Pulmonary Vascular Bed Research Articles

Vascular access in a post-lung transplant patient on maintenance hemodialysis: a case report

BackgroundAn arteriovenous fistula (AVF) is the most common type of vascular access for hemodialysis. As it causes volume overload and sometimes increases pulmonary artery pressure, it is unsuitable for some patients. Herein, we describe a patient with acute kidney disease who required maintenance hemodialysis with vascular access other than an AVF owing to post-lung transplant pulmonary hypertension.Case presentationA 50-year-old man with interstitial pneumonia underwent living-donor lobar lung transplantation at our hospital. Weaning from venoarterial extracorporeal membrane oxygenation was achieved; however, the patient required mechanical ventilation owing to pulmonary hypertension. He developed acute kidney disease and required maintenance hemodialysis with sustainable vascular access. Although echocardiography showed a normal ejection fraction, we expected volume overload after arteriovenous access construction to worsen his pulmonary hypertension because of his inadequate pulmonary vascular bed. Therefore, a tunneled central vein catheter was implanted into the right femoral vein as a bridge, and superficialization of the right brachial artery was performed for long-term vascular access.ConclusionsAs this patient had sustained post-transplant pulmonary hypertension and small grafts, we avoided creating arteriovenous access because of concern over the aggravation of pulmonary hypertension. Evaluation of right heart function and pulmonary hypertension is important before arteriovenous access construction.

Resuscitation arterial waveform quantification and outcomes in pediatric bidirectional Glenn and Fontan patients.

Resuscitation with chest compressions and positive pressure ventilation in Bidirectional Glenn (BDG) or Fontan physiology may compromise passive venous return and accentuate neurologic injury. We hypothesized that arterial pressure and survival would be better in BDG than Fontan patients. Secondary analyses of the Pediatric Intensive Care Quality of CPR and Improving Outcomes from Pediatric Cardiac Arrest databases. P-values were considered significant if < 0.05. In total, 64 patients had either BDG (42/64, 66%) or Fontan (22/64, 34%) anatomy. Return of spontaneous circulation was achieved in 76% of BDG patients versus 59% of Fontan patients and survival with favorable neurologic outcome in 22/42 (52%) BDG versus 6/22 (27%) Fontan patients, p = 0.067. Twelve of 24 (50%) BDG and 2/7 (29%) Fontan patients who survived to discharge suffered new morbidity as defined by worsening Functional Status Score. More BDG patients achieved adequate DBP (≥25 mmHg for neonates and infants; ≥ 30 mmHg for children) than Fontan patients (21/23 (91%) vs. 5/11 (46%), p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after CPR, likely driven by inadequate diastolic blood pressure during resuscitation. One half of the BDG patients who survived to hospital discharge had new neurologic morbidity. Cardiac arrest in patients with congenital heart disease (CHD) may present challenges to resuscitation based on the unique cardiovascular physiology resulting from surgical palliation. Recent resuscitation guidelines for CHD patients highlight the lack of data surrounding these special patient populations.1 Univentricular heart disease is palliated by a series of cardiac surgeries that stepwise result in passive pulmonary perfusion from the systemic venous system directly to the pulmonary vascular bed. The bidirectional Glenn (BDG) palliation directly anastomoses the superior vena cava (SVC) to the pulmonary arterial system and leaves normal inferior vena cava (IVC) venous return to the heart.2 The Fontan palliation baffles IVC flow directly to the pulmonary vascular bed which relieves cyanosis due to right to left shunting, but requires systemic ventricular preload to be directly dependent upon pulmonary vascular resistance and intrathoracic pressures.3 IMPACT STATEMENT: Hemodynamic waveforms from 2 large prospective observational studies now allow for exploration of physiology during cardiopulmonary resuscitation for unique anatomy associated with single ventricle congenital heart disease. Fewer patients with Fontan physiology (46%) achieved an adequate diastolic blood pressure (defined as ≥ 25 mmHg for neonates and infants and ≥ 30 mmHg for children) than bidirectional Glenn patients during cardiopulmonary resuscitation (91%, p = 0.007). Only 27% of Fontan patients survived to hospital discharge with favorable neurologic outcome after cardiopulmonary resuscitation. Of the bidirectional Glenn patients who survived, 50% developed a new morbidity as quantified by the Functional Status Score.

Ventilator strategies in congenital diaphragmatic hernia

This review focuses on contemporary mechanical ventilator practices used in the initial management of neonates born with congenital diaphragmatic hernia (CDH). Both conventional and non-conventional ventilation modes in CDH are reviewed. Special emphasis is placed on the rationale for gentle ventilation and the current evidence-based clinical practice guidelines that are recommended for supporting these fragile infants. The interplay between CDH lung hypoplasia and other key cardiopulmonary elements of the disease, namely a reduced pulmonary vascular bed, abnormal pulmonary vascular remodeling, and left ventricular hypoplasia, are discussed. Finally, we provide insights into future avenues for mechanical ventilator research in CDH.

Tactics of Surgical Repair of Single Ventricle with Excessive Pulmonary Blood Flow and Obstruction of the Distal Arch of the Aorta in Newborns

Pulmonary artery stenosis with distal aortic arch reconstruction and coarctation of the aorta in newborns is an effective palliative procedure for single ventricle and high pulmonary hypertension on the way to total cavo-pulmonary anastomosis. The aim. To present a case of complex correction of a single ventricle of the heart with tricuspid valve atresia and high pulmonary hypertension, obstruction of the distal aortic arch and coarctation of the aorta, and a final effective Fontan procedure with a good long-term outcome. Case report. On December 15, 2011, a 9-day-old newborn patient M. was admitted for treatment at the Department of Cardiovascular Surgery of Odesa Regional Children’s Clinical Hospital with a diagnosis of: a single ventricle of the heart, transposition of the great arteries, tricuspid atresia, distal arch hypoplasia, coarctation of the aorta, patent ductus arteriosus, high pulmonary hypertension. The first stage of surgical treatment was carried out on December 19, 2011: main pulmonary artery banding, reconstruction of the distal arch of the aorta through modified Amato technique, closure of the patent ductus arteriosus, resection of the coarctation of the aorta and extended end-to-end aortoplasty. At the age of 1 year (December 27, 2012), the second stage was performed: bidirectional Glenn procedure with plastic surgery of bifurcation and right pulmonary artery branch. The third stage was performed at the age of 3 years 11 months (November 19, 2015): Fontan procedure with extracardiac conduit. Conclusions. Early elimination of pulmonary hypertension by pulmonary artery banding ensures the preservation of the pulmonary vascular bed with low resistance, which is a crucial condition for the effective final hemodynamic correction of the single ventricle of the heart – the Fontan procedure. In case of hypoplasia of the distal aortic arch with coarctation in newborns, one of the alternative approaches is the use of modified Amato technique avoiding artificial circulation.

Morphofunctional characteristics of the vessels of the small circle of blood circulation in those who died from severe and extremely severe forms of new coronavirus infection

BACKGROUND: An important feature of COVID-19 is the development of pronounced hypercoagulation with an increased risk of thrombotic damage to the pulmonary vascular bed, mainly the pulmonary arteries. Thrombosis of the pulmonary blood vessels causes a local violation of hemodynamics with the development of hyperemia, edema, which leads to a decrease in ventilation of the lung tissue area and serves as one of the causes of respiratory failure.&#x0D; AIM: This study aimed to conduct a morphological and morphometric analysis of the vascular bed of lung tissues in deceased with severe and extremely severe forms of new coronavirus infection who were on inpatient treatment in the period 2020-2022.&#x0D; METHODS: A pathomorphologic study of 129 autopsy cases with a confirmed diagnosis of a new coronavirus infection COVID-19 was performed. Morphometric analysis and statistical data processing of the pulmonary vascular system in histologic preparations stained with hematoxylin and eosin stain, orcein stain and Martius Scarlet Blue (MSB) stain was performed. The control group consisted of 14 patients who died of cardiovascular disease with bilateral focal confluent pneumonia.&#x0D; RESULTS: It was found that the proportion of thrombosed vessels in the lung tissues of the deceased was 27.6%. In 87.2% of cases, thrombosis develops in small arteries (lumen diameter 30-500 microns) and small veins (lumen diameter 40-500 microns). The vascular-functional indices of Kernogan and Vogenworth were statistically significantly increased in small arteries and small veins of the 4th order (p=0.001), small arteries (p=0.001) and small veins of the 5th order (p=0.014) compared with the control group.&#x0D; CONCLUSION: Diffuse involvement of small caliber blood vessels in the pathological process reflects the severity of specific hemocoagulopathic disorders in the lung tissue. Such disorders lead to the development of ventilation-perfusion disorders and entail an increase in right ventricular failure.

Pulmonary CT perfusion robustly measures cardiac output in the context of multilevel pulmonary occlusion: a porcine study

BackgroundTo validate pulmonary computed tomography (CT) perfusion in a porcine model by invasive monitoring of cardiac output (CO) using thermodilution method.MethodsAnimals were studied at a single center, using a Swan-Ganz catheter for invasive CO monitoring as a reference. Fifteen pigs were included. Contrast-enhanced CT perfusion of the descending aorta and right and left pulmonary artery was performed. For variation purposes, a balloon catheter was inserted to block the contralateral pulmonary vascular bed; additionally, two increased CO settings were created by intravenous administration of catecholamines. Finally, stepwise capillary occlusion was performed by intrapulmonary arterial injection of 75-μm microspheres in four stages. A semiautomatic selection of AFs and a recirculation-aware tracer-kinetics model to extract the first-pass of AFs, estimating blood flow with the Stewart-Hamilton method, was implemented. Linear mixed models (LMM) were developed to calibrate blood flow calculations accounting with individual- and cohort-level effects.ResultsNine of 15 pigs had complete datasets. Strong correlations were observed between calibrated pulmonary (0.73, 95% confidence interval [CI] 0.6–0.82) and aortic blood flow measurements (0.82, 95% CI, 0.73–0.88) and the reference as well as agreements (± 2.24 L/min and ± 1.86 L/min, respectively) comparable to the state of the art, on a relatively wide range of right ventricle-CO measurements.ConclusionsCT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by referencing the invasive CO.Relevance statementPossible clinical applications of CT perfusion for measuring CO could be in acute pulmonary thromboembolism or to assess right ventricular function to show impairment or mismatch to the left ventricle.Key points• CT perfusion measures flow in vessels.• CT perfusion measures cumulative cardiac output in the aorta and pulmonary vessels.• CT perfusion validly measures CO using LMMs at both individual and cohort levels, as demonstrated by using the invasive CO as a reference standard.Graphical

The place of tadalafil in the treatment of PAH in the light of new clinical guidelines of the Eurasian Association of Cardiologists

Pulmonaryarterialhypertension(PAH)isalife-threateningcardiovascular disease that is characterized by a marked increase in pulmonary vascular resistance and pulmonary artery pressure due to obstructive remodeling of the pulmonary vascular bed with the development of right ventricular heart failure as a cause of premature mortality. Impaired synthesis and reduced bioavailability of nitric oxide is one of the key pathophysiological mechanisms of the development and progression of the disease. The review paper presents key data from the evidence base on the clinical use of tadalafil, a phosphodiesterase type 5 inhibitor (PDE5), which in August 2023 approved by the Pharmaceutical Committee of the Russian Ministry of Health for the indication – treatment of patients with PAH. Tadacardil from Canonpharma Production is the first and only drug in Russian practice today with the active substance tadalafil with the registered indication “PAH”, approved in the Eurasian Guidelines for the diagnosis and treatment of pulmonary hypertension 2023 and available on the territory of the Russian Federation and the EAEU. Tadacardil is indicated for use in adult patients with PAH functional class II and III according to the WHO classification to increase exercise tolerance. The efficacy of tadalafil has been shown in idiopathic PAH and PAH associated with connective tissue diseases. The recommended dose is 40 mg (2 tablets of 20 mg) once a day. The paper describes the mechanism of action and pharmacological effects of PDE5 inhibitors, features of the pharmacokinetics of tadalafil in comparison with other drugs of the class. The advantages of Tadacardil from Canonpharma Production are the proven effecacy of use in patients with PAH, ease of use due to a single dose of 2 tablets of 20 mg once a day in a standard dose; good tolerability and favorable safety profile; proven bioequivalence to the reference drug. In light of the new Eurasian recommendations for the diagnosis and treatment of PH, tadalafil has a wide field for clinical use, which will improve the treatment options for patients with PAH both in mono- and combination therapy.

Novel echocardiographic parameters in pulmonary hypertension assessment and the relationship between echocardiography and 6-minute walking test.

Pulmonary artery stiffness (PAS) has been shown to be related to pulmonary artery pressure in patients with pulmonary artery hypertension (PAH). The aim of this study was to determine the correlation between functional capacity and echocardiographic indices of PAS in patients with PAH. This cross-sectional study was performed on patients with PAH who were confirmed by right heart catheterization and referred to Imam Reza PAH clinic for routine follow-up between November 2019 and January 2020. All patients underwent echocardiography and the maximum Doppler frequency shift, pulmonary acceleration time, peak velocity of the pulmonary flow, and velocity time integral, as well as PAS, were measured. All patients performed a 6-minute walk test. Fifty patients with a mean age of 41.90 ± 14.73 years old participated in this study. The majority of the patients were female (74%). The most common cause of PAH was idiopathic (74%). There was a significant correlation between PAS and pulmonary artery systolic pressure (r = 0.302, P = .041), second pulmonary valve pulse Doppler velocity (V2) (r = -0.461, P = .003), time from onset of pulmonary flow ejection to V2/first pulmonary valve pulse Doppler velocity (r = -0.311, P = .037) and Z3 ratio (r = -0.346, P = .023). There was no significant correlation between PAS and 6-minute walk test, pulmonary vascular resistance, and tricuspid annular plane systolic excursion (P > .05). There was a significant correlation between V2 and pulmonary vascular resistance (r = 0.359, P = .049). PAS and first pulmonary valve pulse Doppler velocity are simple, noninvasive, available tools for the evaluation of pulmonary vascular beds and diagnosis of presymptomatic clinical status in patients with PAH.

Should we "eliminate" PDA shunt in preterm infants? A narrative review.

The patent ductus arteriosus frequently poses a significant morbidity in preterm infants, subjecting their immature pulmonary vascular bed to substantial volume overload. This, in turn, results in concurrent hypoperfusion to post-ductal organs, and subsequently alters cerebral blood flow. In addition, treatment has not demonstrated definitive improvements in patient outcomes. Currently, the optimal approach remains a subject of considerable debate with ongoing research controversy regarding the best approach. This article provides a comprehensive review of existing literature.

Giant Left Atrial Aneurysm In A Three Year Old

Background: The PA to the LA fistula is a rare cause of central cyanosis. Embryologically, incomplete degeneration of septum between the arterial and venous plexus of the pulmonary vascular bed or defective capillary loop leads to formation of thin-walled sacs resulting in formation of pulmonary arteriovenous fistula. The more restrictive the fistula is, the more subtle is the extent of cyanosis and the less evident is the clinical presentation Case Description We describe the case of three years-old patient, who presented with unresolving pneumonia, that necessitated CT imaging. CT imaging revealed a mass in the posterior mediastinum that was communicating with the left atrium. Originally it was thought that this is an aneurysmal dilation of one of the pulmonary veins, that could have resulted from mitral regurge. Echocardiography showed an aneurysmal dilation of the left atrium, with an abnormal retrograde flow across the roof of the left atrium, pulmonary hypertension and mitral regurge were excluded. 3D CT angiographic reconstruction revealed the presence of a fistulous communication between the RPA and left atrium, this explains the low normal oxygen saturations of this patient due to mixing (90-92%) and the high hemoglobin concentration (160) due to chronic subclinical hypoxia. Conclusion and learning points Aneurysmal dilation of left atrium is commonly encountered with severe mitral regurge, rare causes such as PA to LA fistulae should be thought of especially if clinical or subclinical hypoxia or polycythemia is present.

Pulmonary hypertension in sickle cell disease

Sickle cell disease (SCD) is a complex genetic disorder that has long challenged both patients and healthcare professionals. One of its chronic and debilitating complications is pulmonary hypertension (PH). SCD-associated PH is often post-capillary, secondary to left heart disease. It can also sometimes be pre-capillary with multiple and often interrelated mechanisms including obstructive remodeling of the pulmonary vascular bed secondary to hemolysis, endothelial dysfunction, thrombosis, hypoxia, or associated risk factors like portal hypertension. Screening symptomatic patients with echocardiographic signs of PH is crucial to determine those who should undergo right heart catheterization, the cornerstone exam to diagnose and categorize patients with PH. The workup following the diagnosis relies on identifying the cause of PH to personalize treatment. Ongoing efforts are made to treat this complex condition, starting with treating the underlying disease with hydroxyurea or chronic blood exchange transfusion. Robust data on the efficacy of PAH-specific therapies are lacking in this specific population. Initiation of such therapies must be made by an expert center after a case-by-case assessment of the benefit-risk ratio according to the phenotype and the mechanisms involved in the development of PH. Efforts are also poured into studying the interventional and medical therapies used on chronic thromboembolic PH for patients presenting with a thrombotic form. The management of those patients requires a multidisciplinary approach, with conjoint efforts from PH and SCD specialists.

Pulmonary hypertension associated with diazoxide: the SUR1 paradox.

The ATP-sensitive potassium channels and their regulatory subunits, sulfonylurea receptor 1 (SUR1/Kir6.2) and SUR2/Kir6.1, contribute to the pathophysiology of pulmonary hypertension (PH). Loss-of-function pathogenic variants in the ABCC8 gene, which encodes for SUR1, have been associated with heritable pulmonary arterial hypertension. Conversely, activation of SUR1 and SUR2 leads to the relaxation of pulmonary arteries and reduces cell proliferation and migration. Diazoxide, a SUR1 activator, has been shown to alleviate experimental PH, suggesting its potential as a therapeutic option. However, there are paradoxical reports of diazoxide-induced PH in infants. This review explores the role of SUR1/2 in the pathophysiology of PH and the contradictory effects of diazoxide on the pulmonary vascular bed. Additionally, we conducted a comprehensive literature review of cases of diazoxide-associated PH and analysed data from the World Health Organization pharmacovigilance database (VigiBase). Significant disproportionality signals link diazoxide to PH, while no other SUR activators have been connected with pulmonary vascular disease. Diazoxide-associated PH seems to be dose-dependent and potentially related to acute effects on the pulmonary vascular bed. Further research is required to decipher the differing pulmonary vascular consequences of diazoxide in different age populations and experimental models.

Preeclampsia and risk of maternal pulmonary hypertension at high altitude in Bolivia.

Women with a history of preeclampsia (PE) have a greater risk of pulmonary arterial hypertension (PAH). In turn, pregnancy at high altitude is a risk factor for PE. However, whether women who develop PE during highland pregnancy are at risk of PAH before and after birth has not been investigated. We tested the hypothesis that during highland pregnancy, women who develop PE are at greater risk of PAH compared to women undergoing healthy highland pregnancies. The study was on 140 women in La Paz, Bolivia (3640m). Women undergoing healthy highland pregnancy were controls (C, n = 70; 29 ± 3.3 years old, mean±SD). Women diagnosed with PE were the experimental group (PE, n = 70, 31 ± 2 years old). Conventional (B- and M-mode, PW Doppler) and modern (pulsed wave tissue Doppler imaging) ultrasound were applied for cardiovascular íííassessment. Spirometry determined maternal lung function. Assessments occurred at 35 ± 4 weeks of pregnancy and 6 ± 0.3 weeks after birth. Relative to highland controls, highland PE women had enlarged right ventricular (RV) and right atrial chamber sizes, greater pulmonary artery dimensions and increased estimated RV contractility, pulmonary artery pressure and pulmonary vascular resistance. Highland PE women had lower values for peripheral oxygen saturation, forced expiratory flow and the bronchial permeability index. Differences remained 6 weeks after birth. Therefore, women who develop PE at high altitude are at greater risk of PAH before and long after birth. Hence, women with a history of PE at high altitude have an increased cardiovascular risk that transcends the systemic circulation to include the pulmonary vascular bed.

The First Local Experience of Use of Extracorporeal Circulatory Support with PROTEKDuo Dual-Lumen Cannula in a Patient with Acute Right Ventricular Failure

Acute right ventricular failure is a life-threatening condition that can occur as a result of a sudden increase in total pulmonary vascular resistance, in particular, as a result of pulmonary embolism. Most patients with thromboembolism are treated with thrombolytic therapy, but in some cases open thrombextraction is preferred. Removal of blood clots from the pulmonary vascular bed and cardiopulmonary bypass can lead to spasm of the pulmonary artery and to the elevation of total pulmonary resistance, which, in turn, increases the afterload on the right ventricle and can lead to a dramatic decrease in its mechanical function.&#x0D; The aim. The aim of this report is to present the first experience of using the right ventricular bypass with the PROTEKDuo cannula for the purpose of temporary mechanical support of the right ventricle.&#x0D; Case presentation. We studied a 63-year-old patient who underwent Studer technique for bladder adenocarcinoma. On the 14th day an acute massive pulmonary embolism occurred with a drop in hemodynamics and the presence of a floating clot on the right atrium. Thrombolysis carried significant risks due to possible bleeding and clot fragmentation in the right atrium with subsequent embolization of the pulmonary arteries. In these circumstances, open thrombectomy under hypothermic arrest was performed. Intraoperatively, the patient developed acute right ventricular failure resistant to all conservative therapy, therefore, right ventricular bypass was connected using PROTEKDuo, which made it possible to overcome the phenomena of acute right ventricular failure in the postoperative period.&#x0D; Conclusions. Our experience with right ventricular bypass using the PROTEKDuo dual-lumen cannula demonstrates another useful option for saving patients with isolated right ventricular failure.

Reconstruction of the pulmonary vascular bed at the stages of hemodynamic correction in patients with functionally single ventricle

The OBJECTIVE was to study the prevalence and nature of congenital and acquired anatomical features of the pulmonary vascular bed in patients with single ventricle and to evaluate their impact on staged hemodynamic correction.METHODS AND MATERIALS. The study was a retrospective cohort study based on the study of the experience of surgical treatment of patients with a single ventricle from 2005 to 2022. 208 patients, 95 females and 113 males met the inclusion criteria. Depending on the type of the first stage of correction, all patients were divided into three groups: 1 – patients after the Norwood operation (n=84), 2 – patients after the isolated systemic-to-pulmonary shunts (n=74), 3 – patients after pulmonary artery band or those who did not need the first stage of surgical treatment (n=50).RESULTS. From all patients who survived the Stage-I (158 patients), 47 (30 %) patients underwent 72 reconstructive interventions on the pulmonary arteries: 8 % – before Stage-II, 46 % – at Stage-II, 17 % – between stages II and III, 11 % – at Stage-III and 18 % – after Stage-III. When comparing freedom from stenosis of the pulmonary arteries, statistically significant differences were found between groups of patients (p=0.005), with the least freedom from stenosis in group 1 (after the Norwood operation) and the greatest freedom from stenosis in group 3 (after pulmonary artery band or without first stage of correction).CONCLUSIONS. Patients with a functionally single ventricle are at risk of developing pulmonary artery stenosis throughout the entire period of staged hemodynamic correction and after its completion. The identified narrowing needs immediate correction, since a long-term existing narrowing can lead to hypoplasia of the pulmonary vascular bed and become an obstacle to the timely Fontan completion. More extensive use of tomographic imaging techniques is recommended in order to fully assess the degree of narrowing.

Association of peak atrial longitudinal strain with right ventricular performance and short-term prognosis in patients with first acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial infarction remains a leading cause of mortality worldwide. The abrupt elevation of left ventricular filling pressures can be backwards transmitted to the left atrium and pulmonary vascular bed leading to pulmonary oedema. Peak atrial longitudinal strain (PALS) is a sensitive surrogate marker of left atrial performance. Its association with right ventricular (RV) impairment and its prognostic role in patients with Acute Coronary Syndrome (ACS) has not been comprehensively explored. Purpose This study sought to identify the impact of PALS in RV contractile function and pulmonary artery pressures in patients presenting with first ACS and investigate its association with in-hospital mortality. Methods Three-hundred consecutive patients (N=300, STEMI=194, Non-STEMI=106) with first ACS were prospectively enrolled (mean age 61.2±11.8 years, 26% females). All patients underwent a transthoracic echocardiographic assessment within 24 hours after revascularization. The association between PALS and conventional indices of left ventricular diastolic dysfunction with RV indices was assessed using Pearson correlation coefficient. Study outcome was in-hospital mortality. Univariable and multivariable Cox Regression analysis was performed to identify outcome predictors. To construct a multivariable model, univariately significant variables (P&amp;lt;0.005) were selected from 3 different categories (clinical variables, laboratory indices, echocardiographic indices). Due to the limited number of events, a maximum of 4 variables were introduced in the multivariable model. To further assess the incremental advantage of PALS and Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure (TAPSE/PASP) over Global Registry of Acute Coronary Event (GRACE) risk score the change in χ2 was assessed using the likelihood ratio test. Results PALS demonstrated a stronger correlation with RV contractile function and pulmonary artery pressure indices compared to mean E/e’ and E/A ratio (Table). A total of 23 (7.7%) patients died in-hospital after revascularization. In univariable Cox Regression analysis PALS was significantly associated with the outcome (HR=0.880, 95% CI=0.839–0.925, P&amp;lt;0.001). In the multivariable model after adjustment for GRACE risk score, LVEF, and white blood cells PALS retained independent association with the outcome (HR=0.828, 95% CI=0.698–0.983, P=0.031). A stepwise addition of PALS and RV/Pulmonary Artery coupling index (TAPSE/PASP) to GRACE risk score significantly improved the predictive value of the model (Figure). Conclusion PALS measured by transthoracic echocardiography within 24 hours of admission in patients with first ACS was a powerful predictor of in-hospital mortality. Progression of left ventricular damage to the left atrial and RV mechanics significantly worsens the risk of in-hospital mortality.

THE ROLE OF CARDIOVASCULAR MAGNETIC RESONANCE IMAGING IN NONINVASIVE ASSESSMENT OF PULMONARY HYPERTENSION SEVERITY

Objective: Pulmonary hypertension characterized by structural and mechanical changes in pulmonary vascular bed. Invasively calculated pulmonary artery (PA) stiffness indeces are associated with mortality in pulmonary hypertension (PH). CMRI-derived pulmonary artery distensibility (PAD) index reflects vascular remodeling in patients with pulmonary PH. The aim of the study was to evaluate the relationship between noninvasive PAD index and invasive PA stiffness indeces and basic determinants of PH severity. Design and method: We included 48 pts with PH (mean age 42.8± 14.7 yrs, m:f = 13:35): 27 idiopathic pulmonary arterial hypertension pts, 5 pts scleroderma PAH, 6 corrected congenital heart disease and 10 with inoperable CTPEH. All pts underwent 6-min walk test (6MWT), right heart catheterization (RHC), ECHO, CMRI, cardiopulmonary exercise testing (CPX). PA stiffness index and elastic modulus were calculated using data from RHC and CMRI. Pulmonary artery distensibility index (%) were derived from cross-sectional images of the main PA on cardiac magnetic resonance imgaging. Results: We revealed increased PA stiffness index 6.1 (4.6–10.2) and elastic modulus 424 mm Hg (254-678), decreased PAD index in PH pts 10% (9 –16.5). There was a significant negative correlation between PAD index and PA stiffness index (r = –0.90; p &lt; 0.0001), so we derived the formula to calculate the invasive PA stiffness using noninvasive PAD index: PA stiffness index = 102.4/ PAD index. There was also a negative correlation between PAD and elastic modulus (r = –0.91; p &lt; 0,0001). Patients with decreased PAD index &lt; 20 % had higher NT-proBNP level (1558 (738-4341) versus 306 (178-370); p&lt;0.05), also ECHO signs of RV systolic dysfunction:lower TAPSE (1.7 ±0.4 cm versus 2.0±0.4 cm; p = 0,04), tricuspid annular systolic velocity (10±2 versus 12±1 cm/sec; p = 0,007), global RV myocardial deformation (13±4% versus 21±5%; p = 0,001) and RV fractional area change ( 24±7%; p = 0,02) and reduced cardiac output which were determined by RHC (4.0 ± 1.1 versus 4.9 ±1.2 l/min; p &lt; 0,05). Conclusions: Noninvasive CMRI-derived PA distensibility index strongly correlated with PA stiffness indeces, and may be used for noninvasive assessment of PH severity.

CAR Selectively Enhances the Pulmonary Vasodilatory Effect of Fasudil in a Microsphere Model of Pulmonary Hypertension.

Despite the approval of several medications for pulmonary hypertension, morbidity and mortality are unacceptably high. Systemic hypotension may limit the use of pulmonary hypertension medications. This study aimed to assess whether the homing peptide CAR (CARSKNKDC) improves the vasodilatory selectivity of fasudil in the pulmonary circulation or systemic circulation in a porcine pulmonary hypertension model. Pulmonary hypertension (to approximately 2/3-3/4 systemic pressure levels) was induced by chronic and acute administration of microspheres in 3 micro Yucatan pigs (mean weight 19.9 kg, mean age 4.3 months). Fasudil (0.3 mg/kg) was administered without and with CAR (1.5 mg/kg), and the effect on aortic (Ao) and right ventricular (RV) pressure was recorded with indwelling catheters. Immediately after fasudil administration, there was a decrease in Ao pressure followed by prompt recovery to baseline. The RV pressure decrease was progressive and sustained. Fasudil alone resulted in a 12% decrease in RV pressure, whereas co-administration of CAR with fasudil resulted in a 22% decrease in RV pressure (p < 0.0001). Fasudil alone caused an average decrease of 34% in the RV/Ao pressure ratio, and fasudil + CAR caused an average decrease of 40% in the RV/Ao pressure ratio (p < 0.0001). The homing peptide CAR selectively enhanced the acute vasodilatory effects of fasudil on the pulmonary vascular bed in a porcine experimental model of pulmonary hypertension.

Sympathetic Denervation and Pharmacological Stimulation of Parasympathetic Nervous System Prevent Pulmonary Vascular Bed Remodeling in Rat Model of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5-2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.

Evaluation of pulmonary artery stiffness and right ventricle functions in polycythemia vera patients by transthoracic echocardiography.

Polycythemia vera (PV) is known to be a subgroup of chronic myeloproliferative neoplasms and is recognized as a cause of pulmonary hypertension (PH). Pulmonary artery stiffness (PAS) is a relatively new noninvasive echocardiographic index developed to evaluate the structural features and functions of the pulmonary vascular bed. In this study, we aimed to evaluate right ventricular (RV) functions and PAS in PV patients and healthy controls. A group of 65 consecutive PV patients and 40 healthy controls were included in the study. RV global longitudinal strain (RVGLS) and RV free wall longitudinal strain were (RVFwLS) evaluated using two-dimensional (2D) strain echocardiography. RV volume, systolic and diastolic functions were evaluated with three-dimensional (3D) echocardiography. PAS was calculated using the maximum frequency shift (MFS) and acceleration time of the pulmonary artery flow trace. PAS values were significantly higher in the PV group than in the control group (25.2 ± 5.2 vs. 18.2 ± 4.2, p < .001). We found that tricuspid annular plane systolic excursion (TAPSE) (p < .001), RV fractional area change (p < .001) and RV ejection fraction (p < .001) measurements evaluated by 3D echocardiography were significantly lower in the PV group. In our study, PAS values were higher in PV patients than in the healthy control group. Patients with PV may have subclinical RV dysfunction, and PAS value can be used in the early diagnosis of PH and RV dysfunction in this patient group.