Submaximal Exercise Capacity In Patients Research Articles

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction

There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. ClinicalTrials.gov Identifier: NCT03066804.

The effect of global longitudinal strain on ımpaired six-minute walk test performance in patients with sarcoidosis.

Background:Sarcoidosis is a multisystem and granulomatous disease associated with impaired functional capacity as a result of pulmonary and cardiac involvement. Factors adversely effecting functional capacity in patients with sarcoidosis have not been systematically assessed including myocardial strain imaging on echocardiography which enable to diagnose subclinical cardiac dysfunction. We aimed to evaluate the effect of left and right ventricular global longitudinal strain (GLS) on submaximal exercise capacity in patients with sarcoidosis who do not have clinically manifest cardiac involvement.Methods:Extracardiac biopsy proven 56 patients with sarcoidosis and 26 controls were included consecutively. Submaximal exercise capacity of the subjects was assessed with six-minute walk test (6 MWT). Pulmonary function tests and standard transthoracic and two-dimensional speckle tracking echocardiography were performed to the all subjects. Linear regression analysis was performed to find independent predictors of 6 MWT.Results:Fifty-six patients (18% male) with a mean age of 52.5 ± 10.7 years were included. Patients with sarcoidosis had low 6 MWT performance and higher New York Heart Association classes and NT-proBNP levels. There were no significant differences between controls and patients with sarcoidosis in parameters of pulmonary function test. Biventricular GLS levels and biatrial reservoir and conduit function values were lower and systolic pulmonary artery pressure (SPAP) was significantly higher in patients with sarcoidosis as compared with controls. Older age and higher SPAP were found as independent predictors of poor 6 MWT performance.Conclusion:Although biventricular GLS levels were lower in the patients with sarcoidosis, only age and SPAP elevations were independent predictors of the submaximal exercise capacity. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 63-73)

Submaximal Exercise Capacity in Juvenile Dermatomyositis after Longterm Disease: The Contribution of Muscle, Lung, and Heart Involvement.

To compare submaximal exercise capacity in patients with juvenile dermatomyositis (JDM) with controls, and analyze contributions of muscle, heart, and lung impairment in patients. Fifty-nine patients with JDM, with a mean 16.9 years after symptom onset, and 59 sex- and age-matched controls completed a 6-min walk test (6MWT) and a timed up and go (TUG) test. Muscle function, disease activity/damage, and health-related quality of life (HRQOL) were assessed by validated tools; heart function by echocardiography and electrocardiography; and lung function by spirometry, DLCO, and body plethysmography. A thoracic high-resolution computed tomography (HRCT) scan and magnetic resonance imaging of the thighs were completed in patients. The 6MWT distance (6MWD) was 592 ± 81 m in patients versus 649 ± 79 m in controls (p < 0.001), and 563 ± 75 m in active versus 622 ± 76 m in inactive JDM (p = 0.004). The TUG time was 13.1 ± 2.1 s in patients versus 12.3 ± 2.0 s in controls (p = 0.034), and 13.7 ± 2.2 s in active versus 12.5 ± 1.8 s in inactive JDM (p = 0.028). No statistically significant difference was found between inactive JDM and controls in either test. In patients, the Childhood Myositis Assessment Score influenced the 6MWD and TUG time the most, followed by a low DLCO and HRCT pathology in the 6MWT and forced vital capacity in the TUG test. Medical Outcomes Study Short Form-36 physical component summary correlated strongly with both tests. Submaximal exercise capacity was reduced in patients with JDM, particularly those with active disease. This reduction was associated with muscle and lung dysfunction and poorer HRQOL.

Iron Status in Chronic Heart Failure: Impact on Symptoms, Functional Class and Submaximal Exercise Capacity

Introduction and objectivesTo evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. MethodsWe undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. ResultsA total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285±101 meters among those with impaired iron status, vs 322±113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. ConclusionsIn patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation.

Estado del hierro en la insuficiencia cardiaca crónica: impacto en síntomas, clase funcional y capacidad de ejercicio submáxima

Introduction and objectivesTo evaluate the effect of iron deficiency and anemia on submaximal exercise capacity in patients with chronic heart failure. MethodsWe undertook a single-center cross-sectional study in a group of stable patients with chronic heart failure. At recruitment, patients provided baseline information and completed a 6-minute walk test to evaluate submaximal exercise capacity and exercise-induced symptoms. At the same time, blood samples were taken for serological evaluation. Iron deficiency was defined as ferritin < 100 ng/mL or transferrin saturation < 20% when ferritin is < 800 ng/mL. Additional markers of iron status were also measured. ResultsA total of 538 heart failure patients were eligible for inclusion, with an average age of 71 years and 33% were in New York Heart Association class III/IV. The mean distance walked in the test was 285±101 meters among those with impaired iron status, vs 322±113 meters (P=.002). Symptoms during the test were more frequent in iron deficiency patients (35% vs 27%; P=.028) and the most common symptom reported was fatigue. Multivariate logistic regression analyses showed that increased levels of soluble transferrin receptor indicating abnormal iron status were independently associated with advanced New York Heart Association class (P < .05). Multivariable analysis using generalized additive models, soluble transferrin receptor and ferritin index, both biomarkers measuring iron status, showed a significant, independent and linear association with submaximal exercise capacity (P=.03 for both). In contrast, hemoglobin levels were not significantly associated with 6-minute walk test distance in the multivariable analysis. ConclusionsIn patients with chronic heart failure, iron deficiency but not anemia was associated with impaired submaximal exercise capacity and symptomatic functional limitation.Full English text available from:www.revespcardiol.org/en

Determinants of submaximal exercise capacity in patients at risk for heart failure with preserved ejection fraction-results from the DIAST-CHF study.

Objectives and BackgroundThe aim of this study was to identify determinants of submaximal exercise capacity as measured by 6 min walking distance in patients at risk for heart failure with preserved ejection fraction (HFpEF).MethodsA cross‐sectional analysis from the prospective cohort programme Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST‐CHF) that included a total of 1937 patients (age, 50–85 years) with >1 risk factor (hypertension, atherosclerotic disease, diabetes mellitus, and obstructive sleep apnoea) was carried out. Besides comprehensive clinical phenotyping, standardized 6 min walk test and state‐of‐the‐art echocardiography were performed, and blood samples for biomarker assessment were obtained. Patients with an ejection fraction <50% or without evaluable exercise test were excluded from this analysis.ResultsOne thousand three hundred eighty‐seven patients fulfilled all criteria for this analysis. In the univariate analysis, 6 min walk distance was inversely related to E/e′ values (P < 0.001). In the multivariate analysis, 6 min walk distance decreased significantly with age, female sex, increasing body mass index, diabetes, chronic obstructive lung disease, and peripheral artery disease. However, the association of 6 min walk distance with resting parameters of diastolic function was significantly attenuated with multivariate regression. In contrast, mid‐regional pro‐adrenomedullin, mid‐regional pro‐atrial natriuretic peptide, and N‐terminal pro‐B‐type natriuretic peptide were independently associated with submaximal exercise capacity when added to the base model (all P < 0.001).ConclusionsClassical risk factors for heart failure and neuroendocrine activation are independently associated with sub‐maximal exercise capacity, while diastolic function parameters obtained at rest were not. This observation substantiates the role of co‐morbidities as relevant contributors to the clinical picture of HFpEF and the limitation of resting indices of diastolic function for diagnosing HFpEF.

Characterization and Functional Implications of Heart Rate Increase and Heart Rate Recovery on Maximal and Submaximal Exercise Capacity in Patients with Advanced Heart Failure

Objective: Heart rate increase early after the initiation of exercise has not been characterized nor related to exercise capacity, heart rate recovery, and gas exchange analyses in patients with advanced heart failure. One hundred and forty-one patients including 121 patients randomized in the GREATER-EARTH trial were investigated. Methods: Exercise capacity was assessed using a treadmill ramp exercise protocol with gas exchange analyses, a fix-load endurance exercise protocol, and a 6-minute walk test. Heart rate increase was computed at 1-, 2- minutes, and 1/3 of exercise time while heart rate recovery was measured at 1- and 2-minutes following maximal exercise. Results: Heart rate increase early after the initiation of exercise test was not related to exercise capacity. In contrast, heart rate recovery was significantly related to maximal and submaximal exercise capacity. Among gas exchange responses, only the VE/VCO2 slope and PetCO2 at peak exercise were significantly associated with maximal but not submaximal exercise capacity. Conclusions: Heart rate increase early after the initiation of exercise yields no relationship with maximal and submaximal exercise capacity in patients with advanced heart failure. Among gas exchange parameters, only some markers of ventilatory inefficiency have significant associations with maximal exercise capacity in patients with heart failure.

Inspiratory muscle training improves submaximal exercise capacity in patients with heart failure: A systematic review of randomized controlled trials

Inspiratory muscle training improves submaximal exercise capacity in patients with heart failure: A systematic review of randomized controlled trials

Cardiac output does not limit submaximal exercise capacity in patients with chronic heart failure

Mechanisms of exercise limitation in patients with chronic heart failure (CHF) are incompletely understood. During matched submaximal, fixed-rate exercise, oxygen uptake is similar in patients and healthy controls. However, the importance of cardiac output (CO) remains unresolved. We aimed to determine the effect of submaximal exercise on CO and other haemodynamic variables in patients with CHF using a validated non-invasive inert gas rebreathing system. Seventy-two subjects with a mean age (+/-SD) of 68.2 (+/-8.1) years, performed fixed-rate exercise for 3 min at 15, 30, 45, and 60 W workloads on a cycle ergometer. Cardiac output/index (CI) and oxygen uptake (VO(2)) were determined at each stage by inert gas rebreathing. Subjects with systolic HF (n = 27) were compared with those without (n = 45). Cardiac index was lower in subjects with CHF at rest and throughout exercise. VO(2) was the same for both groups at rest and during exercise. There was no difference in the relative or absolute increase in CI from rest to 60 W (1.70 +/- 0.69 vs. 1.99 +/- 0.56 L/min/m(2), P = 0.102, respectively). Arterio-venous O(2) saturation difference at peak exercise was 75.4 +/- 10.4 vs. 63.0 +/- 12.1%, P = 0.001, for CHF and non-CHF subjects, respectively. During submaximal exercise, patients with systolic heart failure are able to increase their CO to a similar extent as those without; with equal levels of oxygen consumption, but requiring a much greater degree of tissue oxygen extraction.

Atriobiventricular pacing improves exercise capacity in patients with heart failure and intraventricular conduction delay

ObjectivesWe sought to assess the efficacy of biventricular pacing with respect to both peak and submaximal measures of exercise in patients with New York Heart Association class III heart failure (HF) and intraventricular conduction delay in a randomized, blinded study. BackgroundSubmaximal and maximal changes in exercise capacity need evaluating in this patient population with this novel therapy. MethodsGraded exercise and 6-min walk tests were performed in patients randomized to three months each of active (atrio-biventricular) and inactive pacing. Minute ventilation (VE), oxygen uptake (VO2), ventilated carbon dioxide (VCO2) and heart rate were measured in patients achieving a respiratory quotient >1 (n = 30). Oxygen pulse, anaerobic threshold (AT) and ventilatory efficiency (VE/VCO2) were calculated. ResultsActive biventricular pacing increased peak VO2(15.8 ± 4.3 vs. 14.4 ± 4.6 ml/kg/min, p = 0.02), exercise time (501 ± 223 s vs. 437 ± 233 s, p < 0.001) and oxygen pulse (9.3 ± 2.8 vs. 8.1 ± 3.1 ml/beat, p < 0.01) compared with inactive pacing. The submaximal measures of exercise capacity significantly increased with active pacing: AT (11.2 ± 4.1 ml/kg/min vs. 9.5 ± 2.3 ml/kg/min, p = 0.02) and 6-min walk (414 ± 94 m vs. 359 ± 94 m, p = 0.001). Minute ventilation/ventilated carbon dioxide improved (32 ± 9 vs. 36 ± 11, p = 0.03) with normalization of the VE/VCO2slope in 59% of patients (chi-square test, p = 0.002) with active pacing. ConclusionsBiventricular pacing may improve maximal and submaximal exercise capacity in patients with advanced HF and intraventricular conduction delay.

The role of supplemental oxygen during submaximal exercise in patients with cystic fibrosis.

Repeated bouts of submaximal exercise are an important part of most pulmonary rehabilitation programmes. Patients with moderate-to-severe cystic fibrosis (CF) often demonstrate oxygen desaturation during submaximal exercise, which may limit their ability to participate in these programmes. This study examines whether arterial desaturation contributes to submaximal exercise limitation by testing whether supplemental O2 improves submaximal exercise capacity. Eight patients with CF (mean forced expiratory volume in one second 41% predicted) each underwent two submaximal exercise tests on a bicycle ergometer at 80% of maximal workload. The two tests were identical except for the addition of supplemental O2 (inspiratory O2 fraction 39%) during one of the tests. Exercise duration was significantly longer in the supplemental O2 study versus control (673+/-63 s versus 835+/-99 s). Arterial O2 saturation was also higher in the supplemental O2 study than the control exercise test (96+/-0.3% versus 86+/-1.5%). There was no statistical difference at end exercise between O2 consumption, minute ventilation and heart rate. There was a significant relationship between improvement in exercise capacity and the amount of desaturation during the control exercise test. Results indicate that supplemental oxygen improves submaximal exercise capacity in patients with moderate-to-severe cystic fibrosis. Oxygen therapy may be an important intervention to improve participation and maximise the benefits of pulmonary exercise rehabilitation programmes.

Effects of Long-Term Therapy with Oral Piroximone on Resting Hemodynamics, Peak Aerobic Capacity, and the Anaerobic Threshold in Patients with Heart Failure

Piroximone (MDL 19205), a new imidazole derivative with positive inotropic and vasodilating properties, was administered to 10 patients with congestive heart failure. After acute intravenous (0.90 +/- 0.12 mg/kg, mean +/- SEM) and oral (1.41 +/- 0.18 mg/kg) administration, cardiac index and stroke volume index increased and were accompanied by a decline in systemic vascular resistance, pulmonary capillary wedge pressure, and right atrial pressure. Mean arterial pressure was unchanged, but heart rate increased modestly after intravenous piroximone. An increase in premature ventricular contractions was documented in four patients after drug administration. Seven of the 10 patients completed 12 weeks of therapy with piroximone; one patient withdrew after 8 weeks because of deterioration in clinical status; one developed severe ventricular arrhythmias and died after 5 days of treatment; and a drug-induced hepatitis was documented in one subject at 4 weeks. No significant improvement in oxygen uptake at peak exercise and the anaerobic threshold was observed after long-term treatment (assessed at 6 and 12 weeks). Hemodynamic responsiveness to piroximone was sustained in five patients who underwent repeat evaluation at 12 weeks. Thus, long-term treatment with piroximone was not associated with an improvement in maximal and submaximal exercise capacity in patients with congestive heart failure. Serious adverse effects were observed with the administration of this drug.