Background Chronic thromboembolic pulmonary hypertension (CTEPH) is most commonly treated with pulmonary endarterectomy (PEA) or with a combination of pulmonary vasodilators and balloon pulmonary angioplasty (BPA). Quality of life (QoL) after treatment is one of many factors used to determine which procedure is most suitable for each patient. Studies evaluating quality of life (QoL) after these interventions have not compared QoL between both procedures in a randomized cohort. In this prospective registry study, we explored QoL as an outcome in patients treated with PEA or BPA treatment and which factors correlated to QoL. Methods CTEPH patients treated in Amsterdam University Medical Centre and Aarhus University Hospital, the living with pulmonary hypertension questionnaire (LPHQ) was recorded to assess QoL before treatment and six months after treatment. Multiple pulmonary and hemodynamic parameters were recorded as part of standard clinical care. Results At baseline 99 LPHQ questionnaires were answered and 67 at 6 months. Baseline parameters did not differ significantly between patients undergoing PEA vs BPA. QoL was similar at baseline in both treatment groups, and both groups experienced a similar improvement in QoL after treatment. The New York Heart Association (NYHA) score and Borg score after the six-minute walking distance (6MWD) were most strongly correlated to QoL at all time points. Baseline carbon monoxide diffusion capacity (DLCO) was inversely correlated to QoL after treatment. Presence of residual PH was not associated with significantly decreased QoL. Conclusions We did not find evidence that QoL differed in two separate groups of patients who underwent either BPA or PEA. Multiple parameters pertaining to dyspnea and basic functionality were moderately correlated to QoL, this was not the case for hemodynamic parameters. These results indicate that when determining invasive treatment in CTEPH, QoL can be expected to improve with both treatments.

Nailfold capillary density is lower in patients with pulmonary arterial hypertension (PAH). It is unclear whether this observation signifies a unique systemic manifestation of PAH, or reflects microcirculatory dysfunction secondary to pulmonary hypertension (PH). Capillary density and loop dimensions were measured by nailfold-capillaroscopy (NC) in 30 PAH (23 idiopathic, or iPAH, 7 hereditary, or hPAH), 17 chronic thromboembolic PH (CTEPH) patients and 48 controls. NC-Measurements were repeated after pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) in CTEPH patients. We examined whether NC-measurements were related to markers of disease severity and predictive of time to clinical worsening (TTCW) as tested by univariate linear/logistic regression and cox-regression analysis, respectively. Capillary density was significantly lower in PAH (7.5 ± 1.1, p < 0.001) and in CTEPH (8.4 ± 1.5, p < 0.001) compared to asymptomatic controls (10.3 ± 1.0 capillaries/mm). Capillary density was similar in iPAH and hPAH and unrelated to hemodynamics in either PAH or CTEPH. A lower capillary density was predictive of clinical worsening in PAH (p 0.05). After normalization of pulmonary artery pressures by PEA or BPA, capillary density remained reduced in CTEPH patients. Capillary loop apex, capillary and venous- and arterial limb diameter were increased in patients with PAH and CTEPH compared to controls. Nailfold capillary density is reduced to a similar extent in iPAH, hPAH and CTEPH. Normalization of hemodynamics by PEA or BPA does not lead to a restoration of capillary density in CTEPH. Capillary dimensions were increased in both patients with PAH and CTEPH. Lower capillary density was predictive of clinical worsening in PAH. Our findings indicate that a loss of peripheral capillaries is not specific to PAH and is not related to the hemodynamic disturbance per se, but that shared mechanisms may account for a simultaneous development of a systemic microangiopathy and pulmonary vascular remodeling.

BACKGROUND:Exact benefits of currently recommended close monitoring in intermediate high risk acute pulmonary embolism (PE) patients are unknown. METHODS:This prospective observational cohort study determined clinical characteristics, and disease course of intermediate high risk acute PE patients in an academic hospital setting . Frequency of hemodynamic deterioration, use of rescue reperfusion therapy and PE related mortality, were outcomes of interest. RESULTS:Of 98 intermediate high risk PE patients included for analysis, 81 patients (83%) were closely monitored. Two deteriorated hemodynamically and were treated with rescue reperfusion therapy. One patient survived after this. CONCLUSIONS:In these 98 intermediate high risk PE patients, hemodynamic deterioration occurred in three patients and rescue reperfusion therapy of two closely monitored patients led to survival of one. Underlining the need for better recognition of patients benefitting from and research in the optimal way of close monitoring.

Background: Surgical removal of thromboembolic material by pulmonary endarterectomy (PEA) leads within months to improvement in right ventricular (RV) function in the majority of chronic thromboembolic pulmonary hypertension (CTEPH) patients. However, little is known about the long-term effects of PEA on RV function. We aimed to describe long-term changes in RV function in PEA treated CTEPH-patients. Methods: In this prospective study we included patients diagnosed with CTEPH who underwent PEA. Structured follow-up measurements were performed using right heart catheterization (RHC) and cardiac magnetic resonance (CMR) imaging before PEA and 6 and 18 months after treatment. Single beat pressure-volume loop analysis was used to determine load-independent RV contractility (Ees) and RV afterload (Ea). RV volume, mass and function were derived from CMR. Results: The study protocol was completed in 25 CTEPH-patients. PEA led to a significant decline in mean pulmonary arterial pressure (mPAP 45±11 to 24±9 mmHg; p<0.0001), pulmonary vascular resistance (PVR 561 [427-711] to 132 [112-194] dynes/s/cm 5 ; p<0.0001) and RV afterload (Ea 0.6 [0.49-0.81] to 0.2 [0.2-0.3] mmHg/ml; p<0.0001) 6 months after treatment. In addition, RV dimensions improved 6 months after PEA as demonstrated by a decrease in indexed RV end-diastolic volume (RVEDVi 91±28 to 71±13 ml/m 2 ; p=0.0009), indexed RV mass (43±15 to 27±11 g/m 2 ; p <0.0001) and increase in RV ejection fraction (RVEF 41±14 to 52±9%; p=0.0003) and Ees (0.7 [0.5-1.1] to 0.3 [0.2-0.4] mmHg/ml; p<0.0001). No further changes were seen in pulmonary hemodynamics and RV dimensions between 6 and 18 months after PEA. Conclusion: Restoration in pulmonary hemodynamics and RV dimensions occurs within 6 months after PEA. No further improvements are observed between 6 and 18 months after PEA.

Introduction: Impairment of lung function and radiological abnormalities are a major concern in COVID-19 survivors, but, as of yet, patients with persistent COVID-19-related ARDS have still not been fully characterized especially regarding long-term lung injury and development of pulmonary fibrosis. The aim of this observational study is to investigate whether long-term pulmonary injury is related to fibroproliferative responses during ICU stay. Methods: Twenty-eight PCR confirmed COVID-19 patients admitted to the ICU of the Amsterdam University Medical Centers (Amsterdam UMC), location VUmc, who underwent a diagnostic bronchoscopy with broncho-alveolar lavage (BAL) because of non-resolving COVID-19 related ARDS, were included. Bronchoscopy was repeated weekly when no clinical improvement was observed. Markers for epithelial injury and fibroproliferation were measured in BALF and plasma using specific Luminex assays or ELISA. Three and 12 months after hospital discharge, chest CT and lung function parameters were obtained during outpatient visits. Results: Pulmonary markers for epithelial injury and fibroproliferation were measured in BALF and compared to healthy controls (HC). Epithelial injury and fibroproliferation markers were significantly increased in critically ill COVID-19 patients as compared to HC. Plasma markers for fibroproliferation were not different as compared to HC. No signs of pulmonary fibrosis were found at 3 and 12 months after hospital discharge. Conclusion: Patients with non-resolving COVID-19 related ARDS show a sustained alveolar fibroproliferative response, however such fibroproliferative response is not associated with pulmonary fibrosis.

BackgroundThe clinical phenotype of idiopathic pulmonary arterial hypertension (IPAH) patients has changed. . Whether or not subgroups of IPAH patients have different vascular phenotypes is a subject of debate.Research questionWhat are the histological patterns and their clinical correlates in patients diagnosed with IPAH or hereditary PAH?Study design and MethodsIn this this cross-sectional registry study lung histology of 50 IPAH patients was qualitatively assessed by two experienced pathologists. In addition, quantitative analysis by means of histopathological morphometry using immunohistochemistry was performed. Histopathological characteristics were correlated with clinical and hemodynamic parameters.ResultsIn this cohort of 50 IPAH patients, a plexiform vasculopathy was observed in 26/50 (52%) of patients, while 24/50 (48%) patients had a non-plexiform vasculopathy. The non-plexiform vasculopathy was characterized by prominent pulmonary microvascular (arterioles and venules) remodeling and vascular rarefaction. While hemodynamic parameters were comparable in plexiform versus non-plexiform vasculopathy, patients with non-plexiform vasculopathy were older, more often male, had a stronger history of cigarette smoking and lower diffusing capacity for carbon monoxide (DLCO) at diagnosis No mutations in established PAH genes were found in the non-plexiform group.InterpretationThis study reveals different vascular phenotypes within the current spectrum of patients diagnosed with IPAH, separated by clinical characteristics (age, sex, , history of cigarette smoking, and DLCO at diagnosis). Potential differences in underlying pathobiological mechanisms between patients with plexiform and non-plexiform / microvascular disease should be taken into account in future research strategies unravelling the pathophysiology of pulmonary hypertension and developing biology-targeted treatment approaches.

Sudden death, especially at a young age, may be caused by an underlying genetic cause. Hereditary conditions with an increased risk of sudden death at a young age include cardiomyopathies, arrhythmia syndromes, and hereditary thoracic aortic aneurysms and dissections. The identification of a genetic cause allows for genetic testing and cardiological surveillance in at-risk relatives. Three sudden death cases from our hospital illustrate the value of autopsy, genetic, and cardiological screening in relatives following a sudden death. On autopsy, histology consistent with hereditary cardiomyopathy is a reason for the referral of relatives. In addition, in the absence of an identifiable cause of death by autopsy in young sudden death patients, arrhythmia syndrome should be considered as a potential genetic cause.

Patients with circulatory arrest due to pulmonary embolism (PE) should be treated with fibrinolytics. Current guidelines do not specify which regimen to apply, and it has been suggested that the regimen of 100 mg rtPA/2 h should be used, because this is recommended for hemodynamic instable PE in the ESC/ERS Guideline. This two hour regimen, however, is incompatible with key principles of cardiopulmonary resuscitation (CPR), such as employment of interventions that allow fast evaluation of effectiveness, and limitation of the total duration of CPR to avoid poor neurological outcomes. Additionally, the low flow-state during CPR has important consequences for the pharmacokinetic properties of rtPA. Arguably, the volume of distribution is lower, the metabolism reduced and the half life time longer. Therefore, these changes largely discard the rationale to use high dosages of rtPA over a prolonged period of time. More importantly, these changes highlight that the guideline recommendations, based on studies in patients without circulatory arrest, cannot be easily translated to the situation of circulatory arrest. An accelerated regimen of rtPA (0.6 mg/kg/15 min., max 50 mg) is mentioned by the 2019 ESC/ERS Guideline. However, empirical support or a rationale is not provided. Due to the rarity of the situation and ethical difficulties associated with randomizing unconscious patients, a randomized head-to-head comparison between the two regimens is unlikely to ever be performed. With this comprehensive overview of the pharmacokinetics of rtPA and current literature, a strong rationale is provided that the accelerated protocol is the regimen of choice for patients with PE-induced circulatory arrest.

Background: Little is known on recovery of patients with COVID-19 after hospital admission. We aimed to gain insights in long-term effects of COVID-19 using an online homemonitoring program including homespirometry (HS) and patient reported outcome measures. Methods: This is an ongoing multicenter prospective observational study in adults hospitalized due to COVID-19 with parenchymal abnormalities on imaging. For 6 months after discharge, patients collect weekly HS measurements (FVC) and Visual analogue scales (VAS), and Fatigue assessment scale (FAS), Global rating of change (GRC) and ABCoV-tool at 4 time points in an app. Data were analyzed with linear mixed models. Results: In total, 99 patients participated (71% male, mean age 61.3±10.5), of whom 85 performed HS. During 6 months, FVC increased linearly (Δ+0.41L, p<0.001). General wellbeing (mean baseline VAS score 5.54, Δ+1.65, p<0.001) and overall health status improved (mean baseline score ABCoV-tool 5.43, Δ+1.65, p<0.001). Dyspnea did not change (mean baseline VAS score 3.03, Δ-0.30, p=0.27). At baseline, patients scored their overall quality of life worse than before COVID-19; however, at 6 months scores were close to before COVID-19 (mean baseline GRC score -3.22, Δ+2.22 points, p<0.001). Patients reported substantial fatigue at baseline with no changes over time (mean baseline FAS score 22.65, Δ+0.59, p=0.72). Conclusion: Six months after hospital admission for COVID-19, patients' general wellbeing and lung function were better than at discharge and still improving, though fatigue persisted. Homemonitoring facilitates detailed and personalized assessment of recovery trajectory after COVID-19, at potentially lower burden for patients and the healthcare system.

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. 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), N‑terminal pro-brain natriuretic peptide (NT-proBNP), 6‑minute 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. 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. BPA performed in a CTEPH expert centre is an effective and safe treatment in patients with inoperable CTEPH.

Background: Patients with lung cancer and co-existing interstitial lung disease (ILD) are at increased risk of treatment-related toxicity after both surgery and radiotherapy. A care path was implemented at our institution for patients presenting to the lung tumor board with a possible ILD, and we report on our experience using this structured approach. Methods: Since 2015, patients with possible lung cancer and ILD were referred to the general ILD clinic for assessment. In 2017, a dedicated ILD lung tumor board was established in order to facilitate quick assessment of treatment-related risks. An ethics-approved institutional database containing details of all these patients was accessed. Results: 24 patients with lung tumors and a co-existing ILD were identified (Table). The mean interval between referral to, and consultation at our ILD-board was 2 weeks. A prior diagnosis of ILD was available in 9 of 17 (53%) patients, but review led to a re-classification of the ILD subtype in 8 of the former. Treatments for lung cancer included radiotherapy alone (n = 14), surgery (n = 6), sequential chemoradiation (n = 3), and concurrent CRT followed by salvage surgery (n = 1). 6 patients developed progression of ILD after radiation; of these, 2 had received nintedanib during treatment. One patient died because of progressive ILD and in another 3 patients ILD-related deaths could not be excluded.Table58P Patient characteristics and outcomesGender (n = 24) Male Female. n = 18 (75%) n = 6 (25%)Age (years) (n = 24) Mean Range. 69 48-88Long function tests FVC (liter) (n = 20) Mean Range FVC (% of predicted) (n = 20) Mean Range FEV1 (liter) (n = 23) Mean Range FEV1 (% of predicted) (n = 24) Mean Range FEV1/FVC ratio (n = 21) Mean Range DLCO (% of predicted) (n = 22) Mean Range. . 3.33 2.08-5.47 . 90.95 54-124 . 2.17 1.46-3.66 . 84.96 54-125 . 0.71 0.53-0.87 . 49.15 21-73ILD exacerbation after (lung) cancer treatment (n = 24) Yes No. . n = 6 (25%) n = 18 (75%)Alive or dead (n = 24) Alive Dead. n = 14 (58%) n = 10 (42%)Cause of death (n = 10) Progression of cancer Exacerbation of ILD Septic shock Complication of surgery Ruptured aortic aneurysm Myocardial infarction Unknown. n = 2 n = 1 n = 1 n = 1 n = 1 n = 1 n = 3Time between end date therapy and date of death (days) (n = 10) Progression of cancer 1 Progression of cancer 2 Exacerbation of ILD Septic shock Complication of surgery Ruptured aortic aneurysm Myocardial infarction Unknown 1 Unknown 2 Unknown 3. . 116 656 45 131 17 73 162 282 342 69List of abbreviationsFVC - forced vital capacity. FEV1 - forced expiratory volume in 1 second. DLCO - diffusing capacity of the lung for carbon monoxide Open table in a new tab Conclusions: A dedicated care path for ILD patients resulted in a fast evaluation of lung cancer patients. A previous ILD-diagnosis was revised in a majority of patients, a process which can allow for a better understanding of treatment-related risks in different subgroups of ILD patients, and also assess the role of ILD-directed therapies. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: S. Senan: Grants, during the conduct of the study: ViewRay Inc.; Personal fees, outside the submitted work: Varian Medical Systems. All other authors have declared no conflicts of interest.

Journal of the European Academy of Dermatology and VenereologyVolume 34, Issue 4 p. e167-e169 Letter to the Editor Tattoos and self-reported adverse events in sarcoidosis patients S.A.S. van der Bent, Corresponding Author S.A.S. van der Bent s.bent@amsterdamumc.nl orcid.org/0000-0003-3380-4075 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsBoth authors contributed equally to this manuscript.Correspondence: S.A.S. van der Bent. E-mail: s.bent@amsterdamumc.nlSearch for more papers by this authorM.J.C. Engel, M.J.C. Engel orcid.org/0000-0001-9303-9171 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsBoth authors contributed equally to this manuscript.Search for more papers by this authorE.J. Nossent, E.J. Nossent Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorR.E. Jonkers, R.E. Jonkers Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorA. Wolkerstorfer, A. Wolkerstorfer Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorT. Rustemeyer, T. Rustemeyer orcid.org/0000-0001-7580-0684 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this author S.A.S. van der Bent, Corresponding Author S.A.S. van der Bent s.bent@amsterdamumc.nl orcid.org/0000-0003-3380-4075 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsBoth authors contributed equally to this manuscript.Correspondence: S.A.S. van der Bent. E-mail: s.bent@amsterdamumc.nlSearch for more papers by this authorM.J.C. Engel, M.J.C. Engel orcid.org/0000-0001-9303-9171 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsBoth authors contributed equally to this manuscript.Search for more papers by this authorE.J. Nossent, E.J. Nossent Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorR.E. Jonkers, R.E. Jonkers Department of Pulmonology, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorA. Wolkerstorfer, A. Wolkerstorfer Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this authorT. Rustemeyer, T. Rustemeyer orcid.org/0000-0001-7580-0684 Department of Dermatology, Academic Tattoo Clinic Amsterdam, Amsterdam University Medical Center, Amsterdam, The NetherlandsSearch for more papers by this author First published: 27 November 2019 https://doi.org/10.1111/jdv.16115Citations: 1 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume34, Issue4April 2020Pages e167-e169 RelatedInformation