Peak Ventilation Reference Standards from Exercise Testing: From the FRIEND Registry

Peak Ventilation Reference Standards from Exercise Testing: From the FRIEND Registry. Med. Sci. Sports Exerc., Vol. 50, No. 12, pp. 2603–2608, 2018. Purpose: Cardiopulmonary exercise testing (CPX) provides valuable clinical information, including peak ventilation (V˙ Epeak), which has been shown to have diagnostic and prognostic value in the assessment of patients with underlying pulmonary disease. This report provides reference standards for V˙ Epeak derived from CPX on treadmills in apparently healthy individuals. Methods: Nine laboratories in the United States experienced in CPX administration with established quality control procedures contributed to the Fitness Registry and the Importance of Exercise National Database from 2014 to 2017. Data from 5232 maximal exercise tests from men and women without cardiovascular or pulmonary disease were used to create percentiles ofV˙ Epeak for both men and women by decade between 20 and 79 yr. Additionally, prediction equations were developed for V˙ Epeak using descriptive information. Results: V˙ Epeak was found to be significantly different between men and women and across age groups (P G 0.05). The rate of decline in V˙ Epeak was 8.0% per decade for both men and women. A stepwise regression model of 70% of the sample revealed that sex, age, and height were significant predictors ofV˙ Epeak. The equation was cross-validated with data from the remaining 30% of the sample with a final equation developed from the full sample (r = 0.73). Additionally, a linear regression model revealed forced expiratory volume in 1 s significantly predicted V˙ Epeak (r = 0.73). Conclusions: Reference standards were developed for V˙ Epeak for the United States population. Cardiopulmonary exercise testing laboratories will be able to provide interpretation of V˙ Epeak from these age and sex-specific percentile reference values or alternatively can use these nonexercise prediction equations incorporating sex, age, and height or with a single predictor of forced expiratory volume in 1 s

Cardiopulmonary Exercise Testing in the Clinical and Prognostic Assessment of Diastolic Heart Failure

ObjectivesThis study sought to define the relative prognostic value of cardiopulmonary exercise testing (CPET) variables in heart failure (HF) patients with preserved versus reduced systolic function.BackgroundCardiopulmonary exercise testing has an established role in the assessment of patients with systolic heart failure (SHF). Two variables, peak Vo2and, more recently, the Ve/Vco2slope, have been shown to be extremely valuable in risk stratification. However, data are lacking in terms of the prognostic value of CPET in patients with diastolic heart failure (DHF).MethodsA total of 409 HF patients underwent CPET. Patients were divided into three groups according to the following left ventricular ejection fraction (LVEF) cutoffs: ≥40%, ≥45%, and ≥50%. The CPET response and the ability of peak Vo2and the Ve/Vco2slope to predict total mortality and hospitalization were examined.ResultsAt univariate Cox regression analysis, both the peak Vo2and the Ve/Vco2slope were significant predictors in SHF and DHF. Multivariate analysis documented a similar prognostic power of Ve/Vco2slope and peak Vo2in all SHF groups. Conversely, in DHF patients, Ve/Vco2slope outnumbered peak Vo2, remaining the only predictor regardless of LVEF. In DHF, the area under the receiver operating characteristic curve for the Ve/Vco2slope identified a cutoff of 32.6 (74% sensitivity, 52% specificity), 33.1 (76% sensitivity, 62% specificity), and 33.3 (97% sensitivity, 40% specificity) for an LVEF cutoff of ≥40%, ≥45%, and ≥50%, respectively.ConclusionsThese results extend the clinical and prognostic applicability of CPET to DHF. An impairment in exercise ventilation rather than peak Vo2holds clinical and prognostic impact in this increasing subset of patients

Impaired myocardial relaxation with exercise determines peak aerobic exercise capacity in heart failure with preserved ejection fraction

Background Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity due to shortness of breath and/or fatigue. Assessment of diastolic dysfunction at rest and with exercise may provide insight into the pathophysiology of exercise intolerance in HFpEF. Aims To measure echocardio-Doppler-derived parameters of diastolic function as they relate to various indices of aerobic exercise capacity in HFpEF. Methods We selected 16 subjects with clinically stable HFpEF, no evidence of volume overload, but impaired functional capacity by cardiopulmonary exercise testing [peak oxygen consumption (VO2)]. We measured the transmitral E and A flow velocities, E/A ratio, and E deceleration time (DT) and tissue Doppler E′ velocity. We also indexed the E′ to the DT, as additional measure of impaired relaxation (E′DT), and calculated the diastolic functional reserve index (DFRI), as the product of E′ at rest and change in E′ with exercise. Results E′ velocity, at rest and peak exercise, as well as the DFRI positively correlated with peak VO2, whereas DT, E′DT, and E/E′ with exercise inversely correlated with peak VO2. Of note, the E′DT at rest also significantly predicted E′ velocity at peak exercise (R = +0.81, P \u3c 0.001). Exercise E′ was the only independent predictor of peak VO2 at multivariable analysis (R = +0.67, P = 0.005). Conclusions The E′ velocity at peak exercise is a strong and independent predictor of aerobic exercise capacity as measured by peak VO2 in patients with HFpEF, providing the link between abnormal myocardial relaxation with exercise and impaired aerobic exercise capacity in HFpEF

Long-Term Use of Sildenafil in the Therapeutic Management of Heart Failure

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Relationship between Arterial Stiffness and Heart Rate Recovery in Apparently Healthy Adults

Ding-Yu Fei1, Ross Arena2, James A Arrowood3, Kenneth A Kraft41Department of Biomedical Engineering, 2Department of Physical Therapy, 3Department of Internal Medicine, Division of Cardiology, 4Department of Radiology, Virginia Commonwealth University, Richmond, VA, USAIntroduction: Arterial stiffness and heart rate recovery (HRR) following exercise testing have emerged as variables holding significant prognostic value in a number of populations. The purpose of the present study is to examine the relationship between arterial stiffness and HRR in a group of apparently healthy subjects.Methods: Two hundred and nine apparently healthy subjects underwent maximal exercise testing. Heart rate at one and two minutes post exercise was subtracted from maximal heart rate during the exercise test to produce two measures of heart rate recovery. Aortic wave velocity, in meters per second, was obtained via a new magnetic resonance technique. Results: Pearson Product Moment Correlation analysis revealed a significant correlation between aortic wave velocity and heart rate recovery. Stepwise linear regression analysis revealed that age, maximal aerobic capacity, heart rate recovery at one minute, and diastolic blood pressure were all significant predictors of aortic wave velocity (r = 0.63, r2 = 0.40, p < 0.001). Conclusions: The results of the present study indicate that heart rate recovery is significantly correlated with a measure of large artery stiffness and adds predictive value to other clinical variables. This analysis provides further evidence that assessment of heart rate recovery should be considered in subjects undergoing exercise testing in clinical practice.Keywords: exercise testing, oxygen consumption, aortic wave velocit

Interleukin-1 blockade in recently decompensated systolic heart failure: study design of the recently decompensated heart failure anakinra response trial (RED-HART)

Heart Failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to impaired cardiac function. The incidence of HF is increasing and represents the leading cause of hospitalization in the United States among patients > 65 years of age. Neurohormonal blockade has proven to reduce morbidity and mortality; however the persistent toll of HF demonstrates the urgent need to continue to develop novel drugs that target other pathophysiological paradigms. The presence of inflammation in cardiovascular disease has been well-established and interleukin-1 (IL-1), the prototypical proinflammatory agent, has been shown in preclinical animal models to induce cardiac dysfunction. The current study will investigate the role of IL-1 as an inflammatory mediator of HF progression and investigate whether IL-1 blockade with anakinra, recombinant human IL-1 receptor antagonist, improves aerobic exercise performance in patients with recently decompensated systolic HF. This study will be composed of 3 treatment arms (20 patients each): 1) anakinra 100mg daily for 12 weeks; 2) anakinra 100mg daily for 2 weeks followed by placebo for 10 weeks; or 3) placebo for 12 weeks. All patients will be followed for at least 24 weeks. The co-primary endpoints will be placebo-corrected interval changes in peak oxygen consumption (VO2) and ventilatory efficiency (VE/VCO2 slope) measured by Cardiopulmonary Exercise Testing (CPX) after 2 weeks of anakinra treatment. Secondary endpoints will include interval changes in 1) CPX variables at 4, 12 and 24 weeks; 2) echocardiographic measures of cardiac dimension/function; 3) quality of life assessments; 4) inflammatory biomarkers; and 5) clinical outcome including days alive outside of the hospital and survival free of re-hospitalization for HF. The RED-HART study will be the first study to address the potential benefits of IL-1 blockade on aerobic exercise performance in patients with recently decompensated HF

Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis of heart failure with preserved ejection fraction

Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that presents clinicians with a diagnostic challenge. The use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide (NT-proBNP) level above and below the proposed cut-off. Methods Stable patients (n = 30) with left ventricular (LV) ejection fraction ≥ 50% were eligible if they had a diagnosis of HF according to the European Society of Cardiology diagnostic criteria. Characteristics of patients with NT-proBNP below (≤125 pg/mL) and above (\u3e125 pg/mL) the diagnostic criterion were compared. Results There were 19 (66%) women with median age 54 years. Half were African American (16, 53%), and most were obese. There were no significant differences in clinical characteristics or medication use between groups. LV end-diastolic volume index was greater in high NT-proBNP patients (P = 0.03). Left atrial volume index, E/e\u27 ratio, and E/e\u27 ratio at peak exercise were not significantly different between NT-proBNP groups. Peak oxygen consumption (VO2), VO2 at ventilatory threshold, and ventilatory efficiency measures were impaired in all patients and were not significantly different between high and low NT-proBNP patients. Conclusions NT-proBNP was below the proposed diagnostic cut-off point of 125 pg/mL in half of this obese study cohort. Cardiac diastolic dysfunction and cardiorespiratory fitness were not significantly different between high and low NT-proBNP patients. These data indicate that excluding the diagnosis of HFpEF based solely on NT-proBNP levels should be discouraged

Systematic Review and Regression Modeling of the Effects of Age, Body Size, and Exercise on Cardiovascular Parameters in Healthy Adults

Purpose Blood pressure, cardiac output, and ventricular volumes correlate to various subject features such as age, body size, and exercise intensity. The purpose of this study is to quantify this correlation through regression modeling. Methods We conducted a systematic review to compile reference data of healthy subjects for several cardiovascular parameters and subject features. Regression algorithms used these aggregate data to formulate predictive models for the outputs—systolic and diastolic blood pressure, ventricular volumes, cardiac output, and heart rate—against the features—age, height, weight, and exercise intensity. A simulation-based procedure generated data of virtual subjects to test whether these regression models built using aggregate data can perform well for subject-level predictions and to provide an estimate for the expected error. The blood pressure and heart rate models were also validated using real-world subject-level data. Results The direction of trends between model outputs and the input subject features in our study agree with those in current literature. Conclusion Although other studies observe exponential predictor-output relations, the linear regression algorithms performed the best for the data in this study. The use of subject-level data and more predictors may provide regression models with higher fidelity. Significance Models developed in this study can be useful to clinicians for personalized patient assessment and to researchers for tuning computational models

Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2)

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of con-firmed HF cases in the United States. However, there are no highly effective evidence-basedtreatments currently available for these patients. Inflammation correlates positively withadverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, hasbeen implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clini-cal trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 ran-domized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespi-ratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation inpatients with HFpEF (http://www.ClinicalTrials.gov NCT02173548). The co–primary endpointswill be placebo-corrected interval changes in peak oxygen consumption and ventilatory effi-ciency at week 12. In addition, secondary and exploratory analyses will investigate the effectsof IL-1 blockade on cardiac structure and function, systemic inflammation, endothelial function,quality of life, body composition, nutritional status, and clinical outcomes. The D-HART2 clinicaltrial will add to the growing body of evidence on the role of inflammation in cardiovascular dis-ease, specifically focusing on patients with HFpEF

The slope of the oxygen pulse curve does not depend on the maximal heart rate in elite soccer players

INTRODUCTION: It is unknown whether an extremely high heart rate can affect oxygen pulse profile during progressive maximal exercise in healthy subjects. OBJECTIVE: Our aim was to compare relative oxygen pulse (adjusted for body weight) curves in athletes at their maximal heart rate during treadmill cardiopulmonary exercise testing. METHODS: A total of 180 elite soccer players were categorized in quartiles according to their maximum heart rate values (n = 45). Oxygen consumption, maximum heart rate and relative oxygen pulse curves in the extreme quartiles, Q1 and Q4, were compared at intervals corresponding to 10% of the total duration of a cardiopulmonary exercise testing. RESULTS: Oxygen consumption was similar among all subjects during cardiopulmonary exercise testing; however subjects in Q1 started to exhibit lower maximum heart rate values when 20% of the test was complete. Conversely, the relative oxygen pulse was higher in this group when cardiopulmonary exercise testing was 40% complete (p<.01). Although the slopes of the lines were similar (p = .25), the regression intercepts differed (p<.01) between Q1 and Q4. During the last two minutes of testing, a flat or decreasing oxygen pulse was identified in 20% of the soccer players, and this trend was similar between subjects in Q1 and Q4. CONCLUSION: Relative oxygen pulse curve slopes, which serve as an indirect and non-invasive surrogate for stroke volume, suggest that the stroke volume is similar in young and aerobically fit subjects regardless of the maximum heart rate reached