Effects of Aerobic Exercise on Cardiopulmonary Function in Postoperative Patients with Congenital Heart Disease: A Meta-analysis.

Background: This meta-analysis aimed to evaluate the impact of aerobic exercise on Peak VO2 (Oxygen Consumption) in postoperative patients with congenital heart disease (CHD). Besides this, we also tried to discover whether the improvement was influenced by patient ages, modes of supervision, types of exercise, the total dose of exercise, intervention periods, and types of CHD. Methods: Following the Population Intervention Comparison Outcome Study Design (PICOS) principle, a comprehensive search of the PubMed, Web of Science, Embase and Cochrane Library databases was conducted for randomized controlled trials (RCTs) evaluating the intervention effects of aerobic exercise on cardiopulmonary function in postoperative CHD patients until December 2023. This meta-analysis and publication bias tests were conducted using Stata 17.0, and the mean differences (MDs) with 95% confidence intervals (CIs) were used as effect sizes in statistics. Results: A total of 15 RCTs (762 cases) were included in this meta-analysis, with 407 cases in the experimental group and 355 cases in the control group. Meta-analysis showed that aerobic exercise had a positive effect on Peak VO2 in postoperative CHD patients (MD = 2.14, 95% CI (1.34, 2.94), p < 0.00001, I2 = 36%). The analysis of subgroups showed that intervention effects of aerobic exercise were superior to the control group when patients were > 18 years old (MD = 2.53, p < 0.00001), ≤ 18 years old (MD = 1.63, p = 0.01), under supervision (MD = 2.23, p < 0.00001), unsupervised (MD = 2.06, p < 0.00400), performing aerobic exercise (MD = 1.87, p = 0.0003), performing aerobic exercise combined with resistance training (MD = 2.57, p < 0.00010), with a total dose of exercise ≥ 1440 minutes (MD = 2.45, p < 0.00010), with the intervention period of 10-12 weeks (MD = 2.31, p < 0.00001), with that > 12 weeks (MD = 1.97, p = 0.00300), or with mixed types of CHD (MD = 2.34, p < 0.00001). Conclusions: This meta-analysis did not deduct points for limitations, inconsistency, indirectness, imprecision, or publication bias, so the quality of evidence was graded as high. Aerobic exercise has a significantly positive impact on improving Peak VO2 in postoperative CHD patients. Moreover, it was found that for patients aged 18 and above, supervised aerobic exercise combined with resistance training, implemented for 10-12 weeks with a total dose of exercise ≥ 1440 minutes, had a better intervention effect on Peak VO2. This finding provided evidence-based medicine for the exercise rehabilitation of postoperative CHD patients, and explored the optimal exercise prescription for clinical practice as well. Clinical Trial registration: Registered on INPLASY No.202440016 (https://inplasy.com).

Development a nomogram prognostic model for survival in heart failure patients based on the HF-ACTION data.

BACKGROUND: The risk assessment for survival in heart failure (HF) remains one of the key focuses of research. This study aims to develop a simple and feasible nomogram model for survival in HF based on the Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) to support clinical decision-making. METHODS: The HF patients were extracted from the HF-ACTION database and randomly divided into a training cohort and a validation cohort at a ratio of 7:3. Multivariate Cox regression was used to identify and integrate significant prognostic factors to form a nomogram, which was displayed in the form of a static nomogram. Bootstrap resampling (resampling = 1000) and cross-validation was used to internally validate the model. The prognostic performance of the model was measured by the concordance index (C-index), calibration curve, and the decision curve analysis. RESULTS: There were 1394 patients with HF in the overall analysis. Seven prognostic factors, which included age, body mass index (BMI), sex, diastolic blood pressure (DBP), exercise duration, peak exercise oxygen consumption (peak VO2), and loop diuretic, were identified and applied to the nomogram construction based on the training cohort. The C-index of this model in the training cohort was 0.715 (95% confidence interval (CI): 0.700, 0.766) and 0.662 (95% CI: 0.646, 0.752) in the validation cohort. The area under the ROC curve (AUC) value of 365- and 730-day survival is (0.731, 0.734) and (0.640, 0.693) respectively in the training cohort and validation cohort. The calibration curve showed good consistency between nomogram-predicted survival and actual observed survival. The decision curve analysis (DCA) revealed net benefit is higher than the reference line in a narrow range of cutoff probabilities and the result of cross-validation indicates that the model performance is relatively robust. CONCLUSIONS: This study created a nomogram prognostic model for survival in HF based on a large American population, which can provide additional decision information for the risk prediction of HF.

The Effects of Aquatic Exercise Training on Functional and Hemodynamic Responses in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Objective: This study aimed to investigate the impacts of water exercise training on functional and hemodynamic responses in HF patients. Methods: A systematic review and meta-analysis were conducted until February 15, 2024, using multiple databases. Mean difference (MD) with corresponding 95% confidence intervals (CIs) were calculated. Results: Sixteen studies, comprising 349 participants with HF, were included. Water exercise led to enhancements in peak VO2 (MD, 2.85 mL/kg/min; 95% CI, 1.89 to 3.80; p < .00001) and resting heart rate (MD, -4.16 bm; 95% CI, -6.85 to -1.46; p = .002) compared to no exercising controls. Water plus land exercise reduced resting heart rate (MD, -1.41 bm; 95% CI, -2.13 to -0.69; p = .0001) compared to land exercise alone. Furthermore, acute water exercises decreased resting heart rate (MD, -3.85 bm; 95% CI, -6.49 to -1.21; p = .004) and increased stroke volume (MD, 14.68 mL/beat; 95% CI, 8.57 to 20.79; p < .00001) and cardiac output (MD, 0.5 L/min; 95% CI, 0.27 to 0.73; p < .00001) compared to baseline. Conclusion: These findings suggest that water exercise holds promise as an effective intervention for enhancing functional capacity and hemodynamic parameters in individuals with HF, highlighting the importance of further research to optimize its implementation and elucidate long-term benefits.

Effects of combined aerobic, resistance and inspiratory training in patients with pulmonary hypertension: A systematic review.

BACKGROUND: Pulmonary hypertension (PH) is a serious progressive disorder of the modern world, characterized by endothelial dysfunction and impaired vasoreactivity. Patients with PH usually present exercise intolerance from the very early stages and reduced exercise capacity. Exercise training has been shown to have beneficial effects in patients with cardiovascular comorbidities. However, data regarding the effects of combined exercise training programs in patients with PH still remains limited. AIM: To investigate the effects of combined exercise training programs on exercise capacity and quality of life in patients with PH. METHODS: Our search included all available randomized controlled trials (RCTs) regarding combined aerobic, resistance and inspiratory training programs in patients with PH in 4 databases (Pubmed, PEDro, Embase, CINAHL) from 2012 to 2022. Five RCTs were included in the final analysis. Functional capacity, assessed by peak VO2 or 6-min walking test (6MWT), as well as quality of life, assessed by the SF-36 questionnaire, were set as the primary outcomes in our study. RESULTS: Peak VO2 was measured in 4 out of the 5 RCTs while 6MWT was measured in all RCTs. Both indices of functional capacity were significantly increased in patients with PH who underwent combined exercise training compared to the controls in all of the included RCTs (P < 0.05). Quality of life was measured in 4 out of 5 RCTs. Although patients improved their quality of life in each group, however, only 2 RCTs demonstrated further improvement in patients performing combined training compared to controls. CONCLUSION: By this systematic review, we have demonstrated that combined aerobic, resistance and inspiratory exercise training is safe and has beneficial effects on aerobic capacity and quality of life in patients with PH. Such exercise training regimen may be part of the therapeutic strategy of the syndrome.

The Effects of Exercise Training on Functional Capacity and Quality of Life in Patients with Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation. The purpose of this systematic review is to evaluate the effectiveness of exercise training on functional capacity and quality of life (QoL) in patients with RA. We performed a search in four databases, selecting clinical trials that included community or outpatient exercise training programs in patients with RA. The primary outcome was functional capacity assessed by peak VO2 or the 6 min walking test, and the secondary outcome was QoL assessed by questionnaires. Seven studies were finally included, identifying a total number of 448 patients. The results of the present systematic review show a statistically significant increase in peak VO2 after exercise training in four out of seven studies. In fact, the improvement was significantly higher in two out of these four studies compared to the controls. Six out of seven studies provided data on the patients' QoL, with five of them managing to show statistically significant improvement after exercise training, especially in pain, fatigue, vitality, and symptoms of anxiety and depression. This systematic review demonstrates the beneficial effects of exercise training on functional capacity and QoL in patients with RA.

Impact of Cancer History on Temporal Changes in the Cardiopulmonary Exercise Test of Patients with Cardiovascular Disease.

The elevated risk of cardiovascular disease (CVD) in cancer patients and survivors is likely the result of normal age-related pathologies coupled with the direct and indirect effects of cancer therapy that extend across multiple systems. The purpose of this study was to investigate the impact of cardiac rehabilitation (CR) on CVD patients with a history of cancer.In this study, patients who had participated in the outpatient CR program were enrolled and were divided into 2 groups (cancer survivor group and no-cancer group) based on their history of cancer. The cardiopulmonary exercise test (CPET) was performed at the beginning (baseline) and at the end of the CR program (follow-up). The results of CPET at baseline and those at follow-up were analyzed retrospectively.A total of 105 patients were analyzed in this study. The cancer survivor group had 25 patients, and the non-cancer group 80. At baseline, peak oxygen uptake (peak VO2) (14.7 [11.9 to 17.6] mL/kg/minute versus 11.3 [9.7 to 14.7] mL/kg/minute; P = 0.003) was significantly lower in cancer survivors. The percent changes in peak VO2 between baseline and follow-up were not significantly different between the 2 groups (7.9 % [-11.5 to 24.5] versus 9.4 % [-7.5 to 27.3] P = 0.520).The percent changes in peak VO2 of CR participants were not significantly different despite their cancer history.

Decreased clinical performance in TGA-ASO patients after RVOT interventions; a multicenter European collaboration.

BACKGROUND: In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT interventions. OBJECTIVES: We aimed to assess cardiopulmonary exercise capacity and right ventricular function in patients stratified for type of RVOT intervention. METHODS: TGA-ASO patients (≥16 years) were stratified by type of RVOT intervention. The following outcome parameters were included: predicted (%) peak oxygen uptake (peak VO2), tricuspid annular plane systolic excursion (TAPSE), tricuspid Lateral Annular Systolic Velocity (TV S'), right ventricle (RV)-arterial coupling (defined as TAPSE/RV systolic pressure ratio), and N-terminal proBNP (NT-proBNP). RESULTS: 447 TGA patients with a mean age of 25.0 (interquartile range (IQR) 21-29) years were included. Patients without previous RVOT intervention (n = 338, 76%) had a significantly higher predicted peak VO2 (78.0 ± 17.4%) compared to patients with single approach catheter-based RVOT intervention (73.7 ± 12.7%), single approach surgical RVOT intervention (73.8 ± 28.1%), and patients with multiple approach RVOT intervention (66.2 ± 14.0%, p = 0.021). RV-arterial coupling was found to be significantly lower in patients with prior catheter-based and/or surgical RVOT intervention compared to patients without any RVOT intervention (p = 0.029). CONCLUSIONS: TGA patients after a successful arterial switch repair have a decreased exercise capacity. A considerable amount of TGA patients with either catheter or surgical RVOT intervention perform significantly worse compared to patients without RVOT interventions.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery: A systematic review.

BACKGROUND: Lack of mobilization and prolonged stay in the intensive care unit (ICU) are major factors resulting in the development of ICU-acquired muscle weakness (ICUAW). ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery, and may be a risk factor for prolonged duration of mechanical ventilation, associated with a higher risk of readmission and higher mortality. Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay. Neuromuscular electrical stimulation (NMES) is an alternative modality of exercise in patients with muscle weakness. A major advantage of NMES is that it can be applied even in sedated patients in the ICU, a fact that might enhance early mobilization in these patients. AIM: To evaluate safety, feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery. METHODS: We performed a search on Pubmed, Physiotherapy Evidence Database (PEDro), Embase and CINAHL databases, selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials (RCTs) that included implementation of NMES in patients before after cardiac surgery. RCTs were assessed for methodological rigor and risk of bias via the PEDro. The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function. RESULTS: Ten studies were included in our systematic review, resulting in 703 participants. Almost half of them performed NMES and the other half were included in the control group, treated with usual care. Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery. Functional capacity was assessed in 8 studies via 6MWT or other indices, and improved only in 1 study before and in 1 after cardiac surgery. Nine studies explored the effects of NMES on muscle strength and function and, most of them, found increase of muscle strength and improvement in muscle function after NMES. NMES was safe in all studies without any significant complication. CONCLUSION: NMES is safe, feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery, but has no significant effect on functional capacity.

Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection.

OBJECTIVES: Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections. METHODS: Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014-August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality. RESULTS: A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality. CONCLUSIONS: VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.

Effect of different types of aerobic training on peak VO2 and ejection fraction for diastolic heart failure patients; a comparative randomized control trial.

BACKGROUND: Heart failure is described by a lack of confirmed efficient therapies and exercise intolerance. Engagement in physical activity decreases the possibility of adverse cardiovascular consequences involving heart failure. THE PURPOSE OF THE STUDY: Determine the effect of different types of aerobic training on peak VO2 and ejection fraction in diastolic heart failure patients. SUBJECT AND METHODS: The study was designed as a randomized control trail. Forty-eight eligible male patients with diastolic heart failure, aged between 50 and 65 years old, enrolled in this study. They were picked up from Police hospital outpatient clinic and were assigned to 2 equal groups in numbers. The first group (A) received aerobic exercise for the upper limb in the form of arm ergometer exercises, while the second group (B) received aerobic exercise for the lower limb in the form of cycling. Training duration for both groups was 3 sessions/week for 12 weeks. Peak VO2, and ejection fraction of both groups were measured and compared pre- and post-treatment. RESULTS: There was no significant difference (p > 0.05) in the ejection fraction between groups post-treatment. However, a significant increase (p < 0.001) was observed in the peak VO2 of group B when compared to group A post-treatment. CONCLUSION: There is no effect of different types of aerobic training on ejection fraction in diastolic heart failure patients, but lower limb exercise is more effective than upper limb exercise in improving peak VO2 in diastolic heart failure patients. Therefore, the current study recommended the use of lower limb exercise over upper limb exercise in training diastolic heart failure patients. CLINICAL TRIAL REGISTRATION: The study was registered in ClinicalTrial.gov as a clinical trial ID (NCT05637125).

Yoga as Adjunct Therapy for Chronic Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Chronic heart failure (CHF) is a prevalent cardiovascular condition that can significantly impact the quality of life and increase mortality risk. Yoga is a mind-body therapy that has been studied as a potential complementary treatment for CHF. However, the effectiveness of yoga in improving outcomes in patients with CHF remains uncertain. Methods We conducted a systematic review of randomized controlled trials (RCTs) evaluating the effects of yoga on outcomes in patients with CHF. We searched the PubMed, Embase, Scopus, Cochrane Library, and IndMED databases from inception to March 2023. The outcomes of interest were left ventricular ejection fraction (LVEF), cardiac biomarkers, exercise capacity, quality of life, and cardiac function. Results We identified 11 RCTs that met our inclusion criteria, involving a total of 552 participants. The meta-analysis showed that yoga was associated with significant improvements in peak VO 2 (mean difference [MD]= 3.29; 95% Confidence Interval [CI]: 1.64 to 4.94; I 2 = 0%), exercise capacity (MD=101.54; 95% CI: 6.24 to 196.83; I 2 = 96%), quality of life (MD = -19.99; 95% CI: -25.76 to -14.22; I 2 = 43%), NT-proBNP (MD = -288.78; 95% CI: -492.20 to -85.37; I 2 = 94%), and 6-minute walk test (MD = 101.54; 95% CI: 6.24-196.83; I 2 = 96%), but not in the left ventricular ejection fraction (MD = 4.28; 95% CI: -1.14 to 9.70; I 2 = 93%). Subgroup analysis suggested that the effect of yoga on the quality of life is more pronounced in patients with the "New York Heart Association" (NYHA) class I and II CHF patients and in those who practiced yoga for longer durations. No serious adverse events related to yoga were reported. Most of the included studies were of "low" quality. Conclusion Current evidence suggests that yoga may be an effective complementary and integrative therapy for improving peak VO 2 exercise capacity, NT-proBNP, and quality of life in patients with CHF. However, the low-quality evidence does not render us to conclude anything beyond doubt or draw any firm clinical recommendation. Future high-quality studies are needed to explore the optimal duration and frequency of yoga practice and its effects on long-term outcomes in this population.

Use of Wearable Devices for Peak Oxygen Consumption Measurement in Clinical Cardiology: Case Report and Literature Review.

BACKGROUND: Oxygen consumption is an important index to evaluate in cardiac patients, particularly those with heart failure, and is measured in the setting of advanced cardiopulmonary exercise testing. However, technological advances now allow for the estimation of this parameter in many consumer and medical-grade wearable devices, making it available for the medical provider at the initial evaluation of patients. We report a case of an apparently healthy male aged 40 years who presented for evaluation due to an Apple Watch (Apple Inc) notification of low cardiac fitness. This alert triggered a thorough workup, revealing a diagnosis of familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. While the use of wearable devices for the measurement of oxygen consumption and related parameters is promising, further studies are needed for validation. OBJECTIVE: The aim of this report is to investigate the potential utility of wearable devices as a screening and risk stratification tool for cardiac fitness for the general population and those with increased cardiovascular risk, particularly through the measurement of peak oxygen consumption (VO2). We discuss the possible advantages of measuring oxygen consumption using wearables and propose its integration into routine patient evaluation and follow-up processes. With the current evidence and limitations, we encourage researchers and clinicians to explore bringing wearable devices into clinical practice. METHODS: The case was identified at Sheba Medical Center, and the patient's cardiac fitness was monitored through an Apple Watch Series 6. The patient underwent a comprehensive cardiac workup following his presentation. Subsequently, we searched the literature for articles relating to the clinical utility of peak VO2 monitoring and available wearable devices. RESULTS: The Apple Watch data provided by the patient demonstrated reduced peak VO2, a surrogate index for cardiac fitness, which improved after treatment initiation. A cardiological workup confirmed familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. A review of the literature revealed the potential clinical benefit of peak VO2 monitoring in both cardiac and noncardiac scenarios. Additionally, several devices on the market were identified that could allow for accurate oxygen consumption measurement; however, future studies and approval by the Food and Drug Administration (FDA) are still necessary. CONCLUSIONS: This case report highlights the potential utility of peak VO2 measurements by wearable devices for early identification and screening of cardiac fitness for the general population and those at increased risk of cardiovascular disease. The integration of wearable devices into routine patient evaluation may allow for earlier presentation in the diagnostic workflow. Cardiac fitness can be serially measured using the wearable device, allowing for close monitoring of functional capacity parameters. Devices need to be used with caution, and further studies are warranted.

Exploring the Relationship Between the Indices of Body Composition With Grip Strength Performance and Peak VO2.

Background The importance of measurements of body composition in terms of various indices including Body Mass Index (BMI), Body Surface Area (BSA), Body Size Index (BSI), and Waist to Height ratio (WtHR) in the diagnosis of health risks and mortality outcome analysis has largely been limited to their use relating to determining abdominal obesity. The understanding of the extent of implications of the newer, underutilized indices of body composition is deficient. Peak VO2 (maximal oxygen uptake) majorly serves for the evaluation of the measure of aerobic capacity. Grip strength performance is a simple, primary, objective predictor of overall physical status and muscular and cardiovascular fitness. This study aimed to derive the relationship between a gamut of parameters such as BMI, BSA, WtHR, BSI, grip strength performance and peak VO2 investigated using the latest scientific methodology in a cross-section of the population in a rural tertiary care center. Methodology This study was a descriptive, cross-sectional study carried out in a rural medical college in central India. Sixty participants from the healthcare setting were considered eligible for the study within the age group of 18 to 45 years. Anthropometric assessments like height (in cm), weight (in kg), waist circumference (in cm), and BMI were carried out. BSA, WtHR, and BSI were calculated using the respective formulae. VO2 max (maximal oxygen uptake) recordings were done using the treadmill/ergometer and metabolic module of LabChart software (Bella Vista, New South Wales, Australia). Grip Strength Performance was quantified by measuring the amount of static force with which the hand is able to squeeze a transducer. It was measured using Grip Force Transducer (MLT004 / ST) from AD Instruments (Bella Vista, New South Wales, Australia). Results Upon analysis, a significant negative correlation was obtained between BSI and BMI (r= -0.51, p<0.0001) whereas a significant positive correlation was found between BSA and BMI (r= 0.71, p< 0.0001). A significant correlation was also seen between WtHR and BMI (r= 0.71, p< 0.0001) while a negative significant correlation between peak VO2 and BMI (r= -024,p=0.0425) was deduced. Similarly, a negative correlation was evident between BSA and BMI (r= -0.46, p=0.0002) with a positive correlation between WtHR and BSA (r= 0.30,p=0.0188). Grip strength performance positively correlated with BSA (r= 0.58, p< 0.0001) whereas peak VO2 showed a significant negative correlation with WtHR (r= -026,p=0.043). There was also a positive significant correlation between grip strength performance and peak VO2 (r= 0.37, p=0.0033) Conclusion The study determined the relationships of grip strength performance and peak VO2, with the body composition indices in order to provide an overview of the mortal risks of an individual which might mediate the prognosis. Based on the relative independence of BSI with peak VO2 and grip strength performance, the unification of these parameters can help assess the overall health of an individual.

Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction, reduced functional capacity and exercise intolerance. Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases. High intensity interval training (HIIT) seems to be superior than moderate-intensity continuous training (MICT) in cardiovascular diseases by improving brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness to a greater extent. However, the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited. AIM: To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM. METHODS: We performed a search on PubMed, PEDro and CINAHL databases, selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials (RCTs) in the English language that included community or outpatient exercise training programs in patients with T2DM. RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database (PEDro). The primary outcome was peak VO2 and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation. RESULTS: Twelve studies were included in our systematic review. The 12 RCTs resulted in 661 participants in total. HIIT was performed in 310 patients (46.8%), MICT to 271 and the rest 80 belonged to the control group. Peak VO2 increased in 10 out of 12 studies after HIIT. Ten studies compared HIIT with other exercise regimens (MICT or strength endurance) and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens. Moreover, 4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients. In 2 of them, HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed. CONCLUSION: Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients. HIIT may be superior by improving these parameters to a greater extent than MICT.

Sacubitril/Valsartan vs. Standard Medical Therapy on Exercise Capacity in HFrEF Patients.

Sacubitril/valsartan (Sac/Val) reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) compared to enalapril. However, its effects on functional capacity remain uncertain; consequently, we sought to compare Sac/Val vs. standard medical therapy, in terms of effects on prognostically significant CPET parameters, in HFrEF patients during a long follow-up period. We conducted a single-center, observational study in an HF clinic; specifically, we retrospectively identified that 12 patients switched to Sac/Val and 13 patients that managed with standard, optimal medical therapy (control group). At each visit, baseline, and follow-up (median time: 16 months; IQ range: 11.5-22), we collected demographic information, medical history, vital signs, cardiopulmonary exercise testing, standard laboratory data, pharmacological treatment information, and echocardiographic parameters. The study's primary end-point was the change from baseline in peak VO2 (adjusted to body weight). We did not observe significant differences between the two study groups at baseline. Similarly, we did not observe any significant differences during the follow-up in mean values of peak VO2 corrected for body weight: Sac/Val baseline: 12.2 ± 4.6 and FU: 12.7 ± 3.3 vs. control group: 13.1 ± 4.2 and 13.0 ± 4.2 mL/kg/min; p = 0.49. No significant treatment differences were observed for changes in VE/VCO2 slope: Sac/Val baseline: 35.4 ± 7.4 and FU: 37.2 ± 13.1 vs. control group: 34.6 ± 9.1 and 34.0 ± 7.3; p = 0.49. In conclusion, after a median follow-up period of 16 months, there was no significant benefit of Sac/Val on peak VO2 and other measures of CPET compared with standard optimal therapy in patients with HFrEF.

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot: Relation With Exercise Capacity.

Background The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min). Methods and Results A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests. Muscle strength was compared with 2 healthy pediatric cohorts from the Northern Netherlands. Handgrip strength, maximal voluntary isometric contraction, and dynamic muscle strength in correlation with peak oxygen uptake, exercise capacity (mL/min) were the main outcomes of the study. The 67 patients with repaired tetralogy of Fallot (42% female; aged 12.9 [interquartile range, 10.0-16.3] years old) were compared with healthy children. The patients showed reduced grip strength (z-score [mean±SD] -1.5±1.2, P<0.001), and total muscle strength (z-score -0.9±1.3, P<0.001). Dynamic strength (Bruininks-Oseretsky test) was significantly reduced (z-score -0.3±0.8, P=0.001), but running, speed, and agility were normal (z-score 0.1±0.7, P=0.4). Univariate correlation analyses showed strong correlations between absolute peak oxygen uptake, exercise capacity (mL/min), and muscle strength (grip strength r=0.83, total muscle strength r=0.88; P<0.001). In multivariate analyses, including correction for age and sex, total muscle strength (B 0.3; P=0.009), and forced vital capacity (B 0.5; P=0.02) correlated with peak oxygen uptake, exercise capacity (mL/min), independent of conventional cardiovascular parameters. Conclusions Children with repaired tetralogy of Fallot show reduced muscle strength, which strongly correlated with their exercise performance.

Impact of the COVID-19 pandemic on exercise tolerance and patient outcomes with Phase III cardiac rehabilitation in Japan: A multicenter study.

This study aimed to determine how behavioural restrictions due to the emergency declaration following the coronavirus disease 2019 (COVID-19) pandemic affect exercise tolerance and its outcomes in patients in Phase III cardiac rehabilitation programme. This is a multicenter retrospective cohort study. Participants in outpatient cardiac rehabilitation programmes and cardiopulmonary exercise testing before and after the emergency declarations were included. A total of 90 participants were included (median age 75.0 years, 69% male), and the changes in physical function and exercise tolerance were compared before and after the emergency declaration. Patients were divided into a decline-in-peak oxygen uptake (VO2 ) group and a nondecline-in-peak VO2 group. Comparison before and after the emergency declaration showed that the anaerobic threshold declined significantly and peak VO2 exhibited a downward trend. The decline-in-peak VO2 group consisted of 16 patients (17%) with better exercise tolerance, multiple comorbidities, and declined lower extremity muscle strength. These patients also had a higher rate of subsequent composite events (hazard ratio, 5.2; 95% confidence interval, 1.4-18.8, p = 0.01). Before and after the emergency declaration, the patient's exercise tolerance may decline, leading to a poor prognosis. This study suggests the importance of maintaining exercise tolerance during the COVID-19 pandemic.

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing.

Background: We aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET). Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex. Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction). Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics.

Optimizing exercise testing-based risk stratification to predict poor prognosis after acute heart failure.

AIMS: The timely selection of severe heart failure (HF) patients for cardiac transplantation and advanced HF therapy is challenging. Peak oxygen consumption (VO2 ) values obtained by the cardiopulmonary exercise testing are used to determine the transplant recipient list. This study reassessed the prognostic predictability of peak VO2 and compared it with the Heart Failure Survival Score (HFSS) in the modern optimized guideline-directed medical therapy (GDMT) era. METHODS AND RESULTS: We retrospectively selected 377 acute HF patients discharged from the hospital. The primary outcome was a composite of all-cause mortality, or urgent cardiac transplantation. We divided these patients into the more GDMT (two or more types of GDMT) and less GDMT groups (fewer than two types of GDMT) and compared the performance of their peak VO2 and HFSS in predicting primary outcomes. The median follow-up period was 3.3 years. The primary outcome occurred in 57 participants. Peak VO2 outperformed HFSS when predicting 1 year (0.81 vs. 0.61; P = 0.017) and 2 year (0.78 vs. 0.58; P < 0.001) major outcomes. The cutoff peak VO2 for predicting a 20% risk of a major outcome within 2 years was 10.2 (11.8-7.0) for the total cohort. Multivariate Cox regression analyses showed that peak VO2 , sodium, previous implantable cardioverter defibrillator (ICD) implantation, and estimated glomerular filtration rate were significant predictors of major outcomes. CONCLUSIONS: Optimizing the cutoff value of peak VO2 is required in the current GDMT era for advanced HF therapy. Other clinical factors such as ICD use, hyponatraemia, and chronic kidney disease could also be used to predict poor prognosis. The improvement of resource allocation and patient outcomes could be achieved by careful selection of appropriate patients for advanced HF therapies, such as cardiac transplantation.