Vericiguat for heart failure and the VICTORIA trial – the dog that didn't bark?

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Investigation of stratiform sulphide mineralisation at Meall Mor, South Knapdale, Argyll

A co-ordinated geochemical-geophysical-geological investigation of copper mineralisation in the Meal1 ?46r area, South Knapdale, Argyll was carried 0th in 1976 and followed by a drilling programme of 3 shallow holes in early 1977. The mineralisation occursin a zone of weak stratiform sulphide mineralisation (the pyrite zone) with a strike length of 1Okm in the Upper &ins Quartz&e of the Middle Dalradian. The geochemical drainage survey showed the existence of a strongly anomalous distribution of Cu and Sb in the Abhainn Srathain draining south from . Meal1 M&- and detailed soil sampling over the pyrite zone outlined a broad area enriched in copper. Deeper soil sampling confirmed the anomalously high copper values and a coincident IP anomaly was found stretching from Meal1 M& south to the old mine workings on Abhainn Srathain, and is probably caused by a local enrichment of pyrite and chalcopyrite within the pyrite zone. Three boreholes were drilled; two on coincident geochemical and geophysical anomalies, and the third beneath the old mines at Abhainn Srathain. Copper values in the first two holes range up to 0.24% Cu over 4.27m, but up to 1.06% Cu over 2.67m in the third and this enrichment may be related to a later remobilisation of the disseminated chalcopyrite. The results of subsequent drilling at two other sites are given in Appendix III

Effects of Chronic Hypoxemia on Chemosensitivity in Patients With Univentricular Heart

AbstractObjectives. We sought to compare the arterial blood gas chemosensitivity in relation to exercise ventilatory response in patients with univentricular heart and cyanosis and in patients with univentricular heart and Fontan-type circulation without cyanosis.Background. Patients with univentricular heart demonstrate excessive ventilation during exercise. Chronic hypoxemia may alter chemoreceptor function, affecting ventilation.Methods. Cardiopulmonary exercise testing was performed in 10 patients with rest or stress-induced cyanosis (cyanotic group: mean age ± SE 30.5 ± 2.3 years; 5 men), 8 patients without cyanosis with Fontan-type circulation (Fontan group: mean age 29.4 ± 1.5 years; 4 men) and 10 healthy control subjects (normal group: mean age 30.7 ± 1.9 years; 5 men). Hypoxic and hypercapnic chemosensitivity were assessed by using transient inhalations of pure nitrogen and the rebreathing of 7% CO2in 93% O2, respectively.Results. Peak O2consumption was comparable in both patient groups (21.7 ± 2.5 [cyanotic group] vs. 21.0 ± 1.9 ml/kg per min [Fontan group]) but was lower than that in the normal group (34.7 ± 1.9 ml/kg per min). The ventilatory response to exercise, characterized by the regression slope relating minute ventilation to CO2output, was higher in the cyanotic group (43.4 ± 4.0) than in the Fontan group (31.4 ± 3.0, p = 0.02) and the normal group (23.1 ± 1.1). Hypoxic chemosensitivity was blunted in the cyanotic group compared with that in the Fontan and normal groups (0.148 vs. 0.448 [p = 0.02] vs. 0.311 liter/min per percent arterial O2saturation, respectively) and did not correlate with the ventilatory response to exercise (r = −0.36, p = 0.29). In contrast, hypercapnic chemosensitivity represented by the slope of the hypercapnic-ventilatory response line was similar in the cyanotic, Fontan and normal groups (1.71 vs. 1.76 vs. 1.70 liter/min per mm Hg, respectively), but the response line had shifted to the left in the cyanotic group (x intercept = 31.9 vs. 39.9 mm Hg [p = 0.026]), compared with 45.2 mm Hg in normal subjects. These findings suggest that in the cyanotic group, ventilation is greater for a given level of arterial CO2tension and thus may partly explain the increased exercise ventilatory response in this group.Conclusions. Hypoxic chemosensitivity is blunted in patients with univentricular heart and cyanosis and does not determine the exercise ventilatory response. CO2elimination appears more important. The blunting of hypoxic chemosensitivity is reversible once chronic hypoxemia is relieved, as evident in the Fontan group

Muscle Ergoreceptor Overactivity Reflects Deterioration in Clinical Status and Cardiorespiratory Reflex Control in Chronic Heart Failure

Background In chronic heart failure (CHF), overactivation of ergoreceptors (afferents sensitive to the metabolic effects of muscular work) may be a link between peripheral changes, sympathetic overactivation, and increased hemodynamic and ventilatory responses to exercise. The relationship between ergoreceptors, autonomic changes, and the progression of the syndrome has not yet been studied. Methods and Results Thirty-eight stable CHF patients (age, 57±1 years; ejection fraction, 26±2%) were compared with 12 age-matched normal control subjects. The ergoreflex contribution to the ventilatory and hemodynamic responses to exercise, together with peripheral and central chemoreceptor sensitivity, arterial baroreflex sensitivity, plasma norepinephrine, epinephrine, and heart rate variability, were measured. Enhanced ergoreflex effects on ventilation (78±2% versus 50±8%), peripheral chemosensitivity (0.6±0.4 versus 0.2±0.1 L/min per percent Sa o 2 ), and central chemosensitivity (2.9±0.2 versus 2.0±0.2 L · min −1 · mm Hg −1 ) and an impaired baroreflex function (4.1±0.6 versus 9.1±5.6 ms/mm Hg) were confirmed in CHF compared with control subjects ( P <0.01 in all comparisons). Ergoreceptor overactivity was associated with a worse symptomatic state (NYHA class, P <0.05), lower exercise tolerance (peak V o 2 , P <0.05), and pronounced exercise hyperventilation (V̇ e /V co 2 , P <0.01). It was also a strong predictor of increased central chemosensitivity (independently of clinical parameters), baroreflex impairment, and sympathetic activation (plasma catecholamines and heart rate variability indexes; all P <0.05). In multivariate analysis, among all reflexes studied, the ventilatory component of the ergoreflex was the only independent predictor of peak V o 2 and V̇ e /V co 2 . Conclusions In CHF, overactivation of the ergoreflex is associated with abnormal cardiorespiratory reflex control, independently of clinical severity. Among impaired reflexes, overactivation of the ergoreflex is an important determinant of exercise hyperventilation and reduced exercise tolerance

Performance of prognostic risk scores in chronic heart failure patients enrolled in the European Society of Cardiology Heart Failure long-term registry

[Abstract] Objectives. This study compared the performance of major heart failure (HF) risk models in predicting mortality and examined their utilization using data from a contemporary multinational registry. Background. Several prognostic risk scores have been developed for ambulatory HF patients, but their precision is still inadequate and their use limited. Methods. This registry enrolled patients with HF seen in participating European centers between May 2011 and April 2013. The following scores designed to estimate 1- to 2-year all-cause mortality were calculated in each participant: CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure), MAGGIC (Meta-analysis Global Group in Chronic Heart Failure), and SHFM (Seattle Heart Failure Model). Patients with hospitalized HF (n = 6,920) and ambulatory HF patients missing any variable needed to estimate each score (n = 3,267) were excluded, leaving a final sample of 6,161 patients. Results. At 1-year follow-up, 5,653 of 6,161 patients (91.8%) were alive. The observed-to-predicted survival ratios (CHARM: 1.10, GISSI-HF: 1.08, MAGGIC: 1.03, and SHFM: 0.98) suggested some overestimation of mortality by all scores except the SHFM. Overprediction occurred steadily across levels of risk using both the CHARM and the GISSI-HF, whereas the SHFM underpredicted mortality in all risk groups except the highest. The MAGGIC showed the best overall accuracy (area under the curve [AUC] = 0.743), similar to the GISSI-HF (AUC = 0.739; p = 0.419) but better than the CHARM (AUC = 0.729; p = 0.068) and particularly better than the SHFM (AUC = 0.714; p = 0.018). Less than 1% of patients received a prognostic estimate from their enrolling physician. Conclusions. Performance of prognostic risk scores is still limited and physicians are reluctant to use them in daily practice. The need for contemporary, more precise prognostic tools should be considered

Gold in the Dalradian terrane : a review of previous work

The Dalradian Supergroup comprises a Late Precambrian sequence of marine clastic sedimentary rocks and minor basic volcanic rocks which was folded and metamorphosed during the early Palaeozoic Caledonian Orogeny. Intrusive igneous rocks are widespread throughout the Dalradian terrane. The most important in terms of gold metallogenesis are the post-tectonic granites which comprise a diverse suite of calc-alkaline intrusions emplaced between 420 and 395 Ma. Numerous occurrences of gold in bedrock and alluvium are documented in the Dalradian terrane of Scotland. Mesothermal vein occurrences are the most important and include the Cononish deposit, near Tyndrum in Perthshire, where planning permission for mining has been granted. Gold mineralisation of several other styles, including intrusion-related, epithermal, stratiform and occurrences associated with mafic-ultramafic intrusions, is also present. This report has been compiled for the BGS Core Programme project ‘Sedimentary Basin Resources: Gold in orogenic extensional basins – the Dalradian’. This project, carried out between 1997–2000, was designed to investigate the factors controlling the distribution of gold in the Dalradian and to develop a predictive metallogenic model for gold mineralisation in this terrane. This report provides a` review of known gold occurrences and the results of past mineral exploration activity in the Dalradian terrane. The latter has been compiled from records held in BGS archives and the available data are summarised in a series of appendices. Exploration for metalliferous mineralisation has been carried out widely in the Dalradian terrane by commercial mining companies and by BGS. In the 1970s most work focused on Cu, Pb, Zn, Ni and Mo, while more recently, from 1981 onwards, precious metals (Au and PGE) were the prime target. Between 1972 and 1984 the DTI sought to encourage private-sector mineral exploration by the provision of grants under the Mineral Exploration and Investment Grants Act (MEIGA). About 150 reports derived from these projects are available on open-file at BGS. Exploration by BGS was carried out mainly through the DTI-funded Mineral Reconnaissance Programme (MRP), which ran between 1972 and 1997. Nearly 150 reports and associated data releases were produced by the MRP. Together the MEIGA and MRP reports have been the major sources of information used in this report. The combination of improved genetic models for gold deposits, the increased availability of multidisciplinary digital geoscience data and the information on previous exploration summarised in this report provides a sound basis for research on gold mineralisation in the Dalradian terrane. Potential exists in a range of settings that may host economic gold deposits

The incidence of all-cause, cardiovascular and respiratory disease admission among 20,252 users of lisinopril vs. perindopril: a cohort study

Background: Major international guidelines do not offer explicit recommendations on any specific angiotensin-converting enzyme inhibitor (ACEI) agent over another within the same drug group. This study compared the effectiveness of lisinopril vs. perindopril in reducing the incidence of hospital admission due to all-cause, cardiovascular disease and respiratory disease. Methods: Adult patients who received new prescriptions of lisinopril or perindopril from 2001 to 2005 in all public hospitals and clinics in Hong Kong were included, and followed up for ≥2 years. The incidence of admissions due to all-cause, cardiovascular disease and respiratory disease were evaluated, respectively, by using Cox proportional hazard regression models. The regression models were constructed with propensity score matching to minimize indication biases. Results: A total of 20,252 eligible patients with an average age of 64.5 years (standard deviation 15.0) were included. The admission rate at 24 months within the date of index prescription due to any cause, cardiovascular disease and respiratory disease among lisinopril vs. perindopril users was 24.8% vs. 24.8%, 13.7% vs. 14.0% and 6.9% vs. 6.3%, respectively. Lisinopril users were significantly more likely to be admitted due to respiratory diseases (adjusted hazard ratios [AHR] = 1.25, 95% CI 1.08 to 1.43, p = 0.002 at 12 months; AHR = 1.17, 95% CI 1.04 to 1.31, p = 0.009 at 24 months) and all causes (AHR = 1.12, 95% CI 1.05 to 1.19, p &lt; 0.001 at 24 months) than perindopril users. Conclusions: These findings support intra-class differences in the effectiveness of ACEIs, which could be considered by clinical guidelines when the preferred first-line antihypertensive drugs are recommended