Pulmonary hypertension in children with chronic bronchopulmonary pathology: a pulmonologist’s perspective to the problem

The respiratory diseases are consistently ranked first in the morbidity pattern among children and adolescents in the Russian Federation. Registry data show that 10-12% of children with pulmonary hypertension have PH-associated chronic lung pathology. Pulmonary hypertension as a life-threatening complication of such chronic lung diseases as hypersensitive pneumonitis, bronchiectasis, bronchial asthma, etc. aggravates the severity of their clinical course and has a great impact on the outcome of the disease. The article summarizes modern data on pulmonary hypertension in children of various ages associated with chronic bronchopulmonary pathology. The issues of classification, pathogenetic mechanisms, criteria and modern methods of diagnosis and treatment, as well as prognosis are considered. The authors come to the conclusion that despite the in-depth study of the pathogenetic aspects of the development of pulmonary hypertension in chronic bronchopulmonary pathology in children, which has recently made it possible to shed light on the understanding of many of its aspects, it should be admitted that the problem as a whole is far from being resolved. Early detection and treatment of pulmonary hemodynamic pathology is extremely important to prevent the formation of cor pulmonale. Pulmonary hypertension, which complicates the chronic lung diseases, is still incurable and is associated with high mortality. Now, young patients with pulmonary hypertension are still often examined and treated using guidelines for adult patients. However, differences in etiology, clinical presentations and diagnostic capabilities require a special approach to studying this problem in children, which raises the question of the need to develop separate clinical guidelines for pediatric practice.

High Right Ventricular Afterload during Exercise in Patients with Pulmonary Arterial Hypertension

The right ventricle (RV) is more sensitive to an increase in afterload than the left ventricle (LV), and RV afterload during exercise increases more easily than LV afterload. Pulmonary arterial hypertension (PAH)-specific therapy has improved pulmonary hemodynamics at rest; however, the pulmonary hemodynamic response to exercise is still abnormal in most patients with PAH. In these patients, RV afterload during exercise could be higher, resulting in a greater increase in RV wall stress. Recently, an increasing number of studies have indicated the short-term efficacy of exercise training. However, considering the potential risk of promoting myocardial maladaptive remodeling, even low-intensity repetitive exercise training could lead to long-term clinical deterioration. Further studies investigating the long-term effects on the RV and pulmonary vasculature are warranted. Although the indications for exercise training for patients with PAH have been expanding, exercise training may be associated with various risks. Training programs along with risk stratification based on the pulmonary hemodynamic response to exercise may enhance the safety of patients with PAH.

Pulmonary hemodynamics in chronic obstructive pulmonary disease (Three decades of study in the Republic of Moldova)

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. COPD is frequently associated with comorbidities, the most common complication being pulmonary hypertension and subsequent right heart failure. The prevalence of pulmonary hypertension and the pathophysiological processes of its installation in patients with COPD remain insufficiently studied, although it is known that its share increases with the severity of COPD, and its rate has been reported ranging from 20% to 90%. in the article, the author summarizes the notorious international discoveries and local contributions in this field, elucidating the opportunities, challenges and perspectives of studying the problem. Multiple investigations conducted in the last three decades by local researchers have deepened the knowledge of the pathophysiology, clinic, diagnosis, treatment and prophylaxis of pulmonary hemodynamic and cardiac function disorders in patients with COPD. Further investigations in this area are needed.

Predictors of diuresis response to levosimendan administration in patients with acute heart failure

Funding Acknowledgements Type of funding sources: None. Levosimendan, a calcium sensitizer and potassium channel-opener, is appreciated for its effects on systemic and pulmonary hemodynamic and for the relief of symptoms in acute heart failure (AHF). Positive effects of levosimendan on renal function have been also described. The aim of the present analysis was to assess the predictors of the diuresis response to levosimendan administration in high risk acute heart failure patients. Methods. We analysed 34 consecutive patients admitted with high risk AHF to one centre and treated in intensive cardiac care unit. Levosimendan was administered on top of other treatment as a 24-hour infusion of 12.5 mg total dose except for 7 patients (1 patient - terminated earlier due to intolerance, 5 patients – 48h infusion, 1 patient - 72h infusion). Decision of levosimendan administration was based on clinical status and left to attending physician. Diuresis and diuretic dosage before (24 hours) and after levosimendan infusion (48 hours) were taken into account for the present study. Results. The AHF was primary of cardiac origin in all patients. In 6 (18%) it was due to recent acute myocardial infarction. In-hospital mortality was 24%. Median length of hospitalization was 26 days (range 6 to 107 days). Mean age of the patients was 66 ± 12 years, 25 (74%) were men. Mean INTERMACS score was 3.4 ± 1.4 with wet-cold clinical profile present in 13 (38%) of patients. Mean left ventricle ejection fraction (LVEF) was 27 ± 13%, mean NTproBNP was 17176 ± 12464 pg/ml, and mean eGFR 48 ± 22 ml/min/1.73m2. At the time of levosimendan administration patients had background treatment with catecholamines (mean number per patient 1.4 ± 1.1, range 0-3) and with diuretics (mean dosage of furosemide 167 ± 102 mg/24h, range 20-500). 48-hours diuresis after levosimendan administration varies from 950 to 11300 ml (mean 4307 ± 2418 ml). It was significantly lower in patients with cold-wet profile (2646 ± 1335 vs. 5335 ± 2381 ml in other clinical profiles, p = 0.0002). Additionally, 48-hour diuresis was negatively correlated with age (r=-0.46, p = 0.0062) and the number of background catecholamines (r=-0.47, p = 0.0047), and not significantly with the furosemide dosage (r=-0.28, p = 0.10) – figure. No association with diuresis was found for LVEF, NTproBNP, and eGFR. In multiple regression analysis (model R2 = 0.63, p = 0.0085) both older age (p = 0.026) and cold-wet profile (p = 0.0074) were significant predictors of poor diuresis after levosimendan administration. Conclusion. Older age and cold-wet profile were significant predictors of poor diuresis response to levosimendan administration in high risk acute heart failure patients. Although concomitant catecholamines and high diuretic dosage use cloud also be markers of non-responders to levosimendan in terms of diuresis. Abstract Figure

Pulmonary hemodaynamic in obesity

Background Higher prevalence of pulmonary hypertension exist in obesity subjects. Little known about pulmonary hemodynamics during exercise in obesity population. Purpose To assess and compare the response of pulmonary vascular resistance during exercise in obese subjects vs healthy controls. Methods Seventeen obesity subjects (gender: 25%men, age: 44±11 years, height: 1.7±0.1 m, weight: 111±17 kilogram, BMI: 38±4 kg/m2) were compared to twenty gender-, age-, height- and race-matched healthy control subjects (age: 46±12 years, height: 1.7±0.1 m, weight: 64±11 kilogram, BMI: 22±2 kg/m2). All subjects underwent an incremental exercise stress echocardiography with measurements of pulmonary artery pressure (PAP), cardiac output (CO), cardiac index (CI) and tricuspid annular plane systolic excursion (TAPSE) at rest and at increasing exercise intensities. Total pulmonary vascular resistance index (PVRi) was calculated as mean PAP/CI and right ventricular-arterial coupling as TAPSE/systolic PAP. Results The results are described in the table 1. Pulmonary hemodynamic was not different at rest between two groups, but lower at maximal exercise in obesity subjects. In obesity subjects, identical exercise level was associated with a higher mean PAP and PVRi, and a lower TAPSE/systolic PAP ratio. Conclusion While pulmonary hemodynamic seems preserved at rest in obesity patients, pulmonary vascular resistance is increased and right ventricular coupling is decreased, particularly at exercise. Funding Acknowledgement Type of funding source: None

Extended Renal Artery Denervation Is Associated with Artery Wall Lesions and Acute Systemic and Pulmonary Hemodynamic Changes: A Sham-Controlled Experimental Study

Objectives. We sought to assess acute changes in systemic and pulmonary hemodynamics and microscopic artery lesions following extended renal artery denervation (RDN). Background. RDN has been proposed to reduce sympathetic nervous system hyperactivation. Although the effects of RDN on systemic circulation and overall sympathetic activity have been studied, data on the impact of RDN on pulmonary hemodynamics is lacking. Methods. The study comprised 13 normotensive Landrace pigs. After randomization, 7 animals were allocated to the group of bilateral RDN and 6 animals to the group of a sham procedure (SHAM). Hemodynamic measures, cannulation, and balloon-based occlusion of the renal arteries were performed in both groups. In the RDN group, radiofrequency ablation was performed in all available arteries and their segments. An autopsy study of the renal arteries was carried out in both groups. Results. The analysis was performed on 12 pigs (6 in either group) since pulmonary thromboembolism occurred in one case. A statistically significant drop in the mean diastolic pulmonary artery pressure (PAP) was detected in the RDN group when compared with the SHAM group (change by 13.0 ± 4.4 and 10.0 ± 3.0 mmHg , correspondingly; P = 0.04 ). In 5 out of 6 pigs in the RDN group, a significant decrease in systemic systolic blood pressure was found, when compared with baseline ( 98.8 ± 17.8 vs. 90.2 ± 12.6 mmHg , P = 0.04 ), and a lower mean pulmonary vascular resistance (PVR) ( 291.0 ± 77.4 vs. 228.5 ± 63.8 dyn ∗ sec ∗ c m − 5 , P = 0.03 ) after ablation was found. Artery dissections were found in both groups, with prevalence in animals after RDN. Conclusions. Extensive RDN leads to a rapid and significant decrease in PAP. In the majority of cases, RDN is associated with an acute lowering of systolic blood pressure and PVR. Extended RDN is associated with artery wall lesions and thrombus formation underdiagnosed by angiography.

Prostanoids in pediatric pulmonary hypertension: clinical response, time-to-effect, and dose–response

For pediatric pulmonary arterial hypertension (PAH) patients treated with parenteral prostanoids, response predictors, and the dose–effect relationship are ill defined. We determined the following: (1) which pulmonary vascular hemodynamic variable, after initiating prostanoids, best correlates with a significant clinical response; (2) the time interval after treatment when if no pulmonary hemodynamic improvement has occurred, none is ever likely to; and (3) the relationship between the prostanoid dose and its hemodynamic effects. This is a retrospective cohort study of 31 pediatric patients with Group 1 PAH treated with parenteral prostanoids. We found the following: (1) A fall in mean pulmonary arterial pressure (mPAP) of ≥25% predicted freedom from adverse clinical events with 80.7% accuracy and was also associated with improved functional class. (2) Thirty-three percent of patients who avoided an adverse clinical event demonstrated a ≥25% reduction in mPAP after 1 year of treatment, and 65% by 2 years. (3) Lower mPAP was seldom seen with doses of epoprostenol >60 ng/kg/min (100 ng/kg/min for treprostinil). Cardiac index was positively correlated with the dose of epoprostenol but not treprostinil; cardiac index >4 l/min/m2 was seen at modest as well as high doses. We conclude that a ≥25% fall in mPAP on prostanoids indicates a positive clinical response which, if validated in other studies, may be useful for patient management or clinical trials. Some patients take more than 2 years for this change. Exceptionally high doses were generally not more effective than lower, although we could not determine whether lower doses would have been as effective.