High Pulmonary Resistance Research Articles

Development and Validation of a Nomogram of Persistent Pulmonary Hypertension in Adult Pretricuspid Shunts After Correction.

Pretricuspid shunts have been associated with poorer survival rates in patients with Eisenmenger syndrome compared with postricuspid shunts and complex lesions. However, the risk stratification for persistent pulmonary hypertension (PH) in this population remains uncertain. We retrospectively enrolled 103 patients with pretricuspid shunts with high total pulmonary resistance >4.5 Wood units (estimated pulmonary vascular resistance ≥3 Wood units). During a mean±SD follow-up of 20.95±24.84 months, 32 patients developed postoperative persistent PH after shunt correction. We identified 3 significant predictors of postoperative persistent PH, including mean pulmonary artery pressure after inhaled oxygen ≥40.5 mm Hg (odds ratio [OR], 7.78 [95% CI, 2.02-30.03]; P<0.01), total pulmonary resistance after inhaled oxygen ≥6.5 Wood units (estimated pulmonary vascular resistance ≥5 Wood units; OR, 12.23 [95% CI, 2.12-70.46]; P<0.01), and artery oxygen saturation at rest <95% (OR, 3.34 [95% CI, 1.07-10.44]; P=0.04). We established the prediction model with the C-statistics of 0.85 (95% CI, 0.77-0.93; P<0.01), and the C-statistic was 0.83 (95% CI, 0.80-0.86) after bootstrapping 10 000 times with a good performance of the nomogram calibration curve for predicting persistent PH. Our study presents a multivariable risk stratification model for persistent PH after shunt correction in adults with pretricuspid shunts. This model, based on 3 hemodynamic predictors after inhaled oxygen, may assist in identifying individuals at higher risk of persistent PH after shunt correction.

Pediatric Heart Transplantation in the Context of Severe Pulmonary Hypertension Secondary to Restrictive Cardiomyopathy—Case Report

The aim of this study is to analyze the feasibility of performing an isolated heart transplant in patients with severe pulmonary hypertension as a result of restrictive cardiomyopathy. The results present the clinical course from the diagnosis of restrictive cardiomyopathy at the age of 2 until the heart transplant at 8 years old. Initially, the patient was considered for multiorgan transplantation, heart and lungs, due to extremely high pulmonary resistance. However, due to the prolonged waiting period for a donor and the worsening condition of the child, a decision was made to perforate the atrial septum with the implantation of an atrial flow regulator system. After conducting control hemodynamic measurements, the qualification was changed to an isolated heart transplant, accepting the high operative risk associated with the still elevated pulmonary resistance index of 4.9 Wood units. This study describes the medical problems that occurred during postoperative treatment. The patient underwent an orthotopic heart transplant in her eighth year of life. Postsurgery, complications were observed, including generalized seizures and heart transplant rejection reaction. Immunosuppressive therapies were applied, and efforts were made to combat anemia and electrolyte disorders. While the cardiovascular system and heart parameters improved, there were some difficulties in controlling heart rhythm and stabilizing electrolyte levels.

228 Management and treatment of an hypertrophic cardiomyopathy phenotype

Abstract Methods and results We are presenting the case of a 75-year-old man who was received in our Cardiomyopathy unit in 1986 with echocardiography showing evidence of left ventricular concentric hypertrophy and a subsequent diagnosis of a sarcomeric hypertrophic cardiomyopathy. During the follow-up, a progressive increase in mid-ventricular pressure gradient was reported and increasing pulmonary arterial pressure, even though the patient was asymptomatic. In 2013, the patient was hospitalized after a resuscitated cardiac arrest due to VF. The coronary angiogram did not show any significant coronary obstructions. The echocardiography showed a systolic anterior motion (SAM) of the mitral valve causing a dynamic pressure gradient in the left ventricular outflow tract reaching 90 mmHg and pulmonary hypertension (PAPs 60 mmHg). A double-chamber ICD was implanted as a secondary prevention of SCD and after a discussion with the Heart-Team, a surgical myectomy with the Morrow technique was performed on the patient. A total of 16 grams of myocardium was removed from the basal interventricular septum, three II order chordae tendineae were dissected from the AML and a mitral valve repair was performed on the patient. The myocardium was reported to show the typical aspects of infiltration; for this reason, a wide genetic analysis was performed which led to the diagnosis of Anderson–Fabry disease (a hemizygous GLA mutation and a homozygous MYBPC3 mutation). Therefore, specific enzymatic therapy was started. The genetic analysis was extended to the patient’s relatives leading to the that the patient’s brother and daughter were both carriers of the mutation. Starting in 2019, the patient began to develop symptoms of cardiac failure (mainly dyspnoea). An echocardiographic investigation showed a moderate to severe aortic regurgitation, a moderate mitral regurgitation, moderate left ventricular dilation, and pulmonary hypertension. The patient’s case was submitted to the Heart-Team’s discussion: due to the patient’s age and clinical conditions, heart transplantation was rejected and medical therapy was decided to be the best option. In 2021 the patient presented with worsening of clinical conditions including dyspnoea during daily activities (NYHA III). An echographic investigation found severe mitral regurgitation with a dilated and hypokinetic LV (EF 30%). The patient was hospitalized for decompensated HF: the coronary angiography did not show CAD and the cardiac catheterization showed low cardiac output without high vascular pulmonary resistances. After the Heart-Team re-evaluation, we decided to perform a percutaneous correction of the mitral regurgitation and in July 2021 Mitraclip implantation was performed on the patient without peri- and post-procedural complications. At the 3-month evaluation the patient was in better clinical conditions with improvement in his functional status (NYHA II). This patient is now continuing outpatient follow-up and we are considering the possibility of a future transcatheter correction of aortic valve regurgitation. Conclusions we submitted this clinical report with the aim to show how, thanks to the development of increasingly advanced diagnostic and therapeutic tools, it is nowadays possible to manage these complex phenotypes and their complications.

Using a General Mathematical Model to Quantify the Fontan Paradox of Elevated Central Venous Pressure and Diminished Cardiac Output

A variety of serious complications often associated with Fontan procedure to palliate single ventricle physiology are related to elevated central venous pressure (CVP) and diminished cardiac output (CO). This “Fontan Paradox” is a fundamental challenge because some interventions benefit one of these variables at the cost of the other. Animal models employed to address the Fontan Paradox are limited, and the multiple mechanical properties affecting CVP and CO are difficult to measure, control, and scale to humans. Although complex mathematical models of the cardiovascular system have provided insights, the need to solve model equations numerically require that all parameter values are known a priori—results only apply to a subject characterized by a specific set of assumed parameter values. In contrast, it has been shown that the equations characterizing minimal closed-loop models can be solved algebraically, yielding algebraic formulas for hemodynamic variables in terms of mechanical properties of the heart and vasculature. Therefore, the purpose of the present work is to derive algebraic formulas for CVP and CO to address the Fontan Paradox. First, we utilized a modified minimal closed-loop model consisting of a single ventricle, arterial and venous vascular compartments, and systemic and pulmonary resistances. The end-diastolic pressure-volume relationship was linearized, and mean arterial pressure was assumed to be regulated by renal control of blood volume. Equations were solved algebraically for CVP, CO, and venous pressures. The resulting formulas for CVP and CO incorporate only five groups of parameters characterizing the 1) efficiency of heart-vascular interaction, 2) relative cardiac contractility, 3) relative pulmonary resistance, 4) theoretical stroke volume at zero ventricular pressure, and 5) theoretical CO at zero CVP. Of these, only mean arterial pressure (controlled by blood volume) and systemic resistance require a choice to be made of either rectifying CVP or CO. Furthermore, these general formulas indicate that altering blood volume or systemic resistance to treat low CO has a greater negative impact on CVP in subjects with diastolic dysfunction or high pulmonary resistance. The present work thus provides a novel tool for clinical investigators to explore the mechanical basis of the Fontan Paradox.

UNUSUAL CAUSE OF ANGINA: PULMONARY ARTERY TO CORONARY ARTERY FISTULA

SESSION TITLE: Fellows Cardiovascular Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Coronary artery anomalies include abnormalities of number, origin or course, termination, or structure of the coronary arteries. We present a rare case of an aberrant communication between right pulmonary arteries and left coronary artery presenting as an acute coronary syndrome. CASE PRESENTATION: A 52-year-old male with a past medical history of hyperlipidemia and hypertension presented to the emergency department with one day of chest pain and palpitations after being referred from his primary doctor’s office for EKG changes; showing deep T wave inversions in lead V1 - V4 with p-wave enlargement. He denied any other cardiac symptoms except for dyspnea on exertion. He stated that he had a similar episode a few weeks before but had not received medical care at that time. He was admitted for management of acute coronary syndrome and to monitor for arrhythmias. Cardiac enzymes were obtained and were found to be normal. Imaging included transthoracic echocardiography, which showed normal left ventricular ejection fraction, right ventricular dilation and systolic dysfunction, elevated pulmonary artery systolic pressure of 80-100 mmHg, and moderate tricuspid regurgitation. Computed tomographic pulmonary angiography (CTPA) was performed and showed rapid tapering of right lower lobe descending pulmonary artery indicative of chronic pulmonary embolism and mosaic attenuation in the pulmonary parenchyma. The patient underwent left and right-sided cardiac catheterization with nitric oxide testing which showed an anomalous branch from the proximal left coronary artery to multiple sites in the right pulmonary arteries. Administration of nitric oxide showed a minimal reduction in the peripheral vascular resistance, and the calculated ratio of pulmonary blood flow vs cardiac output of 1.27 was suggestive of high pulmonary artery resistance and pressure which was decreasing the left to right shunt. Cardiac CTA was performed to further characterize the anatomic anomaly which showed fistulization from the right pulmonary artery to the circumflex artery with extensive collaterals in the subcarinal region. DISCUSSION: We believe that pulmonary hypertension was secondary to this fistula and the resulting chronic pressure/volume pulmonary overload resulting in right heart dysfunction along with CTEPH. This patient was discharged after initial stabilization and was referred for surgical evaluation for pulmonary artery thrombectomy. He was treated with clot retrieval and Riociguat at an advanced pulmonary arterial hypertension center CONCLUSIONS: The vascular connection between the coronary artery and branches of pulmonary artery can cause angina due to admixture of deoxygenated blood in the coronary circulation. Conventional angiography or multidetector computed tomography examinations of the coronaries can detect such anomalies which can present as a complex clinical presentation of acute coronary syndrome. Reference #1: Lee CM, Leung TK, Wang HJ, Lee WH, Shen LK, Chen YY. Identification of a coronary-to-bronchial-artery communication with MDCT shows the diagnostic potential of this new technology: case report and review. J Thorac Imaging. 2007;22(3):274-276. doi:10.1097/RTI.0b013e31802f134d Reference #2: Battal B, Saglam M, Ors F, Akgun V, Dakak M. Aberrant right bronchial artery originating from right coronary artery - MDCT angiography findings. Br J Radiol. 2010;83(989):e101-e104. doi:10.1259/bjr/49596063 DISCLOSURES: No relevant relationships by Lillian Chow, source=Web Response No relevant relationships by Chetana Pendkar, source=Web Response

MSCs attenuate hypoxia induced pulmonary hypertension by activating P53 and NF-kB signaling pathway through TNFα secretion

Hypoxia could cause vascular smooth muscle hypertrophy, leading to high pulmonary circulation resistance, pulmonary artery (PA) pressure, even pulmonary arterial hypertension (PAH). Recent studies have demonstrated the ability of mesenchymal stem cell (MSC) to ameliorate PAH but the mechanism was controversial. In this study, we revealed that the growth rate of pulmonary artery smooth muscle cells (PASMCs) treated with hypoxia was significantly increased than normal and showed lower expression of potassium channels. However, cells co-cultured with MSC showed decreased proliferation capability and down-regulated expression of ion channel of PAMSCs. The protein array data showed that the changes of PAMSCs was substantially associated with a high level of tumor necrosis factor alpha (TNFα) secretion from MSC. We further demonstrated that TNFα rescued the cell behavior of PAMSCs through activating the expression of P53 and NF-kB and inducing cell cycle arrest by P21/CDK2/CDK4 downregulation. These findings suggested that MSCs could attenuate abnormal function of PAMSCs by TNFα secretion, which was more or less associated with the beneficial effects of MSC on improving PAH.

Exercise Responses to Metabolic Function on High Altitude Pulmonary Edema Susceptible Individuals

&lt;p&gt;The study was aimed to evaluate and compare resting and exercise induced metabolic responses between acclimatized high altitude pulmonary edema (HAPE) susceptible (HAPE-s) and HAPE resistance (HAPE-r) volunteers at sea level. A group of 14 Indian soldiers volunteered for this study, divided into two groups, (i) HAPE-s, with past history of HAPE [n&lt;sub&gt;1&lt;/sub&gt; = 7; age = 33.3 ± 4.5 (M ± SD)] and (ii) HAPE-r, with prior history of repeated exposure to high altitude and without suffering HAPE [n&lt;sub&gt;2&lt;/sub&gt; = 7; age = 31.9 ± 4.2 (M ± SD)]. Respiratory frequency (f&lt;sub&gt;R&lt;/sub&gt;), tidal volume (&lt;sub&gt;T&lt;/sub&gt;), minute ventilation (&lt;sub&gt;E&lt;/sub&gt;), oxygen consumption (O&lt;sub&gt;2&lt;/sub&gt;), carbon dioxide output (CO&lt;sub&gt;2&lt;/sub&gt;), heart rate (HR) and respiratory quotient (RQ) were recorded on all the volunteers during resting and exercise conditions. Ventilatory equivalent for oxygen (EqO&lt;sub&gt;2&lt;/sub&gt;) and oxygen pulse (O&lt;sub&gt;2&lt;/sub&gt;P) were calculated. Significant differences were observed between HAPE-s and HAPE-r volunteers in f&lt;sub&gt;Rrest &lt;/sub&gt;(25.3% higher), O&lt;sub&gt;2&lt;/sub&gt;P&lt;sub&gt;rest &lt;/sub&gt;(23.7% lower), &lt;sub&gt;Emax&lt;/sub&gt; (50.9% lower) (all P&amp;lt;0.05), f&lt;sub&gt;Rmax &lt;/sub&gt;(55.7% lower), O&lt;sub&gt;2max &lt;/sub&gt;(55.5% lower), O&lt;sub&gt;2&lt;/sub&gt;P&lt;sub&gt;max &lt;/sub&gt;(34.2% lower) (all P&amp;lt;0.01) and CO&lt;sub&gt;2max&lt;/sub&gt; (42.1% lower, P&amp;lt;0.001). Rest of the parameters did not show any significant differences between the study groups. The study revealed that resting and exercise induced metabolic responses of HAPE-r volunteers was better as compared to acclimatized HAPE-s volunteers at sea level.&lt;/p&gt;

Surgical Strategy Toward Biventricular Repair for Severe Ebstein Anomaly in Neonates and Infancy

Neonates with severe forms of Ebstein anomaly present a surgical challenge, and the Starnes operation as single ventricle palliation is highly advocated. Cone reconstruction for tricuspid valvuloplasty (TVP) has become a widely accepted technique, although very few cases of TVP have been reported in neonates. This report describes a surgical strategy for neonatal Ebstein anomaly, with an aim toward biventricular repair. Since 2007, 7 neonates or young infants with severe Ebstein anomalies have received TVP at the National Taiwan University Hospital, Taipei, Taiwan. The principle of cone reconstruction was applied with mobilization of all three leaflets and reattachment to the normal tricuspid annulus. The atrialized right ventricle was not plicated. In patients with pulmonary stenosis, the interatrial communication was not totally closed (n= 5), and a systemic-pulmonary shunt was added if needed (n= 3). All patients presented with intractable heartfailure or severe cyanosis requiring mechanical ventilation, or both. All patients had marked adherence of the anterior leaflet to the right ventricular free wall. Intracardiac anomalies including ventricular septal defect (n= 2) and tetralogy of Fallot (n= 1) were also repaired simultaneously. Six of the 7 patients (86%) survived. There were no late deaths or repeat TVPs for a median follow-up of 4.3 years (range, 0.8 to 9.9 years). Reconstruction of the tricuspid valve is an acceptable surgical strategy in patients with severe neonatal Ebstein anomaly. Fenestrated atrial septal defect and systemic-pulmonary shunt can help overcome anatomic pulmonary stenosis and high pulmonary resistance in the neonatal period. This surgical strategy has a good survival outcome and preserves the possibility of complete biventricular repair.

Prognosis in children with pulmonary arterial hypertension: 10-year single-centre experience.

Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary arterioles with an unfavourable prognosis. To evaluate survival and prognostic factors in patients with PAH diagnosed and treated at a single centre in the years 2004–2013. The study included 55 children (33 girls; 66%, 22 boys; 33%), with an average age 6.2 ± 6.0 years, with idiopathic PAH — n = 23 (42%), PAH associated with systemic-to-pulmonary shunts — n = 17 (31%), and PAH after corrective cardiac surgery — n = 15 (27%). Forty-seven of them (87%) were treated with advanced therapy. During the follow-up with an average time of 5.6 ± 4.7 years 15 (27.3%) children died. The one-, three-, five-, and ten-year survival was, respectively, 83.1%, 77.1%, 70.7%, and 65.2%. The analysis of the survival curves revealed a better prognosis in patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level < 605 pg/mL (p = 0.024) and a higher probability of survival of three and five years in children at baseline I/II World Health Organisation functional class (WHO-FC). The higher risk of death was associated with a higher pressure in the right atrium (HR 1.23, p < 0.01) and higher pulmonary resistance (HR 1.1, p < 0.01), whereas no history of syncope had a better prognosis (HR 0.31, p = 0.03). Survival in the study group was comparable to the currently published register data. Mortality risk factors were connected with the severity of the disease at diagnosis.

SUCCESSFUL MEDICATION THERAPY OF ACUTE RIGHT VENTRICLE INSUFFICIENCY IN RECIPIENT WITH SIGNIFICANT PULMONARY HYPERTENSION AFTER HEART TRANSPLANTATION

Acute right ventricular failure in the early period after orthotopic heart transplantation is a severe complication and can often lead to a fatal outcome. This is especially important in patients with high pulmonary arteries resistance. Drug therapy has shown effectiveness only for the treatment of primary pulmonary hypertension. Patient K., 23 years old with signifi cant pulmonary hypertension (mean pulmonary artery pressure of 60 mm Hg, PVR – 6 Wood units) underwent orthotopic heart transplantation. Acute right ventricular failure occurred at early postoperative period which required multicomponent inotropic support. In order to reduce resistance of the pulmonary circulation the patient received sildenafi l (daily dose 50 mg) in combination with inhaled Ventavis (5 mcg a dose every 3 hours) and receipt of Tracleer (bosentan) (at a dose of 125 mg per day). Complex drug therapy resulted in reduction of right ventricular failure, normalization of biochemical parameters. Invasive pulmonary artery pressure decreased to 30 mm Hg and pulmonary vascular resistance was 1.1 Wood units at the moment of discharge. We also revealed right ventricle end-diastolic volume reduction from 70 ml to 62 ml and ejection fraction of the right ventricle (RV EF) increased from 47,7% to 62% in 2 months. Our clinical observation demonstrates the high effi ciency of acute right heart failure complex therapy including inotropic agents in combination with drugs that reduce the pulmonary vascular resistance.

Advanced therapies in patients with congenital heart disease-related pulmonary arterial hypertension: results from a long-term, single center, real-world follow-up.

Pulmonary arterial hypertension (PAH) is a common finding in patients with congenital heart disease (CHD), and has relevant prognostic implications. The recent introduction of advanced therapies (AT) considerably improved the clinical outcome of these patients, but real-world data are still lacking. We aimed at reporting the results of a long-term follow-up of CHD patients with PAH undergoing AT, followed at a tertiary Center during the two last decades. The study population included a total of 34 patients with an established diagnosis of CHD-related PAH. In addition to conventional treatment, 97% of patients started AT during the follow-up. Over a median follow-up of 9 [3-31] years, 11 (32.4%) patients died: 7 of them were affected by Eisenmenger syndrome and the majority of patients were in NYHA class ≥3 at the time of death. Among the 23 patients who were alive at the last follow-up, the majority were in NYHA class I-II. Oxygen saturation and 6-min walking distance improved in all subjects within the first 6 months after starting of AT. One patient with ventricular septum defect and high pulmonary resistances was successfully treated with AT to lower resistances and underwent defect closure. A good clinical outcome was also observed in the subset (n = 8) with Down syndrome. The results of this real-world experience suggest that, despite a relatively high mortality rate mostly related to late commencement of AT, the clinical outcome of subjects with CHD-related PAH undergoing AT are characterized by a good quality of life and clinical improvement in most patients.

0381: Heart failure and mechanical circulatory support: experience of a “medico-surgical unit “

With the shortage of grafts, mechanical circulatory support has emerged as an alternative to heart transplantation. This activity requires a multidisciplinary team specialized in the treatment of heart failure. This is a single-center prospective cohort of patients under long-term intracorporeal and continuous-flow left assist device type HeartMate II, between january 2008 and january 2014. Thirty-four devices were implanted in 30 men (88.2%) and 4 women (11.8%) with a mean age of 57.8 years. It concerned ischemic cardiomyopathy in 25 cases (73.5%) and primitive dilation in 9 cases (26.5%). The objective was a « destination therapy » in 11 patients (32.4%) and a « bridge-to-transplant » in 23 patients (67.6%). The 30-day mortality was 4 cases (11.8%), there were 11 deaths (32.4%) with a 1-year survival of 89.5%. Right ventricular failure, defined by a use of inhaled nitrogen monoxide > 48 hours and/or inotropes >14 days, appeared in 14 cases (41.2%). Associated factors were: young age, high pulmonary arterial resistances and right pressures, increased bilirubin and cavitary dilation. The mean duration of intubation was 5 days and ICU stay of 13.2 days. Initial suites were marked by 6 surgical re-openings for bleeding (17.6%), 5 acute renal failures requiring dialysis (14.7%) and 10 acute respiratory distresses (29.4%). Follow-up was performed in a dedicated unit, with functional, ultrasound and rythmological assessment, dietary and psycho-social support, and finally therapeutic education. The main late complications included 4 strokes (11.8%), ischemic or haemorragic, and 9 driveline infections (26.5%). Two patients were transplanted, two others are on waiting list. Thanks to close collaboration between cardiologists and surgeons, the management of patients with en-stage heart failure has improved with our growing experience in the field of long-term assistance.

Novel techniques of mechanical circulatory support for the right heart and Fontan circulation

BackgroundCurrently available ventricular assist devices are designed primarily for use in patients with left sided heart failure. This study evaluated the efficacy of the Jarvik 2000 ventricular assist device (VAD) as a pulmonary pump to power a Fontan circuit in a large animal model. MethodsWithout the use of cardiopulmonary bypass, Fontan circulations were surgically created in 4 pigs (50kg) using synthetic grafts from the inferior and superior vena cavas to the main pulmonary artery. Subsequently, the VAD was implanted within the common Fontan graft to provide a pulmonary pump. Direct chamber pressures and epicardial Doppler images were taken during the various phases of the experiment. Heart rate, femoral artery blood pressure, oxygen saturation, and aortic flow rate were continuously recorded. The outflow cannula of the VAD was then partially banded by 50% and then 75% to mimic increased afterload. ResultsFontan and VAD implantation was successfully performed in all 4 animals. Arterial pressure and aortic flow decreased dramatically with institution of the Fontan but were restored to baseline upon activation of the VAD. The pressure within the systemic venous circulation rose precipitously with institution of the Fontan circulation and improved appropriately with activation of the VAD. Adequate perfusion was maintained during increased afterload. ConclusionsAn axial flow VAD can restore normal hemodynamics and cardiac output when used as a pulmonary pump in a Fontan circulation. A VAD can rescue a failing Fontan as a bridge to transplant or recovery, even in the setting of high pulmonary resistance.

N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats.

BackgroundThe outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function.MethodsSaline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis.ResultsThe treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71 ± 0.05 for MCT group to 0.50 ± 0.06 for MCT + NAC group, p < 0.05). Right ventricular function was also improved with NAC treatment associated with a significant decrease in cardiomyocyte hypertrophy (625 ± 69 vs. 439 ± 21 μm2 for MCT and MCT + NAC group respectively, p < 0.001) and heart fibrosis (14.1 ± 0.8 vs. 8.8 ± 0.1% for MCT and MCT + NAC group respectively, p < 0.001).ConclusionsThrough its immuno-modulatory and cardioprotective properties, NAC has beneficial effect on pulmonary vascular and right heart function in experimental PH.

Vasoactive mediators in congenital heart diseases with shunt lesions and pulmonary hypertension

Increased pulmonary flow in left-to-right shunt lesions and decreased pulmonary flow and hypoxia in right-to-left shunt lesions constitute the main cause of morbidity and mortality in congenital heart diseases. This study was planned to determine the relation of vasoactive mediators and pulmonary hypertension in congenital heart disease with shunt lesions. Materials and methods: Patients (31 females, 22 males; 5 months to 16 years old) were divided into 2 groups according to their shunt lesions (acyanotic, cyanotic), pulmonary artery mean pressure (below 30 mmHg: nonhypertensive, above 30 mmHg: hypertensive), and pulmonary resistance (below 2 U/m2: low, above 2 U/m2: high). The acyanotic group was further divided into subgroups based on pulmonary artery mean pressure values. Vascular endothelial growth factor, interleukin 6, interleukin 8, fibroblast growth factor, and endothelin levels were determined in systemic arterial, pulmonary artery, and venous blood samples. Results: All vascular endothelial growth factor levels were significantly elevated in the high pulmonary resistance group. Arterial and venous endothelin levels were significantly elevated in the cyanotic group and high pulmonary resistance group. Positive correlations were found between vascular endothelial growth factor and interleukin 6, interleukin 8, and pulmonary artery systolic pressures. Conclusion: Vascular endothelial growth factors play an important role in the development of irreversible pulmonary hypertension; therefore, evaluation of vascular endothelial growth factor levels could guide the management of treatment.

Anesthésie et hypertension artérielle pulmonaire chez l’enfant en chirurgie non cardiaque

Paediatric pulmonary arterial hypertension (PAH) is a challenge for the paediatric anaesthetist. Due to its high morbidity and mortality, support should be provided by a dedicated team. Understanding the pathophysiology of PAH allows performing an appropriate therapeutic approach. In case of high vascular pulmonary resistance, the main objectives of anaesthetic management are to maintain an optimal pulmonary flow and to avoid the decrease in systemic arterial pressure. Haemodynamic monitoring is essential to detect the onset of an acute PAH crisis but also to give direct information on the efficacy of treatment.

Impulse oscillometry may be of value in detecting early manifestations of COPD

Spirometry is used to diagnose chronic obstructive pulmonary disease (COPD). The Impulse oscillometry system (IOS) allows determination of respiratory impedance indices, which might be of potential value in early COPD, although previous experience is limited. We examined pulmonary resistance and reactance measured by IOS in subjects with or without self-reported chronic bronchitis or emphysema or COPD (Q+ or Q-) and subjects with or without COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (G+ or G-). From a previous population-based study 450 subjects were examined with spirometry and IOS and answered a questionnaire on respiratory symptoms and diseases. Seventy-seven subjects were Q+, of whom 34 also were G+. Q+/G- subjects (n = 43) reported respiratory symptoms more frequently (35-40% vs 8-14%) but had higher FEV(1) (100% vs 87%) than Q-/G+ subjects (n = 90), p < 0.05 for both comparisons. Q+ subjects had higher pulmonary resistance and lower pulmonary reactance than Q- subjects (p < 0.01 for all comparisons). The same pattern was seen both in G+ subjects ((Q+/Q-) R5 0.39/0.32, R5-R20 0.10/0.07, X5 0.13/0.09, AX 0.55/0.27, p < 0.05 for all) and G- subjects ((Q+/Q-) R5 0.35/0.29, R5-R20 0.08/0.06, X5 0.10/0.08, AX 0.31/0.19 p < 0.05 for all) except for R20 (adjusted for gender and age). Self-reported chronic bronchitis or emphysema or COPD was associated with higher pulmonary resistance and lower pulmonary reactance measured by IOS, both among subjects with and without COPD according to GOLD criteria. IOS may have the potential to detect pathology associated with COPD earlier than spirometry.

Heart failure in a patient with corrected transposition of the great arteries. When is biventricular pacing indicated?

This report presents a patient with complex congenitally corrected transposition of the great arteries (ccTGA) and concomitant ventricular septal defect (VSD), who developed symptomatic heart failure further aggravated after dual-chamber pacemaker implantation.The initial disqualification from surgery based on high vascular pulmonary resistance was verified in repeated catheterization. The oxygen test was positive, therefore the patient underwent surgical correction. Despite successful repair with the use of two prosthetic valves (mechanical and biological) and an intraventricular patch, the symptoms of heart failure persisted. In view of the prolonged QRS complex on the ECG and the signs of significant intraventricular mechanical dyssynchrony measured by Tissue Doppler Imaging (TDI), the patient was referred for cardiac resynchronization therapy (CRT). A biventricular pacemaker allowed a larger synchronicity of systemic RV systolic function and the improvement of the patient’s general condition.The case described indicates that optimal care in patients with ccTGA can require implementation of both surgical and electrophysiological methods of treatment.

Effects of inducible nitric oxide synthase inhibitors on asthma depending on administration schedule

The effectiveness of two inducible nitric oxide synthase (iNOS) inhibitors on allergic airway inflammation was investigated under different administration schedules. Rats sensitized to ovalbumin (OVA) were exposed to OVA for 3 consecutive days. Both iNOS inhibitors showed markedly different effects between two pretreatment schedules: pretreatment before each of three OVA exposures (S1) and before the third exposure alone (S2). S1 pretreatment resulted in higher pulmonary resistance than triple OVA alone. This potentiation was associated with increased eosinophil infiltration and malondialdehyde levels in the lungs, which were suppressed by superoxide dismutases (SODs) but not by methylprednisolone. However, the S2 administration of both iNOS inhibitors completely suppressed the airway response. Administration by schedule S1 completely suppressed plasma nitrite and nitrate levels, but that by S2 caused only a slight suppression. The triple OVA exposures resulted in the upregulation of iNOS in alveolar macrophages and arginase activity, Mn- and Cu/Zn-SOD expression, and nitrotyrosine and lipid peroxide deposition in the airway. However, inhibitors administered by schedule S1 suppressed this upregulation, but further potentiated nitrotyrosine, which in turn was inhibited by SOD. Although iNOS inhibitors may be beneficial for asthma, repeated administration may be detrimental because of extensive reduction of NO and downregulation of SOD.

Cardiac Catheterization Is Necessary Before Bidirectional Glenn and Fontan Procedures in Single Ventricle Physiology

There are significant mortality and morbidity in bidirectional Glenn (stage II) and Fontan (stage III) procedures for congenital heart diseases with single ventricle physiology. In order to minimize the mortality and morbidity, the presence or absence of hemodynamic and anatomical abnormalities, such as poor ventricular function, coarctation of the aorta, pulmonary artery distortion, high pulmonary resistance, and abnormal collateral vessels, should be evaluated. Echocardiography and magnetic resonance imaging (MRI) can visualize ventricular size and coarctation of the aorta but may fail to visualize pulmonary artery distortion. Furthermore, cardiac catheterization is needed to measure pulmonary resistance. If the pulmonary resistance is > 3 Wood units/m2 before stage II, the risk for the bidirectional Glenn operation may be high. Abnormal aortopulmonary collateral vessels may develop after the stage II procedure and echocardiography and MRI may not visualize these vessels. Coil embolization may be required to treat these vessels. In conclusion, cardiac catheterization is required to evaluate abnormalities, which may be treated by interventional catheterization, and to reduce mortality and morbidity of stage II and III procedures.