Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Outcomes and risk assessment in pulmonary veno-occlusive disease.

Introduction: Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension (PAH). Although European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines advise assessing PAH severity at baseline and during follow-up, no existing risk assessment methods have been validated for PVOD. This study aimed to identify prognostic factors, examine the impact of treatment strategies and evaluate risk assessment methods for PVOD patients. Methods: The study analysed all incident PVOD patients included in the French Pulmonary Hypertension Registry between 2006 and 2021. Survival was assessed based on initial treatment strategy and risk status and compared to a matched (age, sex, pulmonary vascular resistance) PAH group. Six risk assessment methods (number of four low-risk and three noninvasive low-risk variables, ESC/ERS guidelines three-strata and four-strata models, REVEAL 2.0 and Lite 2) were applied at baseline and early follow-up, and their accuracy was compared using Harrell's c-statistic. Results: Among the 327 included PVOD patients, survival rates at 1, 3 and 5 years were 86%, 50% and 27%, respectively. Multivariate analysis showed that only 6-min walk distance was associated with survival, with no significant difference based on initial treatment strategy. All six risk assessment methods could discriminate mortality risk, and the ESC/ERS four-strata model was the most accurate at both baseline and follow-up (C-index 0.64 and 0.74). PVOD survival rates were consistently lower than PAH when comparing baseline risk status using the ESC/ERS four-strata model. Conclusion: PVOD is associated with poor outcomes, and initial treatment strategies do not significantly affect survival. Risk assessment methods can be useful in predicting survival for PVOD patients.

Healthcare resource use and associated costs in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis.

BACKGROUND: Real-world data regarding health-care resource use (HCRU) and costs of idiopathic pulmonary fibrosis (IPF) are scarce. In France, at the time of the study, pirfenidone and nintedanib were reimbursed for documented IPF only, with similar reimbursement criteria with regard to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in a multidisciplinary setting. The objective of this study was to evaluate costs related to HCRU in patients newly treated with pirfenidone or nintedanib in 2015-2016, in France, using the exhaustive claims data of the French National Health System. METHODS: Patients aged <50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. HCRU-related costs up to 31 December 2017 were compared using generalized linear models adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period. RESULTS: During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical visits prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with higher costs for medications (1.2; 95% CI, 1.1-1.3) and medical visits (1.3; 95% CI, 1.2-1.4), as well as a higher global cost (1.1; 95% CI, 1.0-1.2). The costs of medical procedures, hospitalizations and indirect HCRU did not statistically differ between the two cohorts. CONCLUSIONS: This observational study identified potential differences in HCRU-related costs under newly prescribed antifibrotic drugs, deserving further explorations.

External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry.

INTRODUCTION: Contemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate or high risk. A minority of patients achieve low risk status with most remaining intermediate risk. Our aim was to validate a four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators. METHODS: We evaluated incident patients from the French PAH Registry and applied a four-stratum risk method at baseline and at first reassessment. We applied refined cut-points for three variables: World Health Organization functional class, 6-min walk distance and N-terminal pro-brain natriuretic peptide. We used Kaplan-Meier survival analyses and Cox proportional hazards regression to assess survival according to three-stratum and four-stratum risk approaches. RESULTS: At baseline (n=2879), the four-stratum approach identified four distinct risk groups and performed slightly better than a three-stratum method for predicting mortality. Four-stratum model discrimination was significantly higher than the three-stratum method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease and portopulmonary hypertension. Using the four-stratum approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the three-stratum approach. Those who achieved or maintained a low risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high risk. CONCLUSIONS: The four-stratum risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the three-stratum approach.

Idiopathic pulmonary fibrosis: Physician and patient perspectives on the pathway to care from symptom recognition to diagnosis and disease burden.

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease that requires ongoing care and is associated with considerable socioeconomic burden. We evaluated the IPF care pathway from symptom recognition to treatment. We describe the impact of IPF on healthcare resource use (HCRU), quality of life (QoL) and work impairment, and report differences in patient and physician perspectives using real-world data from France, Germany, Japan and the United States. METHODS: Quantitative, point-in-time data were collected as part of the Adelphi IPF II Disease Specific Programme™. Physician-reported data (patient demographics, medical history, diagnoses, treatment) were matched to patient-reported data (HCRU, QoL, work impairment). HCRU was measured as physician visits and hospitalizations. QoL and work impairment were measured using the EuroQol-5 Dimensions (EQ-5D) and Work Productivity and Activity Impairment questionnaires. RESULTS: Overall, 244 physicians reported data on 1249 patients, 739 of whom self-reported data. Diagnostic delays of 0.8 (Germany) to 2.0 (Japan) years after symptom onset were reported; treatment initiation was further delayed. In all countries, patients more often reported symptoms in the survey than did their physicians. On average, patients underwent 7-10 clinical tests before diagnosis. Antifibrotic use increased from 57% (2016) to 69% (2019); only 50% of patients with moderate/severe IPF were satisfied with their treatment. The 12-month hospitalization rates were 24% (Japan) to 64% (United States). Patients reported low QoL (mean EQ-5D visual analogue scale: 61.7/100). CONCLUSION: Patients with IPF experience considerable diagnostic and treatment delays. More effective therapies and management are needed to reduce the disease burden.

Hospital costs of Balloon Pulmonary Angioplasty (BPA) procedure and management for CTEPH patients: An observational study based on the French national hospital discharge database (PMSI).

INTRODUCTION: Since 2014, Balloon Pulmonary Angioplasty (BPA) has become an emerging and complementary strategy for chronic thromboembolic hypertension (CTEPH) patients who are not suitable for pulmonary endarterectomy (PEA) or who have recurrent symptoms after the PEA procedure. OBJECTIVE: To assess the hospital cost of BPA sessions and management in CTEPH patients. METHODS: An observational retrospective cohort study of CTEPH-adults hospitalized for a BPA between January 1st, 2014 and June 30th, 2016 was conducted in the 2 centres performing BPA in France (Paris Sud and Grenoble) using the French national hospital discharge database (PMSI-MCO). Patients were followed until 6 months or death, whichever occurred first. Follow-up stays were classified as stays with BPA sessions, for BPA management or for CTEPH management based on a pre-defined algorithm and a medical review using type of diagnosis (ICD-10), delay from last BPA procedure stay and length of stay. Hospital costs (including medical transports) were estimated from National Health Insurance perspective using published official French tariffs from 2014 to 2016 and expressed in 2017 Euros. RESULTS: A total of 191 patients were analysed; mainly male (53%), with a mean age of 64,3 years. The first BPA session was performed 1.1 years in median (IQR 0.3-2.92) after the first PH hospitalisation. A mean of 3 stays with BPA sessions per patient were reported with a mean length of stay of 8 days for the first stay and 6 days for successive stays. The total hospital cost attributable to BPA was € 4,057,825 corresponding to €8,764±3,435 per stay and €21,245±12,843 per patient. Results were sensitive to age classes, density of commune of residence and some comorbidities. CONCLUSIONS: The study generated robust real-world data to assess the hospital cost of BPA sessions and management in CTEPH patients within its first years of implementation in France.

Low income and outcome in idiopathic pulmonary fibrosis: An association to uncover.

BACKGROUND: Low income, a known prognostic indicator of various chronic respiratory diseases, has not been properly studied in idiopathic pulmonary fibrosis (IPF). We hypothesize that a low income has an adverse prognostic impact on IPF. METHODS: Patients were selected from the French national prospective cohort COFI. Patients' income was assessed through the median city-level income provided by the French National Institute of Statistics and Economic Studies according to their residential address. Patients were classified in two groups as "low income" vs. "higher income" depending on whether their annual income was estimated to be < or ≥18 170 €/year (the first quartile of the income distribution in the study population). The survival and progression-free survival (PFS) of the groups were compared by a log-rank test and a Cox model in multivariate analysis. RESULTS: 200 patients were included. The average follow-up was 33.8 ± 22.7 months. Patients in the low income group were significantly more likely to be of non-European origin (p < 0.006), and to have at least one occupational exposure (p < 0.0001), and they tended to have a higher cumulative exposure to fine particles PM2.5 (p = 0.057). After adjusting for age, gender, forced vital capacity at inclusion, geographical origin, and occupational exposure having a low-income level was a factor associated with a worse PFS (HR: 1.81; CI95%: 1.24-2.62, p = 0.001) and overall survival (HR: 1.49; CI95%: 1.0006-2.23, p = 0.049). CONCLUSIONS: Low income appears to be a prognostic factor in IPF. IPF patients with low incomes may also be exposed more frequently to occupational exposures.

Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study).

BACKGROUND: There is a paucity of data on the epidemiology, survival estimates and healthcare resource utilisation and associated costs of patients with progressive fibrosing interstitial lung disease (PF-ILD) in France. An algorithm for extracting claims data was developed to indirectly identify and describe patients with PF-ILD in the French national administrative healthcare database. METHODS: The French healthcare database, the Système National des Données de Santé (SNDS), includes data related to ambulatory care, hospitalisations and death for 98.8% of the population. In this study, algorithms based on age, diagnosis and healthcare consumption were created to identify adult patients with PF-ILD other than idiopathic pulmonary fibrosis between 2010 and 2017. Incidence, prevalence, survival estimates, clinical features and healthcare resource usage and costs were described among patients with PF-ILD. RESULTS: We identified a total of 14,413 patients with PF-ILD. Almost half of them (48.1%) were female and the mean (± standard deviation) age was 68.4 (± 15.0) years. Between 2010 and 2017, the estimated incidence of PF-ILD ranged from 4.0 to 4.7/100,000 person-years and the estimated prevalence from 6.6 to 19.4/100,000 persons. The main diagnostic categories represented were exposure-related ILD other than hypersensitivity pneumonitis (n = 3486; 24.2%), idiopathic interstitial pneumonia (n = 3113; 21.6%) and rheumatoid arthritis-associated ILD (n = 2521; 17.5%). Median overall survival using Kaplan-Meier estimation was 3.7 years from the start of progression. During the study, 95.2% of patients had ≥ 1 hospitalisation for respiratory care and 34.3% were hospitalised in an intensive care unit. The median (interquartile range) total specific cost per patient during the follow-up period was €25,613 (10,622-54,287) and the median annual cost per patient was €18,362 (6856-52,026), of which €11,784 (3003-42,097) was related to hospitalisations. Limitations included the retrospective design and identification of cases through an algorithm in the absence of chest high-resolution computed tomography scans and pulmonary function tests. CONCLUSIONS: This large, real-world, longitudinal study provides important insights into the characteristics, epidemiology and healthcare resource utilisation and costs associated with PF-ILD in France using a comprehensive and exhaustive database, and provides vital evidence that PF-ILD represents a high burden on both patients and healthcare services. Trial registration ClinicalTrials.gov, NCT03858842. ISRCTN, ISRCTN12345678. Registered 3 January 2019-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03858842.

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer.

INTRODUCTION: Interstitial lung diseases (ILDs) can be caused by mutations in the SFTPA1 and SFTPA2 genes, which encode the surfactant protein (SP) complex SP-A. Only 11 SFTPA1 or SFTPA2 mutations have so far been reported worldwide, of which five have been functionally assessed. In the framework of ILD molecular diagnosis, we identified 14 independent patients with pathogenic SFTPA1 or SFTPA2 mutations. The present study aimed to functionally assess the 11 different mutations identified and to accurately describe the disease phenotype of the patients and their affected relatives. METHODS: The consequences of the 11 SFTPA1 or SFTPA2 mutations were analysed both in vitro, by studying the production and secretion of the corresponding mutated proteins and ex vivo, by analysing SP-A expression in lung tissue samples. The associated disease phenotypes were documented. RESULTS: For the 11 identified mutations, protein production was preserved but secretion was abolished. The expression pattern of lung SP-A available in six patients was altered and the family history reported ILD and/or lung adenocarcinoma in 13 out of 14 families (93%). Among the 28 SFTPA1 or SFTPA2 mutation carriers, the mean age at ILD onset was 45 years (range 0.6-65 years) and 48% underwent lung transplantation (mean age 51 years). Seven carriers were asymptomatic. DISCUSSION: This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance.

Cost-effectiveness of pirfenidone compared to all available strategies for the treatment of idiopathic pulmonary fibrosis in France.

Objective: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. Methods: A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. Results: Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at €99,477 per patient, €104,610 in nintedanib, and €14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -€5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was €85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738€/QALY when compared to BSC. Conclusion: Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.

Haemodynamics and serial risk assessment in systemic sclerosis associated pulmonary arterial hypertension.

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min-1·m-2Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9-6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56-0.69) and at first follow-up (AUC 0.71, 95% CI 0.64-0.78).Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH.

Health economic evaluation in idiopathic pulmonary fibrosis in France.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. To date, there is no specific cure for IPF, and only two treatments (pirfenidone and nintedanib) have marketing authorizations and recommendations in international and French guidelines. OBJECTIVES: A cost-utility analysis (CUA) has been conducted to evaluate the efficiency of nintedanib, in comparison to all available alternatives, in a French setting using the official methodological guidelines. METHODS: A previously developed lifetime Markov model was adapted to the French setting by simulating the progression of IPF patients in terms of lung function decline, incidence of acute exacerbations, and death. Considering the effect of IPF on patients' quality-of-life, a CUA integrating quality adjusted life years (QALY) was chosen as the primary outcome measure in the main analysis. One-way, probabilistic, and scenario sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: Treatment with nintedanib resulted in an estimated total cost of €76,414 (vs €82,665 for pirfenidone). In comparison with all other available options, nintedanib was predicted to provide the most QALY gained (3.34 vs 3.29). This analysis suggests that nintedanib has a 59.0% chance of being more effective than pirfenidone and s 77.3% chance of being cheaper than pirfenidone. Sensitivity analyses showed the results of the CUA to be robust. CONCLUSIONS: In conclusion, this CUA has found that nintedanib appears to be a more cost-effective therapeutic option than pirfenidone in a French setting, due to fewer acute exacerbations and a better tolerability profile.

Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.

Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ≥2.5 L·min-1·m-21017 patients were included (mean age 57 years, 59% female, 75% idiopathic PAH). After a median follow-up of 34 months, 238 (23%) patients had died. Each of the four low-risk criteria independently predicted transplant-free survival at first re-evaluation. The number of low-risk criteria present at diagnosis (p<0.001) and at first re-evaluation (p<0.001) discriminated the risk of death or lung transplantation. In addition, in a subgroup of 603 patients with brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements, the number of three noninvasive criteria (WHO/NYHA functional class, 6MWD and BNP/NT-proBNP) present at first re-evaluation discriminated prognostic groups (p<0.001).A simplified risk assessment tool that quantifies the number of low-risk criteria present accurately predicted transplant-free survival in PAH.

CT Imaging Assessment of Response to Treatment in Chronic Pulmonary Aspergillosis.

BACKGROUND: Long-term antifungal therapy is usually the only treatment option for chronic pulmonary aspergillosis. However, response rates are difficult to compare because the reported clinical, mycologic, or radiologic criteria are not standardized. Objective parameters are therefore needed. To define the most relevant CT imaging variables in assessment of response to treatment, we investigated changes over time in CT imaging variables. METHODS: Changes in CT imaging variables were assessed by systematic analysis of the CT scan findings of 36 patients at diagnosis and 6 months after initiation of treatment. The relevant radiologic variables were determined by selecting those showing significant changes over time. Two experienced thoracic radiologists, blinded for clinical and serologic response, independently performed CT scan analyses. Interreader agreement and concordance between radiologic and clinical response were evaluated. RESULTS: Of the 36 patients, seven experienced clinical deterioration while undergoing therapy. Significantly evolving radiologic variables included cavity and pleural wall thickening (P < .05), which were associated with clinical improvement. There was a strong association between fungus ball disappearance and cavity/pleural wall thickening reduction and clinical improvement (P = .04). There was poor agreement between size changes of cavities or nodules, and clinical evolution (Cohen's κ, -0.13 to -0.24). CONCLUSIONS: Variations in cavity and pleural wall thickness may be the most relevant CT imaging variables for assessing response to treatment. Loss of fungus ball is strongly associated with clinical and radiologic improvement, but cavity size changes are unrelated to chronic pulmonary aspergillosis evolution. All these CT imaging variables may be applied in future clinical trials to assess treatment outcome.

Rare lung disease and orphan drug development.

Rare diseases are a major health-care burden worldwide. Very little is known about the cause, behaviour, and treatment of these disorders, and thus non-specialist health-care providers and patients are left without sufficient knowledge to manage these diseases. Up to 3 million Europeans are estimated to have a rare lung disease. Several organisations-many of which are patient led-attempt to raise the profile of rare lung diseases to improve understanding and management of these disorders. Incentives have now been introduced in the USA and Europe that encourage the pharmaceutical industry to invest in targets that might otherwise not appeal because of small target populations. Despite many intrinsic challenges and obstacles, considerable progress is constantly being made in the research and development of drugs for rare disorders.

4D time-resolved magnetic resonance angiography for noninvasive assessment of pulmonary arteriovenous malformations patency.

PURPOSE: To assess the capability of four-dimensional (4D) time-resolved magnetic resonance angiography (MRA) to assess pulmonary arteriovenous malformations (PAVMs) patency by analyzing pulmonary arterial and venous enhancement kinetics. MATERIALS AND METHODS: Seven patients with eight documented patent PAVMs underwent a 4D-MRA with keyhole and viewsharing compression at 3T with the following parameters: spatial resolution 0.87 × 0.87 × 1.4 mm(3); field of view 500 × 350 × 238 mm(3); dynamic scan time (temporal resolution) 1.2 seconds; total acquisition time 18.1 seconds for six dynamic datasets (6 × 1.2 sec + reference scan: 10.9 sec). All images were reviewed by two experienced radiologists. Image quality was rated on a qualitative 5-point scale (1: not assessable to 5: excellent). Signal value was measured on cross-sectional planes for the afferent arteries and efferent veins of the PAVM, and for normal reference healthy arteries and veins. The difference in time to peak for each coupled artery/vein (dTTPav) was calculated and compared with a Mann-Whitney test between PAVMs and reference vessels. RESULTS: Mean image quality was 3.2 ± 0.9. dTTPav was significantly smaller in PAVMs (0.15 ± 0.76 sec) than in reference vessels (3.75 ± 1.62 sec), P < 0.001. CONCLUSION: 4D-MRA is a promising tool for noninvasive assessment of PAVM patency.