Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction: Technique Principles, Current Evidence, and Future Perspectives.

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.

COVID-19 and liver injury: An ongoing challenge.

The new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019, in Wuhan, China. The virus was rapidly spread worldwide, causing coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 is presented, usually, with typical respiratory symptoms (i.e., dyspnea, cough) and fever, extrapulmonary manifestations are also encountered. Liver injury is a common feature in patients with COVID-19 and ranges from mild and temporary elevation of liver enzymes to severe liver injury and, even, acute liver failure. The pathogenesis of liver damage is not clearly defined; multiple mechanisms contribute to liver disorder, including direct cytopathic viral effect, cytokine storm and immune-mediated hepatitis, hypoxic injury, and drug-induced liver toxicity. Patients with underlying chronic liver disease (i.e., cirrhosis, non-alcoholic fatty liver disease, alcohol-related liver disease, hepatocellular carcinoma, etc.) may have greater risk to develop both severe COVID-19 and further liver deterioration, and, as a consequence, certain issues should be considered during disease management. The aim of this review is to present the prevalence, clinical manifestation and pathophysiological mechanisms of liver injury in patients with SARS-CoV-2 infection. Moreover, we overview the association between chronic liver disease and SARS-CoV-2 infection and we briefly discuss the management of liver injury during COVID-19.

Brain oxygenation during multiple sets of isometric and dynamic resistance exercise of equivalent workloads: Association with systemic haemodynamics.

Brain function relies on sufficient blood flow and oxygen supply. Changes in cerebral oxygenation during exercise have been linked to brain activity and central command. Isometric- and dynamic-resistance exercise-(RE) may elicit differential responses in systemic circulation, neural function and metabolism; all important regulators of cerebral circulation. We examined whether (i) cerebral oxygenation differs between isometric- and dynamic-RE of similar exercise characteristics and (ii) cerebral oxygenation changes relate to cardiovascular adjustments occurring during RE. Fourteen men performed, randomly, an isometric-RE and a dynamic-RE of similar characteristics (bilateral-leg-press, 2-min×4-sets, 30% of maximal-voluntary-contraction, equivalent tension-time-index/workload). Cerebral-oxygenation (oxyhaemoglobin-O2Hb; total haemoglobin-tHb/blood-volume-index; deoxyhemoglobin-HHb) was assessed by NIRS and beat-by-beat haemodynamics via photoplethysmography. Cerebral-O2Hb and tHb progressively increased from the 1st to 4th set in both RE-protocols (p < 0.05); HHb slightly decreased (p < 0.05). Changes in NIRS-parameters were similar between RE-protocols within each exercise-set (p = 0.91-1.00) and during the entire protocol (including resting-phases) (p = 0.48-0.63). O2Hb and tHb changes were not correlated with changes in systemic haemodynamics. In conclusion, cerebral oxygenation/blood-volume steadily increased during multiple-set RE-protocols. Isometric- and dynamic-RE of matched exercise characteristics resulted in similar prefrontal oxygenation/blood volume changes, suggesting similar cerebral haemodynamic and possibly neuronal responses to maintain a predetermined force.

Renin-angiotensin system blockers during the COVID-19 pandemic: an update for patients with hypertension and chronic kidney disease.

Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin-angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.

Meta-analysis addressing the impact of cardiovascular-acting medication on peak oxygen uptake of patients with HFpEF.

As our therapeutic armamentarium for HFpEF is insufficient, research has been focusing on the potential beneficial effect of existing pharmaceutical regimens on this specific patient population. A series of RCTs have recently examined the impact of various pharmaceutical treatments with proven benefit in HFrEF, on the improvement of symptoms of HFpEF patients. This systematic review and meta-analysis comprised studies of adult patients with HFpEF and evaluated the impact of different cardiovascular acting medication on cardiorespiratory fitness, reflected by peak VO2 values measured during CPET. The primary outcome was difference between groups in the change of peak VO2 (ΔpeakVO2). Literature search involved PubMed/MEDLINE, Scopus and Web of Science databases. Our search identified 3634 records and 19 studies were included in qualitative analysis; 12 studies with 1341 patients were finally included in primary outcome analysis. ΔpeakVO2 between baseline and study-end did not significantly change after treatment with spironolactone, ivabradine, sildenafil, or oral inorganic nitrate and neither did difference in 6MWT distance after treatment with spironolactone. Spironolactone led to statistically significant reduction in E/E' ratio study-end values (WMD - 1.64, 95%CI - 2.42 to - 0.86, I2 = 87%, p < 0.0001), as well as to a significant increase in MLHFQ values (WMD 0.75, 95%CI 0.02 to 1.48, I2 = 0%, p = 0.65), indicating deterioration in HRQoL among HFpEF patients. A series of established cardiovascular acting medication in HFrEF seems not to confer significant benefit in peak VO2 and 6MWT distance in HFpEF. Spironolactone is associated with improvements in diastolic function and with a significant deterioration in HRQoL of this population.

Cardiopulmonary reserve examined with cardiopulmonary exercise testing in individuals with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) often present reduced physical activity and exercise tolerance due to factors relevant to co-existing disturbances of the cardiac, nervous and muscular systems. Cardiopulmonary exercise testing (CPET) is used for clinical evaluation of exercise limitation and related symptoms (i.e., dyspnea, fatigue) in several medical fields. OBJECTIVES: This is a systematic review and meta-analysis of studies using CPET technology to examine cardiopulmonary reserve in individuals with versus without CKD. METHODS: Literature search involved PubMed, Web of Science and Scopus databases; manual search of article references and of gray literature was also performed. Observational studies and randomized trials that used CPET for patients with CKD stage 1-5 versus controls were eligible. The primary outcome was peak oxygen uptake (VO2peak). The Newcastle-Ottawa Scale was used to evaluate the quality of retrieved studies. RESULTS: From an initial 4944 literature records, we identified 29 studies fulfilling the inclusion criteria; of these, 25 studies (2,213 participants) with complete data were included in the final meta-analysis. VO2peak was significantly lower in CKD patients than controls without CKD [standardized mean difference (SMD) -1.40, 95% confidence interval (CI) -1.68; -1.13)]. Values were lower for CKD than non-CKD individuals for oxygen consumption at anaerobic threshold (SMD -1.06, 95% CI -1.34; -0.79) and maximum workload [weighted mean difference (WMD) -58.26, 95% CI 74.14; -42.38]. In 3 studies, CKD patients had higher VO2peak than controls with heart failure without CKD (WMD 6.60, 95% CI 3.02; 10.18). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: VO2peak and other commonly analyzed CPET variables were lower in patients with CKD than controls, which indicates reduced functional cardiopulmonary reserve in CKD. In contrast, patients with CKD performed better than controls with heart failure without CKD. Overall, rehabilitation programs should be more widely applied to individuals with CKD. PROSPERO REGISTRATION NUMBER: CRD42021227805.

Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise.

Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001-0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise.

Effects of different exercise programs on the cardiorespiratory reserve in HFpEF patients: a systematic review and meta-analysis.

HFpEF represents a heterogeneous syndrome with complex pathophysiological substrates and multiple clinical manifestations. Recently, much attention has been focused on cardiac rehabilitation programs for HFpEF patients, and several studies have examined the effects of exercise training on this specific population. This systematic review and meta-analysis included studies on adult patients with HFpEF and evaluated the impact of exercise on the cardiorespiratory fitness variables measured during CPET. The primary outcome was the difference in the change in the peak oxygen uptake (Δpeak VO2) between the groups. Literature search involved PubMed/MEDLINE, Cochrane/CENTRAL and Scopus databases. From an initial 5,143 literature records, we identified 18 studies fulfilling the inclusion criteria; 11 studies with 515 patients were finally included in the primary outcome analysis. Δpeak VO2 between baseline and study end was significantly higher in the groups of exercise training versus control (WMD 2.25 ml/kg/min, 95% CI 1.81-2.70). Exercise training resulted in greater change in the 6-minute walking test (6MWT) distance (WMD 2.25 m, 95% CI 1.81-2.70). Health-related quality of life (HRQoL) (WMD: -3.36, 95% CI -9.42 to 2.70, I2 = 14%, p = 0.33) and echocardiographic indices of diastolic function showed no differences between exercise and control groups at study end. In the subgroup analysis, no difference between resistance versus aerobic exercise was noted in Δpeak VO2, but high-intensity interval training showed a greater increase in peak VO2 versus aerobic exercise (WMD 1.62 ml/kg/min, 95% CI 0.96-2.29, I2 = 0%, p = 0.82). Exercise training in HFpEF results in significant improvements in peak VO2 and 6MWT distance as compared to those for controls. High-intensity interval training may offer greater enhancement of the exercise capacity of these patients than standard aerobic exercise.

Impaired Cardiovascular Response to Exercise in Patients with Severe Asthma: A Case-Control Study.

Background: Although asthmatics may present reduced exercise capacity, data on their cardiovascular responses during exercise testing have been scarcely investigated. The aim of this pilot case-control study is to test: a) whether double product (DP), an index of cardiovascular reserve, differs among patients with severe and mild-moderate asthma, and b) whether DP is associated with asthma control level, physical activity (PA) and exercise capacity, in asthmatics population. Materials and Methods: A group of patients with severe asthma (group S) and a matched group of patients with mild-moderate asthma (group M) was studied. All participants completed asthma control and physical activity (IPAC) questionnaires, lung function measurements and six-minute walk test. The exercise capacity (as 6-minute walk distance (6MWD) and corresponding work), the Borg Dyspnea, the rating of perceived excursion and the average PA METS were recorded. Results: A total of 18 patients were studied. DP at exercise end was significantly lower in group S, compared to group M (16412.2±4732.1 vs. 18594.8±3984.4 mmHgXbpm; p=0.041) and was moderately associated with % predicted 6MWD (r=0.592; p=0.001). Group S patients were also presented with lower moderate intensity PA, compared to group M, while exercise capacity was similar between the groups. Asthma control level had no impact on exercise capacity nor PA parameters. Conclusion: Patients with severe asthma may have impaired cardiovascular reserve as established by DP, even when exercise capacity is indifferent from patients with milder disease. As an easy-to-assess parameter, DP may offer further information in the functional evaluation of these patients.

Long COVID-19 Pulmonary Sequelae and Management Considerations.

The human coronavirus 2019 disease (COVID-19) and the associated acute respiratory distress syndrome (ARDS) are responsible for the worst global health crisis of the last century. Similarly, to previous coronaviruses leading to past pandemics, including severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS), a growing body of evidence support that a substantial minority of patients surviving the acute phase of the disease present with long-term sequelae lasting for up to 6 months following acute infection. The clinical spectrum of these manifestations is widespread across multiple organs and consists of the long-COVID-19 syndrome. The aim of the current review is to summarize the current state of knowledge on the pulmonary manifestations of the long COVID-19 syndrome including clinical symptoms, parenchymal, and functional abnormalities, as well as highlight epidemiology, risk factors, and follow-up strategies for early identification and timely therapeutic interventions. The literature data on management considerations including the role of corticosteroids and antifibrotic treatment, as well as the therapeutic potential of a structured and personalized pulmonary rehabilitation program are detailed and discussed.

Endothelial dysfunction in COPD: a systematic review and meta-analysis of studies using different functional assessment methods.

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in COPD. Endothelial dysfunction is suggested to be one of the pathogenetic mechanisms involved. This is a systematic review and meta-analysis of studies using any available functional method to examine differences in endothelial function between patients with COPD and individuals without COPD (controls). METHODS: Literature search involved PubMed and Scopus databases. Eligible studies included adult patients and evaluated endothelial damage via functional methods. The Newcastle-Ottawa scale was applied to evaluate the quality of retrieved studies. Subgroup analyses were performed to explore heterogeneity across the studies. Funnel plots were constructed to evaluate publication bias. RESULTS: Of the 21 reports initially identified, 19 studies with a total of 968 participants were included in the final meta-analysis. A significantly impaired response in endothelium-dependent (weighted mean between-group difference (WMD) -2.59, 95% CI -3.75 to -1.42) and -independent vasodilation (WMD -3.13, 95% CI -5.18 to -1.09) was observed in patients with COPD compared to controls. When pooling all studies together, regardless of the technique used for assessment of vascular reactivity, pronounced endothelial dysfunction was observed in COPD compared to controls (standardised mean difference (SMD) -1.19, 95% CI -1.69 to -0.68). Subgroup analysis showed that the difference was larger when patients with COPD were compared with nonsmoking controls (SMD -1.75, 95% CI -2.58 to -0.92). Sensitivity analyses confirmed the results. CONCLUSIONS: Patients with COPD have significantly impaired endothelial function compared to controls without COPD. Future studies should delineate the importance of endothelial dysfunction towards development of cardiovascular disease in COPD.

Effects of oxygen supplementation in autonomic nervous system function during exercise in patients with idiopathic pulmonary fibrosis and exertional desaturation.

INTRODUCTION: Patients with idiopathic pulmonary fibrosis (IPF) have reduced exercise capacity and often present exertional dyspnea and desaturation. The role of autonomic nervous system (ANS) as a pathogenetic contributor to this dysfunction has not been evaluated. OBJECTIVE: To evaluate whether improvement of arterial oxygen saturation (SpO2 ) via oxygen supplementation results to ANS function improvement, during steady state submaximal exercise. METHODS: This is a secondary analysis of a single-blind, randomized, placebo-controlled, cross-over trial, including 12 IPF patients, with isolated exertional desaturation. Following a maximal cardiopulmonary test, participants underwent two submaximal steady state tests during which they received either supplementary oxygen or medical air. Continuous beat-to-beat blood pressure measurements were recorded (Finapres Medical Systems, Amsterdam, The Netherlands). Autonomic function was assessed non-invasively by heart rate variability (HRV); root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Entropy and detrended fluctuation analysis (DFA) were also used. RESULTS: During rest, oxygen supplementation did not significantly alter RMSSD and SD1. During exercise, subjects presented no significant alterations compared with baseline, in most HRV indices examined. There was no improvement of this behavior with O2 -supplementation. Approximate-entropy increased during exercise, with no differences between protocols. CONCLUSIONS: IPF patients presented an inadequate adaptive response of their ANS to exercise and recovery. Although oxygen supplementation significantly prolonged exercise duration and prevented the substantial exertional desaturation, the blunted vagal response to steady-state exercise in these patients was not improved, suggesting that acute oxygen supplementation does not sufficiently improve ANS dysfunction in these patients.

Cardiorespiratory fitness in kidney transplant recipients compared to patients with kidney failure: a systematic review and meta-analysis.

Patients with kidney failure often present with reduced cardiovascular functional reserve and exercise tolerance. Previous studies on cardiorespiratory fitness examined with cardiopulmonary exercise testing (CPET) in kidney transplant recipients (KTR) had variable results. This is a systematic review and meta-analysis of studies examining cardiovascular functional reserve with CPET in KTR in comparison with patients with kidney failure (CKD-Stage-5 before dialysis, hemodialysis or peritoneal dialysis), as well as before and after kidney transplantation. Literature search involved PubMed, Web-of-Science and Scopus databases, manual search of article references and grey literature. From a total of 4,944 identified records, eight studies (with 461 participants) were included in quantitative analysis for the primary question. Across these studies, KTR had significantly higher oxygen consumption at peak/max exercise (VO2 peak/VO2 max) compared to patients with kidney failure (SMD = 0.70, 95% CI [0.31, 1.10], I2  = 70%, P = 0.002). In subgroup analyses, similar differences were evident among seven studies comparing KTR and hemodialysis patients (SMD = 0.64, 95% CI [0.16, 1.12], I2  = 65%, P = 0.009) and two studies comparing KTR with peritoneal dialysis subjects (SMD = 1.14, 95% CI [0.19, 2.09], I2  = 50%, P = 0.16). Across four studies with relevant data, oxygen consumption during peak/max exercise showed significant improvement after kidney transplantation compared to pretransplantation values (WMD = 2.43, 95% CI [0.01, 4.85], I2  = 68%, P = 0.02). In conclusion, KTR exhibit significantly higher cardiovascular functional reserve during CPET compared to patients with kidney failure. Cardiovascular reserve is significantly improved after kidney transplantation in relation to presurgery levels.

A randomized placebo-control trial of the acute effects of oxygen supplementation on exercise hemodynamics, autonomic modulation, and brain oxygenation in patients with pulmonary hypertension.

BACKGROUND: The integrative physiological effects of O2 treatment on patients with pulmonary hypertension (PH) during exercise, have not been fully investigated. We simultaneously evaluated, for the first time, the effect of oxygen supplementation on hemodynamic responses, autonomic modulation, tissue oxygenation, and exercise performance in patients with pulmonary arterial hypertension (PAH)/Chronic Thromboembolic PH(CTEPH). MATERIAL-METHODS: In this randomized, cross-over, placebo-controlled trial, stable outpatients with PAH/CTEPH underwent maximal cardiopulmonary exercise testing, followed by two submaximal trials, during which they received supplementary oxygen (O2) or medical-air. Continuous, non-invasive hemodynamics were monitored via photophlythesmography. Cerebral and quadriceps muscle oxygenation were recorded via near-infrared spectroscopy. Autonomic function was assessed by heart rate variability; root mean square of successive differences (RMSSD) and standard-deviation-Poincare-plot (SD1) were used as indices of parasympathetic output. Baroreceptor sensitivity (BRS) was assessed throughout the protocols. RESULTS: Nine patients (51.4 ±â€¯9.4 years) were included. With O2-supplementation patients exercised for longer (p = 0.01), maintained higher cerebral oxygenated hemoglobin (O2Hb;p = 0.02) levels, exhibited an amelioration in cortical deoxygenation (HHb;p = 0.02), and had higher average cardiac output (CO) during exercise (p < 0.05), compared to medical air; with no differences in muscle oxygenation. With O2-supplementation patients exhibited higher BRS and sample-entropy throughout the protocol (p < 0.05) vs. medical air, and improved the blunted RMSSD, SD1 responses during exercise (p = 0.024). CONCLUSION: We show that O2 administration improves BRS and autonomic function during submaximal exercise in PAH/CTEPH, without significantly affecting muscle oxygenation. The improved autonomic function, along with enhancements in cardiovascular function and cerebral oxygenation, probably contributes to increased exercise tolerance with O2-supplementation in PH patients.

Changes in the respiratory function of COVID-19 survivors during follow-up: A novel respiratory disorder on the rise?

BACKGROUND: The Human Coronavirus Disease 2019 (COVID-19) is a highly contagious respiratory disorder that may result in acute respiratory distress syndrome. The aim of this review was to investigate the incidence and type of respiratory function abnormalities during the follow-up of patients who recovered from COVID-19. METHODS: A systematic search of MEDLINE was conducted, utilising various term combinations. Studies that assessed any respiratory function parameter during the re-evaluation of patients who recovered from COVID-19 and were published as full-text articles in English are included in this review. RESULTS: Amongst 183 articles initially retrieved, 8 fulfilled the criteria and were included in this review; they involved a total of 341 adult patients. Four were retrospective studies, one was a prospective cohort study, one was a randomised control trial and two were case reports/case series. The follow-up time ranged from 1 month since symptom onset to 3 months after discharge. The most frequent abnormality was reduced lung diffusion for carbon monoxide (DLCO), followed by a restrictive pattern. Other findings are the lack of resting hypoxemia, the reduced respiratory muscle strength and the decreased exercise capacity, although relative data are extremely limited. CONCLUSION: Patients who recovered from COVID-19 present with abnormal respiratory function at short-term follow-up, mainly with reduced lung diffusion and a restrictive pattern. However, results are currently very limited in order safe conclusions to be made, regarding the exact incidence of these abnormalities and whether they may be temporary or permanent.

Exercise as a Therapeutic Intervention in Gestational Diabetes Mellitus.

Gestational Diabetes Mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Regular exercise is important for a healthy pregnancy and can lower the risk of developing GDM. For women with GDM, exercise is safe and can affect the pregnancy outcomes beneficially. A single exercise bout increases skeletal muscle glucose uptake, minimizing hyperglycemia. Regular exercise training promotes mitochondrial biogenesis, improves oxidative capacity, enhances insulin sensitivity and vascular function, and reduces systemic inflammation. Exercise may also aid in lowering the insulin dose in insulin-treated pregnant women. Despite these benefits, women with GDM are usually inactive or have poor participation in exercise training. Attractive individualized exercise programs that will increase adherence and result in optimal maternal and offspring benefits are needed. However, as women with GDM have a unique physiology, more attention is required during exercise prescription. This review (i) summarizes the cardiovascular and metabolic adaptations due to pregnancy and outlines the mechanisms through which exercise can improve glycemic control and overall health in insulin resistance states, (ii) presents the pathophysiological alterations induced by GDM that affect exercise responses, and (iii) highlights cardinal points of an exercise program for women with GDM.

Vascular endothelial damage in COPD: current functional assessment methods and future perspectives.

Introduction: Cardiovascular disease is a major cause of death in chronic obstructive pulmonary disease (COPD), but the relationship between these two entities is not fully understood; smoking, inflammation, arterial stiffness and endothelial dysfunction are significant determinants. Endothelial dysfunction is not only associated with cardiovascular disease, but also with COPD severity.Areas covered: Several functional methods have been developed to evaluate endothelial function in healthy and diseased individuals; from the invasive angiography of epicardial coronary arteries and Venous-Occlusion-Plethysmography, to more modern, noninvasive approaches such as Flow-Mediated-Dilatation, Peripheral-Arterial-Tonometry and Near-Infrared-Spectroscopy, all these methods have boosted clinical research in this field. In this context, this narrative review, which included articles published in PubMed and Scopus up to 25-November-2020, summarizes available functional methods for endothelial damage assessment in COPD and discusses existing evidence on their associations with comorbidities and outcomes in this population.Expert opinion: Accumulated evidence suggests that endothelial dysfunction occurs in early stages of CΟPD and worsens with pulmonary obstruction severity and during acute exacerbations. Novel methods evaluating endothelial function offer a detailed, real-time assessment of different parameters related to vascular function and should be increasingly used to shed more light on the role of endothelial damage on cardiovascular and COPD progression.