Right atrial and ventricular strain detects subclinical changes in right ventricular function in precapillary pulmonary hypertension.

Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension (pPH) patients, but is insensitive to early changes. Strain might provide incremental information. In this study, we compare right atrial (RA) and RV strain in pPH patients to healthy controls, and evaluate the prognostic value of strain in pPH. In this cross-sectional study, 45 pPH patients and 20 healthy controls underwent CMR, and feature-tracking derived RA and RV strain were evaluated. pPH patients had impaired RA reservoir and conduit strain, and RV longitudinal strain (LS), compared to healthy controls. In pPH patients with preserved RVEF (≥ 50%, n = 18), RA reservoir (35% ± 9 vs. 41% ± 6, p = 0.02) and conduit strain (16% ± 8 vs. 23% ± 5, p = 0.004), and RV-LS (-25% ± 4 vs. -31% ± 4, p < 0.001) remained impaired, compared to healthy controls. The association of strain with the primary endpoint (combination of all-cause death, lung transplantation, and heart failure hospitalization) was evaluated using a multivariable Cox regression model. RV-LS (HR 1.18, 95%-CI 1.04-1.34, p = 0.01) and RA strain (reservoir: HR 0.87, 95%-CI 0.80-0.94, p = 0.001; conduit: HR 0.85, 95%-CI 0.75-0.97, p = 0.02, booster: HR 0.81, 95%-CI 0.71-0.92, p = 0.001) were independent predictors of outcome, beyond clinical and imaging features. In conclusion, pPH patients have impaired RA strain and RV-LS, even when RVEF is preserved. In addition, RA strain and RV-LS were independent predictors of adverse prognosis. These results emphasize the incremental value of RA and RV strain analyses, to detect alterations in RV function, even before RVEF declines.

Idiopathic and hereditary haemorrhagic telangiectasia associated pulmonary arteriovenous malformations: comparison of clinical and radiographic characteristics.

AIM: To determine whether there are differences between idiopathic and hereditary haemorrhagic telangiectasia (HHT) associated pulmonary arteriovenous malformations (PAVMs) (HHT-PAVM) regarding clinical and radiographic characteristics, and the results of embolotherapy. MATERIALS AND METHODS: A retrospective analysis was undertaken of all adult and adolescent patients who were diagnosed with a PAVM on chest computed tomography (CT) from January 2006 until August 2019. RESULTS: In total, 41 patients with idiopathic PAVMs and 194 patients with genetically confirmed HHT and PAVMs were included. Idiopathic PAVMs were more frequently observed in female patients, were more solitary, and predominantly located in the lower lobes. The diameter of the feeding artery and type of PAVM (simple versus complex) were similar. Embolotherapy results were comparable between both groups with similar re-embolisation rates. CONCLUSIONS: PAVMs of idiopathic origin are predominantly found in women, more frequently located in the lower lobes, and solitary compared to HHT-PAVMs; however, the outcome of treatment is the same, suggesting that treatment and follow-up should be similar in both groups.

Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study.

The inhibiting effects of itraconazole, an antifungal drug on vascular endothelial growth factor (VEGF) have recently been discovered. By inhibiting VEGF, itraconazole has shown potential in clinical trials as anti-cancer treatment. In hereditary hemorrhagic telangiectasia (HHT) patients, VEGF levels are elevated and inhibition of VEGF can decrease bleeding. Itraconazole could potentially serve as anti-angiogenic therapy for HHT-related bleeding. We report a proof of concept study with HHT patients and severe epistaxis. Patients were treated with daily 200 mg orally administered itraconazole for sixteen weeks. Twenty-one HHT patients, 8 females (38%), 13 males (62%), median age of 59 years (interquartile range (IQR) 55-69) were enrolled. Of these patients, 13 (62%) were diagnosed with HHT type 1, seven (33%) with HHT type 2 and in one patient (5%), no pathognomonic HHT mutation was found. Four patients (19%) prematurely terminated the study (3 due to mild or moderate side-effects) resulting in 17 patients included in the analyses. The median epistaxis severity score significantly decreased during treatment from 6.0 (IQR 5.1-7.2) to 3.8 (IQR 3.1-5.2) (p = 0.006). The monthly epistaxis frequency decreased from 56 to 38 epistaxis episodes (p = 0.004) and the monthly duration from 407 to 278 minutes (p = 0.005). Hemoglobin levels did not significantly change. The quality of life showed a small but significant improvement. In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated.

Safety of macitentan in sarcoidosis-associated pulmonary hypertension: a case-series.

BACKGROUND: Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis and is associated with higher morbidity and mortality. Currently, there are no approved PH-targeted therapies for sarcoidosis-associated pulmonary hypertension (SAPH). Macitentan is frequently used as treatment for pulmonary arterial hypertension, but no results are known in the SAPH population. OBJECTIVE: We investigated the safety and effect of macitentan as treatment for SAPH. METHODS: We retrospectively reviewed our patient database for all SAPH patients receiving macitentan as treatment, with a minimum follow-up of twelve months for monitoring safety. Safety outcomes included reported side-effects, hospitalisations and mortality. Furthermore, six-minutes walking distance, New York Heart Association functional class and NT-proBNP levels were collected. RESULTS: Six cases (three men) with a median age of 64 years (range 52-74 years) were identified. During macitentan treatment, one patient experienced side effects and aborted therapy after five days of treatment and died 16 months later. Three patients were hospitalised during treatment for congestive heart failure. Four patients showed improvement of their functional class and three patients in exercise capacity after 12 months of therapy. CONCLUSION: Macitentan was well tolerated in five out of six cases with severe pulmonary sarcoidosis and PH. Functional capacity improved in four cases. Prospective controlled trials are warranted before therapeutic recommendations can be made. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 74-78).

Does combination therapy work in chronic thromboembolic pulmonary hypertension?

OBJECTIVE: The current experience with combination therapy in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. We present the first survival results up to 5 years for dual combination therapy versus monotherapy in CTEPH. METHODS: All consecutive, non-operated CTEPH or residual PH after pulmonary endarterectomy patients treated with PH-specific medical therapy between January 2002 and November 2019 were included. We report and compare survival between monotherapy and (upfront or sequential) dual combination therapy until five years after medication initiation. RESULTS: In total, 183 patients (mean age 65 ± 14 years, 60% female, 66% WHO FC III/IV, 86% non-operated) were included, of which 83 patients received monotherapy and 100 patients received dual combination therapy. At baseline, patients receiving combination therapy had a higher NT-proBNP (p = 0.02) mean pulmonary artery pressure (p = 0.0001) and pulmonary vascular resistance (p = 0.02), while cardiac index was lower (p = 0.03). Total follow-up duration was 3.3 ± 1.8 years, during which 31 (17%) patients died. Estimated 1-, 3- and 5-year survival for monotherapy were 99%, 92% and 79%, respectively. For combination therapy percentages were 98%, 89% and 70%, respectively. Survival did not significantly differ between both groups (p = 0.22). CONCLUSION: Survival up to 5 years for patients treated with combination therapy, regardless of the combination strategy, was similar as patients with monotherapy, despite worse clinical and haemodynamic baseline characteristics.

Long-term real world clinical outcomes of macitentan therapy in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Macitentan treatment for chronic thromboembolic pulmonary hypertension (CTEPH) in the routine clinical setting is increasing. However, 'real world' macitentan experience is scarce and is needed to differentiate from controlled clinical trial settings. OBJECTIVE: We describe our outcomes and clinical 'real world' experience of macitentan mono- and combination therapy with riociguat or sildenafil in CTEPH. METHODS: We included all consecutive CTEPH patients, either non-operated or with residual PH after pulmonary endarterectomy (PEA), treated with macitentan in the St. Antonius hospital in Nieuwegein, the Netherlands, between 01-2014 and 11-2019. We describe clinical outcomes and adverse events (AEs) until 2 years after macitentan initiation. RESULTS: In total 73 CTEPH patients on macitentan were included, of which 18 patients were clinically inoperable (n = 7 declined PEA, n = 11 nonacceptable risk-benefit) and 55 had technically inoperable CTEPH (n = 48)/residual PH (n = 7). Clinically inoperable patients (mean age 72.4 ± 10.2 years, 61% female, 28% macitentan monotherapy, observation period 2.0 (1.9-2.0) years) had a survival of 100% and clinical worsening (CW)-free survival of 88% at 2-year follow-up respectively, with a significant increased 6-min walking distance (6MWD). Technically inoperable/residual PH patients (mean age 62.1 ± 14.1 years, 60% female, 27% macitentan monotherapy, observation period 2.0 (1.0-2.0) years) had a 2-year survival and CW-free survival of 86% and 68% respectively, with significant improved 6MWD and NT-proBNP. Nonsevere AEs were reported in 30% of all patients. CONCLUSION: Macitentan mono- and combination therapy in non-operated CTEPH and residual PH is safe and improves clinical outcomes till 2-year follow-up.

Predicting pulmonary hypertension in sarcoidosis; value of PH probability on echocardiography.

Pulmonary hypertension (PH) is a well-recognised complication of sarcoidosis. Non-invasive diagnosis is challenging due to limited accuracy of echocardiography in interstitial lung disease. This study evaluates the value of echocardiographic PH probability for diagnosing PH in pulmonary sarcoidosis. All consecutive patients between August 2015 and November 2018 were prospectively screened for PH, and classified as low, intermediate or high PH probability. Patients with intermediate or high PH probability were referred for right heart catheterisation. PH was defined as a mean pulmonary artery pressure of ≥ 25 mm Hg. Additional data on pulmonary function and chest-CT was collected. Of all 479 patients, PH was present in 17 and absent in 19 patients. Six patients refused right heart catheterisation. PH was present in 33% and 75% of patients with intermediate and high PH probability respectively (n = 36). TRV max was measurable in 46% of all patients. Measurability did not correlate with FVC% predicted or presence of significant fibrosis. In intermediate and high PH probability, TRV max < 2.9 m/s successfully ruled out PH whereas a TRV max > 3.4 confirmed PH in all patients. If TRV max was absent or in between 2.9 and 3.4, secondary echocardiographic signs were not able to improve the diagnostic accuracy. PH is unlikely in patients with a TRV max < 2.9 m/s on echocardiography, whereas PH is highly suspected in a TRV max > 3.4 m/s. Discrimination is challenging if the TRV max is between 2.9-3.4 m/s or absent. Additional secondary signs do not improve discrimination. Decision making for further investigations should be made by an expert team.

Percutaneous Atrial Septal Defect Closure Using the Occlutech Figulla Device in Adults: More than 800 Patient-Years of Follow-Up.

PURPOSE: The Occlutech Figulla occluder has been proven safe and effective at midterm follow-up after percutaneous atrial septal defect (ASD) closure. We describe the safety and efficacy at long-term follow-up in adults. METHODS: All consecutive adult patients that underwent ASD closure between 2008 and 2015 were included. All complications were registered. Residual left-to-right shunt (LRS) was diagnosed using color-Doppler transthoracic echocardiography (TTE). Right-to-left shunting was diagnosed using contrast TTE. Successful closure was defined as no LRS at follow-up. RESULTS: In total, 166 patients (mean age 56.7 ± 16.1 years; 62% female) underwent percutaneous ASD closure using the Occlutech Flex I (70%) or Flex II (30%) device (diameter 24 mm; range 10-40 mm) under general anaesthesia and transoesophageal echocardiographic guidance. Long-term follow-up data were available for 144 patients (87%) with a mean follow-up of 5.9 ± 2.6 years, a total of 814 patient-years. During hospitalization, device embolization occurred in three patients (1.8%) with successful extraction in all. During the long-term follow-up, 15 patients (9.8%) suffered new-onset atrial fibrillation and stroke occurred in 2.1%. There was no residual LRS at 12-month follow-up. No device embolization occurred during the long-term follow-up. CONCLUSION: Percutaneous ASD closure using the Occlutech device appears to be safe at long-term follow-up with a high successful closure rate at one year.

Safety and efficacy of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension in the Netherlands.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging treatment in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease (CTED). We describe the first safety and efficacy results of BPA in the Netherlands. METHODS: We selected all consecutive patients with inoperable CTEPH and CTED accepted for BPA treatment who had a six-month follow-up in the St. Antonius Hospital in Nieuwegein and the Amsterdam University Medical Center (UMC) in Amsterdam. Functional class (FC), N­terminal pro-brain natriuretic peptide (NT-proBNP), 6­minute walking test distance (6MWD) and right-sided heart catheterisation were performed at baseline and six months after last BPA. Complications for each BPA procedure were noted. RESULTS: A hundred and seventy-two BPA procedures were performed in 38 patients (61% female, mean age 65 ± 15 years). Significant improvements six months after BPA treatment were observed for functional class (63% FC I/II to 90% FC I/II, p = 0.014), mean pulmonary artery pressure (-8.9 mm Hg, p = 0.0001), pulmonary vascular resistance (-2.8 Woods Units (WU), p = 0.0001), right atrial pressure (-2.0 mm Hg, p = 0.006), stroke volume index (+5.7 ml/m2, p = 0.009) and 6MWD (+48m, p = 0.007). Non-severe complications occurred in 20 (12%) procedures. CONCLUSIONS: BPA performed in a CTEPH expert centre is an effective and safe treatment in patients with inoperable CTEPH.

Bosentan or Macitentan Therapy in Chronic Thromboembolic Pulmonary Hypertension?

OBJECTIVE: Research comparing bosentan and macitentan in chronic thromboembolic pulmonary hypertension (CTEPH) is scarce, although macitentan might have superior pharmacologic properties. We present the first real-world, 2-year follow-up results and compare clinical outcomes of both drugs in CTEPH. METHODS: All consecutive, technical inoperable or residual CTEPH patients receiving bosentan or macitentan, diagnosed in our multidisciplinary team between January 2003 and January 2019, were included. We report and compare survival, clinical worsening (CW), adverse events, WHO FC, NT-proBNP and 6-min walking test (6MWT) until 2 years after medication initiation. RESULTS: In total, 112 patients receiving bosentan or macitentan (58% female, mean age 62 ± 14 years, 68% WHO FC III/IV, 51% bosentan) could be included. Mean treatment duration was 1.9 ± 0.4 years for bosentan and 1.2 ± 0.6 years for macitentan. Two-year survival rate was 91% for bosentan and 80% for macitentan (HR mortality macitentan 1.85 [0.56-6.10], p = 0.31). Two-year CW-free survival was 81% and 58%, respectively (HR CW macitentan 2.16 [0.962-4.87], p = 0.06). Right atrial pressure, cardiac output (for mortality alone) and 6MWT lowest saturation were multivariate predictors at baseline. Overall adverse event rates were comparable and WHO FC, NT-proBNP and 6MWT distance improved similar for both drugs till 2-year follow-up. CONCLUSION: CTEPH patients receiving bosentan or macitentan have improved clinical outcomes till 2-year follow-up, without significant differences in outcomes between both therapies.

Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension.

BACKGROUND: To improve clinical outcome, patients with inoperable and residual chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with riociguat. The aim of this study is to explore long-term outcomes and to compare our 'real world' data with previous research. METHODS: We included all consecutive patients with technical inoperable and residual CTEPH, in whom riociguat therapy was initiated from January 2014 onwards, with patients followed till January 2019. Survival, clinical worsening (CW), functional class (FC), N-terminal pro brain natriuretic peptide (NT-proBNP) and 6-minute walking distance (6MWD) were described yearly after riociguat initiation. RESULTS: Thirty-six patients (50% female, mean age 64.9 ±â€¯12.1 years, 54% WHO FC III/IV and 6MWD 337 ±â€¯138 m could be included, with a mean follow-up of 2.3 ±â€¯1.2 years. Survival and CW-free survival three years after initiation of riociguat were 94% and 78%, respectively. The 6MWD per 10 m at baseline was a significant predictor (HR 0.90 [0.83-0.97], p = 0.009) for CW. At three years follow-up the WHO FC and 6MWD improved and NT-proBNP decreased compared to baseline. CONCLUSION: Our study confirms that riociguat is an effective treatment in patients with technical inoperable and residual CTEPH at long-term follow-up. Although our results are consistent with previous studies, more 'real world' research is necessary to confirm long-term results.

Reproducibility of right-to-left shunt quantification using transthoracic contrast echocardiography in hereditary haemorrhagic telangiectasia.

AIM: Transthoracic contrast echocardiography (TTCE) is recommended for screening of pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia. Shunt quantification is used to find treatable PAVMs. So far, there has been no study investigating the reproducibility of this diagnostic test. Therefore, this study aimed to describe inter-observer and inter-injection variability of TTCE. METHODS: We conducted a prospective single centre study. We included all consecutive persons screened for presence of PAVMs in association with hereditary haemorrhagic telangiectasia in 2015. The videos of two contrast injections per patient were divided and reviewed by two cardiologists blinded for patient data. Pulmonary right-to-left shunts were graded using a three-grade scale. Inter-observer and inter-injection agreement was calculated with κ statistics for the presence and grade of pulmonary right-to-left shunts. RESULTS: We included 107 persons (accounting for 214 injections) (49.5% male, mean age 45.0 ± 16.6 years). A pulmonary right-to-left shunt was present in 136 (63.6%) and 131 (61.2%) injections for observer 1 and 2, respectively. Inter-injection agreement for the presence of pulmonary right-to-left shunts was 0.96 (95% confidence interval (CI) 0.9-1.0) and 0.98 (95% CI 0.94-1.00) for observer 1 and 2, respectively. Inter-injection agreement for pulmonary right-to-left shunt grade was 0.96 (95% CI 0.93-0.99) and 0.95 (95% CI 0.92-0.98) respectively. There was disagreement in right-to-left shunt grade between the contrast injections in 11 patients (10.3%). Inter-observer variability for presence and grade of the pulmonary right-to-left shunt was 0.95 (95% CI 0.91-0.99) and 0.97 (95% CI 0.95-0.99) respectively. CONCLUSION: TTCE has an excellent inter-injection and inter-observer agreement for both the presence and grade of pulmonary right-to-left shunts.

Percutaneous closure of a patent foramen ovale after cryptogenic stroke.

A patent foramen ovale is a common intracardiac finding that is located between the left and right atrium. It can cause right-to-left shunting and has a high prevalence in patients who suffer a cryptogenic stroke. Earlier trials did not show superiority of percutaneous patent foramen ovale closure with standard medical therapy over standard medical therapy alone in the treatment of cryptogenic stroke. Interestingly, several meta-analyses show positive results regarding closure, suggesting underpowering of the individual trials. Recently, two large prospective trials and one long-term follow-up study showed benefit of percutaneous closure over standard medical therapy in treatment of cryptogenic stroke. A larger right-to-left shunt or the presence of an atrial septal aneurysm were predictors for a recurrent event. Therefore, percutaneous patent foramen ovale closure after cryptogenic stroke should be recommended over antiplatelet therapy alone in patients younger than 55 years of age with a high-risk patent foramen ovale.

SMAD4 gene mutation increases the risk of aortic dilation in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls. METHODS: Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area. RESULTS: In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (ß-coefficient 3.5, p<0.001) and ascending aorta diameter (ß-coefficient 1.6, p=0.04). CONCLUSIONS: SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls.

Life expextancy of parents with Hereditary Haemorrhagic Telangiectasia.

BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death. METHOD: We investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands). RESULTS: Two hundred twenty five/407 (55%) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95%) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5%) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4-67.7 years). CONCLUSION: Our study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.

Chronic thromboembolic pulmonary hypertension.

Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.

Direct haemodynamic effects of pulmonary arteriovenous malformation embolisation.

BACKGROUND: Transcatheter embolisation is widely used to close pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT). Data on the direct cardiovascular haemodynamic changes induced by this treatment are scarce. OBJECTIVES: We investigated the direct haemodynamic effects of transcatheter embolisation of PAVMs, using non-invasive finger pressure measurements. METHODS: During the procedure, blood pressure, heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and delta pressure/delta time (dP/dt) were continuously monitored using a Finometer®. Potential changes in these haemodynamic parameters were calculated from the pressure registrations using Modelflow® methodology. Absolute and relative changes were calculated and compared using the paired sample t-test. RESULTS: The present study includes 29 HHT patients (mean age 39 ± 15 years, 11 men) who underwent transcatheter embolotherapy of PAVMs. The total number of embolisations was 72 (mean per patient 2.5). Directly after PAVM closure, SV and CO decreased significantly by -11.9 % (p = 0.01) and -9.5 % (p = 0.01) respectively, without a significant change in HR (1.8 %). Mean arterial blood pressure increased by 4.1 % (p = 0.02), while the TPR and dP/dt did not increase significantly (5.8 % and 0.2 %, respectively). CONCLUSIONS: Significant haemodynamic changes occur directly after transcatheter embolisation of PAVMs, amongst which a decrease in stroke volume and cardiac output are most important.

CT evaluation of chronic thromboembolic pulmonary hypertension.

The educational objectives of this article are to provide an overview of the computed tomography (CT) findings in chronic thromboembolic pulmonary hypertension. This article reviews the key imaging findings at CT in patients with chronic thromboembolic pulmonary hypertension. After reading this article, the reader should have an improved awareness of the condition, its imaging features, and the CT imaging features associated with surgically accessible disease.

Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level.

BACKGROUND: Low NT-proBNP levels are associated with an uncomplicated course in patients with pulmonary embolism (PE). The aim of this multicenter management study was to investigate the safety of home treatment of patients with PE with low (< 500 pg mL(-1)) NT-proBNP. METHODS AND RESULTS: Hemodynamically stable outpatients with acute PE and NT-proBNP level < 500 pg mL(-1) were included. Patients were discharged immediately from the emergency room or within a maximum of 24 h after admission. The primary study objective was the absence of mortality during the first 10 days of treatment. Secondary objectives were the incidence of re-admission due to PE or its treatment and the patient's satisfaction during the first 10 days of treatment as well as the incidence of serious adverse events during the 3-month follow-up period. Of 351 patients, 152 (43%) fulfilled the inclusion criteria and were treated as outpatients. No deaths, major bleedings or recurrent venous thromboembolism occurred in the first 10 days of treatment or in the follow-up period of 3 months in these patients. Seven patients required readmission in the first 10 days: three because of complaints that could be related to PE and four due to an illness unrelated to PE. The HADS-A anxiety score did not change significantly between day 0 and day 10. The PSQ-18 showed a high score for satisfaction with home treatment. CONCLUSION: Out of hospital treatment is safe in hemodynamically stable patients with PE with low (< 500 pg mL(-1)) NT-proBNP levels. Approximately 45% of patients with PE can be treated in an outpatient setting. Patients do not consider out of hospital treatment as inconvenient and have no increase in anxiety scores. CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/show/NCT00455819.