Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

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.

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.

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.

Effects of chronotropic incompetence on exercise capacity in people with heart failure versus age-matched controls.

Chronotropic incompetence (CI) is an inability to adequately raise heart rate during physiological stress. We established CI prevalence and exercise capacity in heart failure versus healthy age-matched controls. We conducted a systematic search (1966-July 1, 2020) and meta-analysis of studies reporting peak VO2 in people with heart failure with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction and controls. Seventeen studies of 4410 participants were included, 4167 with heart failure and 243 age-matched controls. In both heart failure phenotypes, CI was more prevalent in HFrEF (51.7%) and HFpEF (55.8%) than in healthy controls (9%). Mortality was 24% higher in people with HFrEF and CI versus those with HFrEF and without CI; OR -1.24 (95% CI -2.20 to -0.28; p = 0.01). People with heart failure and CI had lower peak VO2 than those without CI (MD) -3.30 ml kg-1 min-1 (95% CI -4.25 to -2.35, p < 0.01), and this was primarily driven by the HFrEF sub-population (MD) -3.86 ml kg-1 min-1 (95% CI -4.83 to -2.89, p < 0.01). Maximum heart rate MD -37.51 beats min-1 (95% CI -41.99 to -33.03, p < 0.01) and maximum-resting heart rate were lower MD -29.44 beats min-1 (95% CI -34.55 to -24.33, p < 0.01) in people with heart failure with CI vs without CI. People with heart failure and CI demonstrated similar respiratory exchange ratios (RER) to people with heart failure but without CI; (MD) -0.02 (95% CI -0.03 to -0.01), p < 0.01, suggesting that poor effort was unlikely to explain CI. CI is more prevalent in heart failure than in age-matched controls and although it is associated with lower peak VO2 in HFrEF, it is unrelated to the lower peak VO2 in HFpEF. RER values suggest poor effort is unlikely to explain these findings.

Feasibility and Consistency of Results with Deployment of an In-Line Filter for Exercise-Based Evaluations of Patients With Heart Failure During the Novel Coronavirus Disease-2019 Pandemic.

BACKGROUND: Exercise testing plays an important role in evaluating heart failure prognosis and selecting patients for advanced therapeutic interventions. However, concern for severe acute respiratory syndrome novel coronavirus-2 transmission during exercise testing has markedly curtailed performance of exercise testing during the novel coronavirus disease-2019 pandemic. METHODS AND RESULTS: To examine the feasibility to conducting exercise testing with an in-line filter, 2 healthy volunteer subjects each completed 2 incremental exercise tests, one with discrete stages of increasing resistance and one with a continuous ramp. Each subject performed 1 test with an electrostatic filter in-line with the system measuring gas exchange and air flow, and 1 test without the filter in place. Oxygen uptake and minute ventilation were highly consistent when evaluated with and without use of an electrostatic filter with a >99.9% viral efficiency. CONCLUSIONS: Deployment of a commercially available in-line electrostatic viral filter during cardiopulmonary exercise testing is feasible and provides consistent data compared with testing without a filter.

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis.

BACKGROUND: The prognostic value of cardiopulmonary exercise testing (CPET) in patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis is unknown. METHODS AND RESULTS: This retrospective study included patients with wtATTR who underwent baseline cardiopulmonary exercise testing and were treated with tafamidis from August 31, 2018, until March 31, 2020. Univariate logistic and multivariate cox-regression models were used to predict the occurrence of the primary outcome (composite of mortality, heart transplant, and palliative inotrope initiation). A total of 33 patients were included (median age 82 years, interquartile range [IQR] 79-84 years), 84% were Caucasians and 79% were males). Majority of patients had New York Heart Association functional class III disease at baseline (67%). The baseline median peak oxygen consumption (VO2) and peak circulatory power (CP) were 11.35 mL/kg/min (IQR 8.5-14.2 mL/kg/min) and 1485.8 mm Hg/mL/min (IQR 988-2184 mm Hg/mL/min), respectively, the median ventilatory efficiency was 35.7 (IQR 31-41.2). After 1 year of follow-up, 11 patients experienced a primary end point. Upon multivariate analysis, the low peak VO2 (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.79, P = .007], peak CP (HR 0.98, 95% CI 0.98-0.99, P = .02), peak oxygen pulse (HR 0.62, 95% CI 0.39-0.97, P = .03), and exercise duration of less than 5.5 minutes (HR 5.82, 95% CI 1.29-26.2, P = .02) were significantly associated with the primary outcome. CONCLUSIONS: Tafamidis-treated patients with wtATTR who had baseline low peak VO2, peak CP, peak O2 pulse, and exercise duration of less than 5.5 minutes had worse outcomes.

Exercise-Based Cardiac Rehabilitation Programs in Heart Failure Patients.

Exercise training is recommended for patients with heart failure by major societies' guidelines. It improves exercise capacity and quality of life, reduces symptoms of depression, can improve survival, and reduce the risk for hospitalizations. Exercise-based cardiac rehabilitation can be offered with different modalities, such as continuous or interval aerobic training, resistance, and inspiratory muscle training. The intervention must follow an accurate evaluation of the patient's cardiovascular conditions and functional capacity. Despite the multiple benefits of exercise training, there is a lack of adherence to exercise-based programs, due to socioeconomic factors, patients' characteristics, and lack of referral.

Physical activity measures in patients with myalgic encephalomyelitis/chronic fatigue syndrome: correlations between peak oxygen consumption, the physical functioning scale of the SF-36 questionnaire, and the number of steps from an activity meter.

BACKGROUND: Most studies to assess effort intolerance in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have used questionnaires. Few studies have compared questionnaires with objective measures like an actometer or an exercise test. This study compared three measures of physical activity in ME/CFS patients: the physical functioning scale (PFS) of the SF-36, the number of steps/day (Steps) using an actometer, and the %peak VO2 of a cardiopulmonary stress test. METHODS: Female ME/CFS patients were selected from a clinical database if the three types of measurements were available, and the interval between measurements was ≤ 3 months. Data from the three measures were compared by linear regression. RESULTS: In 99 female patients the three different measures were linearly, significantly, and positively correlated (PFS vs Steps, PFS vs %peak VO2 and Steps vs %peak VO2: all P < 0.001). Subgroup analysis showed that the relations between the three measures were not different in patients with versus without fibromyalgia and with versus without a maximal exercise effort (RER ≥ 1.1). In 20 patients re-evaluated for symptom worsening, the mean of all three measures was significantly lower (P < 0.0001), strengthening the observation of the relations between them. Despite the close correlation, we observed a large variation between the three measures in individual patients. CONCLUSIONS: Given the large variation in ME/CFS patients, the use of only one type of measurement is inadequate. Integrating the three modalities may be useful for patient care by detecting overt discrepancies in activity and may inform studies that compare methods of improving exercise capacity.

Clinical outcomes after cardiac rehabilitation in elderly patients with and without diabetes mellitus: The EU-CaRE multicenter cohort study.

BACKGROUND: The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. METHODS: 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. RESULTS: 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. CONCLUSIONS: While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166.

The efficacy of exercise training in kidney transplant recipients: a meta-analysis and systematic review.

BACKGROUND: The effectiveness of exercise in kidney transplant recipients is not well established. We, therefore, performed a systematic review of the effects of exercise training in kidney transplantation recipients. METHODS: We searched two electronic databases for articles up to April 2017. Inclusion criteria were as follows: randomized controlled trial and kidney transplant recipients aged 18 years or older. The main outcomes were allograft function (estimated glomerular filtration rate, eGFR), exercise tolerance (VO2 peak), and quality of life (QOL). RESULTS: After screening of 1303 references in PubMed and Ichushi, six randomized control trials were analyzed. For kidney transplant recipients, supervised exercise training was shown to significantly improve VO2 peak [mean difference 2.42; 95% confidence interval (95%CI) 0.22-4.63] and QOL (mean difference 7.23; 95%CI 0.94-13.52). However, exercise training did not improve allograft kidney function (mean difference 6.22; 95%CI - 13.00 to 25.44). No reporting bias was observed in any of the outcomes. There were no reports including patient survival rates and the harm associated with exercise training. CONCLUSIONS: Exercise training for kidney transplant recipients significantly improved exercise tolerability and QOL, but a significant improvement was not obtained with respect to allograft kidney function. Evaluation of patient survival rates and the harm associated with exercise training has not been reported, therefore, future studies are needed to resolve these issues.

Cardiorespiratory fitness as a predictor of short-term and lifetime estimated cardiovascular disease risk.

Development of cardiovascular disease (CVD) remains a public health concern for young to middle-aged adults, now exacerbated by the increasing prevalence of obesity and sedentary lifestyles. Cardiorespiratory fitness (CRF) improves the reclassification of short-term (10-year) CVD risk, but has not been uniformly defined across studies. This study evaluated cross-sectional differences in short-term and lifetime CVD risk scores, across both absolute metabolic equivalent (MET) and sex- and age-standardized CRF categories in 805 apparently healthy young to middle-aged adults (68% male; 47.4 ± 7.2 years). CVD risk factors were evaluated, and estimated cardiorespiratory fitness (CRF) measurements (METS and peak VO2 ) were derived from a submaximal Bruce treadmill test. CRF measures also included post-exercise heart rate recovery (HRR) data. Consistent trends showing more favorable risk factor profiles and lower short-term CVD (QRISK2), and CVD mortality (SCORE) scores, associated with higher levels of CRF were evident in both sexes. Lifetime CVD risk (Q-Lifetime) was highest in the lowest CRF categories. Peak VO2 and HRR following submaximal exercise testing contributed to the variability in short-term and lifetime CVD risk. Global CVD risk predictions were examined across different contemporary CRF classifications with inconsistent findings. Recommended absolute MET and sex- and age-standardized CRF categories were significantly associated with both short-term and lifetime risk of CVD outcomes. However, compared to internationally derived normative CRF standards, cohort-specific CRF categories resulted in markedly different proportion of individuals classified in the "poor" CRF category at higher CVD risk.

Ivabradine Improves Cardiac Function and Increases Exercise Capacity in Patients with Chronic Heart Failure.

To systematically review and conduct a meta-analysis of the ivabradine-induced improvement in cardiopulmonary function, exercise capacity, and primary composite endpoints in patients with chronic heart failure (CHF).This study was a systematic review and meta-analysis.Databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinical Trials and European Union Clinical Trials, were searched for randomized placebo-controlled trials. The efficacy and safety of ivabradine treatment in patients with CHF were assessed and compared to those of the standard anti-heart failure treatment. Review Manager 5.3 software was used to analyze the relative risk (RR) for dichotomous data and the mean difference (MD) for continuous data.In total, 22 studies with 24,562 patients were included. Cardiopulmonary function analysis showed that treatment with added ivabradine reduced the heart rate (MD = -17.30, 95% confidence interval (CI): 19.52--15.08, P < 0.00001), significantly increased the left ventricular ejection fraction (LVEF) (MD = 3.90, 95% CI: 0.40-7.40, P < 0.0001), and led to a better New York Heart Association (NYHA) classification. Ivabradine significantly reduced the minute ventilation/carbon dioxide production (VE/VCO2) (MD = -2.68, 95% CI: -4.81--0.55, P = 0.01) and improved the peak VO2 (MD = 2.80, 95% CI: 1.05-4.55, P = 0.002) and the exercise capacity, including the exercise duration with a submaximal load (MD = 7.82, 95% CI: -2.57--18.21, P < 0.00001) and the 6-minute walk distance. The RR of cardiovascular death or worsening heart failure was significantly decreased (RR = 0.93, 95% CI: 0.87--0.98, P = 0.01) in the patients treated with ivabradine. Additionally, the RRs of heart failure and hospitalization also decreased (RR = 0.91, 95% CI: 0.85--0.97, P = 0.006; RR = 0.86, 95% CI: 0.79--0.93, P = 0.0002). Safety analysis showed no significant difference in the RR of severe adverse events between the ivabradine group and the standard anti-heart failure treatment group (P = 0.40). However, ivabradine significantly increased the RR of visual symptoms in CHF patients (RR = 3.82, 95% CI: 1.80--8.13, P = 0.0005).Existing evidence showed that adding ivabradine treatment significantly improved the cardiopulmonary function and increased the exercise capacity of patients with CHF. Adding ivabradine to the standard anti-heart failure treatment reduced the mortality and hospitalization risk and improved the quality of life. Finally, ivabradine significantly increased the RR of visual symptoms in CHF patients.This is the first systematic review and meta-analysis to focus on the efficacy of ivabradine, which improved the cardiac function and increased the exercise capacity in patients with chronic heart failure (CHF). Therefore, this study will help evaluate the quality of life after adding ivabradine to the treatment of patients with CHF, even though there are differences in the standard for resting heart rate, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class in the included studies. This hybrid effect might be smaller when analyzed separately but might have a higher heterogeneity when analyzed in multiple studies.

Characteristics of patients with a relatively greater minimum VE/VCO2 against peak VO2% and impaired exercise tolerance.

PURPOSE: Cardiopulmonary exercise testing (CPX) is used to evaluate functional capacity and assess prognosis in cardiac patients. Ventilatory efficiency (VE/VCO2) reflects ventilation-perfusion mismatch; the minimum VE/VCO2 value (minVE/VCO2) is representative of pulmonary arterial blood flow in individuals without pulmonary disease. Usually, minVE/VCO2 has a strong relationship with the peak oxygen uptake (VO2), but dissociation can occur. Therefore, we investigated the relationship between minVE/VCO2 and predicted peak VO2 (peak VO2%) and evaluated the parameters associated with a discrepancy between these two parameters. METHODS: A total of 289 Japanese patients underwent CPX using a cycle ergometer with ramp protocols between 2013 and 2014. Among these, 174 patients with a peak VO2% lower than 70% were enrolled. Patients were divided into groups based on their minVE/VCO2 [Low group: minVE/VCO2 < mean - SD (38.8-5.6); High group: minVE/VCO2 > mean + SD (38.8 + 5.6)]. The characteristics and cardiac function at rest, evaluated using echocardiography, were compared between groups. RESULTS: The High group had a significantly lower ejection fraction, stroke volume, and cardiac output, and higher brain natriuretic peptide, tricuspid regurgitation pressure gradient, right ventricular systolic pressure, and peak early diastolic LV filling velocity/peak atrial filling velocity ratio compared with the Low group (p's < 0.01). In addition, the Low group had a significantly higher prevalence of pleural effusion than did the High group (26 vs 11%, p < 0.01). CONCLUSIONS: Patients with a relatively greater minVE/VCO2 in comparison with peak VO2 had impaired cardiac output as well as restricted pulmonary blood flow increase during exercise, partly due to accumulated pleural effusion.

Efficacy of Sports Club Activities on Exercise Tolerance Among Japanese Middle and High School Children and Adolescents After Fontan Procedure.

The exercise tolerance of Fontan patients is poorer than that of healthy people. Some previous studies reported that exercise tolerance can be improved in this population by cardiac rehabilitation. This study aimed to determine the factors associated with peak oxygen uptake (VO2) and to subsequently clarify the correlation between participation in sports club activities and variables related to exercise tolerance. Cardiopulmonary exercise tests were performed by 115 Fontan patients aged between 6 and 20 years. The patients completed questionnaires on their daily physical activities including participation in extracurricular sports clubs in middle (junior high school) and high school. Peak VO2 had a significant negative correlation with age and a positive correlation with hemoglobin, stroke volume, and resting tidal volume in the entire study group. Additionally, the sports club participants who were middle and high school students had significantly higher peak VO2 and resting tidal volume. Exercise habits including participation in sports club activities may promote exercise tolerance by improving respiratory function in Fontan adolescents.

Comparison Between the Kansas City Cardiomyopathy Questionnaire and New York Heart Association in Assessing Functional Capacity and Clinical Outcomes.

OBJECTIVE: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has emerged as a patient-centered heart failure-specific health status measure. It currently lacks routine and widespread use in clinical practice and trials. The purpose of this study was to examine the correlation between KCCQ and cardiopulmonary exercise testing (CPET) parameters and clinical outcomes, compared with the New York Heart Association functional classification (NYHA). METHODS AND RESULTS: We performed a single-centered observational analysis of 432 patients who presented to the Heart Failure Department, completed the KCCQ, and underwent CPET. The 1-year clinical outcome assessed was a composite of mortality, heart failure hospitalization, and need for heart transplantation or left ventricular assist device. In the KCCQ, the physical limitation domain had a correlation with peak VO2 similar to NYHA (r = 0.48; P < .001; and r = -0.48; P < .001; respectively), and slightly better correlation with ventilatory threshold (r = 0.42; P < .001; and r = -0.40; P < .001; respectively). According to model validation, the KCCQ physical limitation domain and NYHA were similar predictors of peak VO2 (r2 = 0.229; and r2 = 0.227; respectively). KCCQ predicted the specified 1-year clinical outcome (hazard ratio 0.75, 95% confidence interval 0.69-0.82; P < .001) and provided incremental predictive ability when added to a model that included NYHA, with a net reclassification index of 76.1% (P < .001). CONCLUSIONS: KCCQ and NYHA provide similar assessment of functional capacity. KCCQ predicts 1-year clinical outcomes, providing incremental value over NYHA. These findings support its routine use in clinical care, as well as its potential to serve as a measure in clinical trials.

Prognostic Markers of Outcome in Patients Undergoing Infra-inguinal Revascularisation: A Prospective Observational Pilot Study.

OBJECTIVES: The aim was to investigate whether cardiopulmonary exercise testing (CPET) variables derived from cycle and arm ergonometry correlate, and whether CPET variables and pre-operative N-terminal pro-brain natriuretic peptide (NT-proBNP) have prognostic significance and if the combination of the two has incremental value. METHODS: A prospective observational pilot study was conducted; 70 patients who underwent infra-inguinal bypass surgery were recruited. Pre-operatively subjects underwent CPET with both arm and leg ergonometry, to measure peak oxygen consumption, anaerobic threshold (AT), and ventilatory equivalents. In addition pre-operative serum samples of NT-proBNP were obtained. The primary endpoint was 1 year all-cause mortality; in addition, data were collected on complications, morbidity, length of stay, and major adverse cardiac events (MACE). RESULTS: The 1 year mortality rate was 6%, the overall complications rate was 23%, and the combined incidence of MACE and 1 year mortality was 10%. Cycle ergonometry peak VO2 14 mL/kg/min (RR 5.5, 95% CI 1.4-22.4, p = .007) and AT < 10mL/kg/min (RR 3.0, 95% CI 1.1-7.0, p = .03) were predictors of post-operative complications. Pre-operative NT-proBNP > 320 ng/L (RR 18, 95% CI 2.5-140 p = .0003) was the sole predictor of 1 year mortality or MACE. CONCLUSION: The measurement of pre-operative NT-proBNP in peripheral vascular disease patients undergoing infra-inguinal bypass can predict 1 year mortality and MACE. CPET variables from cycle ergonometry are predictors of post-operative complications in this patient group.

Impact of BNP level and peak VO2 on future heart failure events: comparison between sinus rhythm and atrial fibrillation.

This study aimed to examine the discrete impacts of peak oxygen consumption (VO2) and brain natriuretic peptide (BNP) levels on future heart failure (HF) events in sinus rhythm (SR) and atrial fibrillation (AF). A total of 1447 patients who underwent symptom-limited cardiopulmonary exercise testing and whose BNP values were determined simultaneously were analysed (SR, N = 1151 and AF, N = 296). HF events were defined as HF hospitalization or HF death. Over a mean follow-up period of 1472 days, 140 HF events were observed. A high BNP value (dichotomized by median value) was independently associated with HF events in SR (HR 8.08; 95 % CI 4.02-16.26; p < 0.0001), but not in AF patients (HR 1.97; 95 % CI 0.91-4.28; p = 0.087) with a significant interaction between the rhythms. By contrast, low-peak VO2 was independently associated with HF events in both rhythms (AF; HR 5.81; 95 % CI 1.75-19.30; p = 0.004, SR; HR 2.04; 95 % CI 1.19-3.49; p = 0.009), with a marginal interaction between them. In bivariate Cox models, low-peak VO2 had much stronger predictive power for HF events than high-BNP in AF, whereas high-BNP was more powerful than low-peak VO2 in SR. The prognostic value of BNP and peak VO2 for future HF events seemed to be different between SR and AF.

Six-Minute Walk Test for Assessing Physical Functional Capacity in Chronic Heart Failure.

PURPOSE OF THE REVIEW: The six-minute walk test (6MWT) is a submaximal exercise test for evaluating physical functional capacity. This review aims to report the research on the use of the 6MWT in chronic heart failure (CHF) that has been published in the past 5 years. RECENT FINDINGS: The 6MWT distance does not accurately reflect peak VO2. Minimal clinically important difference in the 6MWT distance, and additional measurements, such as heart rate recovery, can assist in the interpretation of the 6MWT distance, so management decisions can be made. Incorporating mobile apps and information technology in measuring the 6MWT distance extends the usefulness of this simple walk test and improve remote monitoring of patients with CHF. The 6MWT is a useful tool in CHF programs. However, interpretation of the 6MWT distance must be with caution. With the advancement in technology, the 6MWT has the potential to facilitate the monitoring of people living in rural and remote areas.

Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure.

Participation in a comprehensive cardiac rehabilitation (CR) program has been shown to reduce mortality and improve exercise capacity and symptoms in patients with chronic heart failure (CHF). Reduced exercise capacity leads to a concomitant reduction of skeletal muscle mass and accumulation of body fat. However, it is currently unknown whether CR reduces visceral adipose tissue (VAT) and/or subcutaneous abdominal adipose tissue (SAT) in patients with CHF. In addition, the body composition associated with improved exercise capacity after CR in patients with CHF has not been previously studied. Nineteen CHF patients who were categorized as NYHA functional class II or III and had received optimal medical treatment including a CR program for 5 months were enrolled in this study. The CR program significantly increased peak VO2 and reduced B-type natriuretic peptide. In addition, fat and body composition analysis showed reductions in the visceral fat tissue (VAT) area, subcutaneous abdominal adipose tissue (SAT) area, body weight, and total fat weight after CR. There were no changes in total water weight and total muscle weight. Single regression analysis revealed that the amelioration of reduced exercise capacity seen after CR is associated with reduced VAT area but not with SAT area or body weight. In conclusion, CR reduces VAT and improves exercise capacity in patients with CHF. This suggests that reducing VAT is important for CR to be most effective in the treatment of CHF.