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.

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.

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.

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.

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.

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.

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.

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.

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.

Elective lower limb orthopedic arthroplasty surgery in patients with pulmonary hypertension.

Patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH) are at increased risk when undergoing anesthesia and major surgery. Data on outcomes for elective orthopedic surgery in patients with PH are limited. A patient pathway was established to provide access to elective lower limb arthroplasty. This included assessment of orthopedic needs, fitness for anesthesia, preoperative optimization, and intra- and postoperative management. Patient data were retrospectively retrieved using patient's hospital records. Between 2012 and 2020, 29 operations (21 total hip replacements [THRs], 7 total knee replacements [TKRs], 1 total hip revision) were performed in 25 patients (mean age: 67 years). Perioperatively, 72% were treated with low-dose intravenous prostanoid. All had arterial lines, and central access and perioperative lithium dilution cardiac output monitoring was used in 86% of cases. Four patients underwent GA, 21 spinal anesthesia, and 4 CSE anesthesia. Supplemental nerve blocks were performed in all patients undergoing general, and 12 of 21 undergoing spinal anesthesia. All were managed in high dependency postoperatively. Hospital length of stay and complication rates were higher than reported in non-PH patients. Perioperative complications included hypotension requiring vasopressors (n = 10), blood transfusion (n = 7), nonorthopedic infection (n = 4), and decompensated right heart failure (n = 1). There was no associated mortality. All implants were functioning well at 6 weeks and subsequent follow-up. EmPHasis-10 quality of score decreased by 5.5 (±2.1) (p = 0.04). A dedicated multiprofessional pathway can be used to safely select and manage patients with PH through elective lower limb arthroplasty.

Imaging and Risk Stratification in Pulmonary Arterial Hypertension: Time to Include Right Ventricular Assessment.

Background: Current European Society of Cardiology and European Respiratory Society guidelines recommend regular risk stratification with an aim of treating patients with pulmonary arterial hypertension (PAH) to improve or maintain low-risk status (<5% 1-year mortality). Methods: Consecutive patients with PAH who underwent cardiac magnetic resonance imaging (cMRI) were identified from the Assessing the Spectrum of Pulmonary hypertension Identified at a Referral centre (ASPIRE) registry. Kaplan-Meier survival curves, locally weighted scatterplot smoothing regression and multi-variable logistic regression analysis were performed. Results: In 311 consecutive, treatment-naïve patients with PAH undergoing cMRI including 121 undergoing follow-up cMRI, measures of right ventricular (RV) function including right ventricular ejection fraction (RVEF) and RV end systolic volume and right atrial (RA) area had prognostic value. However, only RV metrics were able to identify a low-risk status. Age (p < 0.01) and RVEF (p < 0.01) but not RA area were independent predictors of 1-year mortality. Conclusion: This study highlights the need for guidelines to include measures of RV function rather than RA area alone to aid the risk stratification of patients with PAH.

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.

Cardiovascular magnetic resonance predicts all-cause mortality in pulmonary hypertension associated with heart failure with preserved ejection fraction.

This study aimed to determine the prognostic value of cardiovascular magnetic resonance (CMR) in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (pulmonary hypertension-HFpEF). Patients with pulmonary hypertension-HFpEF were recruited from the ASPIRE registry and underwent right heart catheterisation (RHC) and CMR. On RHC, the inclusion criteria was a mean pulmonary artery pressure (MPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure > 15 mmHg and, on CMR, a left atrial volume > 41 ml/m2 with left ventricular ejection fraction > 50%. Cox regression was performed to evaluate CMR against all-cause mortality. In this study, 116 patients with pulmonary hypertension-HFpEF were identified. Over a mean follow-up period of 3 ± 2 years, 61 patients with pulmonary hypertension-HFpEF died (53%). In univariate regression, 11 variables demonstrated association to mortality: indexed right ventricular (RV) volumes and stroke volume, right ventricular ejection fraction (RVEF), indexed RV mass, septal angle, pulmonary artery systolic/diastolic area and its relative area change. In multivariate regression, only three variables were independently associated with mortality: RVEF (HR 0.64, P < 0.001), indexed RV mass (HR 1.46, P < 0.001) and IV septal angle (HR 1.48, P < 0.001). Our CMR model had 0.76 area under the curve (P < 0.001) to predict mortality. This study confirms that pulmonary hypertension in patients with HFpEF is associated with a poor prognosis and we observe that CMR can risk stratify these patients and predict all-cause mortality. When patients with HFpEF develop pulmonary hypertension, CMR measures that reflect right ventricular afterload and function predict all-cause mortality.

Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry.

Pulmonary hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce. We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000-2017 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer term outcomes in survivors to hospital discharge. 242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons, respectively. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II (Acute Physiology and Chronic Health Evaluation) score, age and lactate, and lower oxygen saturation measure by pulse oximetry/inspiratory oxygen fraction (S pO2 /F iO2 ) ratio, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (oxygen (S pO2 /F iO2 ) ≤185; platelets ≤196×109·L-1; age ≥37.5 years; lactate ≥2.45 mmol·L-1; sodium ≤130.5 mmol·L-1), identified medical patients at increasing risk of hospital mortality. One (11%) out of nine patients who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge. These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation.

Characterisation of the patients with suspected heart failure: experience from the SHEAF registry.

OBJECTIVES: To characterise and risk-stratify patients presenting to a heart failure (HF) clinic according to the National Institute for health and Care Excellence (NICE) algorithm. METHODS: This is an observational study of prospectively collected data in the Sheffield HEArt Failure registry of consecutive patients with suspected HF between April 2012 and January 2020. Outcome was defined as all-cause mortality. RESULTS: 6144 patients were enrolled: 71% had HF and 29% had no HF. Patients with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) >2000 pg/mL were more likely to have HF than those with NT-proBNP of 400-2000 pg/mL (92% vs 64%, respectively). Frequency of HF phenotypes include: HF with preserved ejection fraction (HFpEF) (33%), HF with reduced ejection fraction (HFrEF) (29%), HF due to valvular heart disease (4%), HF due to pulmonary hypertension (5%) and HF due to right ventricular systolic dysfunction (1%). There were 1485 (24%) deaths over a maximum follow-up of 6 years. The death rate was higher in HF versus no HF (11.49 vs 7.29 per 100 patient-years follow-up, p<0.0001). Patients with HF and an NT-proBNP >2000 pg/mL had lower survival than those with NT-proBNP 400-2000 pg/mL (3.8 years vs 5 years, p<0.0001). Propensity matched survival curves were comparable between HFpEF and HFrEF (p=0.88). CONCLUSION: Our findings support the use by NICE's HF diagnostic algorithm of tiered triage of patients with suspected HF based on their NT-proBNP levels. The two pathways yielded distinctive groups of patients with varied diagnoses and prognosis. HFpEF is the most frequent diagnosis, with its challenges of poor prognosis and paucity of therapeutic options.

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.

Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension.

Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension (PAH), but limited data exist on the routine use of maximal exercise testing.Objectives: This study evaluates a simple-to-perform maximal test (the incremental shuttle walking test) and its use in risk stratification in PAH.Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) registry (2001-2018). Thresholds for levels of risk were identified at baseline and tested at follow-up, and their incorporation into current risk stratification approaches was assessed.Results: Of 4,524 treatment-naive patients with pulmonary hypertension who underwent maximal exercise testing, 1,847 patients had PAH. A stepwise reduction in 1-year mortality was seen between levels 1 (≤30 m; 32% mortality) and 7 (340-420 m; 1% mortality) with no mortality for levels 8-12 (≥430 m) in idiopathic and connective tissue disease-related PAH. Thresholds derived at baseline of ≤180 m (>10%; high risk), 190-330 m (5-10%; intermediate risk), and ≥340 m (<5%; low risk of 1-yr mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) 2.0 risk score calculator and French low-risk approach to risk stratification, and distinct categories of risk remained.Conclusions: We have demonstrated that maximal exercise testing in PAH stratifies mortality risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute walking test, combining some of the advantages of maximal exercise testing and maintaining the simplicity of a simple-to-perform field test.

Clinical predictors of all-cause mortality in patients presenting to specialist heart failure clinic with raised NT-proBNP and no heart failure.

AIMS: Clinical outcomes for patients suspected of having heart failure (HF) who do not meet the diagnostic criteria of any type of HF by echocardiography remain unknown. The aim of this study was to investigate the clinical predictors of all-cause mortality in patients with suspected HF, a raised N-terminal pro-b-type natriuretic peptide (NTproBNP) and who do not meet the diagnostic criteria of any type of HF by echocardiography. METHODS AND RESULTS: Relevant data were taken from the Sheffield HEArt Failure (SHEAF) registry (222349P4). The inclusion criteria were presence of symptoms raising suspicion of HF, NTproBNP > 400 pg/mL, and preserved left ventricular function. Exclusion criteria were any type of HF by echocardiography. The outcome was defined as all-cause mortality. Cox proportional-hazards regression model was used to investigate the association between the survival time of patients and clinical variables; 1031 patients were identified with NTproBNP > 400 pg/mL but who did not have echocardiographic evidence of HF. All-cause mortality was 21.5% (222 deaths) over the mean follow-up (FU) period of 6 ± 2 years. NTproBNP was similar in patients who were alive or dead (P = 0.96). However, age (HR 1, P < 0.01), chronic kidney disease (CKD, HR 1.2, P < 0.01), chronic pulmonary obstructive disease (COPD, HR 1.6, P < 0.01), dementia (HR 5.9, P < 0.01), male gender (HR 1.4, P < 0.01), first-degree atrioventricular block (HR 2.1, P < 0.01), left axis deviation (HR 1.6, P = 0.04), and diabetes (HR 1.4, P = 0.03) were associated with all-cause mortality. In multivariate regression, age, gender, CKD stage, COPD, and dementia were independently associated with mortality. In patients with NTproBNP > 627 pg/mL, NYHA class predicted death (II, 19.6%; III, 27.4%; IV, 66.7%; P < 0.01). CONCLUSIONS: Patients with no HF on echocardiography but raised NTproBNP suffer excess mortality particularly in the presence of certain clinical variables. Age, male gender, worsening CKD stage, presence of COPD, and dementia are independently associated with all-cause mortality in these patients. An NTproBNP > 627 pg/mL coupled with NYHA class could identify patients at greatest risk of death.

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.