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Introduction and Objectives In the randomized controlled TRITON (NCT02558231) study, both initial triple oral (macitentan, tadalafil, selexipag) and initial double oral (macitentan, tadalafil, placebo) therapy improved pulmonary vascular resistance (primary endpoint; by 54% and 52%) and 6-minute walk distance (secondary endpoint; by 55 and 56 m) at week 26 in patients with newly diagnosed PAH, with no difference between groups. This analysis further explored long-term outcome data in patients initiated on triple versus double oral therapy in TRITON. Methods We analysed the treatment effect on the secondary endpoint of time to first disease progression event (centrally adjudicated) until end of the observation period +7 days and time to all-cause death (post-hoc) until end of the observation period (Cox regression model). Results Baseline characteristics were balanced between the initial triple (n=123) and initial double therapy (n=124) groups, median follow-up was 77.6 and 75.8 weeks, respectively. There was a 41% reduction in the risk of first disease progression event with initial triple vs initial double therapy (hazard ratio 0.59, 95% CI 0.32–1.09; figure 1), driven by PAH-related hospitalisation and all-cause death. Adverse events were consistent with known safety profiles of study drugs. Two patients died in the initial triple therapy group and 9 in the initial double therapy group (hazard ratio 0.23, 95% CI 0.05–1.04). Conclusions Exploratory analysis indicated a signal for improved long-term outcome with initial triple versus initial double therapy. Please refer to page A240 for declarations of interest related to this abstract.

Background Primary mitral regurgitation (MR) is one of the most common heart valvular pathologies. However, optimum timing of surgery remains controversial. Purpose To describe changes in cardiopulmonary exercise testing (CPET) parameters after surgery for severe primary MR. Methods In a single centre prospective study, patients undergoing surgery under current ESC guidelines for severe primary MR underwent assessment with transthoracic echocardiogram, CPET, cardiac MRI and quality of life questionnaire pre-operatively and at six months after surgery. The primary outcome was a per protocol analysis of impaired post-operative functional capacity (defined as post-operative left ventricular ejection fraction on transthoracic echocardiogram Results 43 of the 50 patients recruited between February 2017 and October 2018 were included in the per protocol analysis. Thirty five patients (72.9%) had impaired post-operative functional capacity. In the overall cohort (n=43), there was a significant fall post-operatively in percentage predicted peak VO2 (ppVO2) (81.8±15.7% vs. 76.2±16.2%, p In the multivariable analysis, pre-operative left ventricular ejection fraction ≤60% (hazard ratio, 1.69; 95% confidence interval, 1.56 to 480.1, p=0.04) and pre-operative percentage predicted peak VO2 ≤84% (hazard ratio, 1.22; 95% confidence interval, 2.13 to 107.1, p Conclusions Pre-operative percentage predicted peak VO2 ≤84% is an independent predictor of impaired post-operative functional capacity. Subject to a confirmatory study, this may help to refine current ESC guidelines for intervention for severe primary MR. Change in ppVO2 after surgery Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Rosetrees Trust and Friends of Hammersmith Hospital

Introduction Long-term outcomes are important in PAH. Purpose To evaluate the long-term efficacy and safety of initial triple oral therapy with selexipag, macitentan and tadalafil vs initial double oral therapy with macitentan and tadalafil in PAH. Methods TRITON, a multicentre, double-blind, placebo-controlled, phase 3b study, randomised 1:1 newly diagnosed, treatment-naïve PAH patients to initial triple vs double therapy. Macitentan and tadalafil were initiated at randomisation and selexipag/placebo at day 15 (uptitrated to wk 12). Efficacy and safety were assessed in a blinded manner until the last patient randomised completed wk 26 (end of observation period). Pulmonary vascular resistance (PVR; primary endpoint) and 6-minute walk distance (6MWD) were assessed at wk 26. Other secondary endpoints included time to first disease progression event (centrally adjudicated) to end of observation period +7 days. Time to all-cause mortality up to end of observation period was analysed post-hoc. Results 247 patients were randomised to initial triple (n=123) or initial double therapy (n=124); baseline characteristics were balanced between groups. Median follow-up was 77.6 (initial triple) and 75.8 wks (initial double). Initial triple and initial double therapy improved PVR (by 54% and 52%) and 6MWD (by 55 and 56 m), with no difference between groups. A 41% reduction in the risk of first disease progression event driven by PAH-related hospitalisation and all-cause death was observed with initial triple vs initial double therapy (hazard ratio 0.59, 95% CI 0.32–1.09, p=0.087; Figure). Two patients died in the initial triple vs 9 in the initial double therapy group (hazard ratio 0.23, 95% CI 0.05–1.04). Adverse events were consistent with the known safety profiles of the study drugs. Conclusions In TRITON, assessments at wk 26 showed marked improvements in both treatment arms, with no difference between groups. Exploratory analysis indicated a signal for improved long-term outcome with initial triple versus initial double therapy. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Actelion Pharmaceuticals Ltd.

Purpose In TRITON (NCT02558231), initial triple (macitentan, tadalafil, selexipag) and initial double (macitentan, tadalafil, placebo) oral therapy in newly diagnosed PAH patients markedly improved hemodynamic and functional parameters at week 26, with no difference between groups. Main analysis up to end of main observation period suggested that initial triple therapy reduced the risk of disease progression vs initial double therapy. Here, we present data from a longer follow-up period (up to end of study [EOS]). Methods In this multicenter, double-blind, randomized, placebo-controlled, phase 3b study, end of the main observation period occurred when the last patient randomized completed week 26. Unblinding occurred after end of main observation period, and patients were further followed-up to EOS, which occurred 30 days after last intake of study treatment. Time to first disease progression event (pre-specified) and all-cause death (post-hoc) were analyzed with Cox regression; all disease progression events were analysed (post-hoc) using a negative binomial model. Events were centrally adjudicated in a blinded fashion. Results Median follow-up time at EOS was 100 weeks in the initial triple therapy group (n=123) and 95 weeks in the initial double therapy group (n=124) (Table). The hazard ratio for the risk of a first disease progression event and the rate of all disease progression events for initial triple vs initial double therapy were similar at end of main observation period and at EOS (Table). Four patients in the initial triple and 12 in the initial double therapy groups died before EOS. Safety up to EOS was consistent with findings at end of main observation period. Conclusion Results at EOS and at end of main observation period are consistent and suggest a signal for improved long-term outcome with initial triple vs initial double oral therapy.

Iron deficiency is known to be common and detrimental in chronic left heart failure, where parenteral iron treatment has been shown to improve exercise capacity, New York Heart Association functional class and patient wellbeing. There is now increasing interest in the role of iron in the natural history of pulmonary arterial hypertension (PAH). Iron availability influences the pulmonary vasoconstrictor response to hypoxia and accumulating evidence indicates that iron deficiency is prevalent in idiopathic and heritable forms of PAH, iron status being related to exercise capacity, symptoms and poorer survival in patients with idiopathic PAH (IPAH). Potential mechanisms behind iron deficiency in IPAH include inhibition of dietary iron uptake by the master iron regulator hepcidin. High hepcidin levels underlie the anaemia of chronic disease. Possible stimuli of the observed high levels of hepcidin in IPAH include dysfunctional bone morphogenetic protein receptor type II signalling and inflammation. Iron status may influence outcomes through modulation of the pulmonary circulation as well as myocardial and skeletal muscle function. Two parallel studies, from our centre (Hammersmith Hospital, London, UK) and others in the UK and Amsterdam (the Netherlands), investigating the safety and potential benefit of iron supplementation in patients with PAH are currently under way.

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.

Poor survival among patients with untreated pulmonary arterial hypertension (PAH) means that timely and accurate diagnosis is of paramount importance. However, the nonspecific nature of PAH symptoms, which include breathlessness and fatigue, make PAH a considerable diagnostic challenge. As a result, many patients are passed among different physicians and are only correctly diagnosed at relatively advanced stages of disease, when they are already significantly compromised and are finding even the basic activities of daily living difficult. Over recent years, the advent of targeted therapies has changed PAH from a rapidly fatal disease to a serious but treatable condition. This makes the need for obtaining a rapid and accurate diagnosis all the more urgent. The diagnostic process itself requires a reason for clinical suspicion and a series of investigations that are intended to confirm the diagnosis, to establish the cause of pulmonary hypertension and to determine the severity. The present paper reviews the routine investigations available to the physician to diagnose PAH, including electrocardiography, chest radiography, transthoracic Doppler echocardiography and right heart catheterisation, and highlights some of the diagnostic pitfalls encountered en route to an accurate diagnosis of PAH.

Aim The treatment of patients with pulmonary arterial hypertension remains a challenge. We set out to investigate the use of sildenafil, a selective inhibitor of phosphodiesterase type 5, in patients with this disease. Methods and results Ten patients (8 females, mean age 34.5±3.3 years) with pulmonary hypertension underwent right heart catheterisation with vasodilator testing using incremental doses of intravenous sildenafil without adverse events. All patients were subsequently commenced on oral sildenafil 50 mg t.d.s. Nine patients had repeat right heart catheterisation 3 months after the commencement of oral therapy. There was a significant reduction in mean pulmonary artery pressure (from 55.8±5.9 to 50.4±6.1 mmHg, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.038\) \end{document}) and pulmonary vascular resistance (from 10.1±1.7 to 8.6±1.5 Wood units, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.009\) \end{document}), and an increase in cardiac output (from 4.7±0.3 to 5.0±0.4 l/min, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.15\) \end{document}). Furthermore, there was a significant increase in the 6-minute walk test, a mean of 112 m. In response to a quality-of-life questionnaire, patients indicated marked clinical improvement on sildenafil. Sildenafil was discontinued in 1 patient due to a transient visual disturbance. The only patient previously awaiting transplantation was removed from the active transplantation list. Conclusions Sildenafil is well tolerated in its intravenous and oral forms and appears to improve both pulmonary haemodynamics and the clinical status of patients with pulmonary hypertension after 3 months of oral therapy.

Pulmonary arteriovenous malformations (PAVMs) carry significant risks [1, 2]. Pulmonary arterial blood passing through these right-to-left shunts cannot be oxygenated, leading to hypoxaemia, with arterial oxygen tension and arterial oxygen saturation ( S a,O2) inversely related to the size of the shunt fraction. The fragile wall of the PAVM sac may rupture, leading to haemoptysis or haemothorax [3]. In addition, the absence of a filtering capillary bed allows particulate matter to reach the systemic circulation where it impacts in other capillary beds, including those of the cerebral circulation, resulting in embolic cerebrovascular accidents and cerebral abscesses. In a recent series of 219 patients that corrected for ascertainment bias, the rates for ischaemic stroke and cerebral abscess were 11.3% and 9%, respectively, with risks unrelated to PAVM severity or symptoms [4]. Treatment of PAVMs by embolisation is an effective means of reducing lifetime risks of paradoxical embolic stroke and cerebral abscess [4], improving oxygenation [1, 5, 6], and treating PAVM-induced haemoptysis [3, 7]. Embolisation usually carries minimal risk in expert hands and, as a result, is generally offered to patients with PAVMs of a size amenable to embolisation, irrespective of the presence of respiratory symptoms. PAVMs themselves have a lower vascular resistance than that of the surrounding normal lung, due to the absence of a microvascular network of capillary vessels. However, most individuals with PAVMs have underlying hereditary …

OBJECTIVE--To assess relations between right ventricular pressure measured with a high fidelity transducer tipped catheter and the characteristics of tricuspid regurgitation recorded with Doppler echocardiography. DESIGN--A prospective non-randomised study of patients with severe pulmonary hypertension referred for consideration of lung transplantation. SETTING--A tertiary referral centre for cardiac and pulmonary disease, with facilities for invasive and non-invasive investigation, and assessment for heart and heart-lung transplantation. PATIENTS--10 patients with severe pulmonary hypertension being considered for lung transplantation. ENDPOINTS--Peak right ventricular, pulmonary artery, and right atrial pressures; peak positive and negative right ventricular dP/dt; peak Doppler right ventricular-right atrial pressure drop; Doppler derived peak positive and negative right ventricular dP/dt; and time intervals of Q to peak right ventricular pressure and to peak positive and negative right ventricular dP/dt. RESULTS--The mean (SD) pulmonary artery systolic pressure was 109 (29) mm Hg. The peak Doppler right ventricular-right atrial pressure drop underestimated peak right ventricular pressure by 38 (21) mm Hg, and by 21 (18) mm Hg when the Doppler value was added to the measured right atrial pressure (P values < 0.05). This discrepancy was greater for higher pulmonary artery pressures. The timing of peak right ventricular pressure differed, with the Doppler value consistently shorter (mean difference 16 ms, P < 0.05). Values of peak positive and negative right ventricular dP/dt and the time intervals Q-peak positive right ventricular dP/dt and pulmonary closure to the end of the pressure pulse differed between the two techniques in individual patients, but not in a consistent or predictable way. CONCLUSIONS--Doppler echocardiography significantly underestimates the peak right ventricular pressure and the time interval to peak right ventricular pressure in pulmonary hypertension, particularly when severe. These differences may be related to orifice geometry. Digitisation of Doppler records of tricuspid regurgitation provides useful semiquantitative estimates of absolute values and timing of peak positive and negative right ventricular dP/dt. Clinically significant differences may exist, however, and must be considered in individual patients.

OBJECTIVE--To evaluate the safety and efficacy of a prototype temporary stent (RX Flow Support Catheter, Advanced Cardiovascular Systems) in maintaining coronary perfusion and improving vessel patency in the event of acutely compromised flow complicating percutaneous transluminal coronary angioplasty. DESIGN--Prospective clinical study as part of a multicentre trial. SETTING--Regional cardiac centre catheterisation laboratory. PATIENTS--Eight patients undergoing routine percutaneous transluminal balloon coronary angioplasty in whom coronary artery dissection resulted in impaired coronary artery flow with angina or electrocardiographic ST segment shift, needing bail-out treatment at the time of the procedure. RESULTS--The RX Flow Support Catheter was successfully used and improved coronary flow in all cases, with a reduction in luminal stenosis and resolution of symptoms. The temporary stent was expanded for an average of 85 (range 30-209) minutes. In six patients it was used as a bridge to further treatment (permanent stent in four and coronary artery surgery in two) and two patients did not need further treatment. CONCLUSION--The temporary stent was safe and effective in the acute management of coronary dissection. The main advantages are its ease and speed of use, and successful restoration of coronary flow both to the distal artery and to affected side branches pending definitive treatment.

To characterise patients who appear to fulfil the diagnosis of heart failure with preserved systolic function clinically, echocardiographically, and by concentrations of brain-type natriuretic peptide (BNP).102 new cases of heart failure were identified over 24 months in 213 patients referred to a rapid access heart failure clinic. Patients with heart failure and preserved systolic function with contemporary markers of diastolic function were assessed to evaluate their cardiac status further.Forty patients (39%) had an ejection fraction (EF)45% and 62 (61%) had an EFor = 45%. Of these 62 patients, 30 (48%) fulfilled the case definition of diastolic heart failure. The remaining 32 (52%) had neither an EF45% nor abnormalities of diastolic function. Dobutamine stress echocardiography was performed on 26 (42%) patients with EFor = 45%, which provided an alternative explanation for symptoms in 15 (58%) patients. Concentrations of BNP were higher in patients with diastolic abnormalities (mean (SEM) 101.4 (32.5) pg/ml v 58.4 (6.78) pg/ml, p = 0.042) and with no diastolic abnormalities (199 (37.9) pg/ml v 58.4 (6.78) pg/ml, p0.0001) than in patients with no heart failure.Among ambulatory patients presenting with suspected heart failure in the community 19% have systolic dysfunction, 14% have diastolic dysfunction, and 15% seemingly have heart failure with neither systolic nor diastolic dysfunction. A new understanding, including alternative parameters of diastolic function, seems to be necessary to classify patients with heart failure and preserved systolic function.

Weight loss greater than 6% independently correlates with reduced survival in patients with congestive heart failure (CHF).1 Cardiac cachexia is a gradual and graded process, with wasting affecting muscle, bone, adipose tissue and the heart.1 Reduced appetite has been proposed as a important factor for weight loss caused by cardiac cachexia.2 The mechanism of cardiac cachexia remains largely unclear. Gastric myoneural inhibition and gastrointestinal hypomotility with delayed gastric emptying is commonly observed, and gut hormones may also play a role, because the anorexia is often characterised by a premature feeling of fullness and loss of hunger.2 The gut hormone ghrelin stimulates hunger, increases food consumption. and was previously shown to be raised in patients with cardiac cachexia and CHF.3 Ghrelin is produced from the stomach and usually rises in anticipation of a meal and then falls after the ingestion of nutrients. The gut hormone PYY3–36, acting as a terminator of hunger, is produced by the L cells in the distal gastrointestinal tract; it reduces appetite and 24 hour food intake by binding to the neuropeptide Y Y2 receptor in the hypothalamic arcuate nucleus.4 Severe pulmonary hypertension results in a low cardiac output and neurohumoral activation. Patients frequently report loss of appetite and weight, and since it occurs in a young population …

Aims New approaches in the treatment of ischaemic left ventricular dysfunction, including revascularization, make it increasingly important to identify heart failure cases resulting from coronary artery disease. Without angiography these cases may be missed. We investigated the frequency of coronary artery disease in incident cases of heart failure in the population. Methods and Results We identified all incident cases of heart failure in a population of 292000 in South London, U.K. by monitoring patients admitted to hospital and through a rapid access heart failure clinic. The presence and severity of coronary artery disease was identified by coronary angiography in patients under 75 years. Myocardial perfusion scanning was used to elucidate the aetiological significance of the coronary artery disease and identify hibernating myocardium. Three hundred and thirty-two cases of new heart failure were identified over 15 months. One hundred and thirty-six cases were under 75 years and angiography was undertaken in 99/136 (73%). Coronary artery disease was the aetiology in 71/136 (52%). In 18 of these 71 cases (25%), the aetiology was not recognised to be due to coronary artery disease prior to angiography, including eight cases with hibernating myocardium. Conclusion Coronary artery disease is the cause of 52% (95% CI 43–61%) of incident heart failure in the general population under 75 years. Clinical assessment without angiography under-estimates the proportion of patients with coronary artery disease, and fails to identify those patients who may benefit from revascularization.

dicators such as S’,E’ at the tricuspid and mitral lateral annulus of RV/LV.We found significant reduce of SPAP during APhT.We found a positive correlation in the evaluation SPAP using two methods:Transthoracic Doppler Echocardiography and RHC.We recieved the following correlation:responders-0.8036 before test and 0.6568 after test; not responders-0.9618 before test and 0.9414 after test respectively. Conclusions: ECHO may be used for an accurate assessment of vasodilator response as compared to RHC data. During APht with iNO only S’, E’ at the lateral annulus of RV/LV may be used for detecting vasoreactive pts.

A National Pulmonary Hypertension Service has been set up in the UK, recognising the need for change in the way this complex and relatively rare condition is investigated and managed in response to therapeutic breakthroughs. In pulmonary hypertension (PH) resting mean pulmonary artery pressure exceeds 25 mm Hg at rest or 30 mm Hg during exercise. PH may complicate many different clinical disease processes or may develop as a primary phenomenon (PPH). Post mortem studies estimate the prevalence to be 1300 per million.1 The incidence of PPH in Europe and the USA is 1–2 cases per million population per year, rising to as high as 25–50 per million per year in patients using certain appetite suppressants.2 The mean age at diagnosis is 36 years with a female preponderance (1.7–3.5:1). There is no ethnic predisposition but familial PPH accounts for roughly 10% of cases.3 In patients with PPH both vasoconstriction and later thickening of the peripheral “resistance” vessel walls (remodelling) with associated thrombosis leads to raised pulmonary vascular resistance. Most of the structural changes that occur in these vessels are attributable to the proliferation of vascular smooth muscle cells. The mechanisms …

Background Circulatingosteopontin levels predict survival in right heart failure and lung tissue expression is increased in hypoxic animal models of pulmonary hypertension. Growth differentiation factor (GDF)-15 and red cell distribution width (RDW) are potential biomarkers in idiopathic pulmonary arterial hypertension (IPAH). Objectives We assessed the prognostic value of these novel biomarkers, along with the more established N-terminal pro-brain natriuretic peptide (NT-proBNP) and other clinical indices, in treatment-naive and treated patients with IPAH. Methods Plasmaosteopontin, GDF-15, and NT-proBNP levels and RDW were determined in 126 patients with IPAH, who were followed for 4.0±2.2 years. Results All four biomarkers correlated with WHO functional class and 6 min walk distance(6MWD) and cut-offs of osteopontin (53.4 ng/ml, p 15.65%) was Conclusions Osteopontin, GDF-15 and RDW all predicted survival in IPAH and were associated with poorer clinical status. Temporal changes in biomarkers appear to hold prognostic information. RDW and NT-proBNP may add the most value to 6MWD and WHO class.

Although the frequency of haemoptysis in Eisenmenger's syndrome is well recognised, the high prevalence of pulmonary artery thrombus has been newly appreciated through the growing use of non-invasive imaging. Three patients with Eisenmenger's syndrome with haemoptysis are reported who underwent computed tomography pulmonary angiography and cardiovascular magnetic resonance. Each patient was found to have aneurysmal dilatation of the right pulmonary artery with large laminar thrombus. These cases illustrate a rising clinical problem in this special population-that is, how to treat and prevent large pulmonary artery thrombosis in the setting of haemoptysis. The authors discuss their approach to these cases and the known literature.

The nature of plasma cardiodilatin, the amino-terminal product of the human pro-atrial natriuretic peptide, was investigated by two separate radioimmunoassays directed against the N-terminal and the putative C-terminal of the cardiodilatin molecule: ANP-[Asn1-Lys16] and ANP-[Lys87-Arg98], respectively. Serial dilutions of normal and cardiac failure plasma exhibited parallelism with the synthetic peptide standard curves in both assays. The concentrations of N- and C-terminal cardiodilatin-immunoreactivity equivalents (-IE) were significantly higher in cardiac failure patients. N-terminal-IE: 912 +/- 87, normal subjects 129 +/- 13 (mean +/- SEM); C-terminal-IE: 7979 +/- 1784, normal subjects 895 +/- 213 (both p less than 0.001). Although the concentrations determined by the two assays were not identical, significant correlations were found between them in both normal subjects (r = .69, p less than 0.001) and cardiac failure patients (r = .72, p less than 0.01). Characterisation by gel permeation and fast protein liquid chromatography demonstrated coelution of the N- and C-terminal cardiodilatin immunoreactivities in a single chromatographic peak. These results suggest that the circulating cardiodilatin in normal subjects and patients with cardiac failure contains the entire prohormone amino-terminal sequence ANP-[Asn1-Arg98].

Variation in pulmonary artery pressure has important consequences for the interpretation of isolated pressure measurements in patients with chronic heart failure. To investigate the nature of diurnal variation in pulmonary artery pressure in chronic heart failure, eight angina-free men (aged 50-72 years) with treated chronic heart failure caused by ischaemic heart disease underwent continuous ambulatory pulmonary artery pressure recording by a transducer tipped catheter. The mean (1 SD) daytime pulmonary artery pressure was 29.6 (5.0) mm Hg systolic and 13.7 (5.6) mm Hg diastolic. The mean change in pressure from day to night was +5.1 (3.2) mm Hg systolic and +3.8 (1.7) mm Hg diastolic; and the mean change from standing to lying +9.3 (2.3) mm Hg systolic and +6.4 (2.1) mm Hg diastolic. In six of the eight patients there was considerable rise in pulmonary artery pressure at night, but in the two patients with the most severe symptoms there was no nocturnal rise. In patients with chronic heart failure, nocturnal pulmonary artery pressure is not determined by postural change alone. But interpretation of isolated pulmonary artery pressure measurements must take the posture of the patient into account.

Regional cerebral [11C]3- O-methyl-d-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 m M), and four were studied at hyperglycaemic plasma glucose levels (mean 13 m M). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 m M had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and d-glucose for the passive facilitated transport carrier system for hexoses across the blood–brain barrier (BBB). It is concluded that the number and affinity of d-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of d-glucose across the BBB.