupo com nível leve de doença, e no consumo de oxigênio no pico e nos limiares ventilatórios nos subgrupos com níveis moderado/grave. Por outro lado, os equivalentes ventilatórios, a inclinação da eficiência do consumo de oxigênio e o pico do pulso de oxigênio não apresentaram alterações significativas. Conclusões A fadiga do músculo periférico foi a etiologia de limitação de exercício mais comum em pacientes pós-COVID-19 independentemente da gravidade da doença. Os dados sugerem que o tratamento deve enfatizar programas de reabilitação abrangentes, incluindo componentes aeróbicos e de fortalecimento muscular.

Abstract Background Post-COVID-19 exercise intolerance is poorly understood. Cardiopulmonary exercise testing (CPET) can identify the underlying exercise limitations. Objectives To evaluate the source and magnitude of exercise intolerance in post-COVID-19 subjects. Methods Cohort study assessing subjects with different COVID-19 illness severities and a control group selected by propensity score matching. In a selected sample with CPET prior to viral infection, before and after comparisons were performed. Level of significance was 5% in the entire analysis. Results One hundred forty-four subjects with COVID-19 were assessed (median age: 43.0 years, 57% male), with different illness severities (60% mild, 21% moderate, 19% severe). CPET was performed 11.5 (7.0, 21.2) weeks after disease onset, with exercise limitations being attributed to the peripheral muscle (92%), and the pulmonary (6%), and cardiovascular (2%) systems. Lower median percent-predicted peak oxygen uptake was observed in the severe subgroup (72.2%) as compared to the controls (91.6%). Oxygen uptake differed among illness severities and controls at peak and ventilatory thresholds. Conversely, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse were similar. Subgroup analysis of 42 subjects with prior CPET revealed significant reduction in only peak treadmill speed in the mild subgroup and in oxygen uptake at peak and ventilatory thresholds in the moderate/severe subgroup. By contrast, ventilatory equivalents, oxygen uptake efficiency slope, and peak oxygen pulse did not change significantly. Conclusions Peripheral muscle fatigue was the most common exercise limitation etiology in post-COVID-19 patients regardless of the illness severity. Data suggest that treatment should emphasize comprehensive rehabilitation programs, including aerobic and muscle strengthening components.

Long-term reduced functional capacity and quality of life in hospitalized COVID-19 patients.

Background: Persistent symptoms and exercise intolerance have been reported after COVID-19, even months after the acute disease. Although, the long-term impact on exercise capacity and health-related quality of life (HRQoL) is still unclear. Research question: To assess the long-term functional capacity and HRQoL in patients hospitalized due to COVID-19. Study design and methods: This is a prospective cohort study, conducted at two centers in Brazil, that included post-discharge COVID-19 patients and paired controls. The cohort was paired by age, sex, body mass index and comorbidities, using propensity score matching in a 1:3 ratio. Patients were eligible if signs or symptoms suggestive of COVID-19 and pulmonary involvement on chest computed tomography. All patients underwent cardiopulmonary exercise testing (CPET) and a HRQoL questionnaire (SF-36) 6 months after the COVID-19. The main outcome was the percentage of predicted peak oxygen consumption (ppVO2). Secondary outcomes included other CPET measures and HRQoL. Results: The study sample comprised 47 post-discharge COVID-19 patients and 141 healthy controls. The mean age of COVID-19 patients was 54 ± 14 years, with 19 (40%) females, and a mean body mass index of 31 kg/m2 (SD, 6). The median follow-up was 7 months (IQR, 6.5-8.0) after hospital discharge. PpVO2 in COVID-19 patients was lower than in controls (83% vs. 95%, p = 0.002) with an effect size of 0.38 ([95%CI], 0.04-0.70). Mean peak VO2 (22 vs. 25 mL/kg/min, p = 0.04) and OUES (2,122 vs. 2,380, p = 0.027) were also reduced in the COVID-19 patients in comparison to controls. Dysfunctional breathing (DB) was present in 51%. HRQoL was significantly reduced in post COVID patients and positively correlated to peak exercise capacity. Interpretation: Hospitalized COVID-19 patients presented, 7 months after discharge, with a reduction in functional capacity and HRQoL when compared to historical controls. HRQoL were reduced and correlated with the reduced peak VO2 in our population.

Reference Standards for Cardiorespiratory Fitness in Brazil: A POOLED ANALYSIS AND OVERVIEW OF HETEROGENEITY IN NATIONAL AND INTERNATIONAL STUDIES.

PURPOSE: This study aimed to propose reference standards for cardiorespiratory fitness (CRF) for Brazil from a pooled analysis and to compare peak oxygen uptake (V˙ o2peak ) in Brazilian, United States (US), and Norwegian samples, exploring possible national and international differences. METHODS: Reference values for treadmill V˙ o2peak in three different Brazilian regions were assessed from previous publications. We analyzed available samples to assess possible differences, generate weighted average data for Brazil, and compared them with US and Norwegian data. RESULTS: Brazilian reference values had a lower V˙ o2peak value for the Northeast region and a higher V˙ o2peak value for the Southeast region for all sex and age groups. International comparisons with the Brazilian pooled data (n = 26661) revealed higher values for the Norwegian sample (n = 3810) and lower values for the US sample (n = 16278). The observed heterogeneity in CRF is possibly related to differences in anthropometric (weight, height) and socioeconomic factors, which differed among the samples. Also, Brazilian data showed a curvilinear V˙ o2peak age reduction trend rather than the linear characteristic commonly utilized, and the regression curves were different from those for US and Norwegian data. CONCLUSION: This study provides new CRF reference standards for Brazil. After pooling data from three Brazilian regions, a comparison revealed notable differences between regions, evidencing a negative gradient from Southern to Northern regions. Similarly, the international comparisons between Brazil, US, and Norway data revealed CRF heterogeneity, with differences in the V˙ o2peak values and in the age relationship patterns. These findings reinforce the importance of using national- or regional-specific V˙ o2peak reference values, ensuring proper CRF evaluation.

Análise biomecânica dos efeitos da crioterapia no tratamento da lesão muscular aguda / Biomechanical analysis of the cryotherapy effects in the treatment of acute muscular injury

A crioterapia é amplamente utilizada por atletas profissionais e amadores no tratamento agudo de lesões musculares. Este trabalho teve como objetivo analisar as propriedades mecânicas do músculo gastrocnêmio lesionado por impacto direto e tratado com crioterapia. Para tanto, foram utilizadas 24 ratas Wistar, divididas em três grupos experimentais: grupo controle (C): animais mantidos em gaiolas-padrão por seis dias; grupo lesionado (L): animais submetidos à lesão por mecanismo de impacto no gastrocnêmio, sem tratamento e mantidos em gaiolas-padrão por seis dias; grupo lesionado e tratado com crioterapia (LC): animais submetidos à lesão, tratados com uma sessão de crioterapia, imediatamente após a lesão e mantidos em gaiolas-padrão por seis dias. Após essas etapas, os animais foram submetidos à eutanásia para que fossem realizados os ensaios mecânicos de tração dos músculos gastrocnêmios direitos, na máquina universal de ensaios (EMIC®). A partir dos gráficos carga versus alongamento de cada ensaio, foram calculadas as seguintes propriedades mecânicas: carga no limite máximo (CLM), alongamento no limite máximo (ALM) e rigidez (R). No ALM, o grupo C apresentou diferença estatística (p < 0,05) somente quando comparado com o L. Quando analisadas carga máxima e rigidez, houve diferença estatística (p < 0,05) nos três grupos. Assim, enquanto os músculos lesionados sem tratamento apresentaram diminuição de todas as propriedades mecânicas analisadas, os tratados com crioterapia mostraram melhora das propriedades, porém, sem alcançar o grupo controle. Dessa forma, podemos concluir que a sessão de crioterapia por imersão imediata após a lesão promoveu melhora das propriedades mecânicas analisadas.

Cryotherapy is widespread used in the acute treatment of muscle injuries of professional and unprofessional athletes. The purpose of this study was the investigation of mechanical properties of gastrocnemius muscle submitted to a impact mechanism of injury and treated with cryoterapy. Therefore, twenty four female Wistar rats were divided into three groups: Control (C): animals housed in standard cages for six days; Lesion (L): animals submitted to a direct impact mechanism of injury in the gastrocnemius muscle, without any treatment and kept into standard cages during six days; Lesion e cryotherapy (LC): animals submitted to the contusion, treated with a single session of cryotherapy immediately after lesion and housed in standard cages during six days. After those protocols, the rats were killed and their right gastrocnemius muscle were dissected and submitted to a mechanical test of traction in a universal assays machine (EMIC®). From the load versus elongation curves, the following mechanical properties were obtained: Maximum limit load (MLL), maximum limit elongation (MLE) and stiffness (St). There was a statistically difference between all groups in MLL and St. However, in the MLE there was statistically difference only between groups C and L (p<0,05). The results showed that the muscle contusion without treatment led to exasperation of all analyzed mechanical properties. Conversely, cryotherapy improved the muscle properties, although they had not reached the control group values. It can be concluded that the cryotherapy applied immediately after muscle contusion improved the muscle mechanical properties.