Systematic pulmonary embolism follow-up increases diagnostic rates of chronic thromboembolic pulmonary hypertension and identifies less severe disease: results from the ASPIRE Registry.

BACKGROUND: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined. METHODS: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included. RESULTS: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents. CONCLUSIONS: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH.

Establishing minimally important differences for cardiac MRI end-points in pulmonary arterial hypertension.

BACKGROUND: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". METHODS: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. RESULTS: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. CONCLUSIONS: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.

Plain language summaryPulmonary arterial hypertension (PAH) is a disease of the vessels of the lung that causes their narrowing and stiffening. As a result, the heart pumping blood into these diseased lung vessels has to work harder and eventually gets worn out. PAH can affect patients' ability to function in daily activities and impact their quality of life. It also reduces their life expectancy dramatically. Patients are, therefore, often monitored and undergo several investigations to adapt treatment according to their situation. These investigations include a survey of how a patient feels (the emPHasis-10 questionnaire), functions (walking test) and how well the heart is coping with the disease (MRI of the heart). Until now, it is unclear how changes on MRI of the heart reflect changes in how a patient feels and functions. Our study identified patients that had the emPHasis-10 questionnaire, walking test and MRI of the heart at both the time of PAH diagnosis and one year later. This allowed us to compare how the changes in the different tests relate to each other. And because previous research identified thresholds for important changes in the emPHasis-10 questionnaire and the walking tests, we were able to use these tests as a benchmark for changes in the MRI of the heart. Our study identified thresholds for change on heart MRI that might indicate whether a patient has improved or worsened. This finding might have implications for how patients are monitored in clinical practice and future research on PAH treatments.

Assessment of Right Ventricular Function-a State of the Art.

PURPOSE OF REVIEW: The right ventricle (RV) has a complex geometry and physiology which is distinct from the left. RV dysfunction and failure can be the aftermath of volume- and/or pressure-loading conditions, as well as myocardial and pericardial diseases. RECENT FINDINGS: Echocardiography, magnetic resonance imaging and right heart catheterisation can assess RV function by using several qualitative and quantitative parameters. In pulmonary hypertension (PH) in particular, RV function can be impaired and is related to survival. An accurate assessment of RV function is crucial for the early diagnosis and management of these patients. This review focuses on the different modalities and indices used for the evaluation of RV function with an emphasis on PH.

Spatiotemporal assessment of aeromycoflora under differing urban green space, sampling height, and meteorological regimes: the atmospheric fungiscape of Thessaloniki, Greece.

We studied the diversity and abundance of the airborne fungal spores in the city of Thessaloniki, Greece, for two consecutive years. Air samples were collected at one rooftop station (at 30 m) and six near-ground stations (at 1.5 m) that differed in the size and composition of adjacent green spaces. The effects of meteorological factors on airborne fungal spore concentrations were also explored. Cladosporium spores were dominant everywhere in the air of the city. The total concentration of the airborne fungal spores at 30 m was 10 times lower than near the ground. Differences in concentration and composition were far less pronounced among near-ground stations. The attributes of the fungal spore season did not change in a consistent way among stations and years. Concentrations at the near-ground stations matched the grouping of the latter into stations of high, intermediate, and low urban green space. Minimum air temperature was the primary meteorological factor affecting spore abundance, followed by relative humidity. Airborne fungal spores are more homogeneously distributed in the air of the city, but their concentrations decrease more rapidly with height than pollen.

EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multicentre study.

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure.1745 patients with idiopathic PAH (IPAH), drug-induced PAH (DPAH), heritable PAH (HPAH) (collectively "(I/D/H)PAH"), or connective tissue disease-associated PAH (CTD-PAH), who had completed emPHasis-10 questionnaires at one of six UK referral centres between 2014 and 2017, were identified. Correlations with exercise capacity and World Health Organization (WHO) functional class were assessed, and exploratory risk stratification thresholds were tested.Moderate correlations were seen between emPHasis-10 scores and 6-min walk distance (r=-0.546), incremental shuttle walk distance (r=-0.504) and WHO functional class (r=0.497) (all p<0.0001). Distribution of emPHasis-10 score differed significantly between each WHO functional class (all p<0.0001). On multivariate analysis, emPHasis-10 score, but not WHO functional class, was an independent predictor of mortality. In a risk stratification approach, scores of 0-16, 17-33 and 34-50 identified incident patients with 1-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO functional class III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 scores had improved exercise capacity (p<0.0001) and patients who transitioned between risk groups demonstrated similar survival to patients originally in those risk groups.The emPHasis-10 score is an independent prognostic marker in patients with (I/D/H)PAH or CTD-PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity.

Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality.Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making.Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort.Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality.Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.

Mild parenchymal lung disease and/or low diffusion capacity impacts survival and treatment response in patients diagnosed with idiopathic pulmonary arterial hypertension.

There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH).Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAHno-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAHmild-LD (n=190).Survival was significantly better in IPAHno-LD than in IPAHmild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p<0.0001). In the combined group of IPAHno-LD and IPAHmild-LD, independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide (D LCO), lower exercise capacity and a diagnosis of IPAHmild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAHno-LD, but not IPAHmild-LD A proportion of patients with IPAHno-LD had a D LCO <45%; these patients had poorer survival than patients with D LCO ≥45%, although they demonstrated improved exercise capacity following treatment.The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced D LCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required.

Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry.

BACKGROUND AND OBJECTIVE: There are limited data regarding patients with PAPVD with suspected and diagnosed PH. METHODS: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry. RESULTS: Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty-seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV-ASD had a significantly larger RV area, pulmonary artery and L-R shunt and a higher % predicted DLCO (all P < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein. CONCLUSION: Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross-sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L-R shunt are higher in patients with an associated SV-ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.

Identifying At-Risk Patients with Combined Pre- and Postcapillary Pulmonary Hypertension Using Interventricular Septal Angle at Cardiac MRI.

Purpose To assess interventricular septal (IVS) angle in the identification of combined pre- and postcapillary pulmonary hypertension (Cpc-PH) in patients with pulmonary hypertension (PH) due to left-sided heart disease. Materials and Methods In this retrospective study, consecutive, incident patients suspected of having PH underwent same-day right-sided heart catheterization (RHC) and MRI at a PH referral center between April 2012 and April 2017. The diagnostic accuracy of the IVS angle to identify Cpc-PH in patients with pulmonary arterial wedge pressure (PAWP) greater than 15 mmHg was assessed by using receiver operator characteristic curves, sensitivity, specificity, and negative and positive predictive values. IVS angle also was assessed as a predictor of all-cause mortality by using Cox uni- and multivariable proportional hazards regression. Results A total of 708 patients underwent same-day MRI and RHC, and 171 patients had PAWP greater than 15 mmHg. Mean age was 70 years (range, 21-90 years) (women: mean age, 69 years; range, 21-88 years) (men: mean age, 71 years; range, 43-90 years). Systolic IVS angle correlated with diastolic pulmonary gradient (DPG) (r = 0.739, P < .001). Receiver operating characteristic curve analysis showed septal angle enabled identification of Cpc-PH (DPG ≥ 7), with an area under the receiver operating characteristic curve of 0.911 (P < .001). A 160° threshold, derived from the first half of patients with raised PAWP, enabled identification of a DPG of at least 7 mmHg with 67% sensitivity and 93% specificity (P < .001) in the second cohort of patients with raised PAWP. IVS angle was predictive of all-cause mortality (standardized univariable hazard ratio, 1.615; P < .01). Conclusion The systolic interventricular septal angle is elevated in patients with combined pre- and postcapillary pulmonary hypertension and enables one to predict those patients who have PH due to left-sided heart disease who have an increased risk of death. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension.

Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH.Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014.Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%) versus technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery.Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients.

Magnetic Resonance Imaging in the Prognostic Evaluation of Patients with Pulmonary Arterial Hypertension.

RATIONALE: Prognostication is important when counseling patients and defining treatment strategies in pulmonary arterial hypertension (PAH). OBJECTIVES: To determine the value of magnetic resonance imaging (MRI) metrics for prediction of mortality in PAH. METHODS: Consecutive patients with PAH undergoing MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) pulmonary hypertension registry. MEASUREMENTS AND MAIN RESULTS: During the follow-up period of 42 (range, 17-142) months 576 patients were studied and 221 (38%) died. A derivation cohort (n = 288; 115 deaths) and validation cohort (n = 288; 106 deaths) were identified. We used multivariate Cox regression and found two independent MRI predictors of death (P < 0.01): right ventricular end-systolic volume index adjusted for age and sex, and the relative area change of the pulmonary artery. A model of MRI and clinical data constructed from the derivation cohort predicted mortality in the validation cohort at 1 year (sensitivity, 70 [95% confidence interval (CI), 53-83]; specificity, 62 [95% CI, 62-68]; positive predictive value [PPV], 24 [95% CI, 16-32]; negative predictive value [NPV], 92 [95% CI, 87-96]) and at 3 years (sensitivity, 77 [95% CI, 67-85]; specificity, 73 [95% CI, 66-85]; PPV, 56 [95% CI, 47-65]; and NPV, 87 [95% CI, 81-92]). The model was more accurate in patients with idiopathic PAH at 3 years (sensitivity, 89 [95% CI, 65-84]; specificity, 76 [95% CI, 65-84]; PPV, 60 [95% CI, 46-74]; and NPV, 94 [95% CI, 85-98]). CONCLUSIONS: MRI measurements reflecting right ventricular structure and stiffness of the proximal pulmonary vasculature are independent predictors of outcome in PAH. In combination with clinical data MRI has moderate prognostic accuracy in the evaluation of patients with PAH.

Feasibility and safety of cardiopulmonary exercise testing in children with pulmonary hypertension.

BACKGROUND: Cardiopulmonary exercise testing helps prognosticate and guide treatment in adults with pulmonary hypertension. Concerns regarding its feasibility and safety limit its use in children with pulmonary hypertension. We aimed to assess the feasibility and safety of cardiopulmonary exercise testing in a large paediatric pulmonary hypertension cohort. METHODS: We reviewed all consecutive cardiopulmonary exercise tests performed between March, 2004 and November, 2013. The exclusion criteria were as follows: height <120 cm, World Health Organization class IV, history of exercise-induced syncope, or significant ischaemia/arrhythmias. Significant events recorded were as follows: patient-reported symptoms, arrhythmias, electrocardiogram abnormalities, and abnormal responses of arterial O2 saturation. RESULTS: A total of 98 children underwent 167 cardiopulmonary exercise tests. The median age was 14 years (inter-quartile range 10-15 years). Peak oxygen uptake was 20.4±7.3 ml/kg/minute, corresponding to 51.8±18.3% of the predicted value. Peak respiratory quotient was 1.08±0.16. All the tests except two were maximal, being terminated prematurely for clinical reasons. Baseline Oxygen saturation was 93.3±8.8% and was 81.2±19.5% at peak exercise. A drop in arterial O2 saturation >20% was observed in 23.5% of the patients. Moreover, five patients (3.0%) experienced dizziness, one requiring termination of cardiopulmonary exercise testing; five children (3.0%) experienced chest pain, with early cardiopulmonary exercise test termination in one patient. No significant arrhythmias or electrocardiogram changes were observed. CONCLUSION: Exercise testing in non-severely symptomatic children with pulmonary hypertension is safe and practical, and can be performed in a large number of children with pulmonary hypertension in a controlled environment with an experienced team. Side-effects were not serious and were resolved promptly with test termination.

Characterisation of the octogenarians presenting to the diagnostic heart failure clinic: SHEAF registry.

INTRODUCTION: Heart failure (HF) incidence is increasing in older adults with high hospitalisation and mortality rates. Treatment is complicated by side effects and comorbidities. We investigated the clinical characteristics of octogenarians presenting to the HF clinic. METHODS: Data were collected on octogenarians (80-89 years) referred to the HF clinic in two periods. The data included demographics, HF phenotype, comorbidities, symptoms and treatment. We investigate the temporal changes in clinical characteristics using χ2 test. We aimed to determine the clinical characteristics which were associated with optimisation of HF pharmacological intervention in the clinic, conducting multivariate regression analysis. Statistical significance is determined at p<0.05. RESULTS: Data were collected in April 2012 to January 2014 and in June 2021 to December 2022. In this cross-sectional study of temporal data, 571 octogenarians were referred to the clinic in the latter period, in whom the prevalence of HF was 68.48% (391 patients). HF with preserved ejection fraction (HFpEF) was the most common phenotype and increased significantly compared with the first period (46.3% and 29.2%, p<0.001). Frailty, chronic kidney disease and ischaemic heart disease increased significantly versus the first period (p<0.001). During the second period, and following the consultation, of the patients with HF with reduced ejection fraction (HFrEF), 86.4% and 82.7% were on a beta blocker and on an ACE inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, respectively. Clinical characteristics associated with further optimisations of HF pharmacological therapy in the HF clinic were: New York Heart Association (NYHA) functional class III and the presence of HFrEF phenotype CONCLUSIONS: With a prevalence of HF at 68% among the octogenarians referred to the HF clinic, HFpEF incidence is rising. The decision to optimise HF pharmacological treatment in octogenarians is driven by NYHA functional class III and the presence of HFrEF phenotype.

Atrial flutter and fibrillation in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension in the ASPIRE registry: Comparison of rate versus rhythm control approaches.

BACKGROUND: The development of atrial flutter and fibrillation (AFL/AF) in patients with pre-capillary pulmonary hypertension has been associated with an increased risk of morbidity and mortality. Rate and rhythm control strategies have not been directly compared. METHODS: Eighty-four patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with new-onset AFL/AF were identified in the ASPIRE registry. First, baseline characteristics and rates of sinus rhythm (SR) restoration of 3 arrhythmia management strategies (rate control, medical rhythm control and DC cardioversion, DCCV) in an early (2009-13) and later (2014-19) cohort were compared. Longer-term outcomes in patients who achieved SR versus those who did not were then explored. RESULTS: Sixty (71%) patients had AFL and 24 (29%) AF. Eighteen (22%) patients underwent rate control, 22 (26%) medical rhythm control and 44 (52%) DCCV. SR was restored in 33% treated by rate control, 59% medical rhythm control and 95% DCCV (p < 0.001). Restoration of SR was associated with greater improvement in functional class (FC) and Incremental Shuttle Walk Distance (p both <0.05). It also independently predicted superior survival (3-year survival 62% vs 23% in those remaining in AFL/AF, p < 0.0001). In addition, FC III/IV independently predicted higher mortality (HR 2.86, p = 0.007). Right atrial area independently predicted AFL/AF recurrence (OR 1.08, p = 0.01). DCCV was generally well tolerated with no immediate major complications. CONCLUSIONS: Restoration of SR is associated with superior functional improvement and survival in PAH/CTEPH compared with rate control. DCCV is generally safe and is more effective than medical therapy at achieving SR.

Betula pendula trees infected by birch idaeovirus and cherry leaf roll virus: Impacts of urbanisation and NO2 levels.

Viruses are frequently a microbial biocontaminant of healthy plants. The occurrence of the infection can be also due to environmental stress, like urbanisation, air pollution and increased air temperature, especially under the ongoing climate change. The aim of the present study was to investigate the hypothesis that worsened air quality and fewer green areas may favour the higher frequency of common viral infections, particularly in a common tree in temperate and continental climates, Betula pendula ROTH. We examined 18 trees, during the years 2015-2017, the same always for each year, in the region of Augsburg, Germany. By specific PCR, the frequency of two viruses, Cherry leaf roll virus (CLRV, genus Nepovirus, family Secoviridae), which is frequent in birch trees, and a novel virus tentatively named birch idaeovirus (BIV), which has been only recently described, were determined in pollen samples. The occurrence of the viruses was examined against the variables of urban index, air pollution (O3 and NO2), air temperature, and tree morphometrics (trunk perimeter, tree height, crown height and diameter). Generalized Non-linear models (binomial logit with backward stepwise removal of independent variables) were employed. During the study period, both CLRV and BIV were distributed widely throughout the investigated birch individuals. CLRV seemed to be rather cosmopolitan and was present independent of any abiotic factor. BIV's occurrence was mostly determined by higher values of the urban index and of NO2. Urban birch trees, located next to high-traffic roads with higher NO2 levels, are more likely to be infected by BIV. Increased environmental stress may lead to more plant viral infections. Here we suggest that this is particularly true for urban spaces, near high-traffic roads, where plants may be more stressed, and we recommend taking mitigation measures for controlling negative human interventions.

Non-invasive detection of severe PH in lung disease using magnetic resonance imaging.

Introduction: Severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg) in chronic lung disease (PH-CLD) is associated with high mortality and morbidity. Data suggesting potential response to vasodilator therapy in patients with PH-CLD is emerging. The current diagnostic strategy utilises transthoracic Echocardiography (TTE), which can be technically challenging in some patients with advanced CLD. The aim of this study was to evaluate the diagnostic role of MRI models to diagnose severe PH in CLD. Methods: 167 patients with CLD referred for suspected PH who underwent baseline cardiac MRI, pulmonary function tests and right heart catheterisation were identified. In a derivation cohort (n = 67) a bi-logistic regression model was developed to identify severe PH and compared to a previously published multiparameter model (Whitfield model), which is based on interventricular septal angle, ventricular mass index and diastolic pulmonary artery area. The model was evaluated in a test cohort. Results: The CLD-PH MRI model [= (-13.104) + (13.059 * VMI)-(0.237 * PA RAC) + (0.083 * Systolic Septal Angle)], had high accuracy in the test cohort (area under the ROC curve (0.91) (p < 0.0001), sensitivity 92.3%, specificity 70.2%, PPV 77.4%, and NPV 89.2%. The Whitfield model also had high accuracy in the test cohort (area under the ROC curve (0.92) (p < 0.0001), sensitivity 80.8%, specificity 87.2%, PPV 87.5%, and NPV 80.4%. Conclusion: The CLD-PH MRI model and Whitfield model have high accuracy to detect severe PH in CLD, and have strong prognostic value.

Co-exposure to highly allergenic airborne pollen and fungal spores in Europe.

The study is aimed at determining the potential spatiotemporal risk of the co-occurrence of airborne pollen and fungal spores high concentrations in different bio-climatic zones in Europe. Birch, grass, mugwort, ragweed, olive pollen and Alternaria and Cladosporium fungal spores were investigated at 16 sites in Europe, in 2005-2019. In Central and northern Europe, pollen and fungal spore seasons mainly overlap in June and July, while in South Europe, the highest pollen concentrations occur frequently outside of the spore seasons. In the coldest climate, no allergy thresholds were exceeded simultaneously by two spore or pollen taxa, while in the warmest climate most of the days with at least two pollen taxa exceeding threshold values were observed. The annual air temperature amplitude seems to be the main bioclimatic factor influencing the accumulation of days in which Alternaria and Cladosporium spores simultaneously exceed allergy thresholds. The phenomenon of co-occurrence of airborne allergen concentrations gets increasingly common in Europe and is proposed to be present on other continents, especially in temperate climate.

A temporally and spatially explicit, data-driven estimation of airborne ragweed pollen concentrations across Europe.

Ongoing and future climate change driven expansion of aeroallergen-producing plant species comprise a major human health problem across Europe and elsewhere. There is an urgent need to produce accurate, temporally dynamic maps at the continental level, especially in the context of climate uncertainty. This study aimed to restore missing daily ragweed pollen data sets for Europe, to produce phenological maps of ragweed pollen, resulting in the most complete and detailed high-resolution ragweed pollen concentration maps to date. To achieve this, we have developed two statistical procedures, a Gaussian method (GM) and deep learning (DL) for restoring missing daily ragweed pollen data sets, based on the plant's reproductive and growth (phenological, pollen production and frost-related) characteristics. DL model performances were consistently better for estimating seasonal pollen integrals than those of the GM approach. These are the first published modelled maps using altitude correction and flowering phenology to recover missing pollen information. We created a web page (http://euragweedpollen.gmf.u-szeged.hu/), including daily ragweed pollen concentration data sets of the stations examined and their restored daily data, allowing one to upload newly measured or recovered daily data. Generation of these maps provides a means to track pollen impacts in the context of climatic shifts, identify geographical regions with high pollen exposure, determine areas of future vulnerability, apply spatially-explicit mitigation measures and prioritize management interventions.

Diagnosing and managing pulmonary hypertension.

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure > or = 25 mmHg at rest as assessed invasively by right heart catheterisation. It can affect patients at any age and presents with non-specific symptoms. Accurate diagnosis is important as while PH is a potentially lethal disease it is treatable. Identification of the cause of PH is crucial to ensure that the patient receives appropriate management. The most common causes are heart and lung disease; specialist drug therapies for PH are contraindicated in these patients. However, PH is also associated with a diverse group of diseases. The most common symptom of PH is breathlessness on exertion. Syncope may be the presenting symptom especially in children. Other PH symptoms include: angina pectoris, palpitations, dry cough, exertional nausea and vomiting. Lack of response to conventional treatment for dyspnoea should alert the GP to search for another cause of the patient's symptoms, one of which could be PH. Patients should have an ECG, a chest radiograph and a full blood count, renal and liver function as well as thyroid function tests. When PH is suspected, referral to the local cardiology or respiratory department is recommended. Referral should be urgent if the patient is syncopal, has rapidly progressing symptoms or is in heart failure. Echocardiogram is the investigation of choice for detecting elevated pulmonary pressures. If the echocardiogram shows signs of PH then the patient should be referred to a designated PH centre if pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension are suspected or if PH is of uncertain cause.

Cardiovascular medication in patients with raised NT-proBNP, but no heart failure in the SHEAF registry.

OBJECTIVES: We aim to assess the association of cardiovascular medications with outcomes of patients referred to the diagnostic heart failure (HF) clinic with symptoms or signs of possible HF, raised N-terminal pro-brain-type natriuretic peptide (NT-proBNP) but no evidence of HF on transthoracic echocardiography (TTE). METHODS: Data were collected prospectively into the Sheffield HEArt Failure (SHEAF) registry between April 2012 and January 2020. The inclusion criteria were symptoms or signs suggestive of HF, NT-proBNP >400 pg/mL, but no evidence of HF on TTE. Cox proportional-hazards regression model was used to investigate the association between the survival time of patients and different cardiovascular medications. The outcome was defined as all-cause mortality. RESULTS: From the SHEAF registry, we identified 1766 patients with raised NT-proBNP with no evidence of HF on TTE. Survival was higher among the younger patients, and among those with hypertension or atrial fibrillation (AF). Mortality was increased with male gender, valvular heart disease and chronic kidney disease. Using univariate Cox proportional-hazards regression, the only cardiac therapeutic agent independently associated with all-cause mortality was beta-blocker (HR 0.86; 95% CI: 0.77 to 0.97; p=0.02). The use of beta-blockers was significantly higher in patients with AF (63% vs 39%, p<0.01) and hypertension (51% vs 42%, p<0.01). However, using multivariate Cox proportional-hazards regression to adjust for all variables associated with mortality, the influence of beta-blockers became non-significant (HR 0.96; 95% CI: 0.85 to 1.1, p=0.49). CONCLUSION: When all variables associated with mortality are considered, none of the cardiovascular agents are associated with the improved survival of patients with suspected HF, raised NT-proBNP but no HF on echocardiography.