Explore the vast range of titles available.

Delayed postexercise heart rate recovery (HRR) has been associated with disability and poor prognosis in chronic cardiopulmonary diseases. The usefulness of HRR to predict exercise impairment and mortality in patients with pulmonary arterial hypertension (PAH), however, remains largely unexplored. Seventy-two patients with PAH of varied etiology (New York Heart Association classes I-IV) and 21 age- and gender-matched controls underwent a maximal incremental cardiopulmonary exercise test (CPET), with heart rate being recorded up to the fifth minute of recovery. Heart rate recovery was consistently lower in the patients compared with the controls (P < .05). The best cutoff for HRR in 1 minute (HRR1min) to discriminate the patients from the controls was 18 beats. Compared with patients with HRR1min ≤18 (n = 40), those with HRR1min >18 (n = 32) had better New York Heart Association scores, resting hemodynamics and 6-minute walking distance. In fact, HRR1min >18 was associated with a range of maximal and submaximal CPET variables indicative of less severe exercise impairment (P < .05). The single independent predictor of HRR1min ≤18 was the 6-minute walking distance (odds ratio [95% CI] 0.99 [0.98-1.00], P < .05). On a multiple regression analysis that considered only CPET-independent variables, HRR1min ≤18 was the single predictor of mortality (hazard ratio [95% CI] 1.19 [1.03-1.37], P < .05). Preserved HRR1min (>18 beats) is associated with less impaired responses to incremental exercise in patients with PAH. Conversely, a delayed HRR1min response has negative prognostic implications, a finding likely to be clinically useful when more sophisticated (and costlier) analyses provided by a full CPET are not available.

Determination of potentially-reversible factors contributing to exertional dyspnea remains an unmet clinical need in chronic thromboembolic pulmonary hypertension (CTEPH). Therefore, we aimed to evaluate the influence of inspiratory muscle weakness (IMW) on exercise capacity and dyspnea during effort in patients with CTEPH. We performed a prospective cross-sectional study that included thirty-nine consecutive patients with CTEPH (48 ± 15 yrs, 61% female) confirmed by right heart catheterization that underwent an incremental cardiopulmonary exercise test, 6-minute walk test and maximum inspiratory pressure (MIP) measurement. MIP < 70%pred was found in 46% of patients. On a multiple linear regression analysis, MIP was independently associated with 6MWD and [Formula: see text]. Patients with MIP < 70% presented greater [Formula: see text] than those with MIP ≥ 70%. Additionally, they also presented stronger sensations of dyspnea throughout exercise, even when adjusted for ventilation. At rest and at different levels of exercise, mean inspiratory flow (VT/TI) was significantly higher in patients with MIP < 70%. In conclusion, IMW is associated with a rapid increase of dyspnea, higher inspiratory load and poor exercise capacity in patients with CTEPH.

Background: Glucagon-like peptide-1 (GLP-1) agonists are an existing treatment option for patients with insulin-resistant states, which elicit further pleiotropic effects related to immune cell recruitment and vascular inflammation. GLP-1 agonists downregulate the cluster of differentiation 147 (CD147) receptor, one of several receptors for the SARS-CoV-2 spike protein that mediate viral infection of host cells. Methods: We conducted an open-label prospective safety and tolerability study including biomarker responses of the GLP-1 agonist Liraglutide, administered for 5 days as an add-on therapy to the standard of care within 48 h of presentation in a cohort of 13 patients hospitalized with COVID-19 pneumonia. Biomarker responses were compared in patients admitted to critical care and those not requiring critical care admission (non-critical group). Results: Liraglutide (0.6 mg, subcutaneously) was well tolerated by all patients and all patients were alive 30 days after diagnosis. Plasma soluble CD147 levels were reduced in the non-critical patient group at day 5 in contrast to critical care-treated patients, who demonstrated an increase in soluble CD147 levels between day 0 and day 5. Patients with milder COVID-19 pneumonia severity also demonstrated improvement in echocardiographic parameters of right and left ventricular function, reduction in plasma Troponin levels, increased CD147 expression on T lymphocytes, and reduction in plasma IL-8. Conclusions: This first-in-disease use of the GLP-1 agonist Liraglutide demonstrates its safety and tolerability in an unselected cohort of patients hospitalized with COVID-19 pneumonia across a range of clinical severities.

During the COVID‐19 pandemic, Brazil was one of the most affected countries. Patients presented higher risk of acute venous thromboembolism (VTE), in particular, pulmonary embolism (PE). However, long‐term implications of these events remain unknown. A retrospective analysis from the FENIX study was conducted, and patients with COVID‐19‐related VTE during hospitalization were included. Further analysis, up to 6 months after the acute event, was performed exclusively in patients with PE. Persistence of dyspnea and exercise intolerance was evaluated through imaging, rest, and exercise functional tests. Cumulative incidence of VTE during hospitalization among COVID‐19 survivors followed at the outpatient clinic was 17.7% (n = 75/423) and of acute PE was 9.9% (n = 42/423). Patients with PE were mostly male (66%), 56 ± 16 years old, and mainly classified as intermediate‐low risk (74%). Dyspnea (mMRC≥ 1) up to 6 months of PE was present in 56% (n = 19/34), with a borderline association with parenchymal lung sequelae on chest CT scan (p = 0.069). Symptomatic patients upon follow‐up presented lower FEV1 and FVC, as well as increased peak VD/VT ratio and ventilatory inefficiency. No signs of pulmonary hypertension (PH) were identified on echocardiogram (ECHO) and cardiopulmonary exercise testing (CPET). Persistence of dyspnea among post‐PE related to COVID‐19 was high. However, no cases of PH were found; follow‐up findings may be related to pulmonary parenchymal and microvascular injury. Also, we cannot exclude association with long‐COVID, in which pathophysiological mechanisms are multifactorial, involving chronic inflammatory changes and multiorgan dysfunction, highlighting the need for comprehensive evaluation of exercise intolerance through invasive CPET.

Inspiratory pressure support (IPS) plus positive end-expiratory pressure (PEEP) ventilation might potentially interfere with the “central” hemodynamic adjustments to exercise in patients with chronic obstructive pulmonary disease (COPD). Twenty-one non- or mildly-hypoxemic males (FEV 1  = 40.1 ± 10.7% predicted) were randomly assigned to IPS (16 cmH 2 O) + PEEP (5 cmH 2 O) or spontaneous ventilation during constant-work rate (70–80% peak) exercise tests to the limit of tolerance ( T lim ). Heart rate (HR), stroke volume (SV), and cardiac output (CO) were monitored by transthoracic cardioimpedance (Physioflow™, Manatec, France). Oxyhemoglobin saturation was assessed by pulse oximetry (SpO 2 ). At similar SpO 2 , IPS 16  + PEEP 5 was associated with heterogeneous cardiovascular effects compared with the control trial. Therefore, 11 patients (Group A) showed stable or increased Δ “isotime” – rest SV [5 (0–29) mL], lower ΔHR but similar ΔCO. On the other hand, ΔSV [−10 (−15 to −3) mL] and ΔHR were both lower with IPS 16  + PEEP 5 in Group B ( N  = 10), thereby reducing ΔCO ( p  < 0.05). Group B showed higher resting lung volumes, and T lim improved with IPS 16  + PEEP 5 only in Group A [51 (−60 to 486) vs. 115 (−210 to 909) s, respectively; p  < 0.05]. We conclude that IPS 16  + PEEP 5 may improve SV and exercise tolerance in selected patients with advanced COPD. Impaired SV and CO responses, associated with a lack of enhancement in exercise capacity, were found in a sub-group of patients who were particularly hyperinflated at rest.

COVID-19 and infectious diseases have been included in strategic development goals (SDG) of United Nations (UN). The CD147 receptor is one of several receptors for the SARS-CoV-2 spike protein that could mediate Covid-19 viral infection of host cells. It has been recently proposed to regulate viral invasion and dissemination among lymphocytes and progenitor/stem cells. A soluble by-product of CD147 (sCD147) exists in plasma and has been previously identified as a marker of diabetes and platelet activation. We examined plasma sCD147 levels in 161 Covid-19 patients at hospital admission. We demonstrated significantly higher plasma sCD147 levels in Covid-19 patients, which correlated with plasma multiorgan dysfunction biomarkers interleukin-6, creatinine and Troponin I. Importantly, sCD147 admission levels were associated with Covid-19 severity and survival, carrying potential value as a biomarker in hospitalized patients with Covid-19 infection.

Pathologic implications of dysregulated pulmonary vascular metabolism to pulmonary arterial hypertension (PAH) are increasingly recognized, but their clinical applications have been limited. We hypothesized that metabolite quantification across the pulmonary vascular bed in connective tissue disease-associated (CTD-associated) PAH would identify transpulmonary gradients of pathobiologically relevant metabolites, in an exercise stage-specific manner. Sixty-three CTD patients with established or suspected PAH underwent exercise right heart catheterization. Using mass spectrometry-based metabolomics, metabolites were quantified in plasma samples simultaneously collected from the pulmonary and radial arteries at baseline and during resistance-free wheeling, peak exercise, and recovery. We identified uptake and excretion of metabolites across the pulmonary vascular bed, unique and distinct from single vascular site analysis. We demonstrated the physiological relevance of metabolites previously shown to promote disease in animal models and end-stage human lung tissues, including acylcarnitines, glycolytic intermediates, and tryptophan catabolites. Notably, pulmonary vascular metabolite handling was exercise stage specific. Transpulmonary metabolite gradients correlated with hemodynamic endpoints largely during free-wheeling. Glycolytic intermediates demonstrated physiologic significance at peak exercise, including net uptake of lactate in those with more advanced disease. Contribution of pulmonary vascular metabolism to CTD-PAH pathogenesis and therapeutic candidacy of metabolism modulation must be considered in the context of physiologic stress.

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients.

This study addressed whether O 2 delivery during recovery from high-intensity, supra-gas exchange threshold exercise would be matched to O 2 utilization at the microvascular level in patients with mitochondrial myopathy (MM). Off-exercise kinetics of (1) pulmonary O 2 uptake (2) an index of fractional O 2 extraction by near-infrared spectroscopy (Δ[deoxy-Hb + Mb]) in the vastus lateralis and (3) cardiac output ( Q T ′ ) by impedance cardiography were assessed in 12 patients with biopsy-proven MM (chronic progressive external ophthalmoplegia) and 12 age- and gender-matched controls. Kinetics of were significantly slower in patients than controls (τ = 53.8 ± 16.5 vs. 38.8 ± 7.6 s, respectively; p  < 0.05). Q T ′ , however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p  > 0.05) being typically slower than in both groups. Importantly, Δ[deoxy-Hb + Mb] dynamics (MRT) were equal to, or faster than, in patients and controls, respectively. In fact, there were no between-group differences in /MRTΔ[deoxy-Hb + Mb] (1.1 ± 0.4 vs. 1.0 ± 0.2, p  > 0.05) thereby indicating similar rates of microvascular O 2 delivery. These data indicate that the slower rate of recovery of muscle metabolism after high-intensity exercise is not related to impaired microvascular O 2 delivery in patients with MM. This phenomenon, therefore, seems to reflect the intra-myocyte abnormalities that characterize this patient population.

Impaired O 2 delivery relative to O 2 demands at the onset of exercise might influence the response profile of muscle fractional O 2 extraction (≅Δ[deoxy-Hb/Mb] by near-infrared spectroscopy) either by accelerating its rate of increase or creating an “overshoot” (OS) in patients with pulmonary arterial hypertension (PAH). We therefore assessed the kinetics of O 2 uptake Δ[deoxy-Hb/Mb] in the vastus lateralis , and heart rate (HR) at the onset of heavy-intensity exercise in 14 females with PAH (connective tissue disease, IPAH, portal hypertension, and acquired immunodeficiency syndrome) and 11 age- and gender-matched controls. Patients had slower and HR dynamics than controls (τ  = 62.7 ± 15.2 s vs. 41.0 ± 13.8 s and t 1/2 -HR = 61.3 ± 16.6 s vs. 43.4 ± 8.8 s, respectively; p  < 0.01). No study participant had a significant reduction in oxyhemoglobin saturation. In OS(−) subjects (6 patients and 7 controls), the kinetics of Δ[deoxy-Hb/Mb] relative to were faster in patients ( p  = 0.05). Larger area under the OS and slower kinetics (MRT) of the “downward” component indicated greater O 2 delivery-to-utilization mismatch in OS(+) patients versus OS(+) controls (477.4 ± 330.0 vs. 78.1 ± 65.6 a.u. and 74.6 ± 18.8 vs. 46.0 ± 17.0 s, respectively; p  < 0.05). Resting pulmonary vascular resistance was higher in OS(+) than OS(−) patients (23.1 ± 12.0 vs. 10.7 ± 4.0 Woods, respectively; p  < 0.05). We conclude that microvascular O 2 delivery-to-utilization inequalities slowed the rate of adaptation of aerobic metabolism at the start of heavy-intensity exercise in women with PAH.