Chronotropic incompetence is more frequent in obese adolescents and relates to systemic inflammation and exercise intolerance

Franssen, Wouter M. A.; Keytsman, Charly; Marinus, Nastasia; Verboven, Kenneth; Eijnde, Bert O.; Ryckeghem, Lisa Van; Dendale, Paul; Zeevaert, Renate; Massa, Guy; Hansen, Dominique

doi:10.1016/j.jshs.2021.01.010

Cited by 9 publications

(6 citation statements)

References 50 publications

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“…59 Elevated inflammatory markers are associated with reduced exercise capacity and chronotropic incompetence among adolescents and adults with obesity. 44, 60 In heart failure, resting heart rate is positively associated with levels of hsCRP, but chronotropic incompetence during exercise is negatively correlated with copeptin (C-terminal portion of arginine) and norepinephrine levels. 61 Inflammation in the setting of stress (as evidenced in the association between amygdalar activity and bone-marrow/arterial inflammation) 62 has also been implicated in the pathophysiology of health disparities 63, 64 and post-traumatic stress disorder.…”

Section: Discussionmentioning

confidence: 99%

“…Young adults recovering from SARS-CoV-2 have elevated sympathetic activation at rest [40]. Chronic inflammation in other settings is associated with parasympathetic and sympathetic imbalance, chronotropic incompetence and reduced exercise capacity [24, 41]. Thus, chronic inflammation could blunt chronotropy in PASC even without autonomic nervous system or sinus node damage.…”

Section: Discussionmentioning

confidence: 99%

“…69 Chronic inflammation in other conditions including obesity and heart failure is associated with imbalance between parasympathetic and sympathetic activation manifest in changes in heart rate variability, reduced exercise capacity and chronotropic incompetence. 49,[70][71][72] In heart failure, chronotropic incompetence during exercise is negatively correlated with copeptin (C-terminal portion of arginine) and norepinephrine levels. 73 FDG-PET studies suggest vascular inflammation 74 and cardiac inflammation 75 may be present in early PASC, consistent with findings of elevated inflammatory markers.…”

Section: Connections Between Inflammation Reduced Exercise Capacity A...mentioning

confidence: 99%

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Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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BACKGROUNDMechanisms underlying persistent cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of cardiopulmonary PASC using multimodality cardiovascular imaging including cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.METHODSIn the Long-Term Impact of Infection with Novel Coronavirus (LIINC) Cohort, we performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after PCR-confirmed SARS-CoV-2 infection. We used logistic and linear regression to compare those with and without cardiopulmonary symptoms (dyspnea, chest pain, palpitations) adjusting for confounders.RESULTSOne hundred twenty individuals were studied, among whom 46 participants (unselected for symptom status) had at least one advanced test performed at median 17 months (IQR 15-18). Median age was 52 (IQR 42-61), 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CMR (n=39), smaller RV volume and stroke volume and higher extracellular volume were present among those with symptoms, but no evidence of late-gadolinium enhancement or differences in T1 or T2 mapping were demonstrated. We did not find arrhythmias on ambulatory monitoring. In contrast, on CPET (n=39), 13/15 (87%) participants with reduced exercise capacity (<85% predicted) reported cardiopulmonary symptoms or fatigue (p=0.008). Adjusted peak VO2 was 2.7 ml/kg/min lower among those with cardiopulmonary symptoms (95%CI −6.9 to 1.5; p=0.20) or −11% predicted (95%CI −27 to 5, p=0.17). Including fatigue along with cardiopulmonary symptoms, the adjusted difference in peak VO2 was −5.9 ml/kg/min (−9.6 to −2.3; p=0.002) or −21% predicted (−35 to −7; p=0.006). Chronotropic incompetence was the primary abnormality among 9/15 with reduced peak VO2. Adjusted heart rate reserve <80% was associated with reduced exercise capacity (OR 15.6, 95%CI 1.30-187; p=0.03). Those with chronotropic incompetence had higher hsCRP, lower heart rate recovery, and lower heart rate variability suggestive of autonomic dysfunction.CONCLUSIONSReduced exercise capacity and reduced heart rate response to exercise, and hsCRP are associated with persistent cardiopulmonary symptoms more than 1 year following COVID-19. Chronic inflammation and autonomic dysfunction may underlie cardiopulmonary PASC.Clinical PerspectiveWhat is New?Impaired chronotropic response to exercise is associated with reduced exercise capacity and cardiopulmonary symptoms more than 1 year after SARS-CoV-2 infection.Findings on ambulatory rhythm monitoring point to perturbed autonomic function, while cardiac MRIfindings argue against myocardial dysfunction and myocarditis.Clinical ImplicationsCardiopulmonary testing to identify etiologies of persistent symptoms in post-acute sequalae of COVID-19 or “Long COVID” should be performed in a manner that allows for assessment of heart rate response to exercise.Therapeutic trials of antiviral, anti-inflammatory, and exercise strategies in PASC are urgently needed and should include assessment of symptoms and objective testing with cardiopulmonary exercise testing.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Connections Between Inflammation Reduced Exercise Capacity A...mentioning

confidence: 99%

See 1 more Smart Citation

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Durstenfeld

Peluso

Kaveti

et al. 2022

Preprint

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“…An association between cardiorespiratory fitness and CR has been reported in individuals with compensated heart failure [41]. Franssen et al [42] reported an inverse association between systemic inflammation and CR in adolescents with obesity. A previous study found a significant association between reduced CR and the risk of carotid atherosclerosis among healthy people [43].…”

Section: Discussionmentioning

confidence: 97%

Chronotropic Response and Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Cross-Sectional Study

Osailan,

Metsios,

Duda

et al. 2023

JCM

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Background: Individuals with rheumatoid arthritis (RA) are at a high risk of cardiovascular diseases (CVD). A reduced chronotropic response (CR), which produces exercise intolerance, is known to be a contributing factor to CVD and mortality. Studies have shown that patients with RA have a reduced CR. However, knowledge of CR-related factors in patients with RA is limited. This study aimed to explore CR-related factors, including CVD risk factors, inflammatory markers, and cardiorespiratory fitness (VO2PEAK). Methods: A total of 106 RA patients underwent a treadmill test, heart rate monitoring, and various assessments, including serological CVD risk factors, inflammatory markers, and VO2PEAK. Results: A total of 34% of participants demonstrated a reduced CR (≤80%). Body mass index, HOMA, hsCRP, and fibrinogen were inversely related to CR, while HDL, QUICKi, VO2PEAK, and RER exhibited a positive association. HDL and VO2PEAK emerged as independent CR-related factors in regression analysis. Conclusions: The current findings suggest that reduced CR in RA is associated with several CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Future studies should investigate the effects of controlling these associated variables on CR in patients with RA.

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“…Undoubtedly, the use of beta-blockers, which are commonly used in patients with cardiac arrhythmias, has a strong influence on chronotropism [ 10 , 11 , 12 ]. CI is often observed in obese patients and in patients with type 2 diabetes, trisomy 21, rheumatoid arthritis, end-stage renal disease, kidney transplantation, or COVID-19 [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In patients with hepatic failure, the altered chronotropic response correlates with the degree of organ failure, making it a valuable criterion in cardiovascular assessment when selecting candidates for liver transplantation [ 21 ].…”

Section: Chronotropic Incompetencementioning

confidence: 99%

Rate-Responsive Cardiac Pacing: Technological Solutions and Their Applications

Świerżyńska

Oręziak

Główczyńska

et al. 2023

Sensors

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Modern cardiac pacemakers are equipped with a function that allows the heart rate to adapt to the current needs of the patient in situations of increased demand related to exercise and stress ("rate-response" function). This function may be based on a variety of mechanisms, such as a built-in accelerometer responding to increased chest movement or algorithms sensing metabolic demand for oxygen, analysis of intrathoracic impedance, and analysis of the heart rhythm (Q-T interval). The latest technologies in the field of rate-response functionality relate to the use of an accelerometer in leadless endocavitary pacemakers; in these devices, the accelerometer enables mapping of the mechanical wave of the heart's work cycle, enabling the pacemaker to correctly sense native impulses and stimulate the ventricles in synchrony with the cycles of atria and heart valves. Another modern system for synchronizing pacing rate with the patient's real-time needs requires a closed-loop system that continuously monitors changes in the dynamics of heart contractions. This article discusses the technical details of various solutions for detecting and responding to situations related to increased oxygen demand (e.g., exercise or stress) in implantable pacemakers, and reviews the results of clinical trials regarding the use of these algorithms.

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Chronotropic incompetence is more frequent in obese adolescents and relates to systemic inflammation and exercise intolerance

Cited by 9 publications

References 50 publications

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

Chronotropic Response and Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Cross-Sectional Study

Rate-Responsive Cardiac Pacing: Technological Solutions and Their Applications

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