Precapillary Pulmonary Arterial Hypertension Research Articles

Cardiac Manifestations of Wegener's Granulomatosis: A Case Report and Literature Review

Wegener's Granulomatosis is a rare systemic vasculitis. Lesions commonly occur in the upper airways, lungs, kidneys, and can also affect the skin, eyes, joints, peripheral nervous system, and the heart. Cardiac involvement is rare and can affect the endocardium, myocardium, or pericardium. Pulmonary arterial hypertension (PAH) has been rarely reported. We report the case of D.R., a 17-year-old without significant personal medical history, referred for the evaluation of new-onset exertional dyspnea. The clinical examination was normal except for an irregular heart rhythm with a pronounced pulmonary B2 sound. The ECG revealed atrial fibrillation (AF) with incomplete right bundle branch block (iRBBB). A chest X-ray showed cardiomegaly primarily affecting the atria without signs of pulmonary congestion. Precapillary PAH was suggested by echocardiography and confirmed through right heart catheterization. Routine blood tests were normal. Contrast-enhanced chest CT showed no evidence of pulmonary embolism or signs of pulmonary parenchymal involvement. Given the patient's young age, a specific vasculitis work-up was conducted, leading to a diagnosis of Wegener's Granulomatosis. Through this case report, we will present the cardiac and extracardiac manifestations of this vasculitis, as well as therapeutic management strategies.

Catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension: a randomized study

Atrial fibrillation (AF), typical atrial flutter (AFL), and other atrial tachycardias (ATs) are common in patients with pulmonary hypertension. Frequently, several supraventricular arrhythmias are successively observed in individual patients. We investigated the hypothesis of whether more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone results in superior clinical outcomes in patients with pulmonary arterial hypertension (PH) and supraventricular arrhythmias. Patients with combined post- and pre-capillary or isolated pre-capillary PH and supraventricular arrhythmia indicated to catheter ablation were enrolled in three centres and randomized 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence >30 s without antiarrhythmic drugs after the 3-month blanking period. A total of 77 patients (mean age 67 ± 10 years; 41 males) were enrolled. The presumable clinical arrhythmia was AF in 38 and AT in 36 patients, including typical AFL in 23 patients. During the median follow-up period of 13 (interquartile range: 12; 19) months, the primary endpoint occurred in 15 patients (42%) vs. 17 patients (45%) in the Extended vs. Limited ablation group (hazard ratio: 0.97, 95% confidence interval: 0.49-2.0). There was no excess of procedural complications and clinical follow-up events including an all-cause death in the Extended ablation group. Extensive ablation, compared with a limited approach, was not beneficial in terms of arrhythmia recurrence in patients with AF/AT and PH. ClinicalTrials.gov; NCT04053361.

Abstract 11386: Double Whammy Complicating Management of Pulmonary Hypertension

Introduction: When presented with challenging cardiac cases, in addition to obvious diagnoses, it is critical to maintain high level of suspicion about other subtle conditions. We describe one such case of pulmonary arterial hypertension (PAH) from severe mitral stenosis (MS) and another less obvious congenital cardiac condition that significantly impacted the clinical course. Case: 32-year-old immigrant male with known heart murmur presented with palpitations due to atrial fibrillation. His resting oxygen saturation was 95% in all extremities and he had no clubbing. He had pectus carinatum and scoliosis, prominent right ventricular lift, normal S1, loud S2, opening snap, rumbling diastolic murmur at the apex, and an ejection systolic murmur at the left upper sternal border. Echocardiogram revealed normal biventricular size and function, severely enlarged left atrium, rheumatic severe MS, moderate mitral regurgitation, a restrictive ventricular septal defect (VSD), and elevated right ventricular systolic pressure. Cardiac catheterization demonstrated mixed pre- and post-capillary PAH with mean pulmonary artery pressure of 80 mmHg, wedge pressure 30 mm Hg and pulmonary vascular resistance of 3.0 woods unit which was underestimated. Since pre-capillary component of the PAH could not be entirely explained by the small VSD, a congenital cardiac CT was performed revealing moderate sized patent ductus arteriosus (PDA). Further management decisions were complicated since MS was not amenable to percutaneous intervention and surgical risks were high given severe pre-capillary PAH- management of which with pulmonary vasodilators was itself high risk in the setting of severe MS and high wedge pressures. After optimal medical management, a multidisciplinary team carefully considered the risks and benefits of multiple interventions. Ultimately, the patient underwent surgical mitral valve replacement, fenestrated patch closure of the PDA, and then initiation of pulmonary vasodilators. The patient continues to do well on oral pulmonary vasodilator therapy 6 months after surgery. Conclusion: We describe an astute critical thought process of a multidisciplinary team utilized to manage a challenging case of mixed PAH from severe rheumatic MS and PDA.

Right ventricular strain related to pulmonary artery pressure predicts clinical outcome in patients with pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters. Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%. RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker.

Abstract 9832: Automated Electrocardiographic Detection of Pulmonary Hypertension Using Deep Learning

Introduction: Pulmonary hypertension (PH) is a progressive, life-threatening disease, often diagnosed late in its course. Treatments are available for some subtypes, including pulmonary arterial hypertension (PAH). Hypothesis: Deep learning applied to interpretation of electrocardiograms (ECGs) can detect PH and clinically important subtypes. Methods: Adults with either right heart catheterization (RHC) or an echocardiogram (echo) within 90 days before or after an ECG at the University of California, San Francisco from 2012 to 2019 were retrospectively identified and defined as PH (mean pulmonary artery pressure [mPAP] &gt;20 mmHg) or non-PH (mPAP ≤20 mmHg) by RHC or by echo, if RHC unavailable (peak tricuspid regurgitation velocity &gt;3.4 m/s or ≤2.8 m/s). A convolutional neural network (CNN) to detect PH was developed and tested using patients’ 12-lead ECG voltage data. Patients were divided into training, validation, and test sets in a ratio of 7:1:2. The ability of the CNN to detect pre-capillary PH (defined by RHC), PAH (defined as presence of any PAH-specific medication over the 3 months prior and 6 months following mPAP &gt;20 mmHg by RHC), and Group 3 PH (identified by Group 3-consistent International Classification of Disease codes in the 3 months before or after RHC) was also tested. CNN performance was assessed by calculating the area under the receiver operating characteristic curve (AUC), sensitivity, specificity and positive and negative predictive values. Results: A total of 24,470 patients and ECGs were identified (5,016 PH and 19,454 non-PH). CNN performance is shown in the Table . When the algorithm was applied to ECGs from PH patients up to 2 years before RHC or echo diagnosis, AUC was ≥0.79 to detect PH. Conclusions: A deep learning ECG algorithm can detect PH and performs well to identify subtypes of PH. The CNN can also detect PH using ECGs up to 2 years before RHC or echo diagnosis. This approach has the potential to reduce delays in the diagnosis and management of PH.

Diagnosis and management of lung involvement in systemic lupus erythematosus and Sjögren’s syndrome: a literature review

Lung involvement in systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) has extensively been outlined with a multiplicity of different manifestations. In SLE, the most frequent finding is pleural effusion, while in pSS, airway disease and parenchymal disorders prevail. In both cases, there is an increased risk of pre-capillary and post-capillary pulmonary arterial hypertension (PAH) and pulmonary venous thromboembolism (VTE). The risk of VTE is in part due to an increased thrombophilic status secondary to systemic inflammation or to the well-established association with antiphospholipid antibody syndrome (APS). The lung can also be the site of an organ-specific complication due to the aberrant pathologic immune-hyperactivation as occurs in the development of lymphoma or amyloidosis in pSS. Respiratory infections are a major issue to be addressed when approaching the differential diagnosis, and their exclusion is required to safely start an immunosuppressive therapy. Treatment strategy is mainly based on glucocorticoids (GCs) and immunosuppressants, with a variable response according to the primary pathologic process. Anticoagulation is recommended in case of VTE and multi-targeted treatment regimens including different drugs are the mainstay for PAH management. Antibiotics and respiratory physiotherapy can be considered relevant complement therapeutic measures. In this article, we reviewed lung manifestations in SLE and pSS with the aim to provide a comprehensive overview of their diagnosis and management to physicians taking care of patients with connective tissue diseases.

TRANSITIONING FROM TYVASO TO LIQ861 IN PULMONARY ARTERIAL HYPERTENSION: A CASE STUDY

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: LIQ861 (Liquidia Technologies) is an investigational, dry-powder formulation of treprostinil designed using PRINT® technology to enhance deep-lung drug deposition and achieve higher dose levels over current nebulized prostacyclin therapies for pulmonary arterial hypertension (PAH) in 1-2 breaths per capsule. INSPIRE (Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil) is a Phase 3, open-label, multicenter study of the long-term safety and tolerability of LIQ861. This case evaluates the clinical impact of transitioning treprostinil administration from a Tyvaso® nebulized device to LIQ861 with a dry-powder inhaler. METHODS: A 42-year-old male with ALK1 mutation PAH (functional class [FC] II) and hereditary hemorrhagic telangiectasia was referred to a PAH comprehensive care center for evaluation. Diagnostic hemodynamics were consistent with precapillary PAH. The patient did not tolerate sildenafil or tadalafil due to worsening nosebleeds or macitentan due to fluid retention, and could only tolerate inhaled treprostinil using a Tyvaso® device. He initially titrated to 6 breaths QID but then decreased to 3 breaths QID due to worsening cough. He remained stable in FC II, with an N-terminal pro-brain natriuretic peptide (NT-proBNP) of 30 pg/ml and a 6-minute walk distance (6MWD) of 542 m with no desaturation. He was considered stable to enroll in the INSPIRE study. Assessments at baseline included pulmonary artery pressure of 71/34 mm Hg, mean pulmonary artery pressure of 46 mm Hg, wedge pressure of 13 mm Hg, and pulmonary vascular resistance of 4.6 Wood units. The ESC/ERS risk score was assessed as low with a 6MWD of 558 m, FC II, and NT-proBNP of 62 pg/ml. The total score of the Minnesota Living with Heart Failure Quality of Life (MLWHF) questionnaire was 70. RESULTS: The patient initiated LIQ861 at 26.5 mcg QID. The dose was increased to 53 mcg QID after 4 weeks but reduced to 26.5 mcg QID after 1 week due to worsening cough. An increase to 53 mcg QID was attempted again at Week 8 but immediately decreased to 26.5 mcg QID due to severe cough and desaturation while on oxygen. The dose remained stable at 26.5 mcg QID through Month 12 with no notable adverse events. Assessments at Month 12 showed a risk score maintained as low, including FC II, a 6MWD of 569 m, and NT-proBNP of 124 pg/ml. The MLWHF total score was stable at 69. The patient remained stable on the same dose throughout the duration of the study (2 months), continued to tolerate the same dose a year later, and maintained his low ESC/ERS risk status. CONCLUSIONS: Transition from monotherapy with Tyvaso® to LIQ861 in this patient was well-tolerated and the patient remained stable during the study. CLINICAL IMPLICATIONS: In low-risk PAH patients monotherapy with inhaled prostacyclin LIQ861 is well-tolerated and maintains clinical status. DISCLOSURES: Speaker relationship with Actelion Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria Speaker relationship with United Therapeutics Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria speaker relationship with Bayer Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria My spouse/partner as a Speaker relationship with BTG Please note: $5001 - $20000 by Sandeep Sahay, source=Web Response, value=honoraria brief interview relationship with Liquidia Technologies Please note: $1-$1000 Added 05/26/2020 by Sandeep Sahay, source=Web Response, value=Honoraria

PULMONARY ARTERIAL HYPERTENSION AS A MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOUS

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Systemic Lupus Erythematosus (SLE) has long been associated with pulmonary manifestations such as pleural effusion, pulmonary hemorrhage, and pleuritis. Rarely, pulmonary arterial hypertension (PAH) develops as a consequence of SLE, usually presenting on average 3.2 years after diagnosis. We present a case of PAH as the initial manifestation of a patient who would later be diagnosed with SLE. CASE PRESENTATION: A 59 year old female with no medical history presented to the pulmonary clinic with dyspnea for two years. She stated that her dyspnea is present at rest but worsened with exertion. She had no other symptoms aside from generalized fatigue and denied cough, sputum production, chest pain, skin lesions or sores. Her symptoms had progressively worsened and previous treatment with prednisone 40mg po daily for a presumptive diagnosis of sarcoidosis had not led to any benefit. Previous biopsies for pulmonary nodules of undetermined significance did not render a diagnosis due to lack of available tissue. Normal spirometry and lung volumes were noted on pulmonary function testing. 6 minute walk test showed an SpO2 of 94% at the start, and 89% at completion and heart rate increased from 113 to 117 beats per minute. High resolution Chest CT was performed that showed no change in pulmonary nodules from previous. There was evidence of pulmonary artery enlargement. A right and left heart catheterization was performed revealing no coronary artery disease, but mean pulmonary artery pressure was elevated at 52mmHg, pulmonary capillary wedge pressure was 4mmHg and pulmonary vascular resistance was 15mmHg. She had adequate reactivity to adenosine. Rheumatologic evaluation later revealed positive ANA with a titer of 1:640, RF IgM, anti-cardiolipin IgM and anti-phospholipid IgM. Complements were decreased. The patient underwent a surgical wedge resection, and pathology revealed bronchial-associated lymphoid tissue. She was diagnosed with SLE as well as group 1 PAH, and initiated on hydroxychloroquine, ambrisentan and nifedipine with subjective and objective improvement in her clinical course. DISCUSSION: Pre-capillary PAH is the form closely linked with SLE-associated histopathological changes affecting small lung vessels. PAH is diagnosed by right heart catheterization revealing a mean pulmonary artery pressure >25mmHg, and can be defined as pre-capillary if the pulmonary capillary wedge pressure is <15mmHg. Bronchus-associated lymphoid tissues have been found in animal studies to be auto-immunologically active, and contribute to pulmonary vascular remodeling and pulmonary hypertension. CONCLUSIONS: This case highlights the close link between autoimmune conditions, small-vessel pulmonary vascular changes related to lymphoid aggregation and pulmonary hypertension. Targeted treatment for both group 1 PAH and SLE should be considered early in such patients, and initiated without delay. Reference #1: Colvin, Kelly L, et al. “Bronchus-Associated Lymphoid Tissue in Pulmonary Hypertension Produces Pathologic Autoantibodies.” American Journal of Respiratory and Critical Care Medicine, vol. 188, 2013, pp. 1126–1136. Reference #2: Perros, Frederic, et al. “Pulmonary Lymphoid Neogenesis in Idiopathic Pulmonary Arterial Hypertension.” American Journal of Respiratory and Critical Care Medicine, vol. 185, 2012, pp. 311-321. Reference #3: Badlam, Jessica B, et al. “Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities.” Therapeutic Advances in Chronic Disease, 8(2-3), pp. 47-64. DISCLOSURES: No relevant relationships by Alexandra Gastesi, source=Web Response No relevant relationships by Julia Ladna, source=Web Response No relevant relationships by Glenn Singer, source=Admin input No relevant relationships by Kenneth Wojnowski, source=Web Response

Легенева гіпертензія, асоційована із захворюванням лівих відділів серця (клінічний випадок)

У статті описується клінічний випадок легеневої гіпертензії, асоційованої із захворюванням лівих відділів серця (ЛГ-ЛВС) на тлі серцевої недостатності (СН) зі збереженою фракцією викиду (ФВ) у жінки віком 63 роки. Історія хвороби (артеріальна гіпертензія, фібриляція передсердь, цукровий діабет, тромбоемболія легеневих артерій, ожиріння, хронічне обструктивне захворювання легень) та дані звичайних інструментальних (відсутність тромбів в легеневих артеріях (ЛА), збільшені розміри правих відділів серця, які значно переважали над лівими, високий рівень розрахованого систолічного тиску в ЛА) і лабораторних (високий рівень мозкового натрійуретичного пептиду) методів дослідження не дозволили класифікувати групу легеневої гіпертензії (ЛГ). Лише застосування катетеризації правих відділів серця допомогло правильно визначитися з типом ЛГ – посткапілярна комбінована ЛГ-ЛВС. У статті також обговорюються останні рекомендації з діагностики та лікування СН зі збереженою ФВ і ЛГ-ЛВС. Розглядається запропонований на Європейському конгресі кардіологів у Парижі (2019) алгоритм визначення СН зі збереженою ФВ і можливість його використання в Україні. Окрім того, розбираються питання щодо морфологічних та патогенетичних відмінностей між прекапілярною легеневою артеріальною гіпертензією (ЛАГ) та посткапілярною ЛГ-ЛВС. Наводять­­ся аргументи щодо неможливості застосування специфічної терапії ЛАГ у пацієнтів із посткапілярною ЛГ. Обго­­ворюються дані щодо можливостей терапевтичних утручань у пацієнтів із СН зі збереженою ФВ. Окремий наголос зроблено на корекції факторів ризику та супутніх станів, зокрема за рахунок модифікації способу життя і немедикаментозного лікування.

The relationship between T-wave peak-to-end interval and hemodynamic parameters in patients with pulmonary arterial hypertension.

BackgroundT‐wave peak‐to‐end interval (TPEI) is a measure of repolarization dispersion on surface electrocardiogram (ECG). TPEI has been reported as a prognostic parameter with heart disorders. In this study, we aimed to evaluate the relationship between echocardiogram‐derived right heart parameters, right heart catheterization (RHC) measurements, and TPEI in patients with precapillary pulmonary arterial hypertension (PAH).MethodsThirty‐eight patients (29 females and 9 males, mean age of 54.9 ± 10.9 years) who had undergone RHC for a preliminary diagnosis of pulmonary hypertension (PH) were included in the study. We performed transthoracic echocardiography (TTE), and resting 12‐lead ECG was recorded before RHC. TPEI was measured from leads of V1‐V6, DII, DIII, and aVF, and these values are averaged to obtain the global TPEI.ResultsDuration of TPEI was significantly correlated with mean PAP, pulmonary vascular resistance (PVR), and cardiac index (CI). Longer TPEI was associated with higher N terminal probrain natriuretic peptide (NT pro‐BNP) level, lower 6‐min walk distance (6MWD), and lower tricuspid annular plane systolic excursion (TAPSE).ConclusionProlongation of TPEI could be a new predictor of adverse outcome in PAH and may provide additional prognostic information for patients with PAH.

Dysregulation of miR-135a-5p promotes the development of rat pulmonary arterial hypertension in vivo and in vitro.

Pulmonary arterial hypertension (PAH) is the most common form of pulmonary hypertension. Pulmonary arterial remodeling is closely related to the abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs), which leads to the thickening of the medial layer of muscular arteries and then results in the narrowing or occlusion of the precapillary arterioles and PAH. However, the mechanisms underlying the abnormal proliferation of PASMCs remain unclear. In this study, we established rat primary PAH models using monocrotaline (MCT) injection or hypoxic exposure, then investigated the expression patterns of seven miRNAs associated with multiple pathogenic pathways central to pulmonary hypertension, and further explored the roles and the possible mechanisms of miR-135a during the development of PAH. In the rat primary PAH models, we observed that the expression of miR-135a-5p in lungs was drastically decreased at the initial stage of PAH development after MCT administration or hypoxic exposure, but it increased by 12-fold or 10-fold at the later stage. In vitro study in PASMCs showed a similar pattern of miR-135a-5p expression, with downregulation at 6 h but upregulation at 18, 24, and 48 h after hypoxic exposure. Early, but not late, administration of a miR-135a-5p mimic inhibited hypoxia-induced proliferation of PASMCs. The protective role of early miR-135a-5p agomir in the PAH rat model further supported the hypothesis that the early decrease in the expression of miR-135a-5p contributes to the proliferation of PASMCs and development of PAH, as early administration of miR-135a-5p agomir (10 nM, i.v.) reversed the elevated mean pulmonary arterial pressure and pulmonary vascular remodeling in MCT-treated rats. We revealed that miR-135a-5p directly bound to the 3'-UTR sequence of rat transient receptor potential channel 1 (TRPC1) mRNA and decreased TRPC1 protein expression, thus inhibiting PASMC proliferation. Collectively, our data suggest that dysregulation of miR-135a-5p in PASMCs contributes to the abnormal proliferation of PASMCs and the pathogenesis of PAH. Increasing miR-135a-5p expression at the early stage of PAH is a potential new avenue to prevent PAH development.

Endothelial nitric oxide synthase genotype is associated with pulmonary hypertension severity in left heart failure patients.

The biological mechanisms behind the development of pulmonary hypertension in the setting of left heart failure (HF-PH), including combined pre- and post-capillary pulmonary hypertension (Cpc-PH), remains unclear. This study aimed to use candidate polymorphisms in nitric oxide synthase (NOS) genes to explore the role of NOS in HF-PH. DNA samples from 118 patients with HF-PH were genotyped for the NOS3 rs1799983 and NOS2 rs3730017 polymorphisms. A multiple regression model was used to compare hemodynamic measurements between genotype groups. Patients with the T/T genotype at rs1799983 possessed a nearly 10 mmHg increased transpulmonary gradient (TPG) compared to those with other genotypes (P = 0.006). This finding was replicated in an independent cohort of 94 HF-PH patients (P = 0.005). However, when tested in a cohort of 162 pre-capillary pulmonary arterial hypertension patients, no association was observed. In a combined analysis of both HF-PH cohorts, mean pulmonary artery pressure (mPAP), diastolic pulmonary gradient (DPG), and CpcPH status were also associated with rs1799983 genotype (P = 0.005, P = 0.03, and P = 0.02, respectively). In patients with HF-PH, the NOS3 rs1799983 polymorphism is associated with TPG, and potentially mPAP and DPG as well. These findings suggest that endothelial NOS (encoded by NOS3) may be involved in the pulmonary vascular remodeling observed in Cpc-PH and warrants further study.

RIGHT ATRIAL STRAIN BY SPECKLE-TRACKING ECHOCARDIOGRAPHY PREDICTS MORTALITY IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

Pulmonary arterial hypertension (PAH) is a devastating disease with variable progression. Prediction of risk remains challenging. We hypothesized that quantification of RA function by strain echocardiography has prognostic value. We studied 151 patients with pre-capillary primary PAH by speckle

Pulmonary hypertension subtypes associated with hereditary haemorrhagic telangiectasia: Haemodynamic profiles and survival probability.

BackgroundDifferent pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT).Methods and resultsWe conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH.ConclusionThis study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.

Loss of Small Vessel Volume Fraction as a Marker for Pulmonary Hypertension in COPD

SESSION TITLE: Pulmonary Hypertension SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Pulmonary hypertension develops in a subset of subjects with COPD, and when present is accompanied by increasing morbidity and mortality. Early diagnosis, prognostication and selection of subjects that may benefit from pulmonary vasodilatory therapy remains challenging. In prior work it has been shown that smokers show evidence of pulmonary vascular pruning in 3D reconstruction of the pulmonary vasculature. In this study we examine changes to the pulmonary vascular tree in patients with COPD and pre-capillary pulmonary hypertension proven by right heart catheterization (PAH). METHODS: A retrospective database query of subjects with diagnosis of COPD and PH possessing ct angiograms yielded approximately 200 subjects. From these, 21 subjects with non-elevated PCWP (<15mmHg), PH (elevated PVR and mPAP) and FEV1/FVC of less than 70% by PFT were selected. Of these, seven had 1mm cuts appropriate for reconstruction. A cohort of 15 subjects having undergone right heart catheterization, imaging and exercise testing with no evidence of cardiopulmonary disease was used as control subjects. Vascular reconstruction was performed as previously described. Small vessel volume fraction, defined as the vascular volume in small vessels (less than 5mm2 in cross-sectional area) divided by total vascular volume, was used to measure pruning. Association was tested using a two-tailed t-test, assuming unequal variances. RESULTS: Seven patients (Age 65.7±10.5) with COPD (FEV1pp 61.7±6.8%) were identified with precapillary PAH (mPAP 45±14.3mmHg; PVR 8.6±6WU; mPCWP 10.8±2.2mmHg, max 14mmHg). Fifteen subjects (Age 46 ; mPAP 15mmHg; PVR 1.1 WU; mPCWP 9mmHg) were used as controls. Subjects with PAH and COPD had significant proximal dilation and distal loss of vasculature, which was quantified by dividing the volume in small vessels (defined as those with cross sectional area of less than 5mm2 ) by the total volume of the vasculature detected. Small vessel volume fraction in the COPD group was lower (0.37 ± 0.12) as compared to control subjects (0.55 ±0.11) with a p-value of 0.006 for the comparison. CONCLUSIONS: The vascular pruning previously described in smokers is quantifiable from CT angiography in subjects with precapillary pulmonary arterial hypertension in the context of significant COPD burden. CLINICAL IMPLICATIONS: Measurement of pulmonary vascular morphology in smokers may be useful in detecting and subtyping the extent of pulmonary vascular disease in smokers. DISCLOSURE: The following authors have nothing to disclose: Farbod Rahaghi, Viviana Paz, James Ross, Raúl San José Estépar, George Washko, Franck Rahaghi Image processing techniques for reconstruction of the vasculature used are currently in exploratory stage and appropriate only for research purposes.

Portopulmonary hypertension in children: a rare but potentially lethal and under-recognized disease.

Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary arterial hypertension (PAH). Very little is known about this process in pediatric patients but prognosis is generally poor. We review our institutional experience and report on five patients with pediatric PoPH. The median age of PoPH diagnosis was six years and PAH was 14 years. PAH diagnosis was made by echocardiogram in all patients, four of whom also had cardiac catheterization. The median mean pulmonary artery pressure (mPAP) was 48.5 mmHg (interquartile range [IQR] = 46–60) with a median pulmonary vascular resistance index (PVRi) of 9 WU*M2 (IQR = 8–22). All were acute pulmonary vasodilator testing non-responsive. All patients received targeted therapies. Three of five patients (60%) died despite an evidence-based approach to care. Of those who died, timing from the PoPH diagnosis to death ranged from three days to three years. Based upon our limited experience, PoPH is a disorder with significant mortality in childhood and challenges in treatment. Future research, focused on screening and early targeted treatment strategies, may alter the current dismal prognosis for these children.

Clinical and hemodynamic profiles of elderly patients with pulmonary arterial hypertension: a single center, prospective study.

BackgroundsPulmonary arterial hypertension (PAH) was previously considered an illness that affects mostly the young, but now it is also increasingly recognized in the elderly. The aim of this study was to compare the features of elderly versus younger patients diagnosed with PAH, and to define the prognostic factors which affect their long-term survival.MethodsIn this prospective, single center study, the clinical, echocardiographic, hemodynamic characteristics, and the outcomes of younger (18–65 years) and elderly (≥ 65 years) patients with definitive diagnosis of precapillary PAH were compared.ResultsA total of 119 patients were analyzed in this study; 43 were elderly (mean age: 71.5 ± 5.5 years), while 76 were non-elderly (mean age 44.5 ± 15.2 years). During the mean follow-up duration of 26.8 ± 25.0 months, 43 deaths occurred, 17 of which were among the elderly group, with 28 among non-elderly group. Comparison of baseline parameters showed that 6 min walking distance, hemoglobin levels, pulmonary artery pressures and pulmonary vascular resistance were significantly lower; and estimated glomerular filtration rate, body mass index, E/e' and pulmonary capillary wedge pressure were significantly higher in the elderly group than in the younger group. Survival analysis demonstrated that the independent predictors of death were tricuspid plane annular systolic excursion (TAPSE; HR: 1.272, 95% CI: 1.079–1.499, P = 0.004) and uric acid (HR: 1.291, 95% CI: 1.042–1.600, P = 0.019) in the elderly group. In contrast, in the non-elderly group, higher brain natriuretic peptide (HR: 1.002, 95% CI: 1.001–1.004, P < 0.001) and higher right atrial pressure (HR: 1.128, 95% CI: 1.026–1.241, P = 0.013) values were the only parameters associated with mortality.ConclusionsOur data suggest that elderly PAH patients have a unique clinical and hemodynamic profile, with totally different prognostic markers compared to younger PAH patients.

Associations between Two Seemingly “Contradictory” Diseases: Hereditary Hemorrhagic Telangiectasia and Pulmonary Hypertension

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder characterized by mucocutaneous telangiectases and arteriovenous malformations (AVMs) predominantly in the liver, lung and brain. Pulmonary hypertension (PH) is a devastating disease of the pulmonary vasculature, which could lead to an increase in pulmonary vascular resistance and eventually cause right heart failure or death. Early epidemiological studies suggested that PH is a rare complication of HHT, however, accumulated evidences have showed that the prevalence of PH in HHT is evaluated up to 74 %. Post-capillary PH is the most common type of PH in HHT, which most often results from hepatic arteriovenous malformations due to a high cardiac output state. Another kind of HHT is less frequent and associated with genetic mutations in ENG or ACVRL1, those patients are more likely to develope into precapillary pulmonary arterial hypertension. PH is associated with a higher mortality rate and worse prognosis, which largely affects the overall life-expectation among those HHT patients. However, ENG and ACVRL1 mutations can only explain the onset of HHT and arteriovenous malformations, revealing the precise mechanisms of the co-occurrence of both diseases deserve further scientific attentions. Our review aims to illustrate the epidemiology, clinical features, molecular biological basis, pathological characteristics and potential treatment options for these two close associated but seemingly “contradictory” diseases.

Red Blood Cell Distribution Width, Hematology, and Serum Biochemistry in Dogs with Echocardiographically Estimated Precapillary and Postcapillary Pulmonary Arterial Hypertension.

BackgroundRed blood cell distribution width (RDW) is a quantitative measurement of anisocytosis. RDW has prognostic value in humans with different cardiovascular and systemic disorders, but few studies have investigated this biomarker in dogs.ObjectivesTo compare the RDW in dogs with precapillary and postcapillary pulmonary hypertension (PH) and a control population of dogs and to correlate RDW with demographic, echocardiographic, and laboratory variables.AnimalsOne hundred and twenty‐seven client‐owned dogs including 19 healthy dogs, 82 dogs with myxomatous mitral valve disease (50 dogs without PH and 32 dogs with postcapillary PH), and 26 dogs with precapillary PH.MethodsProspective study. Dogs were allocated to groups according to clinical and echocardiographic evaluation. RDW and selected laboratory and echocardiographic variables were compared among dog groups. Associations between RDW and demographic, laboratory, and echocardiographic variables were analyzed using correlation and multiple regression analysis.ResultsMedian RDW in dogs with precapillary PH (13.8%, interquartile range 13.2–14.9%) and postcapillary PH (13.7, 13.2–14.7%) was significantly increased compared to healthy dogs (13.3, 12.3–13.7%; P < .05 for both comparisons), but only dogs with severe PH had significantly increased RDW compared to dogs without PH (P < .05). Peak tricuspid regurgitation pressure gradient was significantly associated with increased RDW (rho = 0.263, P = .007). Serum urea concentration, hematocrit, age, and white blood cell number were significantly associated with RDW in the multivariate analysis.Conclusions and Clinical ImportanceUnderlying pathophysiologic processes associated with PH instead of severity of PH are likely responsible for increased RDW in dogs with PH.

Pulmonary Veno-Occlusive Disease as a Cause of Pulmonary Arterial Hypertension

Pulmonary veno-occlusive disease (PVOD) represents a rare form of precapillary pulmonary arterial hypertension. We present a young patient hospitalized with progressive dyspnea, with initial workup suggestive of pulmonary hypertension and unexplained noncardiogenic pulmonary edema. His subsequent clinical course was consistent with the diagnosis of PVOD.