CTEPH remains underdiagnosed and can be difficult to differentiate on routine CTPA from acute PE and from patients without pulmonary thromboembolism. We developed and evaluated a fully automated CTPA-based machine learning algorithm combining vascular blood volume metrics with clot and periclot imaging features. In this retrospective multicenter study, intraparenchymal pulmonary vessels were segmented using a scale-space particle approach, deep learning models estimated vessel radius, clot probability, and clot area from cross-sectional patches along the vessel axis, and subject-level radiomic and blood volume features were used to train an XGBoost classifier on a Northwestern University (NU) cohort (89 CTEPH; 176 controls). The trained model was then applied (without retraining) to held-out NU data, an independent acute PE cohort (152 patients) as an exploratory generalization test, and an external cohort from Brigham and Women's Hospital (23 CTEPH; 34 controls). Among 474 participants (mean age, 51 years ± 16; 299 men), the model achieved an AUC of 0.87 (95% CI: 0.79, 0.94) for CTEPH versus controls in internal testing, 0.74 (95% CI: 0.61-0.86) in external testing, and 0.89 (95% CI 0.83-0.93) for CTEPH versus acute PE. Excluding periclot features reduced discrimination, particularly for CTEPH versus acute PE (AUC 0.71; 95% CI: 0.63, 0.79). These findings support the feasibility of automated CTPA-derived vascular, clot, and periclot features for differentiating CTEPH from acute PE and controls without evidence of pulmonary thromboembolism, with further validation needed to assess generalizability across institutions.
Acute-on-chronic thromboembolic pulmonary hypertension (acute-on-CTEPH) is associated with rapid clinical deterioration, yet the role of invasive intervention in the acute phase remains poorly defined. We retrospectively analyzed consecutive patients with acute-on-CTEPH presenting with severe hypoxemia and/or cardiogenic shock at a single center between 2023 and 2026. Acute-on-CTEPH was defined as acute clinical deterioration requiring ventilatory or circulatory support, including ECMO, with imaging evidence of chronic thromboembolic disease and superimposed acute thrombi. Invasive strategies included pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA), selected based on multidisciplinary assessment. The primary outcome was change in pulmonary hemodynamics; secondary outcomes included acute-phase mortality and clinical recovery after stabilization. A total of 15 patients (median age 69 years; 53% male), all in World Health Organization functional class IV, were included. Mechanical ventilation and ECMO were required in 53% and 47% of patients, respectively. Initial treatment consisted of PEA (40%) or BPA (60%), with combined approaches in selected cases. Acute-phase mortality was 20%. Among survivors, mean pulmonary artery pressure decreased from 42 to 17 mmHg, pulmonary vascular resistance from 11.6 to 2.4 WU, and cardiac index increased from 1.7 to 2.7 L/min/m2. Among patients requiring ECMO, 5 were successfully weaned and 4 survived to discharge. At follow-up, 11 of the 12 survivors were in WHO functional class I or II, and 8 (67%) had discontinued home oxygen therapy. Despite substantial acute-phase mortality, invasive strategies were associated with marked hemodynamic improvement and may represent a potential therapeutic option in this life-threatening clinical setting.
Pulmonary arterial hypertension (PAH) is a life-limiting disease with psychosocial burden, although US population-level estimates of incident mental health (MH) disorders remain limited. In this retrospective cohort study using Komodo Research Data (01/01/2016-03/31/2024), we evaluated the association between PAH diagnosis and risk of newly diagnosed MH conditions. Adults (≥ 18 years) with incident PAH were identified alongside a non-PAH control group. Among patients with PAH (N = 4005), the risks of newly diagnosed MH conditions were compared before and after the PAH diagnosis date (index date). Between-group comparisons of newly diagnosed MH conditions post-index used inverse probability weighting to balance PAH and non-PAH patients. Outcomes included 12-month cumulative incidence and hazard ratios (HRs) from Cox models for any MH condition and prespecified categories (anxiety, mood, sleep-wake, substance use). Post-diagnosis, the 12-month risk of any newly diagnosed MH condition nearly doubled compared with pre-diagnosis (48.1% vs 24.9%; HR: 2.29; p < 0.001). Post-diagnosis risks were also higher for sleep-wake (27.1% vs 11.5%; 2.59), anxiety-spectrum (11.4% vs 8.4%; 1.37), mood (9.7% vs 6.0%; 1.65), and opioid use disorders (1.5% vs 0.7%; 2.07; all p < 0.05). Compared with matched controls (N = 421,987), PAH patients had higher risks of any MH condition (39.5% vs 17.8%; HR: 2.57), anxiety (10.1% vs 6.5%; 1.58), mood (8.7% vs 5.3%; 1.68), and substance use disorders (5.2% vs 3.4%; 1.53; all p < 0.001). Adults with PAH experienced marked increases in newly diagnosed MH conditions after PAH onset and significantly higher risk than matched non-PAH controls, supporting routine MH screening and integrated, proactive MH care in PAH management.
In patients with pulmonary arterial hypertension, pressure-based right ventricular ejection fraction (RVEF) estimated from routine right heart catheterisation correlated with RVEF from magnetic resonance imaging. A framework combining Weibull distribution-derived theoretical isovolumic pressure and time-varying elastance-derived end-systolic pressure showed the closest correlation and was responsive to initial oral combination therapy.
Sotatercept, an activin signaling inhibitor for pulmonary arterial hypertension (PAH), has demonstrated significant improvements in clinical outcomes though its off-target effects are still an area for discovery. Anecdotal increases in total body weight not attributable to fluid retention have been observed. Understanding the potential for weight gain and body composition changes is important as excessive weight gain in the PAH population is deleterious whereas increases in lean body mass may favorably affect exercise capacity. Therefore, we conducted a single-center retrospective observational cohort study of adult Group 1 PAH patients seen at a Pulmonary Hypertension Association-accredited Comprehensive Care Center treated with sotatercept for a minimum of 12 weeks. The primary endpoint was the proportion of patients who experienced clinically significant weight gain of ≥ 5% with sotatercept treatment. Secondary endpoints were the frequency of sotatercept dose adjustments required due to changes in body weight. Exploratory analyses were conducted to identify potential relationships between weight change and covariates of interest. Of 23 patients included, clinically significant weight gain was observed in 43.5% (n = 10). The median absolute change from baseline weight was 3.18 kg (Q1-Q3, -0.80-7.43 kg), and the median percent change was 4.43 (Q1-Q3, -0.78-9.01). Dosage adjustments based on dosing weight changes (increase or decrease) occurred at an incidence of 1.56 per patient-year. These results suggest the importance of ongoing monitoring of body weight throughout sotatercept treatment and that weight gain is commonly associated with treatment, although not previously observed or evaluated in clinical trials to date.
Contrast-enhanced micro-computed tomography (micro-CT) provides high-resolution, three-dimensional visualization of small vascular structures in situ, enabling detailed analysis of morphological changes in the perinatal vasculature. The ductus arteriosus (DA) connects the aorta and pulmonary artery (PA), diverting placentally oxygenated blood away from the lungs in utero. Both DA and PA undergo rapid changes in tone with the first breath during the transition from fetal to neonatal oxygen conditions. This study aimed to optimize contrast-enhanced micro-CT protocols to enable simultaneous visualization of the DA and pulmonary vasculature during this transition in fetal rabbits. Two contrast agents, an iodine-based agent (Omnipaque, 300 mg/mL) and two forms of a barium sulphate suspension, were compared to determine which optimally opacified the DA and pulmonary circulation in fetal rabbit kits (n = 22) from new-term New Zealand white rabbits (n = 4). Micro-CT imaging was performed to assess DA patency and changes in PA caliber across a wide range of vessel diameters from ~50 µm to > 1 mm under hypoxia versus normoxia in anesthetized kits. Omnipaque provided adequate opacification of the DA but limited visualization of the pulmonary vasculature. However, unfiltered 25% barium sulfate in 3% gelatin achieved robust, simultaneous visualization of the DA and pulmonary circulation. This agent optimally enhanced contrast in both large vessels and small PAs, enabling simultaneous assessment of DA constriction and pulmonary arterial vasodilation within 20 min of breathing oxygen. This study established an optimal contrast agent and micro-CT imaging strategy for post-mortem assessment of DA and pulmonary vascular morphology during the perinatal transition.
Pulmonary arterial hypertension (PAH) in Latin America and the Caribbean (LAC) remains poorly characterized, with limited regional data on clinical presentation, hemodynamics, treatment patterns, and outcomes. We aimed to characterize demographic features, clinical presentation, hemodynamic severity, treatment patterns, and survival outcomes of right heart catheterization-confirmed PAH cohorts across LAC. We performed a systematic review and meta-analysis of retrospective and prospective cohort studies of adults with right heart catheterization-confirmed PAH in LAC, searching six databases in English, Spanish, and Portuguese without date restrictions. Study-level aggregate data were pooled using random-effects models. Sixteen studies from eight countries (1999-2025) including 2,553 patients were analyzed. Mean age was 43.6 years and 81.5% were female. Etiologies included idiopathic PAH (40.3%), congenital heart disease-associated PAH (25.6%), connective tissue disease-associated PAH (20.6%), and schistosomiasis-associated PAH (15.3% in Brazilian cohorts). At diagnosis, 51% were in functional class III/IV, mean 6-min walk distance was 406 m, mean pulmonary arterial pressure was 55.8 mmHg, and cardiac index was 2.63 L/min/m2. Treatment consisted primarily of monotherapy (56%) or dual therapy (33%). Pooled survival was 93.9% at 1 year, 87.5% at 2 years, and 83.0% at 3 years. Predominantly reflecting South American PAH care, our findings establish the first regional benchmark for PAH in LAC. Patients are younger and predominantly female, with a high burden of CHD-PAH and schistosomiasis-associated PAH. Despite delayed diagnosis and limited combination therapy access, survival is comparable to high-income registries, highlighting priorities such as earlier referral, risk assessment, expanded therapy access, and prospective registry development. Trail Registration:PROSPERO CRD420251131636.
Pulmonary hypertension (PH) is a frequent complication of fibrotic interstitial lung diseases (ILDs), but its detection remains challenging due to overlapping clinical features. We aimed to evaluate the discriminatory power of physiological and exercise-based markers that differentiate right heart catheterization (RHC)-confirmed PH from low-probability ILD cases. In this prospective observational study of 59 patients with ILD, we evaluated pulmonary function tests (PFTs), cardiopulmonary exercise testing (CPET), and the 6-min walk test (6MWT). Patients deemed at high probability for clinically relevant PH following a multidisciplinary assessment were referred for RHC. Receiver operating characteristic (ROC) analysis was used to compare RHC-confirmed PH cases (n = 18) with a clinically low-probability ILD cohort (n = 19). Patients with RHC-confirmed PH had significantly lower diffusing capacity for carbon monoxide (DLCO) (43.44 ± 13.73% vs. 59.11 ± 13.50%, p = 0.002) and higher ventilatory inefficiency, as measured by the VE/VCO2 slope (47.00 ± 7.90 vs. 40.71 ± 8.48, p = 0.035). DLCO showed moderate discriminatory performance (AUC 0.799; optimal cut-off 50.5% predicted; sensitivity 72%; specificity 72%), whereas VE/VCO2 slope showed fair discrimination (AUC 0.711; cut-off ≈ 41.5; sensitivity 75%; specificity 59%). Although 6MWT distance did not differentiate the groups, post-exercise oxygen desaturation and heart rate were significant indicators. In fibrotic ILD, gas exchange and ventilatory inefficiency parameters-specifically DLCO and VE/VCO2 slope-effectively discriminate RHC-confirmed PH from clinically low-probability cases. These markers offer a practical screening approach to identify patients who should be prioritized for further PH testing.
Pulmonary hypertension (PH) is a multifaceted disorder characterized by the crucial involvement of activated hypoxia-inducible factors (HIFs). Recent investigations have unveiled HIFs' ability to orchestrate a wide array of signaling cascades, encompassing voltage-gated potassium channels, non-selective cation channels (NSCCs), Ca2+/PKC/MAPKs, PI3K/Akt, RhoA/ROCK, Notch, VEGF, and miRNA pathways. The interplay of these signaling cascades drives critical events, namely hypoxic pulmonary vasoconstriction (HPV) and hypoxic pulmonary vascular remodeling (HPVR), which collectively contribute to the pathogenesis of PH. This review summarizes the role of HIF signaling in hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, metabolic reprogramming, inflammation, non-coding RNA regulation, and emerging HIF-targeted therapies.
Pulmonary hypertension caused by fibrosing mediastinitis (PH-FM) is a high-risk condition with limited validated tools for prognostic assessment. Although diffusing capacity of the lung for carbon monoxide (DLCO) predicts outcomes in several cardiopulmonary diseases, its prognostic value in PH-FM remains unclear. In this multicenter retrospective cohort study, we included 106 patients with confirmed PH-FM from 14 centers across China. The primary endpoint was all-cause mortality. Cox proportional hazards models were used to assess the association between baseline percent-predicted DLCO and mortality, with sequential adjustment for clinical, hemodynamic, and spirometric variables. The final cohort included 106 patients, of whom 60 had DLCO ≥ 60% predicted and 46 had DLCO < 60% predicted. Over a median follow-up of 36 months (interquartile range [IQR], 14.0-50.8), 27 deaths occurred. Across Cox models, each 10-percentage-point increase in percent-predicted DLCO was associated with a 30% lower risk of all-cause mortality. DLCO < 60% predicted was associated with higher all-cause mortality compared with DLCO ≥ 60% predicted, with hazard ratios ranging from 6.90 to 7.80 across models. Lower baseline percent-predicted DLCO was independently associated with a higher risk of all-cause mortality in patients with PH-FM. DLCO may provide a simple, noninvasive measure to complement current risk assessment in this population.
Balloon pulmonary angioplasty (BPA) has emerged as a guideline-recommended therapy for surgically inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Lung injury occurs in approximately 6% of BPA sessions and is the leading cause of procedure-related mortality. While lung injury post-BPA has recently been associated with vascular injury and hemorrhage, pathologic evidence is lacking regarding whether injury is uniformly hemorrhagic or whether a permeability-mediated pattern, such as seen in reperfusion edema, predominates in some cases. We present a case of severe BPA-associated lung injury resulting in mortality, report the first histopathologic characterization of the parenchymal injury pattern in this setting, and describe how these findings informed successful rescue veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in a second case.
The optimal use of vasoactive medications in patients with pulmonary arterial hypertension with shock remains unknown. Using a national database, we benchmarked initial vasoactive practices. Twenty-five distinct strategies were identified, most commonly norepinephrine, vasopressin, phenylephrine, and milrinone. Marked practice variation underscores clinical equipoise and the need for comparative effectiveness studies.
Pulmonary arterial hypertension (PAH) is a progressive illness that may require therapy with parenteral prostacyclin pathway agents (PPA) (epoprostenol and treprostinil). These parenteral PPA's are continuous ambulatory infusions that require a high level of skill and knowledge to maintain safety and effectiveness. Depending on the clinical context, transition to oral prostacyclin receptor agonist therapy (selexipag) is sometimes pursued. To prevent abrupt withdrawal from parenteral PPA's, overlap transitions are typically used. This report describes 35 inpatient, rapid transitions from parenteral PPA's to oral selexipag. Planned hospital admissions for transition were common (n = 27, 77%), and all patients successfully transitioned without a return to parenteral PPA's in the immediate post-transition period. Most patients transitioned due to difficulties with current parenteral PPA therapy (n = 20, 57%), followed by an improved clinical status on parenteral PPA therapy (n = 8, 23%). The median length of transition was 36 h (IQR 24-48 h) and hospital stay was 3 days (IQR 2-6 days). Following transition, the cohort demonstrated stability in PAH-specific risk scores and functional status. All patients survived to outpatient pulmonary hypertension follow up (median 5.5 weeks, IQR 1.4-9.6 weeks), and the majority were alive at 1-year post-transition (n = 32, 91%). Based on these results, we conclude that transition from parenteral PPA's to selexipag can be done in the inpatient setting safely, quickly, and effectively.
Preterm birth survivors reaching adulthood are a growing population, with bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, common among this cohort. Infants with BPD are at increased risk for pulmonary vascular disease (PVD) including the development of pulmonary hypertension (PH). We present three preterm patients with a history of BPD-associated PH (BPD-PH) with monitoring throughout their childhood and young adulthood, highlighting the variation in management and late outcomes of each patient. Resolution of PH is reported on transthoracic echocardiogram (TTE) in all patients early in their life. Long-term follow-up was discontinued for one patient, while long-term monitoring in the other two individuals showed evidence of cardiopulmonary complications requiring PH-specialty management. The burden of cardiopulmonary disease associated with prematurity exists beyond early childhood and further research on the long-term management of this population is necessary to mitigate complications.
Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (mPAP). Pulmonary vascular resistance (PVR) and SvO2 (mixed venous oxygenation), measured by right heart catheterization (RHC), are key determinants of disease severity and prognosis. The right-to-left ventricular (RV/LV) blood-pool T2 ratio (T2RV/LV) by MRI has been proposed as a surrogate of RV-LV blood oxygenation differences and SvO2. Therefore, we analyzed 31 consecutive patients with PH (precapillary = 13, postcapillary = 6, combined = 12) compared to data from four patients with no PH and 21 healthy subjects. All subjects underwent 1.5 T MRI with cine for RV/LV and atrial volumes and T2 mapping. Blood T2RV/LV was measured on mid-ventricular short-axis images. Hemodynamic data (including mPAP, PVR, pulmonary arterial wedge pressure (PAWP) and oxygen saturations) were obtained from recent (within 1.5 months) RHC. We found that the T2RV/LV was significantly lower in PH patients than in healthy controls (0.76 ± 0.09 vs. 0.91 ± 0.05; p < 0.001) and correlated with pulmonary artery oxygen saturations (SvO2) (r = 0.77; p < 0.001). It also correlated with PVR (ρ = -0.74; p < 0.001), mPAP (r = -0.54; p < 0.001), RVEF (r = -0.61; p < 0.001). In multivariable analysis, T2RV/LV independently predicted mPAP (p < 0.001; R 2 = 0.64 with LA volume index and RVEF) and PVR (p < 0.001; R 2 = 0.63 with RVEF). Inter- and intra-observer variability for T2RV/LV was excellent (R = 0.96-0.97). In conclusion, blood T2RV/LV independently predicts invasive hemodynamic indices and is a non-invasive biomarker of SvO2, which might enable noninvasive risk stratification and treatment monitoring in PH.
The gut microbiota has been implicated in pulmonary vascular diseases, yet a direct causal link to pulmonary embolism (PE) remains unestablished. This study aimed to investigate the causal effects of gut microbiota on PE and to explore the mediating role of circulating metabolites in this relationship. We performed a two-sample Mendelian randomization (MR) analysis using summary statistics from large-scale genome-wide association studies. The gut microbiota data were sourced from the MiBioGen consortium, PE data from the FinnGen consortium (R10), and metabolite data from a meta-analysis of 136,016 participants. The inverse variance weighting method was used as the primary analytical approach, supplemented by sensitivity analyzes to ensure robustness. At the nominal level (p < 0.05), 12 gut microbial taxa showed suggestive associations with PE. Among these, genera LachnospiraceaeUCG010 and Defluviitaleaceae showed protective effects, while Subdoligranulum, Lentisphaerae, and Erysipelatoclostridium were associated with increased risk. In contrast, 26 circulating metabolites exhibited robust causal associations with PE, with several surviving Bonferroni correction. Mediation analyzes further revealed that specific metabolites, including histidine, triglycerides in small HDL, and docosahexaenoic acid ratio, significantly mediated the suggestive effects of nominal microbial taxa on PE risk, identifying potential metabolic pathways in the gut-vascular axis. This study generates hypothesis-generating evidence for the gut-pulmonary vascular axis, with identified metabolic mediators warranting further experimental validation. The potential effects of gut microbiota on PE provide exploratory leads for future mechanistic studies. These findings highlight the gut-pulmonary vascular axis as a potential target for novel preventive and therapeutic strategies against PE.
Neonates and infants with FOXF1 mutation develop alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), which is typically considered a uniformly fatal neonatal lung disorder due to marked hypoxemic respiratory failure with severe pulmonary hypertension (PH). Survival beyond infancy is exceedingly rare, with limited reports of FOXF1 genetic abnormalities in older children or adult cases of severe PH. Here, we report the case of a male patient with a pathogenic FOXF1 variant who presented with severe PH in early infancy whose disease stabilized and improved with early and aggressive PH therapy. The patient subsequently died at the age of 30 years, however, due to severe right ventricular failure due to the acute onset of pneumonia. This case highlights that survival into adulthood is feasible in patients with FOXF1-related pulmonary vascular disease and supports the inclusion of FOXF1 in pulmonary hypertension genetic panels for subjects who develop PH across the lifespan.
Rheumatic heart disease (RHD) is frequently complicated by pulmonary hypertension (PH) and right ventricular (RV) dysfunction. However, the prognostic significance of invasive hemodynamic parameters obtained at index right heart catheterization (RHC) in adults with RHD and echocardiographic RV-pulmonary artery (PA) uncoupling remains incompletely defined. We evaluated their associations with all-cause mortality and a composite adverse clinical outcome. We conducted a single-center retrospective cohort study of a clinically selected group of adults with RHD and echocardiographic RV-PA uncoupling who underwent index RHC for invasive hemodynamic assessment and pre-intervention risk stratification. Parsimonious multivariable logistic regression models were used to examine adjusted associations between selected invasive hemodynamic variables and study outcomes during the available hospital-record observation period. Among 56 patients, 14 (25.0%) died during the available hospital-record observation period after the index RHC, and 23 (41.1%) experienced the composite adverse clinical outcome. In parsimonious multivariable analysis, higher pulmonary vascular resistance (PVR) remained associated with all-cause mortality after adjustment (OR 1.573, 95% CI 1.012-2.447; p = 0.044), whereas lower RV fractional area change (FAC) (OR 0.885, 95% CI 0.814-0.962; p = 0.004) and lower right ventricular stroke work index (RVSWI) (OR 0.819, 95% CI 0.670-1.000; p = 0.020) remained associated with the composite adverse clinical outcome. All patients met hemodynamic criteria for combined pre- and post-capillary pulmonary hypertension. In adults with RHD and echocardiographic RV-PA uncoupling who underwent clinically indicated invasive evaluation, higher PVR was associated with mortality, whereas lower FAC and lower RVSWI were associated with the composite adverse clinical outcome. These findings should be interpreted as exploratory associations derived from a clinically selected cohort and warrant confirmation in larger prospective studies.
Mechanosensitive cation channels expressed in pulmonary arterial smooth muscle (SMC) and endothelial (EC) cells contribute to the regulation of vasoconstriction and vasodilation of the pulmonary vasculature. Here, we report that activating Piezo1, a mechanosensitive cation channel, with Yoda1 induced a mild increase in pulmonary arterial pressure (PAP) via vasoconstriction in the intact pulmonary vascular system. Inhibition of nitric oxide (NO) synthase (NOS) with l-NAME significantly potentiated Yoda1-mediated pulmonary vasoconstriction. The Yoda1-mediated vasoconstriction was inhibited by Gd3+, a non-selective blocker of cation channels, but not affected by nifedipine, a dihydropyridine blocker of voltage-dependent Ca2+ channels (VDCC). Alveolar hypoxia alone increased PAP via hypoxic pulmonary vasoconstriction (HPV); Yoda1-mediated pulmonary vasoconstriction overlaps with HPV in the isolated and perfused/ventilated lung. On top of the Yoda1-mediated increase in PAP, intrapulmonary perfusion of high K+ (25 mM) solution or phenylephrine (PE, 30 µM) induced an additional increase in PAP. These data indicate that, under normal conditions, the activation of Piezo1 (by Yoda1) caused pulmonary vasodilation due to Ca2+-associated activation of NOS in ECs and vasoconstriction due to Ca2+ influx in SMCs. In conclusion, Piezo1 or Ca2+ influx through Piezo1 in ECs and SMCs functions differently in the regulation of pulmonary vasculature. When the endothelium-derived relaxing factor (e.g., NO) is decreased due to EC injury and/or inflammation, Piezo1 or Ca2+ influx through Piezo1 channels is an important trigger for pulmonary vasoconstriction in the whole-lung vascular system.
Diagnosing pulmonary hypertension (PH) requires invasive right heart catheterization (RHC). However, mean pulmonary artery pressure (mPAP) can be non-invasively estimated using 4D analysis of cardiovascular magnetic resonance (CMR) flow imaging to assess the duration of pathological vortex flow (Tvortex) in the main pulmonary artery (MPA). Early systolic pressure reversal has been hypothesized to drive vortex formation but has yet to be quantified in-vivo. The virtual work-energy relative pressure (vWERP) method enables accurate temporal characterization of intravascular pressure gradients from 4D analysis of CMR flow images. We aimed to characterize the relationship between Tvortex and early systolic pressure reversal in the MPA using 4D analysis of CMR flow images from patients with a range of RHC-determined mPAP. A total of 36 patients who underwent a clinically indicated RHC for any reason were recruited for a research-motivated CMR-exam. Intravascular MPA pressure gradients were estimated from a stack of multidirectional 2D-flow slices covering the pulmonary artery using vWERP. Correlations between continuous variables were assessed using linear regression analysis. There were significant but weak correlations between time to systolic pressure reversal (Trev) and Tvortex (R 2: 0.17; p = 0.012), pulmonary vascular resistance (PVR) (R 2: 0.29; p = 0.001), and mPAP (R 2: 0.27; p = 0.001), respectively. Multivariable analysis showed no independent correlation between Tvortex and Trev once either PVR or mPAP were added as predictor variables. Our results suggest that early systolic pressure reversal is associated with, but is unlikely to be the sole cause of, observed vortical flow in the MPA.
