Impaired Aerobic Capacity Research Articles

Changes in peak oxygen consumption in Fabry disease and associations with cardiomyopathy severity

BackgroundFabry disease (FD) causes multiorgan sphingolipid accumulation, with cardiac involvement responsible for the largest burden of morbidity and mortality. Exercise intolerance in FD is prevalent, yet the mechanisms of this...

Post COVID symptoms of fatigue or dyspnea in young patients are not related to impaired aerobic capacity measured be cardiopulmonary exercise testing

Post COVID symptoms of fatigue or dyspnea in young patients are not related to impaired aerobic capacity measured be cardiopulmonary exercise testing

Aerobic physical capacity and health-related quality of life in children with sickle cell disease.

Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. The aim is to evaluate the aerobic capacity by cardiopulmonary exercise test (CPET) in children with sickle cell disease in comparison with healthy matched controls. Controlled cross-sectional study. A total of 72 children (24 with sickle cell disease and 48 healthy controls), aged 6-17 years old were enrolled. Children with sickle cell disease had a poor aerobic capacity, with median VO2max Z-score values significantly lower than matched controls (-3.55[-4.68; -2.02] vs. 0.25[-0.22; 0.66], P < 0.01, respectively), and a high proportion of 92% children affected by an impaired aerobic capacity (VO2max Z-score < -1.64). The VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease and health-related quality of life. Aerobic capacity is poor in children with sickle cell disease. VO2max decrease is associated with the level of anemia, the existence of a homozygote HbS/S mutation, lung function, and health-related quality of life. These results represent a signal in favor of early initiation of cardiac rehabilitation in patients with sickle cell disease. NCT05995743. Aerobic fitness is a predictor of cardiovascular health which correlates with health-related quality of life in the general population. Aerobic capacity (VO2max) is poor in children with sickle cell disease, despite the absence of any pattern of heart failure. VO2max decrease was associated with the level of anemia, the existence of a homozygote HbS/S mutation, restrictive lung disease, and health-related quality of life. These results are in favor of early initiation of cardiac rehabilitation in children with sickle cell disease.

Long-term outcomes of pulmonary embolism in children and adolescents

AbstractKnowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction

Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. The primary end point was oxygen consumption (V̇o2) at anaerobic threshold (V̇o2,AT); secondary end points were peak V̇o2, ventilatory efficiency (V̇e/V̇co2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇o2 and V̇o2 at anaerobic threshold (V̇o2,AT) were both correlated with peak exercise heart rate (r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇o2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, -0.5 to 1.0] mL/kg/min; P = .46), peak V̇o2, minute ventilation (V̇e)/carbon dioxide production (V̇co2) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (-24 mL [95% CI, -43 to -5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. ClinicalTrials.gov Identifier: NCT02145351.

Determinants of ventilatory inefficiency in transthyretin cardiac amyloidosis: The role of excessive ventilatory drive.

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase. Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included. Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (β = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency. Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.

Cardiovascular Mechanisms of Exercise Intolerance in Older Patients with Heart Failure.

Exercise intolerance, measured by peak oxygen consumption (V̇O2), is a hallmark feature of heart failure (HF). The effect is compounded in the elderly HF patient by aging-associated changes such as a reduction in lean muscle mass, an increase in adiposity, and a reduction in maximal heart rate and peripheral blood flow with exercise. There is a non-linear reduction in peak V̇O2 with age that accelerates in the later decades of life. Peak V̇O2 is further reduced due to central and peripheral maladaptation from HF. Central mechanisms include impaired peak heart rate, stroke volume, contractility, increased filling pressures, and a blunted vasodilatory response. Peripheral mechanisms include endothelial dysfunction, reduced blood flow to muscles, and impaired skeletal muscle oxidative capacity. This review presents a focused update on mechanisms leading to impaired aerobic capacity in older HF patients.

Determinants of Aerobic Capacity After Tricuspid Valve Replacement in Congenitally Corrected Transposition of Great Arteries

BackgroundSystemic tricuspid regurgitation and impaired aerobic capacity are common in adults with congenitally corrected transposition of great arteries (cc-TGA), but it is unknown whether systemic tricuspid valve replacement (sTVR) is associated with improvement in aerobic capacity. ObjectivesThe purpose of this study was to determine whether sTVR was associated with postoperative improvement in aerobic capacity as measured by peak oxygen consumption (VO2). MethodsThis is a retrospective cohort study of adults with cc-TGA and ≥moderate tricuspid regurgitation that underwent sTVR and exercise test pre- and post-sTVR (2003-2019). We selected a propensity-matched control group of patients with cc-TGA and ≥moderate tricuspid regurgitation that did not undergo sTVR between exercise tests. Improvement in aerobic capacity was calculated as the difference between baseline and follow-up exercise tests. ResultsThe study comprised 48 patients in each group, and both groups had similar peak VO2 at baseline. Compared to the baseline exercise test, the sTVR group had more improvement in peak VO2 (6 ± 4% vs −8 ± 3%-predicted, P = 0.001), and the factors associated with postoperative improvement in peak VO2 were baseline systolic blood pressure (<120 mm Hg), systemic right ventricular global longitudinal strain (<−16%), and preoperative peak VO2 (>60%-predicted). ConclusionsThere was an improvement in aerobic capacity after sTVR in patients with cc-TGA and severe tricuspid regurgitation. The determinants of improvement in aerobic capacity were baseline systolic blood pressure, systemic right ventricular global longitudinal strain, and preoperative peak VO2. Further studies are required to determine whether strict blood pressure control and optimal timing of sTVR based on these indices would result in improved clinical outcomes in this population.

Identification of Patients with Preclinical Heart Failure with preserved Ejection Fraction Using the H2FPEF Score.

Heart failure with preserved ejection fraction (HFpEF) is a common disorder with few effective treatments. There is currently no evidence-based method to identify preclinical HFpEF. The H2FPEF score is a validated instrument to identify patients with overt HFpEF. Here we show the H2FPEF score can identify individuals with preclinical HFpEF. Among individuals where heart failure was excluded (n=160), increasing H2FPEF score was shown to be associated with greater left atrial dilation, left ventricular hypertrophy, and more severe diastolic dysfunction. Patients with increasing H2FPEF score displayed higher pulmonary artery pressures, higher left heart filling pressures, lower cardiac index, and more severely impaired aerobic capacity during exercise. In summary, we show that among adults without heart failure, higher H2FPEF score is associated with subclinical abnormalities that resemble those observed in HFpEF. These findings broaden the external validity of the H2FPEF score and suggest that this instrument may help identify patients positioned to benefit from preventive interventions.

Response of Aerobic Capacity to Low-Level Laser Therapy in Burned Patients.

Severe burns lead to decreased pulmonary function and impaired aerobic capacity for long periods postinjury. Low-level laser therapy is a modality used to improve aerobic capacity, enhance exercise performance, and increase the time until fatigue when used before aerobic exercises. This work aims to determine the impacts of pre-exercise low-level laser therapy on aerobic capacity in burn cases. Sixty adults burned cases of both sex, aged from 25 to 40 years, with second-degree healed thermal burns, and the total burned body surface area ranged from 20 to 40% participated in this study after complete wound healing. They were randomly categorized into two groups of equal numbers. The study group received low-level laser therapy before aerobic exercises, three sessions per week for 12 weeks, while the control group performed aerobic exercises three times weekly for 12 weeks. All cases received the routine physical treatment program. Aerobic capacity was assessed for both groups by measuring maximum oxygen consumption and time to exhaustion at baseline and 12 weeks following interventions. There was a statistically significant rise in the mean values of maximum oxygen usage and time to fatigue after 12 weeks of treatment in both groups. However, after comparison, the improvements in the study group were statistically significant than those in the control group with P < .01 and P < .05, respectively. Low-level laser therapy has a beneficial therapeutic impact on promoting aerobic capacity, improving maximum oxygen consumption, and increasing treadmill time in burned cases when preceding aerobic exercises.

Prognostic role and hemodynamic mechanism of impaired aerobic capacity in adults with Ebstein anomaly

BackgroundPatients with Ebstein anomaly have impaired aerobic capacity, but the relationship between aerobic capacity and clinical outcomes are unknown. The purpose of this study was to determine the prognostic role of aerobic capacity and the hemodynamic mechanism underlying temporal deterioration in aerobic capacity in this population. MethodsRetrospective cohort study of adults with Ebstein anomaly that underwent exercise test (2000–2018). Primary objective was to determine the relationship between aerobic capacity (%-predicted peak oxygen consumption, VO2) and cardiovascular adverse events (death, heart transplant, aborted sudden death, and heart failure hospitalization). Secondary objective was to delineate the relationship between temporal change in hemodynamic indices and subsequent decline in peak VO2. ResultsWe studied 248 patients (peak VO2 22.4 ​± ​7.1 ​ml/kg/min; 64 ​± ​21 %-predicted), and these events occurred during follow-up (death n ​= ​12, transplant n ​= ​1, aborted sudden death n ​= ​7, and heart failure hospitalization n ​= ​11). Peak VO2 was an independent predictor of cardiovascular adverse events (hazard ratio 1.32; 95% confidence interval 1.18–1.59, p ​= ​0.002 per 5%-point decrease). Of 101 patients with ≥2 exercise tests, %-predicted peak VO2 decreased by 2.3%-points/year, and rate of decline correlated with change in right atrial (RA) strain and left heart hemodynamics. Hemodynamic deterioration started with RA dysfunction, followed by left heart hemodynamic impairment, and then decline in peak VO2. ConclusionsPeak VO2 is a predictor of cardiovascular adverse events in Ebstein anomaly. Temporal decline in peak VO2 was preceded by RA dysfunction and left heart hemodynamic impairment suggesting that impaired aerobic capacity represents a late stage in disease pathogenesis.

Sarcopenia Screening Allows Identifying High-Risk Patients for Allogenic Stem Cell Transplantation.

Simple SummaryAllogenic stem cell transplantation is a treatment option for various hematological diseases. Due to the intensity of the therapy regimes used, there is a substantial therapy associated mortality and morbidity. Therefore, it is crucial to identify patients with increased risk for treatment associated complications. Sarcopenia, defined as the loss of muscle mass and strength is a risk factor in various diseases. Aim of our study was to implement and evaluate the predictive power of a sarcopenia assessment, based on muscle mass, muscle strength and aerobic capacity (by measuring peak oxygen uptake), on all-cause and non-relapse mortality. A total of 178 patients were screened, with 28% suffering from sarcopenia before transplantation. Our results show a three-fold increase in all-cause and non-relapse mortality in this subpopulation compared to non-sarcopenic patients within a 12-month follow up. The importance of physical performance status demonstrated, raises the question, if exercise interventions might even allow to decrease mortality and morbidity.Allogenic stem cell transplantation (aSCT) is the only potentially curative treatment for high-risk hematological diseases. Despite advancements in supportive measures, aSCT outcome is still affected by considerable transplant-related mortality. We implemented a new sarcopenia assessment prior to aSCT to evaluate its predictive capability for all-cause and non-relapse mortality. Therefore all patients initially scheduled for aSCT within a 25-month period were screened during pre-transplantation-routine for muscle mass, grip strength, and aerobic capacity (AC) by measuring peak oxygen uptake (VO2peak). Patients were assigned to one of five groups adapted according current sarcopenia guidelines. Primary endpoints were all-cause and non-relapse mortality within a follow up time of up to 12 months. A total of 178 patients were included and rated as normal (n = 48), impaired aerobic capacity (n = 56), pre-sarcopenic (n = 26), sarcopenic (n = 27), and severe sarcopenic (n = 22) without significant age-differences between groups. Patients presenting with sarcopenia showed a significant three-fold increase in all-cause and non-relapse mortality compared to patients with normal screening results. AC showed to be the strongest single predictor with a more than two-fold increase of mortality for low AC. We conclude that risk stratification based on combination of muscle mass, grip strength, and AC allowed identifying a subgroup with increased risk for complications in patients undergoing aSCT.

Associations between peak oxygen uptake, lung function, and bronchiectasis in children with cystic fibrosis in the era of CFTR modulators.

With the emergence of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, forced expiratory volume in 1 s (FEV1 ) may become a less sensitive measure of pulmonary disease progression in children with cystic fibrosis (CF). Increasing evidence shows that peak oxygen uptake (VO2peak ) is a strong predictor of prognosis in CF. The primary aim of this study was to describe the associations between peak oxygen uptake, lung function, and bronchiectasis in children with CF in the era of CFTR modulators. Spirometry and a maximal cardiopulmonary exercise test (CPET) were performed on the same day and compared to markers of disease severity. Markers of disease severity included a number of pulmonary exacerbations resulting in hospital admission within the preceding 12 months, body mass index, Pseudomonas aeruginosa (PsA) infection, and bronchiectasis. Fifty-two subjects (24 female) with CF participated in the study with a mean (SD) age of 13.8 (2.4) years, range 8-18 years. Forty-nine participants met satisfactory criteria for a maximal CPET. A significant correlation was found between relative VO2peak %predicted and FEV1 %predicted (r = .546, p < .001). A total of 4/49 children demonstrated an impaired aerobic capacity despite normal spirometry. Participants who had experienced one or more pulmonary exacerbations in the previous 12 months had a significantly lower relative VO2peak %predicted (p = .02). In children with CF who have mild pulmonary disease, there is significant correlation between FEV1 and VO2peak . In all, 8.2% of participants had an abnormal CPET result despite normal spirometry, and preceding pulmonary exacerbations were associated with poorer CPET outcomes. CPET may offer important prognostic information for clinical decision making in this new era of CFTR modulators.

Central Command and the Regulation of Exercise Heart Rate Response in Heart Failure With Preserved Ejection Fraction.

Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is linked to impaired aerobic capacity. Whether upstream autonomic signaling pathways responsible for raising exercise heart rate are impaired in HFpEF is unknown. We investigated the integrity of central command and muscle metaboreceptor function, 2 predominant mechanisms responsible for exertional increases in heart rate, in patients with HFpEF and senior controls. Fourteen healthy senior controls (7 men, 7 women) and 20 carefully screened patients with HFpEF (8 men, 12 women) underwent cardiopulmonary exercise testing (peak Vo2) and static handgrip exercise at 40% of maximal voluntary contraction to fatigue with postexercise circulatory arrest for 2 minutes to assess central command and metaboreceptor function, respectively. Peak Vo2 (13.1±3.4 versus 22.7±4.0 mL/kg/min; P<0.001) and heart rate (122±20 versus 155±14 bpm; P<0.001) were lower in patients with HFpEF than senior controls. There were no significant differences in peak heart rate response during static handgrip between groups (patients with HFpEF versus controls: 90±13 versus 93±10 bpm; P=0.49). Metaboreceptor function, defined as mean arterial blood pressure at the end of postexercise circulatory arrest, was not significantly different between groups. Central command (vagally mediated) and metaboreceptor function (sympathetically mediated) in patients with HFpEF were not different from those in healthy senior controls despite significantly lower peak whole-body exercise heart rates. These results demonstrate key reflex autonomic pathways regulating exercise heart rate responsiveness are intact in HFpEF.

Mechanisms of Chronotropic Incompetence in Heart Failure With Preserved Ejection Fraction.

Chronotropic incompetence is common in heart failure with preserved ejection fraction (HFpEF) and is associated with impaired aerobic capacity. We investigated the integrity of cardiac β-receptor responsiveness, an important mechanism involved in exertional increases in HR, in HFpEF and control subjects. Thirteen carefully screened patients with HFpEF and 13 senior controls underwent exercise testing and graded isoproterenol infusion to quantify cardiac β-receptor-mediated HR responses. To limit autonomic neural influences on heart rate (HR) during isoproterenol, dexmedetomidine and glycopyrrolate were given. Isoproterenol doses were increased incrementally until HR increased by 30 beats per minute. Plasma levels of isoproterenol at each increment were measured by liquid chromatography with electrochemical detection and plotted against HR. Peak VO2 and HR (117±15 versus 156±15 beats per minute; P<0.001) were lower in HFpEF than senior controls. Cardiac β-receptor sensitivity was lower in HFpEF compared to controls (0.156±0.133 versus 0.254±0.166 beats per minute/[isoproterenol ng/mL]; P<0.001). Seven of 13 HFpEF subjects had β-receptor sensitivity similar to senior controls but still had lower peak HRs (122±14 versus 156±15 beats per minute; P<0.001). Contrary to our hypothesis, patients with HFpEF displayed impaired cardiac β-receptor sensitivity compared with senior controls. In the 7 out of 13 patients with HFpEF with age-appropriate β-receptor sensitivity, peak HR remained low, suggesting impaired sinus node β-receptor function may not fully account for low exercise HR response. Rather in some patients with HFpEF, chronotropic incompetence might reflect premature cessation of exercise before maximal sinus node activation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02524145.

Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy

Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy.Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. Patients' medical records, pulmonary function and cardiopulmonary exercise testing, including non-invasive cardiac hemodynamics and chronotropic response were studied. Compared with age-matched controls, maximal workload (91 ± 8 vs. 65 ± 20 watts) and peak VO2 (19.5 ± 3.0 vs. 14.4 ± 4.1 mL.kg−1.min−1) were lower in ATTRv patients. Despite reaching similar age-predicted maximal HR, ATTRv patients displayed smaller changes in stroke volume (SV) index relative to change in VO2 (49 ± 26 vs. 67 ± 18%). Adequate chronotropic-metabolic index was prevalent in ATTRv patients. HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients.Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.

Alterations in mitochondrial functions and morphology in muscle and non-muscle tissues in type 1 diabetes: implications for metabolic health.

What is the topic of this review? Evidence of impaired mitochondrial functions and/or morphology in people with type 1 diabetes across various organ systems. What advances does it highlight? Impairments to mitochondrial functions and morphology may be a primary mechanism underlying the pathophysiology of various complications in people with type 1 diabetes. We recently made the observation that there are significant alterations to the ultrastructure and functions of mitochondria in skeletal muscle of people with type 1 diabetes (T1D). These alterations are proposed to lead to decreased energy production in skeletal muscle during exercise and thus may contribute to the impaired aerobic exercise capacity reported in some people with T1D. This Symposium Review summarizes the evidence that similar alterations also occur in the mitochondria present in organ systems outside skeletal muscle in people with T1D, and that this may contribute to the development and progression of the known complications of T1D, which eventually lead to the reported premature mortality.

The aerobic capacity in patients with antisynthetase syndrome and dermatomyositis

BackgroundThis study was aimed at evaluating the aerobic capacity of patients with antisynthetase syndrome (ASS) and dermatomyositis (DM) and analyzing possible relationships between aerobic capacity and disease status, cardiovascular diseases and their risk factors.MethodsThe study was a cross-sectional, single-center study that assessed the aerobic capacity of 22 women (13 with DM and 9 with ASS) who were matched by age and body mass index to 17 healthy women (control group). The aerobic capacity (oxygen uptake [VO2 peak], anaerobic threshold, respiratory compensation point and time-to-exhaustion) was evaluated using the cardiopulmonary treadmill test. Disease status was assessed using International Myositis Assessment & Clinical Studies Group (IMACS) set scores.ResultsThe patients had low IMACS parameters that showed low or absent disease activity. The distribution of cardiovascular diseases and their risk factors was similar between the patients and the control group (P > 0.05) at the time of the analysis. The patients with DM and the control group had similar aerobic capacity. However, the patients with ASS exhibited significantly reduced aerobic capacity (relative VO2 peak, anaerobic threshold, respiratory compensation point and time to exhaustion) when compared to the control group. In addition, patients with ASS had a lower anaerobic threshold compared to the DM group. There were no significant relationships between the aerobic capacity and disease status, cardiovascular diseases and their risk factors.ConclusionIn contrast to DM patients and healthy individuals, patients with stable ASS have significantly impaired aerobic capacity, which is unlikely to be totally explained by traditional cardiovascular diseases, their risk factors and disease status. Further studies are needed to corroborate our data and to clarify the cause of this reduced aerobic capacity in ASS.

P3104Complementary impact of glycated haemoglobin and B-natriuretic peptide on cardiopulmonary exercise capacity in patients with ischemic heart disease

Abstract Background Glycemic control, even in non-diabetes mellitus (DM) patients, has been associated with ventilation pump inefficiency leading to an impaired aerobic capacity. Brain natriuretic peptide (BNP) levels have also been correlated with exercise capacity, particularly in patients with heart failure. Purpose Assess the complementary impact of glycated haemoglobin (HbA1c) and BNP levels on cardiopulmonary exercise capacity in patients with ischemic heart disease (IHD). Methods Retrospecive cohort of 91 consecutive patients (57±10 years, 90% men; 29% type 2 DM) who underwent a cardiopulmonary exercise testing (CPX) at the beginning of an standard phase-II cardiac rehabilitation program, 2–3 months after an acute coronary syndrome. Results HbA1c and BNP levels correlated with peak oxygen uptake (VO2), anaerobic threshold (AT) and pulse O2 trajectory (Table). HbA1c correlated with ventilation CPX parameters (Table) and independently predicted minute ventilation (VE) and tidal volume (VT), regardless of age, waist circumference and β-blocker therapy. BNP levels correlated with echocardiographic (LVEF, left atrium size and pulmonary artery systolic pressure) and ventilation-perfusion (V/Q) mismatch parameters (Table), and independently predicted VE/VCO2-slope (P=0.037) regardless of age, echocardiographic parameters and β-blocker therapy. Patients were divided into three groups according to HbA1c levels above or below the DM diagnosis cut-off point (6.5%) and median value of BNP levels (44.6 pg/mL). VO2 and AT significantly decreased with elevated HbA1c and/or BNP levels (Figure). CPX parameters HbA1c (%) BNP (pg/mL) r P value r P value Peak VO2 (mL/min/kg) −0.421 &lt;0.001 −0.295 0.005 VO2 at AT (mL/min/kg) −0.352 0.001 −0.271 0.009 O2 pulse trajectory (mL/beat) −0.345 0.001 −0.235 0.025 Minute ventilation (VE) (L/min)* −0.377 &lt;0.001 – NS Tidal volume (VT) (L)* −0.348 0.001 – NS VE/VCO2-slope – NS 0.375 &lt;0.001 PETCO2 at AT (mmHg) – NS −0.315 0.002 HR/VO2-slope – NS 0.307 0.003 *At peak exercise. NS: Non-significant. Conclusions HbA1c and BNP levels were associated with a reduced cardiopulmonary capacity in IHD patients, mediated by a ventilation impairment and a ventilation-perfusion mismatching, respectively. HbA1c and BNP are independent and additive predictors of cardiopulmonary capacity.