Abstract Objective Exercise intolerance is a common clinical manifestation of CTD. Frequently, CTD patients have associated cardio-pulmonary disease, including pulmonary hypertension or heart failure that impairs aerobic exercise capacity (pVO2). The contribution of the systemic micro-vasculature to reduced exercise capacity in CTD patients without cardiopulmonary disease has not been fully described. In this study, we sought to examine the role of systemic vascular distensibility, α in reducing exercise capacity (i.e. pVO2) in CTD patients. Methods Systemic and pulmonary vascular distensibility, α (%/mmHg) was determined from multipoint systemic pressure-flow plots during invasive cardiopulmonary exercise testing with pulmonary and radial arterial catheters in place in 42 CTD patients without cardiopulmonary disease and compared with 24 age and gender matched normal controls. Results During exercise, systemic vascular distensibility, α was reduced in CTD patients compared with controls (0.20 ± 0.12%/mmHg vs 0.30 ± 0.13%/mmHg, P =0.01). The reduced systemic vascular distensibility α, was associated with impaired stroke volume augmentation. On multivariate analysis, systemic vascular distensibility, α was associated with a decreased exercise capacity (pVO2) and decreased systemic oxygen extraction. Conclusion Systemic vascular distensibility, α is associated with impaired systemic oxygen extraction and decreased aerobic capacity in patients with CTD without cardiopulmonary disease.
Abstract Aims Dyspnoea is common in heart failure (HF) but non‐specific. Lung ultrasound (LUS) could represent a non‐invasive tool to detect subclinical pulmonary congestion in patients with undifferentiated dyspnoea. Methods and results We assessed the feasibility of an abbreviated LUS protocol (eight and two zones) in a prospective pilot study of 25 ambulatory patients with undifferentiated dyspnoea undergoing clinically indicated invasive cardiopulmonary exercise testing (iCPET) at rest (LUS 1) and after peak exercise (LUS 2). We also related LUS findings (B‐lines) to invasive haemodynamics stratified by supine pulmonary capillary wedge pressure (PCWP) (Congestion, >15 mmHg; Control, ≤15 mmHg). All enrolled patients (median age 68, 60% women, 32% prior HF, median ejection fraction 59%) had interpretable LUS 1 images in eight zones, and 20 (80%) had adequate LUS 2 images. LUS images were adequate in two posterior zones in 24 patients (96%) for LUS 1 and 18 (72%) for LUS 2. Although B‐line number was numerically higher in the Congestion group at rest and after peak exercise, this difference did not reach statistical significance. In the entire cohort, there was an association between B‐lines and rest systolic pulmonary artery pressure ( r = 0.46, P = 0.02) and PCWP ( r = 0.54, P = 0.005). There was an inverse relationship between B‐lines and peak VO 2 ( r = −0.65, P = 0.002). Conclusions Among ambulatory patients with undifferentiated dyspnoea, an abbreviated LUS protocol before and after iCPET is feasible in the majority of patients. B‐line number at rest was associated with invasively measured markers of haemodynamic congestion and was inversely related with peak VO 2 .
Measurement by mass spectrometry of 200 blood metabolites reveals that individuals who are more fit respond more effectively to exercise, as shown by larger exercise-induced increase in glycerol.
The relationships among the lactate threshold (LT), ventilatory threshold (VT), and intracellular biochemical events in exercising muscle have not been well defined. Therefore 14 normal subjects performed incremental plantar flexion to exhaustion on 2 study days, the first for determination of LT and VT and the second for continuous 31P nuclear magnetic resonance spectroscopy of calf muscle. Exercising calf muscle pH fell precipitously at 66.4 +/- 3.4% (SE) of the maximum O2 uptake (VO2max) and was termed the intramuscular pH threshold. This did not occur at a significantly different metabolic rate from that at the LT (78.6 +/- 5.9% VO2max) or at the VT (75.0 +/- 4.1% VO2max, P = 0.15 by analysis of variance). Four subjects showed an intramuscular pH threshold and VT without a perceptible rise in forearm venous blood lactate. It is concluded that traditional markers of the “anaerobic threshold,” the LT and VT, occur as intramuscular pH becomes acid for a group of normal subjects undergoing incremental exercise to exhaustion. It is speculated that neuronal pathways linking intramuscular biochemical events to the ventilatory control center may explain the intact VT in those subjects without an “intermediary” LT.
Introduction: Patients with pulmonary arterial hypertension (PAH) have exertional intolerance; however, the biological mediators relevant for PAH that are affected by this phenomenon remain incompletely characterized. Aim: To examine the transpulmonary gradient of proteins in PAH and how these are perturbed by an exercise challenge. Methods: Twelve patients with PAH and 12 age- and sex-matched patients with unexplained dyspnea underwent level 3 cardiopulmonary exercise testing with blood sampling from the pulmonary artery and pulmonary capillary wedge compartments at rest, peak exercise, and post-exercise. Proteomics were performed on plasma samples using an aptamer-based technology. Pathway and functional enrichment analyses were used to cluster proteins. Results: Patients with PAH (mPAP 39±6, PVR 376±189 dyn‑s-cm-5) had a cardiac output similar to patients with unexplained dyspnea, but exercised to a lower workload and had lower peak lactate levels (5±2 vs. 8±2 mmol/L, p<0.01). Proteomic analysis demonstrated that following exercise, compared to patients with unexplained dyspnea, PAH patients had changes in the transpulmonary gradient of proteins related to glucose and insulin signaling, kinase receptor activation, oxidant stress, growth factor receptor binding, activation of the immune system, and complement activation (p<10-6 for all). Conclusions: Patients with PAH have a differentiated transpulmonary profile of proteins following an exercise challenge. Changes in the transpulmonary gradient of these proteins suggest that they might play a role in the pathophysiology of PAH and serve as a biomarker of exercise intolerance in the disease.
The purpose of this study was to describe cerebrovascular, neuropathic, and autonomic features of post-acute sequelae of coronavirus disease 2019 ((COVID-19) PASC).This retrospective study evaluated consecutive patients with chronic fatigue, brain fog, and orthostatic intolerance consistent with PASC. Controls included patients with postural tachycardia syndrome (POTS) and healthy participants. Analyzed data included surveys and autonomic (Valsalva maneuver, deep breathing, sudomotor, and tilt tests), cerebrovascular (cerebral blood flow velocity [CBFv] monitoring in middle cerebral artery), respiratory (capnography monitoring), and neuropathic (skin biopsies for assessment of small fiber neuropathy) testing and inflammatory/autoimmune markers.Nine patients with PASC were evaluated 0.8 ± 0.3 years after a mild COVID-19 infection, and were treated as home observations. Autonomic, pain, brain fog, fatigue, and dyspnea surveys were abnormal in PASC and POTS (n = 10), compared with controls (n = 15). Tilt table test reproduced the majority of PASC symptoms. Orthostatic CBFv declined in PASC (-20.0 ± 13.4%) and POTS (-20.3 ± 15.1%), compared with controls (-3.0 ± 7.5%, p = 0.001) and was independent of end-tidal carbon dioxide in PASC, but caused by hyperventilation in POTS. Reduced orthostatic CBFv in PASC included both subjects without (n = 6) and with (n = 3) orthostatic tachycardia. Dysautonomia was frequent (100% in both PASC and POTS) but was milder in PASC (p = 0.002). PASC and POTS cohorts diverged in frequency of small fiber neuropathy (89% vs 60%) but not in inflammatory markers (67% vs 70%). Supine and orthostatic hypocapnia was observed in PASC.PASC following mild COVID-19 infection is associated with multisystem involvement including: (1) cerebrovascular dysregulation with persistent cerebral arteriolar vasoconstriction; (2) small fiber neuropathy and related dysautonomia; (3) respiratory dysregulation; and (4) chronic inflammation. ANN NEUROL 2022;91:367-379.
