The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

AIMS: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. METHODS AND RESULTS: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. CONCLUSION: In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.

Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial.

BACKGROUND: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. METHODS: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%. Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments. The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point. Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation. Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified. This study is registered with ClinicalTrials.gov, NCT02937454, and has now been completed. FINDINGS: Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups. Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62-1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64-1·00, p=0·050). There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70-1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58-0·94, p=0·013). The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66-0·98, p=0·030). Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47-0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group. INTERPRETATION: In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death. FUNDING: Vifor Pharma.

Characteristics and outcome of acute heart failure patients according to the severity of peripheral oedema.

BACKGROUND: Most trials of patients hospitalized for heart failure focus on breathlessness (alveolar pulmonary oedema) but worsening peripheral oedema is also an important presentation. We investigated the relationship between the severity of peripheral oedema on admission and outcome amongst patients with a primary discharge death or diagnosis of heart failure. OBJECTIVES: We tested the hypothesis that severity of peripheral oedema is associated with length of hospital stay and mortality. METHODS: Patient variables reported to the National Heart Failure Audit for England & Wales between April 2008 and March 2013 were included in this analysis. Peripheral oedema was classified as 'none', 'mild', 'moderate' or 'severe'. Length of stay, mortality during the index admission and for up to three years after discharge are reported. RESULTS: Of 121,214 patients, peripheral oedema on admission was absent in 24%, mild in 24%, moderate in 33% and severe in 18%. Median length of stay was, respectively, 6, 7, 9 and 12 days (P- < 0.001), index admission mortality was 7%, 8%, 10% and 16% (P- < 0.001) and mortality at a median follow-up of 344 (IQR 94-766) days was 39%, 46%, 52% and 59%. In an adjusted multi-variable Cox model, the hazard ratio for death was 1.51 for severe (P- < 0.001, CI 1.50-1.53), 1.21 for moderate (P- < 0.001, CI 1.20-1.22) and 1.04 (P- < 0.001, CI 1.02-1.05) for mild peripheral oedema compared to patients without peripheral oedema at presentation. CONCLUSION: Length of hospital stay and mortality during index admission and after discharge increased progressively with increasing severity of peripheral oedema at admission.

Declining Risk of Sudden Death in Heart Failure.

BACKGROUND: The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. METHODS: We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. RESULTS: Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P=0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. CONCLUSIONS: Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.).

Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases.

Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.

Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction: An Analysis From the High-Risk Myocardial Infarction Database Initiative.

BACKGROUND: Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF). METHODS AND RESULTS: We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (P<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (P<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (P for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14-1.77); P=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (P>0.05 for all outcomes). CONCLUSIONS: In post-myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay.

Variation in hospital performance for heart failure management in the National Heart Failure Audit for England and Wales.

OBJECTIVE: Investigation of variations in provider performance and its determinants may help inform strategies for improving patient outcomes. METHODS: We used the National Heart Failure Audit comprising 68 772 patients with heart failure with reduced left ventricular ejection fraction (HFREF), admitted to 185 hospitals in England and Wales (2007-2013). We investigated hospital adherence to three recommended key performance measures (KPMs) for inhospital care (ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on discharge, ß-blockers on discharge and referral to specialist follow-up) individually and as a composite performance score. Hierarchical regression models were used to investigate hospital-level variation. RESULTS: Hospital-level variation in adherence to composite KPM ranged from 50% to 97% (median 79%), but after adjustments for patient characteristics and year of admission, only 8% (95% CI 7% to 10%) of this variation was attributable to variations in hospital features. Similarly, hospital prescription rates for ACE-I/ARB and ß-blocker showed low adjusted hospital-attributable variations (7% CI 6% to 9% and 6% CI 5% to 8%, for ACE-I/ARB and ß-blocker, respectively). Referral to specialist follow-up, however, showed larger variations (median 81%; range; 20%, 100%) with 26% of this being attributable to hospital-level differences (CI 22% to 31%). CONCLUSION: Only a small proportion of hospital variation in medication prescription after discharge was attributable to hospital-level features. This suggests that differences in hospital practices are not a major determinant of observed variations in prescription of investigated medications and outcomes. Future healthcare delivery efforts should consider evaluation and improvement of more ambitious KPMs.

Galectin-3 and cardiac function in survivors of acute myocardial infarction.

BACKGROUND: Galectin-3 is a biomarker associated with inflammation and fibrosis that predicts adverse outcome and relates to biomarkers of extracellular matrix turnover in patients with heart failure, particularly when left ventricular (LV) systolic function is preserved. Whether galectin-3 is related to LV remodeling after acute myocardial infarction is unknown. METHODS AND RESULTS: Circulating galectin-3 and various extracellular matrix biomarkers were measured in 100 patients (age, 58.9±12.0 years; 77% men) admitted with acute myocardial infarction and LV dysfunction, at baseline (mean 46 hours) and at 24 weeks, with cardiac MRI at each time-point. LV remodeling was defined as change in LV end-systolic volume index. Relationships among galectin-3, biomarkers, and LV remodeling were analyzed across the entire cohort, then according to median baseline LV ejection fraction. Galectin-3 levels were elevated in 22 patients (22%) at baseline and increased significantly over time from 14.7±5.5 to 16.3±6.6 ng/mL (P=0.007). Baseline galectin-3 did not correlate with any LV parameters at baseline or change in any parameter over time. Galectin-3 was positively associated with remodeling in patients with supramedian baseline LV ejection fraction (ie, >49.2%; r=0.40; P=0.01) but not when LV ejection fraction was ≤49.2%. Galectin-3 correlated significantly with matrix metalloproteinase-3 and monocyte chemoattractant protein-1 at baseline, biomarkers that have been shown to relate to LV remodeling in this cohort. CONCLUSIONS: Galectin-3 correlated significantly with certain biomarkers involved in extracellular matrix turnover, although no definite relationship was identified with LV remodeling. Whether galectin-3 plays a pathological role in remodeling remains unclear but merits further study. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00132093.

Peripheral artery disease and outcomes after myocardial infarction: an individual-patient meta-analysis of 28,771 patients in CAPRICORN, EPEHESUS, OPTIMAAL and VALIANT.

OBJECTIVES: To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI). BACKGROUND: PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown. METHODS: Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT). RESULTS: Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7 years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15-1.37; p<0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16-1.33; p<0.001). CONCLUSIONS: PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies.

Demonstration of blood pressure-independent noninfarct myocardial fibrosis in primary aldosteronism: a cardiac magnetic resonance imaging study.

BACKGROUND: Primary aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy in humans and animals possibly mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in human subjects with PA and essential hypertension using contrast-enhanced cardiac magnetic resonance imaging as well as explore the mechanistic basis for any observed differences. METHODS AND RESULTS: Twenty-seven subjects with recently diagnosed PA and 54 essential hypertension controls were recruited. Subjects underwent gadolinium-enhanced cardiac magnetic resonance; noninfarct related myocardial fibrosis was identified by a diffuse pattern of late gadolinium enhancement. Patients also underwent assessment of pulse wave velocity, measurement of circulating superoxide anion and C-reactive protein, as well as blood pressure and biochemical assessment. Subjects were well matched with no difference in severity or duration of hypertension. There was a significant increase in the frequency of noninfarct late gadolinium enhancement in PA (70%) when compared with essential hypertension subjects (13%; P<0.0001) with no difference in left ventricular mass. Pulse wave velocity, superoxide, and C-reactive protein were significantly higher in subjects with PA. CONCLUSIONS: These data illustrate that patients with PA exhibit frequent myocardial fibrosis as demonstrated by late gadolinium enhancement using cardiac magnetic resonance imaging; this finding is independent of blood pressure. This may be mediated partly through inflammation and oxidative stress. This study highlights the importance of specific targeting of aldosterone excess as well as blood pressure reduction to minimize cardiac morbidity in PA.

Interleukin-21--a biomarker of importance in predicting myocardial function following acute infarction?

INTRODUCTION: Following acute myocardial infarction (AMI), the acute inflammatory response contributes to wound healing but also to progressive myocardial injury. Interleukin-21 (IL-21) plays a key role in immunoregulation; whether IL-21 is associated with left ventricular (LV) remodelling after AMI is unknown. METHODS: Plasma IL-21 concentrations were measured in 100 patients (age 58.9 ± 12.0 years, 77% male) admitted with AMI and LV dysfunction, at baseline (mean 46 h) and again at 24 weeks; cardiac magnetic resonance and measurement of B-type natriuretic peptide, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-2, -3, -9, and tissue inhibitor of metalloproteinase (TIMP)-1, -2, -4 occurred at both time-points. Remodelling was defined as change in LV end-systolic volume index (ΔLVESVI). RESULTS: Plasma IL-21 concentration was unchanged over time (48.1 [SD 35.4]pg/mL at baseline vs. 48.8 [61.3]pg/mL at 24 weeks, p=0.92). Baseline IL-21 correlated significantly with ΔLVESVI (r=0.30, p=0.005) and change in LV end-diastolic volume index (r=0.33, p=0.003). On multivariate analysis, plasma IL-21 was an independent predictor of remodelling. IL-21 was also significantly associated with higher TIMP-4 concentrations and lower MMP-9 concentrations at baseline. CONCLUSIONS: IL-21 predicts adverse remodelling following AMI in patients with LV dysfunction. Whether it plays a direct pathophysiological role in remodelling merits further study.

Altered relative concentrations of high-energy phosphates in patients with uraemic cardiomyopathy measured by magnetic resonance spectroscopy.

BACKGROUND: Premature sudden cardiovascular death is the commonest cause of death in end-stage renal disease (ESRD) patients and is associated with uraemic cardiomyopathy [left ventricular hypertrophy (LVH), systolic dysfunction (LVSD) or LV dilation]. High-energy phosphates (HEP), quantified using phosphorus-31 magnetic resonance spectroscopy, are reduced in patients with diabetes, heart failure and uraemia. Phosphocreatine:ß adenosine triphosphate (PCr:ATP) ratio is an index of metabolic activity. We compared resting HEPs in ESRD patients and hypertensive patients (with and without LVH) who had normal renal function (LVH-only or normal myocardia). We also assessed associations of HEP levels with abnormalities of uraemic cardiomyopathy. METHODS: Fifty-three ESRD and 30 hypertensive patients (18 with LVH, 12 with normal myocardia) underwent phosphorus magnetic resonance spectroscopy of their left ventricle. PCr:ATP ratios were calculated from (31)P-MR spectra obtained from long-axis views of the left ventricle. RESULTS: There were no significant differences in age, LV mass, chamber sizes and ejection fraction between patient groups. PCr:ATP was significantly lower in ESRD patients compared to hypertensive patients, irrespective of the presence or absence of LVH (P = 0.01). In the ESRD group, PCr:ATP was significantly lower in patients with LVSD (P = 0.05) and LV dilation (P = 0.01). LVH was not associated with significant difference in PCr:ATP. CONCLUSIONS: ESRD patients have lower HEP levels compared to hypertensive patients. Lower PCr:ATP ratio, indicating altered myocardial metabolic function in ESRD patients, is associated with features of uraemic cardiomyopathy.

A low pulse pressure predicts mortality in subjects with heart failure after an acute myocardial infarction: a post-hoc analysis of the CAPRICORN study.

BACKGROUND: In patients with cardiovascular disease, a high pulse pressure is related to an increased risk of cardiovascular events but in patients with advanced heart failure, a low pulse pressure is predictive of adverse (cardiovascular) events. AIM: We studied the prognostic importance of pulse pressure in a group of post-myocardial infarction patients, with and without signs and symptoms of heart failure. Subjects had been randomised in the CAPRICORN clinical trial, and followed up for a mean of 1.3 years. METHODS: Blood pressure was measured in 1,955 patients with a left ventricular ejection fraction ≤40%, between 3 and 21 days post myocardial infarction. Cox proportional survival models were reproduced for those with Killip Class I (n = 1342) versus classes II/III/IV heart failure (n = 613). RESULTS: Overall mean (SD) age was 63 (12) years, mean (SD) left ventricular ejection fraction 33(6)%, mean (SD) baseline blood pressure was 121 (17)/74 (10) mmHg and most (73%) were male. In patients with Killip Class 1, pulse pressure was not predictive for any outcome. However, in patients with Killip Class II-IV, a low pulse pressure independently predicted all cause mortality (HR 0.83 per 10 mmHg, CI 0.71-0.98, p = 0.025), cardiovascular mortality (HR 0.83 per 10 mmHg, CI 0.70-0.98, p = 0.025) and sudden death (HR 0.77 per 10 mmHg, CI 0.60-1.00, p = 0.047). A lower pulse pressure did not predict hospitalisation for worsening heart failure. CONCLUSION: A low pulse pressure is an independent predictor of mortality in subjects with depressed left ventricular ejection fraction after a recent myocardial infarction and evidence of Killip Class II-IV heart failure.

Clinical trials in acute heart failure: simpler solutions to complex problems. Consensus document arising from a European Society of Cardiology cardiovascular round-table think tank on acute heart failure, 12 May 2009.

This European consensus document aims to identify the main reasons for the apparent lack of progress in the introduction of new medicines for acute heart failure. Relevant issues include not only the heterogeneity of the patient group but also the pharmacology of the medicines themselves and the design of the trials. Above all, this document attempts to provide some pragmatic solutions to this complex syndrome to simplify the execution of meaningful therapeutic endeavours in this area of undoubted unmet clinical need in the future.

Cardiovascular magnetic resonance activity in the United Kingdom: a survey on behalf of the British Society of Cardiovascular Magnetic Resonance.

BACKGROUND: The indications, complexity and capabilities of cardiovascular magnetic resonance (CMR) have rapidly expanded. Whether actual service provision and training have developed in parallel is unknown. METHODS: We undertook a systematic telephone and postal survey of all public hospitals on behalf of the British Society of Cardiovascular Magnetic Resonance to identify all CMR providers within the United Kingdom. RESULTS: Of the 60 CMR centres identified, 88% responded to a detailed questionnaire. Services are led by cardiologists and radiologists in equal proportion, though the majority of current trainees are cardiologists. The mean number of CMR scans performed annually per centre increased by 44% over two years. This trend was consistent across centres of different scanning volumes. The commonest indication for CMR was assessment of heart failure and cardiomyopathy (39%), followed by coronary artery disease and congenital heart disease. There was striking geographical variation in CMR availability, numbers of scans performed, and distribution of trainees. Centres without on site scanning capability refer very few patients for CMR. Just over half of centres had a formal training programme, and few performed regular audit. CONCLUSION: The number of CMR scans performed in the UK has increased dramatically in just two years. Trainees are mainly located in large volume centres and enrolled in cardiology as opposed to radiology training programmes.

Aldosterone and cortisol predict medium-term left ventricular remodelling following myocardial infarction.

AIMS: Mineralocorticoid receptor (MR) antagonists improve cardiovascular outcomes in patients with heart failure complicating acute myocardial infarction (AMI) and in chronic heart failure. It is unclear whether these beneficial effects are due solely to aldosterone blockade, as MR has a similar affinity for cortisol. We examined the relationships between plasma and urinary steroid hormones and left ventricular (LV) remodelling in patients with LV dysfunction following AMI. METHODS AND RESULTS: Plasma concentrations of renin, aldosterone, and N-terminal pro-brain natriuretic peptide (NT-proBNP), and 24 h urinary excretion rates of tetrahydroaldosterone (THAldo) and total cortisol metabolites were measured in 93 patients at a mean of 46 h following AMI prior to contrast-enhanced cardiac magnetic resonance (ceCMR). Patients were then randomized to 24 weeks of placebo or eplerenone therapy in addition to standard treatment, after which ceCMR was repeated. In placebo-treated patients, aldosterone, NT-proBNP, and excretion rates of THAldo and total cortisol metabolites were univariate predictors of remodelling (i.e. change in LV end-systolic volume index); aldosterone (P = 0.040) and total cortisol metabolite excretion (P = 0.038) remained independent predictors on multivariate analysis. None of the measured biomarkers predicted remodelling in the presence of eplerenone. Plasma and urinary aldosterone measures, and urinary cortisol metabolites, were not only related to larger infarct volumes and greater infarct remodelling over time, but were also higher in patients with microvascular obstruction on baseline ceCMR. CONCLUSION: Aldosterone and cortisol are associated with medium-term LV remodelling when measured early after AMI. The beneficial effects of MR antagonism may relate to blockade of both aldosterone- and cortisol-induced MR activation.