Exercise Intolerance In Patients Research Articles

Improvement of Maximal Exercise Performance After Catheter-Ablation of Atrial Fibrillation and Its Prognostic Significance for Long-Term Rhythm Outcome.

BackgroundRhythm control may improve functional capacity in patients with atrial fibrillation (AF). Long‐term exercise tolerance improvement and its prognostic implications following catheter‐ablation (CA) of paroxysmal and nonparoxysmal AF are underreported.Methods and ResultsConsecutive patients underwent cardiopulmonary exercise testing just before and 12 months after their index CA of AF. Follow‐up 24‐hour Holter recordings were obtained at 6‐month intervals post‐CA, and any atrial arrhythmia >30 seconds detected after 3 months postprocedure was considered AF recurrence. Of 110 patients (mean age 57.5±10.6 years, 77.2% males) with paroxysmal AF (n=66) or nonparoxysmal AF (n=44), the 12‐month exercise tolerance improved significantly in those who maintained sinus rhythm during the first 12 months post‐CA (n=96), but not in patients with AF recurrence (n=14). After CA, the 12‐month respiratory exchange ratio at maximal workload significantly increased in patients with paroxysmal AF, whereas those with nonparoxysmal AF significantly reduced their heart rate during the 12‐month cardiopulmonary exercise testing (all P≤0.001). During the follow‐up of 42.8±7.8 months, a total of 29 patients (26.3%) experienced recurrent AF. On multivariate analysis including patients without recurrent AF at 12 months after CA, the extent of work time improvement at follow‐up cardiopulmonary exercise testing was independently associated with the rhythm outcome beyond 12 months postprocedure (hazard ratio of 0.936 [95% CI, 0.894–0.979] for each 10 seconds increase in the work time following ablation, P=0.004).ConclusionsCA of AF was associated with recovery of exercise intolerance in patients with paroxysmal AF or nonparoxysmal AF. Inability to improve exercise capacity at 12 months post‐CA was an independent risk factor for later AF recurrence.

Factors Contributing to Exercise Intolerance in Patients With Atrial Fibrillation

Reduced exercise capacity and exercise intolerance are commonly reported by individuals with atrial fibrillation (AF). Our objectives were to evaluate the contributing factors to reduced exercise capacity and describe the association between subjective measures of exercise intolerance versus objective measures of exercise capacity. Two hundred and three (203) patients with non-permanent AF and preserved ejection fraction undergoing cardiopulmonary exercise testing (CPET) were recruited. Clinical characteristics, AF-symptom evaluation, and transthoracic echocardiography measures were collected. Peak oxygen consumption (VO2peak) was calculated during CPET as an objective measure of exercise capacity. We assessed the impact of 16 pre-defined clinical features, comorbidities and cardiac functional parameters on VO2peak. Across this cohort (Age 66±11 years, 40.4% female and 32% in AF), the mean VO2peak was 20.3±6.3 mL/kg/min. 24.9% of patients had a VO2peak considered low (<16 mL/kg/min). In multivariable analysis, echocardiography-derived estimates of elevated left ventricular (LV) filling pressure (E/E') and reduced chronotropic index were significantly associated with lower VO2peak. The presence of AF at the time of testing was not significantly associated with VO2peak but was associated with elevated minute ventilation to carbon dioxide production indicating impaired ventilatory efficiency. There was a poor association between VO2peak and subjectively reported exercise intolerance and exertional dyspnoea. Reduced exercise capacity in AF patients is associated with elevated LV filling pressure and reduced chronotropic response rather than rhythm status. Subjectively reported exercise intolerance is not a sensitive assessment of reduced exercise capacity. These findings have important implications for understanding reduced exercise capacity amongst AF patients and the approach to management in this cohort. (ACTRN12619001343190).

Exercise Intolerance in Patients with Chronic Iliocaval Venous Occlusion: Initial Experience with Noninvasive Exercise Testing before and after Intervention

Patients with chronic iliocaval occlusions after thrombosis often present with exercise intolerance, which improves after venous reconstruction. Three male patients with chronic iliocaval occlusions underwent a cardiorespiratory fitness test before and 2.5–11 months after venous reconstruction using stents. After the intervention, average absolute oxygen consumption increased by 29.5%, maximal oxygen consumption relative to body weight increased by 38.7%, total work at maximum exercise increased by 74.4%, and exercise time increased by 18.7%. The cardiorespiratory fitness test may be a useful noninvasive tool to objectively evaluate exercise intolerance due to chronic venous occlusions and response to therapy.

Combined Echocardiographic and Cardiopulmonary Exercise to Assess Determinants of Exercise Limitation in Chronic Obstructive Pulmonary Disease

Current methods do not allow a thorough assessment of causes associated with limited exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Twenty patients with COPD and 20 matched control subjects were assessed using combined cardiopulmonary and stress echocardiographic testing. Various echocardiographic parameters (left ventricular [LV] volumes, right ventricular [RV] area, ejection fraction, stroke volume, S', and E/e' ratio) and ventilatory parameters (peak oxygen consumption [Vo2] and A-Vo2 difference) were measured to evaluate LV and RV function, hemodynamics, and peripheral oxygen extraction (A-VO2 difference). Significant differences (both between groups and for group-by-time interaction) were seen in exercise responses (LV volume, RV area, LV volume/RV area ratio, S', E/e' ratio, tricuspid regurgitation grade, heart rate, stroke volume, and Vo2). The major mechanisms of reduced exercise tolerance in patients with COPD were bowing of the septum to the left in 12 (60%), abnormal increases in E/e' ratio in 12 (60%), abnormal stroke volume reserve in 16 (80%), low peak A-Vo2 difference in 10 (50%), chronotropic incompetence in 13 (65%), or a combination of several mechanisms. Patients with COPD and poor exercise tolerance showed attenuated increases in stroke volume, heart rate, and A-Vo2 difference and exaggerated changes in LV/RV ratio and LV compliance (ratio of LV volume to E/e' ratio) compared with patients with COPD with good exercise tolerance. Combined cardiopulmonary and stress echocardiographic testing can be helpful in determining individual mechanisms of exercise intolerance in patients with COPD. In patients with COPD, exercise intolerance is predominantly the result of chronotropic incompetence, limited stroke volume reserve, exercise-induced elevation in left filling pressure, and peripheral factors and not simply obstructive lung function. Limited stroke volume is related to abnormal RV contractile reserve and reduced LV compliance introduced through septal flattening and direct ventricular interaction.

Exercise intolerance and fatigue in chronic heart failure: is there a role for group III/IV afferent feedback?

Exercise intolerance and early fatiguability are hallmark symptoms of chronic heart failure. While the malfunction of the heart is certainly the leading cause of chronic heart failure, the patho-physiological mechanisms of exercise intolerance in these patients are more complex, multifactorial and only partially understood. Some evidence points towards a potential role of an exaggerated afferent feedback from group III/IV muscle afferents in the genesis of these symptoms. Overactivity of feedback from these muscle afferents may cause exercise intolerance with a double action: by inducing cardiovascular dysregulation, by reducing motor output and by facilitating the development of central and peripheral fatigue during exercise. Importantly, physical inactivity appears to affect the progression of the syndrome negatively, while physical training can partially counteract this condition. In the present review, the role played by group III/IV afferent feedback in cardiovascular regulation during exercise and exercise-induced muscle fatigue of healthy people and their potential role in inducing exercise intolerance in chronic heart failure patients will be summarised.

Impact of right ventricular contractile reserve on exercise capacity in patients with heart failure: clinical application of low-load exercise stress echocardiography

Abstract Background The peak oxygen uptake (VO2) evaluated by the cardiopulmonary exercise test (CPX) is an established marker of exercise capacity in patients with heart failure (HF). In particular, peak VO2 &amp;lt;14 ml/kg/min is used to be one of the criteria for heart transplantation. However, given exercise intolerance in patients with HF, it is difficult for refractory HF patients to reach sufficient exercise load. A recent report has highlighted significant impact of right ventricular (RV) function on mortality and urgent heart transplantation. Taken together, we hypothesized that the assessment of RV function was helpful to predict exercise capacity by using low-load exercise stress echocardiography (low-load ESE) in patients with HF. Purpose We evaluated whether RV dysfunction assessed by the low-load ESE determined a low peak VO2 &amp;lt;14 ml/kg/min in patients with HF. Methods We studied 67 consecutive hospitalized patients with HF (mean age, 65 years; 75% male; mean LV ejection fraction, 36%) who underwent ESE and CPX after stabilized HF condition, and the time interval of CPX and ESE tests was within 48 hours. CPX was performed using an upright cycle ergometer by a ramp protocol, while ESE was performed using ergometer in semi-supine position and the workload was generally increased by 25 watts every 3 minutes. The low-load ESE was defined as the 25 watts exercise. The increments of RV s' velocity at tricuspid annulus and RV strain in the free wall were considered as a preservation of RV contractile reserve. Among the study population, 26 patients were performed right heart catheterization and RV dP/dt/Pmax was estimated as an invasive marker of RV contractility. Results The achieved intensity of exercise was 50.4±21.0 watts, and all patients completed the low-load ESE. The invasive study showed that the change of RV s' velocity during the low-load ESE significantly correlated with RV dP/dt/Pmax (r=0.706, p&amp;lt;0.001). As shown in Figure, the non-invasive parameters of RV contractile reserve during the low-load ESE were significantly correlated with peak VO2 (RV s' velocity: r=0.787, p&amp;lt;0.001; RV strain: r=0.244, p=0.047). ROC analysis showed that the change of RV s' velocity during the low-load ESE correctly identified patients with peak VO2 &amp;lt;14 ml/kg/min (AUC=0.95, sensitivity 92.3%, specificity 85.2%). In terms of inter- and intra-observer variabilities, ICCs of the change of RV s' velocity were 0.86 and 0.96, and ICCs of the changes of RV strain were 0.63 and 0.70, respectively. Conclusion The change of RV s' velocity during the low-load ESE could determine exercise tolerance in patients with HF. The assessment of RV contractile reserve might be clinically useful to discriminate high risk HF patients. Figure 1 Funding Acknowledgement Type of funding source: None

Relation between left atrial strain and exercise tolerance in patients with mild mitral stenosis: An insight from 2D speckle-tracking echocardiography.

Mild mitral stenosis (MS) is a progressive disease but unfortunately, its clinical course is still unclearly studied. We aimed to study the left atrial (LA) deformation in such patients and how it is related to exercise intolerance. Seventy-five patients with mitral valve area of 1.81±0.13cm2 and 40 healthy control subjects were enrolled. All participants had sinus rhythm, and they underwent conventional echocardiography and LA strain analysis with speckle-tracking study. The following parameters were obtained: left atrial reservoir strain (LAS-s), LA conduit strain (LAS-e), and LA contraction strain (LAS-a). All participants underwent symptoms limited stress ECG using modified Bruce protocol. Comparing with control subjects, patients with mild MS had significant lower LAS-s value (P<.01) and LAS-e (<0.03). Patients with exercise intolerance (METs<8) had lower LAS-s (P<.001), LAS-e (P<.01), and LAS-a (P<.05) values compared to those with METs≥8. We found that METs was significantly related to LAS-s (P<.001), brain natriuretic peptide (P<.001), and Δ TAPSE (P<.03). Multivariate analysis showed that LAS-s was an independent predictor of reduced exercise capacity. With ROC analysis, LAS-s≤26.5% was the optimal value for prediction of exercise intolerance in patients with mild MS. A significant percentage of patients with mild mitral stenosis had exercise intolerance. We found that LAS-s was significantly associated with exercise capacity in patients with mild MS. Hence, we thought that LA deformation could be of great value in the follow-up of patients with mild MS.

Aerobic Exercise Training in Patients With mtDNA-Related Mitochondrial Myopathy.

In patients with mitochondrial DNA (mtDNA) mutation, a pathogenic mtDNA mutation is heteroplasmically distributed among tissues. The ratio between wild-type and mutated mtDNA copies determines the mtDNA mutation load of the tissue, which correlates inversively with oxidative capacity of the tissue. In patients with mtDNA mutation, the mutation load is often very high in skeletal muscle compared to other tissues. Additionally, skeletal muscle can increase its oxygen demand up to 100-fold from rest to exercise, which is unmatched by any other tissue. Thus, exercise intolerance is the most common symptom in patients with mtDNA mutation. The impaired oxidative capacity in skeletal muscle in patients with mtDNA mutation results in limitation in physical capacity that interferes with daily activities and impairs quality of life. Additionally, patients with mitochondrial disease due to mtDNA mutation often live a sedentary lifestyle, which further impair oxidative capacity and exercise tolerance. Since aerobic exercise training increase mitochondrial function and volume density in healthy individuals, studies have investigated if aerobic training could be used to counteract the progressive exercise intolerance in patients with mtDNA mutation. Overall studies investigating the effect of aerobic training in patients with mtDNA mutation have shown that aerobic training is an efficient way to improve oxidative capacity in this condition, and aerobic training seems to be safe even for patients with high mtDNA mutation in skeletal muscle.

High Submaximal Exercise Heart Rate Impacts Exercise Intolerance in the Postural Orthostatic Tachycardia Syndrome.

Exercise intolerance is a hallmark of the postural orthostatic tachycardia syndrome (POTS). However, no data are available on the implications of an exaggerated submaximal heart rate (HR) on exercise intolerance in patients. We investigated whether exaggerated HR responses occurring early on during incremental stress testing relate with increased odds of POTS and exercise intolerance. Clinical characteristics and stress test HRs were compared between adults with POTS achieving ≥85% predicted metabolic equivalents (METs) (EX-TL, n = 101; body mass index [BMI] 24 ± 5 kg·m; 95% women) or <85% (EX-INTL, n = 71; BMI 28 ± 7 kg·m; 79% women) and sedentary controls (n = 30; BMI 36 ± 3 kg·m; 87% women). Multivariate logistic regressions were performed to estimate ORs and the probability of POTS and exercise intolerance associated with exercise HRs. Exercise tolerance was increased in EX-TL, but not in EX-INTL (10.0 ± 1.3 and 8.3 ± 1.5 METs vs 8.0 ± 1.6 METs, respectively) versus controls. Absolute peak HR was increased in EX-TL and EX-INTL versus controls (P < .01), whereas percent predicted did not differ. Exercise within the first-to-second stress stages was performed at exaggerated HRs (122 ± 17 bpm vs 103 ± 15 and 113 ± 15 bpm, P < .001) and percent HR reserve in EX-INTL versus controls and EX-TL (49% ± 12% vs 34% ± 11% and 41% ± 11%, P < .001), respectively. In multivariate analyses, peak HR was not significant, whereas increased submaximal HR (either variable) was associated with increased odds of EX-TL or EX-INTL. Lastly, odds of EX-INTL increased as METs decreased, whereas METs was not a predictor of EX-TL. An exaggerated submaximal exercise HR is predictive of POTS and exercise intolerance, and this chronotropic phenotype is exacerbated in patients achieving <85% predicted METs.

Near-infrared Spectroscopy of Vastus Lateralis Muscle during Incremental Cycling Exercise in patients with Type 2 Diabetes.

It is clinically important to elucidate the precise mechanism of exercise intolerance in patients with type 2 diabetes (T2DM). The aim of this study was to examine whether there is a difference in the time course change of the oxygenation in the vastus lateralis (VL) muscle during submaximal incremental cycling exercise between patients with T2DM and age-matched healthy subjects. Nine elderly men with T2DM and 10 age-matched healthy men (CON) participated in this study. All participants performed an incremental cycling exercise.Total, deoxygenated and oxygenated hemoglobin/myoglobin in the VL muscle were assessed using near-infrared spectroscopy, and cardiorespiratory response was also evaluated during the exercise. There were no significant differences in the time course changes of deoxygenated hemoglobin/myoglobin between groups ( p > 0.05). However, the oxygenated hemoglobin/myoglobin in T2DM was significantly higher than that in CON at an intensity above ventilatory threshold during the incremental cycling exercise ( p< 0.05). This study suggests that patients with T2DM had early limitation of oxygen extraction and lower capacity of oxygenated myoglobin dissociation in the VL muscle. The fact that patients with T2DM showed different oxygen kinetics in a peripheral tissue from healthy subjects may partly explain the potential mechanisms of exercise intolerance in T2DM.

Epicardial adipose tissue is tightly associated with exercise intolerance in patients with type 2 diabetes mellitus with asymptomatic left ventricular structural and functional abnormalities

AimsThis study aimed to elucidate whether the volume of epicardial adipose tissue (EAT) is associated with left ventricular (LV) structural and functional abnormalities and exercise capacity in patients with type 2 diabetes mellitus (T2DM). MethodsEAT thickness and LV structural and functional abnormality components (e.g., global longitudinal strain, E/e', LV mass index, relative wall thickness) were measured using echocardiography in 176 patients with asymptomatic stage A and B heart failure (SAHF and SBHF, respectively) and 62 healthy controls (HC). Peak oxygen uptake (peakVO2) was measured by using cardiopulmonary exercise testing. ResultsEven when matching study participants for age, sex, and body mass index, the EAT was thicker (HCs 5.5 ± 1.2 versus SAHF 6.4 ± 1.0 and SBHF 9.3 ± 1.7 mm) and peakVO2 was lower (HC 24.1 ± 3.3 versus SAHF 19.1 ± 2.0 and SBHF 16.9 ± 3.1 ml/kg/min) in the heart failure (HF) group than in the HC group (p < 0.001). EAT thickness (β = −0.189, p < 0.001) and peakVO2 were significantly associated, even after adjusting for multivariates (R2 = 0.457). ConclusionsIn T2DM patients with asymptomatic HF, EAT may be associated with LV structural and functional abnormalities and exercise intolerance.

P1743 The contribution of left atrial dysfunction to exercise intolerance in early heart failure with preserved left ventricular ejection fraction

Abstract Background Diagnosis of early heart failure with preserved ejection fraction (HFpEF) may be challenging because exertional dyspnea is not specific for heart failure, and biomarkers and indicators of volume overload may be absent at rest. We aimed to characterize the contribution of abnormal left atrial (LA) mechanical properties to exercise intolerance in early HFpEF (normal left ventricular filling pressures at rest but elevated during exercise). Methods Diastolic stress testing (DST) was performed in 104 patients with left ventricular ejection fraction ≥50%, in sinus rhythm, and no more than LV diastolic dysfunction grade I, referred for assessment of exertional dyspnoea. Patients exercised supine cycle ergometry at 60 rpm starting with a 3-min period of low-level 25-W workload followed by 25-W increments in 3-minute stages to maximum tolerated levels. According to DST, 43 patients were diagnosed with HFpEF (average mitral E-to-annular e′ ratio [E/e′] &amp;gt; 14, and peak TR velocity &amp;gt;2.8 m/sec at maximal exertion) and 61 as non-cardiac dyspnea (NCD). During the test, two-dimensional images, mitral E/e′, peak tricuspid regurgitation (TR) velociry, and two-dimensional LA mechanical parameters (longitudinal LA strain [LASR] and strain rate [LASRR] during reservoir phase and LA stiffness assessed as a ratio of mitral E/e′ ratio to LASR) were analysed at baseline, and at peak. Results HFpEF and NCD patients were similar in regard to the LA volume index (34.4 [30.2;39.4] vs. 33.6 [28.4;37.1] ml/m2), and NT-proBNP level (132 [80;238] vs. 129 [80;197] pg/ml). As compared with NCD patients, HFpEF patients displayed reduced LA reservoir function assessed by LASR (22.3 [18.9;25.6] vs. 24.2 [21.2;29.8] % at rest, and 25.3 [21.4;30.2] vs. 29.0 [24.2;33.3] % with exercise) and LASRR (0.78 [0.58;0.96] vs. 0.90 [0.68;1.12] /s at rest, and 1.10 [0.79;1.31] vs. 1.24 [1.03;1.56] s–1 with exercise) with increased LA stiffness (0.57 [0.44;0.70] vs. 0.42 [0.30;0.49] mmHg/% at rest, and 0.61 [0.46;0.74] vs. 0.40 [0.32;0.51] mmHg/% with exercise, all P &amp;lt; 0.05). Additionally, HFpEF patients showed smaller exercise elevation in LASRR (+31 [-5;77] vs. +47 [12;85] % as compared with resting values, P &amp;lt; 0.05). Exercised LA stiffness and reservoir strain correlated with exercise LV filling pressures estimated by mitral E/e′ ratio (r = 0.72 and r =–0.35, P &amp;lt; 0.001). LA stiffness showed a good diagnostic accuracy (area under the curve 0.75), and LA stiffness &amp;gt; 0.46 mmHg/% demonstrated reasonable sensitivity (79%) and specificity (71%) to diagnose HFpEF. Neither LV global longitudinal strain and ejection fraction at rest nor their exercise-induced elevation differed between HFpEF and NCD. Conclusion Impaired LA reservoir function and increased stiffness are associated with exercise intolerance in patients with early HFpEF, while LV systolic function seems preserved in this stage of the disease. LA stiffness provides HFpEF diagnostic potential in ambulatory patients with dyspnea

Non-pulmonary Contributors of Exercise Intolerance in Patients With Cystic Fibrosis

Non-pulmonary Contributors of Exercise Intolerance in Patients With Cystic Fibrosis

Correlation between ventricular function as assessed by echocardiography and six-minute walk test as a surrogate of functional capacity in patients with chronic obstructive pulmonary disease

BackgroundExercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD), which has multiple mechanisms underlying its progression. Ventricular dysfunction may play a role in the development of exercise incapacity in patients with COPD.AimTo investigate the possible contribution of left ventricular (LV) and right ventricular (RV) dysfunction (either systolic or diastolic) in development of exercise intolerance in patients with COPD.Patients and methodsA total of 60 patients with diagnosis of COPD were categorized according to GOLD spirometric stage into two groups (group 1: mild to moderate COPD, and group 2: severe to very severe COPD). Both groups were evaluated by spirometry, ECG, chest radiography, routine laboratory investigation, 6-min walk test, and echocardiography including tissue Doppler imaging.ResultsThe average age in the whole study group was 56.63 ±10.33 years. Male patients in the study were 46 (76.7%) and female patients were 14 (23.3%). Mean maximum walk distance among the whole group was 342.75±54.85 m. There was a significant correlation between 6-min walk distance and transtricuspid E velocity, tricuspid E/A, and transtricuspid deceleration time (P=0.011, 0.015, and 0.021, respectively). There was no significant correlation between 6-min walk distance and parameters of LV diastolic dysfunction. Prevalence of ventricular dysfunction was as follow: LV systolic dysfunction 3.3%, LV diastolic dysfunction 30%, RV systolic dysfunction 21%, and RV diastolic dysfunction 46%.ConclusionRV diastolic dysfunction may be a contributing factor in the progression of exercise intolerance in COPD. Although LV diastolic dysfunction may not be associated with exercise intolerance, it is still prevalent in COPD and must be assessed and managed through the course of the disease and especially during exacerbation.

Mechanisms of exercise intolerance in patients with heart failure and preserved ejection fraction. Part II: The role of right heart chambers, vascular system and skeletal muscles

The main clinical manifestation of heart failure with preserved ejection fraction is poor exercise tolerance. In addi-tion to the dysfunction of the left heart chambers, which were presented in the first part of this review, many other disorders are involved in poor exercise tolerance in such patients: impairments of the right heart, vascular system and skeletal muscle. The second part of this review presents the mechanisms for the development of these disorders, as well as possible ways to correct them.

Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure

Skeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF. Fifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO2), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO2 after adjustment for age, gender, body mass index, and QMT: β-coefficient = -11.80, 95%CI (-20.73, -2.86), P= .011. Enhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.

Diaphragm function does not independently predict exercise intolerance in patients with precapillary pulmonary hypertension after adjustment for right ventricular function.

Background: Several determinants of exercise intolerance in patients with precapillary pulmonary hypertension (PH) due to pulmonary arterial hypertension and/or chronic thromboembolic PH (CTEPH) have been suggested, including diaphragm dysfunction. However, these have rarely been evaluated in a multimodal manner. Methods: Forty-three patients with PH (age 58 ± 17 years, 30% male) and 43 age- and gender-matched controls (age 54 ± 13 years, 30% male) underwent diaphragm function (excursion and thickening) assessment by ultrasound, standard spirometry, arterial blood gas analysis, echocardiographic assessment of pulmonary artery pressure (PAP), assay of amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac magnetic resonance (CMR) imaging to evaluate right ventricular systolic ejection fraction (RVEF). Exercise capacity was determined using the 6-min walk distance (6MWD). Results: Excursion velocity during a sniff maneuver (SniffV, 4.5 ± 1.7 vs. 6.8 ± 2.3 cm/s, P<0.01) and diaphragm thickening ratio (DTR, 1.7 ± 0.5 vs. 2.8 ± 0.8, P<0.01) were significantly lower in PH patients versus controls. PH patients with worse exercise tolerance (6MWD <377 vs. ≥377 m) were characterized by worse SniffV, worse DTR, and higher NT-pro-BNP levels as well as by lower arterial carbon dioxide levels and RVEF, which were all univariate predictors of exercise limitation. On multivariate analysis, the only independent predictors of exercise limitation were RVEF (r = 0.47, P=0.001) and NT-proBNP (r = −0.27, P=0.047). Conclusion: Patients with PH showed diaphragm dysfunction, especially as exercise intolerance progressed. However, diaphragm dysfunction does not independently contribute to exercise intolerance, beyond what can be explained from right heart failure.

Mechanisms of exercise intolerance in patients with heart failure and preserved ejection fraction. Part I: The role of impairments in the left heart chambers

During exercise an increase in oxygen delivery to working muscles is achieved through well‑coordinated interaction of many organs and systems: the heart, lungs, blood vessels, skeletal muscles, and the autonomic nervous system. In heart failure with preserved left ventricular ejection fraction, all mechanisms involved in the normal exercise tolerance are impaired. In the first part of this review, the impairments of the left heart chambers are considered ‑ left ventricular diastolic dysfunction, the weakening of the contractile and chronotropic reserves, left atrium dysfunction; the possible ways of their medical correction are also presented.

Exercise intolerance in comorbid COPD and heart failure: the role of impairedaerobic function.

Impaired aerobic function is a potential mechanism of exercise intolerance in patients with combined cardiorespiratory disease. We investigated the pathophysiological and sensory consequences of a low change in oxygen uptake (ΔV'O2 )/change in work rate (ΔWR) relationship during incremental exercise in patients with coexisting chronic obstructive pulmonary disease (COPD) and systolic heart failure (HF).After clinical stabilisation, 51 COPD-HF patients performed an incremental cardiopulmonary exercise test to symptom limitation. Cardiac output was non-invasively measured (impedance cardiography) in a subset of patients (n=18).27 patients presented with ΔV'O2 /ΔWR below the lower limit of normal. Despite similar forced expiratory volume in 1 s and ejection fraction, the low ΔV'O2 /ΔWR group showed higher end-diastolic volume, lower inspiratory capacity and lower transfer factor compared to their counterparts (p<0.05). Peak WR and peak V'O2 were ∼15% and ∼30% lower, respectively, in the former group: those findings were associated with greater symptom burden in daily life and at a given exercise intensity (leg discomfort and dyspnoea). The low ΔV'O2 /ΔWR group presented with other evidences of impaired aerobic function (sluggish V'O2 kinetics, earlier anaerobic threshold) and cardiocirculatory performance (lower oxygen pulse, lower stroke volume and cardiac output) (p<0.05). Despite similar exertional hypoxaemia, they showed worse ventilatory inefficiency and higher operating lung volumes, which led to greater mechanical inspiratory constraints (p<0.05).Impaired aerobic function due to negative cardiopulmonary-muscular interactions is an important determinant of exercise intolerance in patients with COPD-HF. Treatment strategies to improve oxygen delivery to and/or utilisation by the peripheral muscles might prove particularly beneficial to these patients.

Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function.

To discuss the impact of deleterious changes in skeletal muscle morphology and function on exercise intolerance in patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), as well as the utility of exercise training and the potential of novel treatment strategies to preserve or improve skeletal muscle morphology and function. Both HFrEF and HFpEF patients exhibit a reduction in percent of type I (oxidative) muscle fibers and oxidative enzymes coupled with abnormal mitochondrial respiration. These skeletal muscle abnormalities contribute to impaired oxidative metabolism with an earlier shift towards glycolytic metabolism during exercise that is strongly associated with exercise intolerance. In both HFrEF and HFpEF patients, peripheral "non-cardiac" factors are important determinants of the improvement in exercise tolerance following aerobic exercise training. Adjunctive strategies that include nutritional supplementation with amino acids and/or anabolic drugs to stimulate anabolic molecular pathways in skeletal muscle show great promise for improving exercise tolerance and treating heart failure-associated sarcopenia, but these efforts remain early in their evolution, with no immediate clinical applications. There is consistent evidence that heart failure is associated with multiple skeletal muscle abnormalities which impair oxygen uptake and utilization and contribute greatly to exercise intolerance. Exercise training induces favorable adaptations in skeletal muscle morphology and function that contribute to improvements in exercise tolerance in patients with HFrEF. The contribution of skeletal muscle adaptations to improved exercise tolerance following exercise training in HFpEF remains unknown and warrants further investigation.