Myocardial adaptation and exercise performance in patients with pulmonary arterial hypertension assessed with patient-specific computer simulations.

Myocardial function and exercise reserve are important determinants of outcome in pulmonary arterial hypertension (PAH) but are incompletely understood. For this study, we performed subject-specific computer simulations, based on invasive measurements and cardiac magnetic resonance imaging (CMR), to investigate whole circulation properties in PAH at rest and exercise and determinants of exercise reserve. CMR and right heart catheterization were performed in nine patients with idiopathic PAH, and CMR in 10 healthy controls. CMR during exercise was performed in seven patients with PAH. A full-circulation computer model was developed, and model parameters were optimized at the individual level. Patient-specific simulations were used to analyze the effect of right ventricular (RV) inotropic reserve on exercise performance. Simulations achieved a high consistency with observed data. RV contractile force was increased in patients with PAH (127.1 ± 28.7 kPa vs. 70.5 ± 14.5 kPa, P < 0.001), whereas left ventricular contractile force was reduced (107.5 ± 17.5 kPa vs. 133.9 ± 10.3 kPa, P = 0.002). During exercise, RV contractile force increased by 1.56 ± 0.17, P = 0.001. In silico experiments confirmed RV inotropic reserve as the important limiting factor for cardiac output. Subject-specific computer simulation of myocardial mechanics in PAH is feasible and can be used to evaluate myocardial performance. With this method, we demonstrate marked functional myocardial adaptation to PAH in the resting state, primarily composed of increased contractile force development by RV myofibers, and we show the negative impact of reduced RV inotropic reserve on cardiac output during exercise.NEW & NOTEWORTHY Computer simulations of the myocardial mechanics and hemodynamics of rest and exercise were performed in nine patients with pulmonary arterial hypertension and 10 control subjects, with the use of data from invasive catheterization and from cardiac magnetic resonance. This approach allowed a detailed analysis of myocardial adaptation to pulmonary arterial hypertension and showed how reduction in right ventricular inotropic reserve is the important limiting factor for an increase in cardiac output during exercise.

Distinct types of plexiform lesions identified by synchrotron-based phase-contrast micro-CT.

In pulmonary arterial hypertension, plexiform lesions are associated with severe arterial obstruction and right ventricular failure. Exploring their structure and position is crucial for understanding the interplay between hemodynamics and vascular remodeling. The aim of this research was to use synchrotron-based phase-contrast micro-CT to study the three-dimensional structure of plexiform lesions. Archived paraffin-embedded tissue samples from 14 patients with pulmonary arterial hypertension (13 idiopathic, 1 with known BMPR2-mutation) were imaged. Clinical data showed high-median PVR (12.5 WU) and mPAP (68 mmHg). Vascular lesions with more than 1 lumen were defined as plexiform. Prior radiopaque dye injection in some samples facilitated 3-D rendering. Four distinct types of plexiform lesions were identified: 1) localized within or derived from monopodial branches (supernumerary arteries), often with a connection to the vasa vasorum; 2) localized between pulmonary arteries and larger airways as a tortuous transformation of intrapulmonary bronchopulmonary anastomoses; 3) as spherical structures at unexpected abrupt ends of distal pulmonary arteries; and 4) as occluded pulmonary arteries with recanalization. By appearance and localization, types 1-2 potentially relieve pressure via the bronchial circulation, as pulmonary arteries in these patients were almost invariably occluded distally. In addition, types 1-3 were often surrounded by dilated thin-walled vessels, often connected to pulmonary veins, peribronchial vessels, or the vasa vasorum. Collaterals, bypassing completely occluded pulmonary arteries, were also observed to originate within plexiform lesions. In conclusion, synchrotron-based imaging revealed significant plexiform lesion heterogeneity, resulting in a novel classification. The four types likely have different effects on hemodynamics and disease progression.

Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH. METHODS: 519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing. RESULTS: 85% of the patients were female; the median age was 34[29-42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6-1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07-0.22], p < 0.01) and ΔPA compliance (Coefficient = -2.51, Beta = -0.43, 95% CI [-4.34-(-0.68)], p = 0.01) had the best performance predicting pVO2 (R2 = 0.66). CONCLUSIONS: In conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.

Peripheral microangiopathy in precapillary pulmonary hypertension: a nailfold video capillaroscopy prospective study.

BACKGROUND: Although pulmonary vascular bed has been the main subject of research for many years in pulmonary hypertension (PH), interest has recently started to divert towards the possibility of a co-existing peripheral microangiopathy. The aim of the current study was to investigate the presence of nailfold video-capillaroscopic (NVC) structural changes in patients with precapillary PH and to identify possible associations of NVC measurements with markers of disease severity. METHODS: Α prospective case-control study was performed in 28 consecutive patients with precapillary PH [14 with idiopathic pulmonary arterial hypertension (IPAH) and 14 with chronic thromboembolic pulmonary hypertension (CTEPH)] and 30 healthy controls. NVC quantitative and qualitative parameters were evaluated using Optilia Digital Capillaroscope. To ensure inter-observer repeatability capillaroscopic images were reviewed by two independent investigators. For multiple comparisons among continuous variables, one-way ANOVA or the Kruskal-Wallis test were used. Differences between the groups were tested with post-hoc analysis with adjustment for multiple comparisons (Bonferroni test). RESULTS: Both IPAH (71.4% were women, mean age 53.1 ± 13.4 years) and CTEPH (64.3% women, mean age 60.9 ± 14.4 years) groups presented reduced capillary density compared to healthy controls (8.4 ± 1.2 loops/mm and 8.0 ± 1.2 loops/mm vs. 9.7 ± 0.81 loops/mm, p < 0.001) and increased loop width (15.7 ± 3.9 µm and 15.8 ± 1.9 µm vs. 11.5 ± 2.3 µm, p < 0.001). More than half of patients with IPAH presented microhaemorrhages on capillary nailfold, while increased shape abnormalities in capillary morphology and more capillary thrombi per linear mm were detected in patients with CTEPH compared to patients with IPAH and healthy controls. All PH patients presented a non-specific NVC pattern compared to controls (p < 0.001). CONCLUSION: The findings of the study reveal a degree of significant peripheral microvascular alterations in patients with IPAH and CTEPH, suggesting a generalized impairment of peripheral microvasculature in pulmonary vascular disease.

Clinical heterogeneity of Pulmonary Arterial Hypertension associated with variants in TBX4.

BACKGROUND: The knowledge of hereditary predisposition has changed our understanding of Pulmonary Arterial Hypertension. Genetic testing has been widely extended and the application of Pulmonary Arterial Hypertension specific gene panels has allowed its inclusion in the diagnostic workup and increase the diagnostic ratio compared to the traditional sequencing techniques. This is particularly important in the differential diagnosis between Pulmonary Arterial Hypertension and Pulmonary Venoocclusive Disease. METHODS: Since November 2011, genetic testing is offered to all patients with idiopathic, hereditable and associated forms of Pulmonary Arterial Hypertension or Pulmonary Venoocclusive Disease included in the Spanish Registry of Pulmonary Arterial Hypertension. Herein, we present the clinical phenotype and prognosis of all Pulmonary Arterial Hypertension patients with disease-associated variants in TBX4. RESULTS: Out of 579 adults and 45 children, we found in eight patients from seven families, disease-causing associated variants in TBX4. All adult patients had a moderate-severe reduction in diffusion capacity. However, we observed a wide spectrum of clinical presentations, including Pulmonary Venoocclusive Disease suspicion, interstitial lung disease, pulmonary vascular abnormalities and congenital heart disease. CONCLUSIONS: Genetic testing is now essential for a correct diagnosis work-up in Pulmonary Arterial Hypertension. TBX4-associated Pulmonary Arterial Hypertension has marked clinical heterogeneity. In this regard, a genetic study is extremely useful to obtain an accurate diagnosis and provide appropriate management.

Differences in right ventricular dysfunction in patients with idiopathic pulmonary hypertension versus secondary pulmonary hypertension.

INTRODUCTION: Right ventricular (RV) function in the setting of pulmonary hypertension based on different etiologies has not been well studied. In this study, we evaluated the RV function in patients with idiopathic pulmonary hypertension (IPH) versus secon-dary pulmonary hypertension (SPH) due to congestive heart failure. MATERIAL AND METHOD: Forty-five patients with pulmonary hypertension and New York Heart Association (NYHA) functional class II or III were enrolled. Of these, 22 were diagnosed with IPH and 23 with SPH. Echocardiographic data, including Doppler and Doppler based strain, were assessed according to the American Society of Echocardiography (ASE) guidelines for detailed evaluation of RV function in these two groups. RESULTS: Mean PAP was 60 ± 14.5 mm Hg in patients with IPH versus 43 ± 11.5 mm Hg in patients with SPH (p = 0.001). Considering conventional indexes of RV function, only Sm and dp/dt were significantly better in the first group compared with the second group (p-value for Sm = 0.042 and for dp/dt = 0.039). RV end diastolic dimension was significantly higher in the IPH group (p = 0.013). Using deformation indexes of RV function, the basal and mid portion of RV free wall strain and basal RV strain rates were significantly worse in the chronic systolic heart failure (PH-HF) group in comparison to the IPH group (p < 0.001 in basal RV strain, p = 0.034 in mid RV strain and p = 0.046 in basal RV strain rate respectively). CONCLUSION: IPH has less impact on RV function in comparison to PH-HF. Considering both entities are in the category of RV pressure overload, we conclude that the etiology of pulmonary hypertension also plays an important role in RV function in addition to pressure overload.

Prognostic impact of right ventricular mass change in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Compensatory remodelling i.e. increased right ventricular (RV) mass frequently occurs as an adaptive response to the chronic pressure overload to maintain contractile function. The prognostic value of the serial change in RV mass is unclear. AIM: The aim of our study was to examine the longitudinal changes in RV mass and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Consecutive newly diagnosed IPAH patients >18 years old were prospectively recruited from a tertiary referral center. All recruited patients were maintained on guideline-based therapy and were followed up with echocardiography and cardiac magnetic resonance for 2 years. RESULTS: Serial measures of RV mass revealed that survivors appeared to have had a compensatory increase in RV mass, which constituted adaptive RV remodelling early in the disease process, which was not seen in those who died. (Hazard ratio of 0.932, 95% confidence interval 0.893-0.973, p = 0.001). CONCLUSION: This study shows that serial measurement of RV mass in IPAH patients provides prognostic information. RV mass regression is an ominous prognostic sign, which may predict early mortality in these patients.

Quantitative CT assessment of bronchial and vascular alterations in severe precapillary pulmonary hypertension.

BACKGROUND: Little is known about in vivo alterations at bronchial and vascular levels in severe pulmonary hypertension (PH) of different etiologies. We aimed to compare quantitative computed tomography (CT) data from the following three groups of severe precapillary PH patients: COPD, idiopathic pulmonary arterial hypertension (iPAH), and chronic thromboembolic PH (CTEPH). PATIENTS AND METHODS: This study was approved by the institutional review board. Severe PH patients (mean pulmonary arterial pressure [mPAP] ≥35 mmHg) with COPD, iPAH, or CTEPH (n=24, 16, or 16, respectively) were included retrospectively between January 2008 and January 2017. Univariate analysis of mPAP was performed in each severe PH group. Bronchial wall thickness (WT) and percentage of cross sectional area of pulmonary vessels less than 5 mm2 normalized by lung area (%CSA<5) were measured and compared using CT, and then combined to arterial partial pressure of oxygen (PaO2) to generate a "paw score" compared within the three groups using Kruskal-Wallis and its sensitivity using Fisher's exact test. RESULTS: WT was higher and %CSA<5 was lower in the COPD group compared to iPAH and CTEPH groups. Mosaic pattern was higher in CTEPH group than in others. In severe PH patients secondary to COPD, mPAP was positively correlated to %CSA<5. By contrast, in severe iPAH, this correlation was negative, or not correlated in severe CTEPH groups. In the COPD group, "paw score" showed higher sensitivity than in the other two groups. CONCLUSION: Unlike in severe iPAH and CTEPH, severe PH with COPD can be predicted by "paw score" reflecting bronchial and vascular morphological differential alterations.

Idiopathic, heritable and veno-occlusive pulmonary arterial hypertension in childhood: computed tomography angiography features in the initial assessment of the disease.

BACKGROUND: In children, idiopathic and heritable pulmonary arterial hypertension present echocardiographic and heart catheterization findings similar to findings in pulmonary veno-occlusive disease. OBJECTIVE: To provide a systematic analysis of CT angiography anomalies in children with idiopathic or heritable pulmonary arterial hypertension, or pulmonary veno-occlusive disease. We also sought to identify correlations between CT findings and patients' baseline characteristics. MATERIALS AND METHODS: We retrospectively analyzed CT features of children with idiopathic and heritable pulmonary arterial hypertension or pulmonary veno-occlusive disease and 30 age-matched controls between 2008 and 2014. We compared CT findings and patient characteristics, including gene mutation type, and disease outcome until 2017. RESULTS: The pulmonary arterial hypertension group included idiopathic (n=15) and heritable pulmonary arterial hypertension (n=11) and pulmonary veno-occlusive disease (n=4). Median age was 6.5 years. Children with pulmonary arterial hypertension showed enlargement of pulmonary artery and right cardiac chambers. A threshold for the ratio between the pulmonary artery and the ascending aorta of ≥1.2 had a sensitivity of 90% and a specificity of 100% for pulmonary arterial hypertension. All children with pulmonary veno-occlusive disease had thickened interlobular septa, centrilobular ground-glass opacities, and lymphadenopathy. In children with idiopathic and heritable pulmonary arterial hypertension, presence of intrapulmonary neovessels and enlargement of the right atrium were correlated with higher mean pulmonary artery pressure (P=0.011) and pulmonary vascular resistance (P=0.038), respectively. Mediastinal lymphadenopathy was associated with disease worsening within the first 2 years of follow-up (P=0.024). CONCLUSION: CT angiography could contribute to early diagnosis and prediction of severity in children with pulmonary arterial hypertension.

Prospective Echocardiographic Evaluation of the Right Ventricle and Pulmonary Arterial Pressure in Hyperthyroid Patients.

BACKGROUND: Pulmonary arterial hypertension (PAH) occurs in 35% to 65% of hyperthyroid patients. Despite this high frequency, only a few authors have examined the effects of hyperthyroidism treatment on PAH and the right ventricle. We evaluated the effects of hyperthyroidism and its reversal on cardiovascular structure and function using Doppler echocardiography. METHODS: We prospectively evaluated 32 patients (42.5±11.9years old) with thyrotoxicosis. Exclusion criteria included previous cardiovascular disease. An echocardiogram was performed at the time of hyperthyroidism diagnosis and after normalisation of free thyroxine (T4) levels. Patients were divided into two groups according to the presence or absence of PAH at the diagnosis, or at two moments, before and after T4 normalisation. RESULTS: Graves' disease was the most frequent aetiology (75%) of hyperthyroidism. Pulmonary arterial hypertension was observed in 43.8% of patients. Free T4 concentration was higher in PAH than non-PAH patients. Free T4 normalised after 5 (2.0-10.5; median and percentiles) months of treatment. Cardiac chamber sizes and cardiac output were higher in PAH. Right ventricular (RV) systolic function was impaired in PAH. Cardiac output and free T4 (r=0.42; p<0.05) correlated with pulmonary artery systolic pressure (PASP). Cardiac chamber size, cardiac output, left ventricular ejection fraction, and PASP (34.0±8.6 to 21.7±4.5mmHg) reduced after treatment. Right ventricular myocardial performance index and fractional area change improved after T4 normalisation. CONCLUSIONS: Pulmonary arterial hypertension is highly prevalent in hyperthyroid patients and is combined with increased cardiac chambers size and cardiac output, and impaired RV function. Cardiovascular changes are reversible after T4 normalisation in patients without cardiovascular disease.

3'-Deoxy-3'-[18F]Fluorothymidine Positron Emission Tomography Depicts Heterogeneous Proliferation Pathology in Idiopathic Pulmonary Arterial Hypertension Patient Lung.

BACKGROUND: Pulmonary vascular cell hyperproliferation is characteristic of pulmonary vascular remodeling in pulmonary arterial hypertension. A noninvasive imaging biomarker is needed to track the pathology and assess the response to novel treatments targeted at resolving the structural changes. Here, we evaluated the application of radioligand 3'-deoxy-3'-[18F]-fluorothymidine (18FLT) using positron emission tomography. METHODS AND RESULTS: We performed dynamic 18FLT positron emission tomography in 8 patients with idiopathic pulmonary arterial hypertension (IPAH) and applied in-depth kinetic analysis with a reversible 2-compartment 4k model. Our results show significantly increased lung 18FLT phosphorylation (k3) in patients with IPAH compared with nonpulmonary arterial hypertension controls (0.086±0.034 versus 0.054±0.009 min-1; P<0.05). There was heterogeneity in the lung 18FLT signal both between patients with IPAH and within the lungs of each patient, compatible with histopathologic reports of lungs from patients with IPAH. Consistent with 18FLT positron emission tomographic data, TK1 (thymidine kinase 1) expression was evident in the remodeled vessels in IPAH patient lung. In addition, hyperproliferative pulmonary vascular fibroblasts isolated from patients with IPAH exhibited upregulated expression of TK1 and the thymidine transporter, ENT1 (equilibrative nucleoside transporter 1). In the monocrotaline and SuHx (Sugen hypoxia) rat pulmonary arterial hypertension models, increased lung 18FLT uptake was strongly associated with peripheral pulmonary vascular muscularization and the proliferation marker, Ki-67 score, together with prominent TK1 expression in remodeled vessels. Importantly, lung 18FLT uptake was attenuated by 2 antiproliferative treatments: dichloroacetate and the tyrosine kinase inhibitor, imatinib. CONCLUSIONS: Dynamic 18FLT positron emission tomography imaging can be used to report hyperproliferation in pulmonary hypertension and merits further study to evaluate response to treatment in patients with IPAH.

Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular-Pulmonary Arterial Coupling.

PURPOSE: To evaluate the influence of riociguat on World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), right heart remodeling, and right ventricular-pulmonary arterial (RV-PA) coupling in patients with idiopathic pulmonary arterial hypertension (IPAH) who are treatment-naïve or who have failed to achieve treatment goals with sildenafil therapy. METHODS: Twenty patients with IPAH were enrolled: 12 had not previously received PAH-targeted therapy (treatment-naïve subgroup) and 8 had been receiving sildenafil therapy but failed to achieve treatment goals; on entering this pilot study these 8 patients were switched from sildenafil to riociguat therapy (treatment-switch subgroup). Patients received riociguat individually dose-adjusted up to a maximum of 2.5 mg three times daily. After 12 weeks, patients were assessed for WHO FC, 6MWD, right heart remodeling, and RV-PA coupling. RESULTS: Riociguat significantly improved WHO FC in treatment-naïve patients (from 0/4/8/0 patients in WHO I/II/III/IV at baseline to 1/6/5/0 at week 12) and in treatment-switch patients (from 0/4/4/0 patients in WHO I/II/III/IV at baseline to 1/4/3/0 at week 12). Additionally, treatment-naïve and treatment-switch patients showed significant improvements at week 12 versus baseline in 6MWD (increases of + 76.8 m and + 71.6 m, respectively), RV systolic function, and RV-PA coupling. CONCLUSION: These results support the proven efficacy of riociguat in patients with IPAH, including treatment-naïve patients and those switching to riociguat following failure to achieve treatment goals with sildenafil, and suggest that it may be possible to delay disease progression in this patient group.

Pregnancy outcome in a pregnant patient with idiopathic Pulmonary Arterial Hypertension: a case report and review of the literature.

BACKGROUND: Idiopathic pulmonary arterial hypertension is a rare and progressive condition which is aggravated by the physiologic changes during pregnancy. Because of high mortality rate, most physicians recommend early termination of pregnancy in patients with idiopathic pulmonary arterial hypertension. CASE PRESENTATION: Here we describe a case of a 30-year-old primigravida Caucasian housewife with functional class 1 idiopathic pulmonary arterial hypertension and a positive vasoreactive response to adenosine who had a full-term non-complicated delivery. Right-sided heart catheterization before the pregnancy showed severe pulmonary hypertension with mean pulmonary arterial pressure of 60 mmHg, and pulmonary vascular resistance of 12.2 WU. Vasoreactivity was positive after infusion of 200 µg/kg per minute adenosine. During pregnancy, she did not receive medication other than prophylactic enoxaparin. She had an elective cesarean section under general anesthesia at 39 weeks of gestation without complication and delivered a healthy baby. After delivery, her hemodynamic status was stable. One month postpartum, she was in a stable clinical condition in functional class 1. CONCLUSIONS: In pregnant patients with pulmonary arterial hypertension, decreased mortality has been observed over recent years particularly in patients with well-controlled pulmonary pressure and a positive vasoreactivity test.

Easily measurable, noninvasive, and novel finding for pulmonary hypertension: Hypertrophy of the basal segment of septomarginal trabeculation of right ventricle.

BACKGROUND: Effect of pulmonary hypertension (PH) on right ventricular (RV) geometry constitutes an ideal target to assess both pulmonary artery pressure (PAP) and its physiological importance. In this study, we evaluated the diagnostic power of the basal segment of septomarginal trabeculation (SMT) in predicting the PH and RV hypertrophy by cardiovascular magnetic resonance (CMR) in patients with idiopathic pulmonary arterial hypertension (IPAH) and Eisenmenger's syndrome (ES). METHODS: Eleven patients with IPAH, seven patients with ES, and 20 healthy controls were enrolled. CMR was used to measure the area and the thickness of the basal segment of SMT and right ventricular free wall (RVFW). Pulmonary artery systolic pressures (PASPs) were estimated by transthoracic echocardiography (TTE) with continuous-wave Doppler analysis measuring maximal tricuspid regurgitation (TR) velocity. Late gadolinium enhancement (LGE) findings of CMR and brain natriuretic peptide (BNP) levels were also obtained in all patients and control group. RESULTS: The area and the thickness of the basal segment of SMT were higher in patients with IPAH and ES than control group (P<.001). Pulmonary artery dimension, end-diastolic diameter of RV, RVFW thickness, and BNP levels were found to be significantly correlated with PAP (P<.001). LGE was present at the insertion point of RV only in patients group (P<.001). CONCLUSIONS: Increased area and thickness of the basal segment of SMT are easily measurable noninvasive markers of PH in patients with IPAH and ES.

Centrilobular nodules in high resolution computed tomography of the lung in IPAH patients - preliminary data concerning clinico-radiological correlates.

INTRODUCTION: Inhomogeneity of lung attenuation pattern is observed in high resolution chest computed tomography (HRCT) in some IPAH patients despite lack of interstitial lung disease. Such radiological changes are described either as ill-defined centrilobular nodules (CN) or as focal ground glass opacities (FGGO). There is no consensus in the literature, whether they indicate the distinct type of IPAH, or pulmonary venoocclusive disease (PVOD) with subtle radiological changes. Thus the aim of the present pilot study was to assess the frequency and clinical significance of inhomogenic lung attenuation pattern in IPAH. MATERIAL AND METHODS: 52 IPAH patients (38 females, 14 males, mean age 41 years ± 15 years), entered the study. All available chest CT scans were reviewed retrospectively by the experienced radiologist, not aware about the clinical data of the patients. RESULTS: CN were found in 10 patients (19%), FGGO - in 12 patients (23%). No lymphadenopathy or interlobular septal thickening suggestive of PVOD were found. The significant differences between CN and the remaining patients included: lower mean age - 31 and 43.5 years, (p = 0.02), lack of persistent foramen ovale (PFO) - 0% and 43% (p = 0.03), and higher mean right atrial pressure (mRAP) - 12.5 mm Hg and 7.94 mm Hg (p = 0.01). No significant survival differences were observed between the groups of CN, FGGO and the remaining patients. CONCLUSION: Centrilobular nodules in IPAH were combined with lack of PFO, higher mRAP and younger age of patients.

Patent foramen ovale in idiopathic pulmonary arterial hypertension: Long-term risk and morbidity.

INTRODUCTION: Little is known about the presence of patent foramen ovale in idiopathic pulmonary arterial hypertension. While there is suspected worsening of hypoxemia confounding assessment and management of pulmonary hypertension, as well as possible increased morbidity from paradoxical emboli, there may be theoretical relief of worsening right-sided pressures by the same mechanism of right-to-left shunting. METHODS: Retrospective review of consecutive patients diagnosed with idiopathic pulmonary arterial hypertension (WHO Group 1) via right heart catheterization, from 1998 to 2010. All patients also underwent a four chamber transthoracic echocardiogram with agitated saline contrast for the evaluation of patent foramen ovale. Primary clinical data was collected and compared between patients with and without patent foramen ovale along with univariable and multivariable predictors of long term survival. RESULTS: One hundred and fifty five patients were included in the study, 42 with patent foramen ovale (27%). Patients with patent foramen ovale were younger at pulmonary arterial hypertension diagnosis and trended towards higher right ventricular systolic pressures on echocardiography and mean pulmonary arterial pressures by right heart catheterization. Predictors of mortality included age, diffusing capacity for carbon monoxide, and severe hypoxemia. Only diffusing capacity and age were predictive of mortality after adjustment for a priori covariables. CONCLUSION: Patent foramen ovale is seen in a quarter of patients with idiopathic pulmonary arterial hypertension and associated with increased prevalence of severe hypoxemia but had no effect on long term survival.