Search Results (18)

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group (n = 10), characterized by an increase in PVR with exertion, and a static PVR group (n = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, p < 0.05), resting PVR (−1.04 WU, p < 0.05), resting mean pulmonary arterial pressure (mPAP) (−5.8 mmHg, p < 0.05), exercise PVR (−1.7 WU, p < 0.05), exercise mPAP (−13 mmHg, p < 0.05), and estimated right ventricular systolic pressure (−9.2 mmHg, p < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil. Full article

Objective: To investigate whether the regular administration of blueberry extract and low-intensity resistance exercise training (RT), either alone or in combination, during the development of monocrotaline (MCT)-induced severe pulmonary arterial hypertension (PAH) in rats protect the left ventricle (LV) from redox dysregulation and pathological remodeling. Methods: Groups of seven male Wistar rats were formed for the experiment: sedentary control; sedentary hypertensive; sedentary hypertensive blueberry; exercise hypertensive; and exercise hypertensive blueberry. PAH was experimentally induced through a single intraperitoneal administration of MCT at a dose of 60 mg/kg. One day after injection, the blueberry groups started receiving a daily dose of blueberry extract (100 mg/kg) by gavage, while the exercise groups initiated a three-week program of RT (ladder climbing; 15 climbs carrying 60% of maximum load; one session/day; 5 times/week). Echocardiographic evaluations were conducted 23 days after injection, and the rats were euthanized the next day to harvest LV tissue. Results: Separately, blueberry extract and RT mitigated augments in pulmonary artery resistance, LV tissue redox dysregulation (i.e., increased PC levels) and detrimental remodeling (i.e., reduced inflammation), and reductions in ejection fraction (EF) and fractional shortening (FS) caused by PAH. The combination of treatments prevented reductions in EF and FS, along with the development of a D-shaped LV. Conclusions: blueberry extract and moderate-intensity resistance training administered during the development of MCT-induced severe PAH in rats prevented LV redox dysregulation and pathological remodeling, thereby preserving its function. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) affects the pulmonary vasculature and cardiac function. While its impact on target organs has been extensively studied, little is known about its effects on highly vascularized organs, such as those from the male reproductive system. This study explores the impact of PAH on testis and epididymis, evaluating the potential role of combined exercise training as a non-pharmacological strategy to mitigate alterations in these organs. Methods: Male Wistar rats (n = 8/group) were assigned to one of three groups: sedentary control, sedentary PAH, and exercise PAH. PAH was induced by monocrotaline administration (60 mg Kg⁻¹, i.p). The exercise PAH group underwent three weeks of combined physical training, including treadmill aerobic activity and resistance training on a ladder. Testis and epididymis were analyzed histologically, histomorphometrically, and biochemically for antioxidant activity, oxidative stress markers, and sperm parameters. Results: Sedentary PAH animals showed reductions in body and epididymis weight, normal seminiferous tubule percentage, and testicular morphometric parameters. These changes led to disorganized seminiferous tubules and compromised sperm production and sperm count in the testis and epididymis. Combined physical training improved testicular morphometric alterations and increased sperm count in hypertensive animals. Conclusions: PAH negatively affects testicular structure and function, leading to low sperm production. Combined physical training mitigated these effects by preserving testicular architecture and improving reproductive parameters, though it appeared less effective for the epididymis. These findings suggest physical training as a potential therapeutic strategy to protect reproductive health in PAH. Full article

Pulmonary hypertension (PH) significantly impairs exercise capacity and the quality of life in patients, which is influenced by dysfunctions in multiple organ systems, including the right ventricle, lungs, and skeletal muscles. Recent research has identified metabolic reprogramming and mitochondrial dysfunction as contributing factors to reduced exercise tolerance in PH patients. In this study, we investigated the therapeutic potential of enhancing mitochondrial function through the activation of the mitochondrial deacetylase SIRT3, using SIRT3 activator Honokiol combined with the SIRT3 co-factor nicotinamide adenine dinucleotide (NAD), in a Sugen/Hypoxia-induced PH rat model. Our results show that Sugen/Hypoxia-induced PH significantly impairs RV, lung, and skeletal muscle function, leading to reduced exercise capacity. Treatment with Honokiol and NAD notably improved exercise endurance, primarily by restoring SIRT3 levels in skeletal muscles, reducing proteolysis and atrophy in the gastrocnemius, and enhancing mitochondrial complex I levels in the soleus. These effects were independent of changes in cardiopulmonary hemodynamics. We concluded that targeting skeletal muscle dysfunction may be a promising approach to improving exercise capacity and overall quality of life in PH patients. Full article

Background: Exercise stress echocardiography (ESE) is commonly employed in adults, but its applicability in pediatric populations remains to be clarified. Methods: A total of 309 consecutive children (C), with a mean age of 14.1 ± 2.6 years (range 6–17 years), underwent treadmill ESE starting in 2002. They were divided into two groups: Group I comprised 258 children, including 237 with symptoms related to exercise (such as chest pain, fatigue, lipothymia/syncope, or one aborted sudden death), 15 with electrocardiogram (ECG) abnormalities, and 6 with a positive ECG stress test showing ST changes. Group II consisted of 10 asymptomatic children whose parents requested routine screening, 11 with symptoms unrelated to exercise, 12 with a family history of sudden death, and 17 with known pathologies (including 10 with hypertrophic cardiomyopathy, 2 with aortic coarctation, and the remainder with various conditions, such as Cortriatriatum sinister, pulmonary stenosis, subaortic stenosis, bicuspid aortic valve, left ventricular hypertrophy related to arterial hypertension, and aortic switch operation). Regional wall motion abnormalities (RWMAs) and transvalvular or intraventricular (IVG) gradients were assessed using 2D and continuous-wave Doppler, respectively, in all cases. Results: The success rate was 100% (309/309). Stress-induced RWMAs were observed in two children. A significant IVG (>30 mmHg) was detected in 101 out of the 258 children (39%) in Group I, who presented with exercise-related symptoms, ECG abnormalities, or positive stress ECG. In Group I, the odds ratio (OR) of ESE reproducing the symptoms in children with IVG compared to those without IVG was 8.22 (95% CI: 4.84–13.99, p < 0.001). Conclusions: Treadmill ESE is both feasible and safe for pediatric populations. RWMAs demonstrated limited utility in our cohort of children, while IVG induced by exercise was frequently observed in symptomatic children. Full article

Sudden cardiac death (SCD) is rare among athletes. However, hypertrophic cardiomyopathy is the leading cause of SCD among those <35 years of age. Meanwhile, coronary artery disease (CAD) is the primary SCD cause among those ≥35 years of age. CAD-induced plaque ruptures are believed to be a significant cause of cardiovascular diseases in middle-aged individuals who participate in extreme long-distance running activities such as marathons. A total of 1970 articles related to EIH were identified using search terms. Out of these, 1946 studies were excluded for reasons such as arterial hypertension, exercise-induced pulmonary hypertension, the absence of exercise stress testing (EST), and a lack of relevance to EIH. The study analyzed 24 studies related to both long-distance runners with exercise-induced hypertension (EIH) and the general public. Among these, 11 studies were quasi-experimentally designed studies used in randomized controlled trials (RCTs) on long-distance runners with EIH. Additionally, 12 studies utilized cohort designs, and one study with a quasi-experimental design was conducted among the general population. Recent studies suggest that an imbalance between oxygen demand and supply due to ventricular hypertrophy may be the actual cause of cardiovascular disease, regardless of CAD. Exercising excessively over an extended period can reduce endothelial function and increase arterial stiffness, which in turn increases afterload and leads to an excessive increase in blood pressure during exercise. Exercise-induced hypertension (EIH), which increases the morbidity rate of resting hypertension and is a risk factor for cardio-cerebro-vascular diseases, is more prevalent in middle-aged long-distance runners than in runners from other age groups, and it increases the prevalence of critical arrhythmias, such as atrial fibrillation or ventricular arrhythmias. EIH is associated with angiotensin II activity, and angiotensin II receptor blockers show promising effects in middle-aged runners. Further, guidelines for preventing excessive participation in races and restricting exercise intensity and frequency would be useful. This review identifies EIH as a potential risk factor for cardiovascular diseases and describes how EIH induces SCD. Full article

Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >20 mm Hg, often presents with non-specific symptoms such as dyspnea and exercise intolerance, making it difficult to diagnose early before the onset of right heart dysfunction. Therefore, exercise testing can be of great utility for clinicians who are evaluating patients with an unclear etiology of exercise intolerance by helping identify the underlying mechanisms of their disease. The presence of PH is associated with adverse clinical outcomes, with distinct differences and patterns in the cardiovascular and ventilatory responses to exercise across various PH phenotypes. We discuss the role of exercise-invasive hemodynamic testing, cardiopulmonary exercise testing, and exercise stress echocardiography modalities across the spectrum of PH. Full article

Left ventricular (LV) valvular diseases, make up one of the most common etiologies for pulmonary hypertension (PH), and it is not well understood how and at which degree it affects prognosis. The aim of the present study was a comprehensive review of the pathophysiologic mechanism of PH in patients with LV valvular diseases and the prognostic value of baseline and post-intervention PH in patients undergoing interventional treatment. The pathophysiology of PH in patients with LV valvular diseases involves gradual elevation of left ventricular filling pressure and left atrial pressure, which are passively transmitted to the pulmonary circulation and raise pulmonary artery systolic pressure (PASP). A long-lasting exposure to elevated PASP progressively leads to initially functional and thereafter irreversible structural changes in the pulmonary vasculature, leading up to high pulmonary vascular resistance. Surgical treatment of severe LV valvular diseases is highly effective in patients without resting PH or those with exercise-induced PH (EIPH) before intervention. In the case of pre-operative PH, successful interventional therapy decreases PASP, but the post-operative cardiac and all-cause mortality remain higher compared to patients without pre-operative PH. Hence, it is of paramount importance to detect patients with severe LV valvulopathies before the development of PH, since they will get greater benefits from early intervention. Full article

Introduction: In stable patients with pulmonary arterial hypertension (PAH), pulmonary rehabilitation (PR) is an effective, safe and cost-effective non-pharmacological treatment. However, the effects of PR on vascular function have been poorly explored. This study aimed to compare the amounts of circulating progenitor cells (PCs) and endothelial microvesicles (EMVs) in patients with PAH before and after 8 weeks of endurance exercise training as markers of vascular competence. Methods: A prospective study of 10 consecutive patients with PAH that successfully finished a PR program (8 weeks) was carried out before and after this intervention. Levels of circulating PCs defined as CD34+CD45low progenitor cells and levels of EMVs (CD31+ CD42b-) were measured by flow cytometry. The ratio of PCs to EMVs was taken as a measure of the balance between endothelial damage and repair capacity. Results: All patients showed training-induced increases in endurance time (mean change 287 s). After PR, the number of PCs (CD34+CD45low/total lymphocytes) was increased (p < 0.05). In contrast, after training, the level of EMVs (CD31+ CD42b-/total EMVs) was reduced. The ratio of PCs to EMVs was significantly higher after training (p < 0.05). Conclusion: Our study shows, for the first time, that endurance exercise training in patients with stable PAH has a positive effect, promoting potential mechanisms of damage/repair in favor of repair. This effect could contribute to a positive hemodynamic and clinical response. Full article

Exercise-induced pulmonary hypertension EIPH has been defined as an increase in mean pulmonary arterial pressure (mPAP) during exercise in otherwise normal values at rest. EIPH reflects heart and/or lung dysfunction and may precede the development of manifest pulmonary hypertension (PH) in a proportion of patients. It is also associated with decreased life expectancy in patients with heart failure with reduced ejection fraction (HFrEF) or left ventricle (LV) valvular diseases. Diastolic dysfunction exacerbated during exercise relates to increased LV filling pressure and left atrial pressure (LAP). In this context backward, transmitted pressure alone or accompanied with backward blood flow promotes EIPH. The gold standard of EIPH assessment remains the right heart catheterization during exercise, which is an accurate but invasive method. Alternatively, non-invasive diagnostic modalities include exercise stress echocardiography (ESE) and cardiopulmonary exercise testing (CPET). Both diagnostic tests are performed under gradually increasing physical stress using treadmill and ergo-cycling protocols. Escalating workload during the exercise is analogous to the physiological response to real exercise. The results of the latter techniques show good correlation with invasive measurements, but they suffer from lack of validation and cut-off value determination. Although it is not officially recommended, there are accumulated data supporting the importance of EIPH diagnosis in the assessment of other mild/subclinical or probably fatal diseases in patients with latent PH or heart failure or LV valvular disease, respectively. Nevertheless, larger, prospective studies are required to ensure its role in clinical practice. Full article

Background and Aim: Exercise-induced pulmonary hypertension (ExPH) predicts clinical outcomes, such as all-cause mortality and cardiovascular (CV) hospitalizations, in patients with dyspnea on effort. We investigated its prognostic significance in human immunodeficiency virus (HIV)-affected patients. Methods: In 52 consecutive HIV patients with either low (n = 47) or intermediate probability (n = 5) of PH at rest, we evaluated—at time 0 and after 2 years—the prognostic determinants of CV risk, according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines. Patients were classified with or without ExPH at stress echocardiography (ESE) and cardiopulmonary exercise test (CPET). We then related ExPH at time 0 with clinical worsening (CV risk score increase >20% after 2 years). Results: Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET. This also occurred in patients with intermediate/high probability compared to those with low probability of ExPH at ESE. The former exhibited worse values of TAPSE and FAC (p < 0.001 and p = 0.01, respectively). A significantly higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p < 0.001), mPAP (p = 0.004) and higher TRV (p = 0.006), as well as higher right atrial area (p < 0.001) and indexed right atrial volume (p = 0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and the velocity-time integral at the level of the right ventricular outflow tract) was higher both in patients with ExPH and in those with intermediate/high probability of ExPH (p < 0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend (p = 0.137) towards clinical worsening compared to those with low probability of ExPH. No patients with low probability of ExPH had a >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p = 0.048 at CPET, p = 0.033 at ESE). Conclusions: The assessment of ExPH may predict a trend of increasing CV risk score over time. If confirmed at a longer follow-up, ExPH could contribute to better risk stratification in HIV patients. Full article

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials. Full article

Background and Aim: Pulmonary hypertension (PH) at rest can be preceded by the onset of exercise-induced PH (ExPH). We investigated its association with the cardiovascular (CV) risk score in patients with human immunodeficiency virus (HIV). Methods: In 46 consecutive patients with HIV with low (n = 43) or intermediate (n = 3) probability of resting PH, we evaluated the CV risk score based on prognostic determinants of CV risk. Diagnosis of ExPH was made by cardiopulmonary exercise test (CPET) and exercise stress echocardiogram (ESE). Results: Twenty-eight % (n = 13) of the enrolled patients had ExPH at both CPET and ESE, with good agreement between the two methods (Cohen’s kappa = 0.678). ExPH correlated directly with a higher CV score (p < 0.001). Patients with a higher CV score also had lower CD4+ T-cell counts (p = 0.001), a faster progression to acquired immunodeficiency syndrome (p < 0.001), a poor immunological response to antiretroviral therapy (p = 0.035), higher pulmonary vascular resistance (p = 0.003) and a higher right atrial area (p = 0.006). Conclusions: Isolated ExPH is associated with a high CV risk score in patients with HIV. Assessment of ExPH may better stratify CV risk in patients with HIV. Full article

Background and Aim: Isolated exercise-induced pulmonary hypertension (ExPH) associates with cardiovascular (CV) events in patients with left heart disease. We investigated its prognostic significance in scleroderma patients at risk for pulmonary arterial hypertension (PAH). Methods: In 26 consecutive scleroderma female patients with either low (n = 13) or intermediate probability (n = 13) of pulmonary hypertension (PH) at rest, we evaluated, both at time 0 and 1 year, prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-minute walking test and at cardiopulmonary exercise test; right atrial area; and pericardial effusion. We assigned a severity score 1–3 to each prognostic determinant, derived an overall CV risk score, and its 0–1 year change. Isolated ExPH during the cardiopulmonary exercise test (CPET) was defined as absence of PH at rest, reduced peak VO₂, VE/VCO₂ >30 at anaerobic threshold, reduced O₂ pulse, and ΔVO₂/ΔW <9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase >20% after 1 year). Results: ExPH was strongly associated with clinical worsening compared to patients without ExPH (p = 0.005). In patients without ExPH, none had > 20% increased CV risk score after 1 year. Conversely, about 50% of patients with ExPH had such an increase, suggesting a worsening of prognosis. Conclusions: Isolated ExPH associates with higher cardiovascular risk and thus clinical worsening in scleroderma patients. The assessment of ExPH by CPET can thus contribute to a better risk stratification and the planning of a more adequate follow-up. Full article

Pulmonary arterial hypertension (PAH) represents a chronic progressive disease characterized by high blood pressure in the pulmonary arteries leading to right heart failure. The disease has been a focus of medical research for many years due to its worse prognosis and limited treatment options. The aim of this study was to systematically assess the effects of different types of exercise interventions on PAH. Electronic databases were searched until July 2019. MEDLINE database was used as the predominant source for this paper. Studies with regards to chronic physical activity in adult PAH patients are compared on retrieving evidence on cellular, physiological, and psychological alterations in the PAH setting. Twenty human studies and 12 rat trials were identified. Amongst all studies, a total of 628 human subjects and 614 rats were examined. Regular physical activity affects the production of nitric oxygen and attenuates right ventricular hypertrophy. A combination of aerobic, anaerobic, and respiratory muscle training induces the strongest improvement in functional capacity indicated by an increase of 6 MWD and VO₂ peak. In human studies, an increase of quality of life was found. Exercise training has an overall positive effect on the physiological and psychological components of PAH. Consequently, PAH patients should be encouraged to take part in regular exercise training programs. Full article