It has been suggested that sudden cardiac death (SCD) contributes around 50% of cardiovascular and 27% of all-cause mortality in hemodialysis patients. The true burden of arrhythmias and arrhythmic ...deaths in this population, however, remains poorly characterised. Cardio Renal Arrhythmia Study in Hemodialysis (CRASH-ILR) is a prospective, implantable loop recorder single centre study of 30 established hemodialysis patients and one of the first to provide long-term ambulatory ECG monitoring.
30 patients (60% male) aged 68±12 years receiving hemodialysis for 45±40 months with varied etiology (diabetes 37%, hypertension 23%) and left ventricular ejection fraction (LVEF) 55±8% received a Reveal XT implantable loop recorder (Medtronic, USA) between August 2011 and October 2014. ECG data from loop recorders were transmitted at each hemodialysis session using a remote monitoring system. Primary outcome was SCD or implantation of a (tachy or bradyarrhythmia controlling) device and secondary outcome, the development of arrhythmia necessitating medical intervention.
During 379,512 hours of continuous ECG monitoring (mean 12,648±9,024 hours/patient), there were 8 deaths-2 SCD and 6 due to generalised deterioration/sepsis. 5 (20%) patients had a primary outcome event (2 SCD, 3 pacemaker implantations for bradyarrhythmia). 10 (33%) patients reached an arrhythmic primary or secondary end point. Median event free survival for any arrhythmia was 2.6 years (95% confidence intervals 1.6-3.6 years).
The findings confirm the high mortality rate seen in hemodialysis populations and contrary to initial expectations, bradyarrhythmias emerged as a common and potentially significant arrhythmic event.
Abstract
Aims
Over the last decades, the profile of chronic coronary syndrome has changed substantially. We aimed to determine characteristics and management of patients with chronic coronary ...syndrome in the contemporary era, as well as outcomes and their determinants.
Methods and results
Data from 32 703 patients (45 countries) with chronic coronary syndrome enrolled in the prospective observational CLARIFY registry (November 2009 to June 2010) with a 5-year follow-up, were analysed. The primary outcome cardiovascular death or non-fatal myocardial infarction (MI) 5-year rate was 8.0% 95% confidence interval (CI) 7.7–8.3 overall male 8.1% (7.8–8.5); female 7.6% (7.0–8.3). A cox proportional hazards model showed that the main independent predictors of the primary outcome were prior hospitalization for heart failure, current smoking, atrial fibrillation, living in Central/South America, prior MI, prior stroke, diabetes, current angina, and peripheral artery disease. There was an interaction between angina and prior MI (P = 0.0016); among patients with prior MI, angina was associated with a higher primary event rate 11.8% (95% CI 10.9–12.9) vs. 8.2% (95% CI 7.8–8.7) in patients with no angina, P < 0.001, whereas among patients without prior MI, event rates were similar for patients with 6.3% (95% CI 5.4–7.3) or without angina 6.4% (95% CI 5.9–7.0), P > 0.99. Prescription rates of evidence-based secondary prevention therapies were high.
Conclusion
This description of the spectrum of chronic coronary syndrome patients shows that, despite high rates of prescription of evidence-based therapies, patients with both angina and prior MI are an easily identifiable high-risk group who may deserve intensive treatment.
Clinical registry
ISRCTN43070564
Aims
For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about ...the effects in subgroups and the impact on mortality. We conducted a meta‐analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.
Methods and results
We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all‐cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval CI 0.61–0.93; p < 0.01) and first HHF or CVD (odds ratio OR 0.72, 95% CI 0.53–0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70–1.05; p = 0.14) and all‐cause mortality (OR 0.93, 95% CI 0.78–1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow‐up, which was less disrupted by the COVID‐19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49–0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74–1.30) (heterogeneity p = 0.07).
Conclusion
In patients with HF and ID, this meta‐analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all‐cause mortality remains inconclusive.
In a meta‐analysis of ten randomized controlled trials (RCTs) including AFFIRM‐AHF and IRONMAN of over 3000 patients with heart failure (HF) and iron deficiency (ID), compared to standard care/placebo, intravenous (IV) iron reduced the primary outcome of recurrent hospitalisations for heart failure (HHF) and cardiovascular mortality (CVM) by 25%. The effect was mainly driven by a reduction in HHF with the effect on CVM being inconconclusive. Created in BioRender.com. Additional icons provided from
http://icon‐library.com/icon/heart‐disease‐icon‐3.html.html Heart Disease Icon #293840. CI, confidence interval; CVM, cardiovascular mortality; HF, heart failure; HHF, hospitalization for heart failure; I, iron deficiency; IV, intravenous/interval variable; OR, odds ratio; RCT, randomized controlled trial; RR, risk rate; SE, standard error; SoC, standard of care.
Inhibitors of the renin-angiotensin-aldosterone (RAAS) system are cornerstones of the management of patients with heart failure with reduced left ventricular ejection fraction (HFrEF). However, RAAS ...inhibitors may cause decline in renal function and/or hyperkalaemia, particularly during initiation and titration, intercurrent illness and during worsening of heart failure. There is very little evidence from clinical trials to guide the management of renal dysfunction. The Renal Association and British Society for Heart Failure have collaborated to describe the interactions between heart failure, RAAS inhibitors and renal dysfunction and give clear guidance on the use of RAAS inhibitors in patients with HFrEF. During initiation and titration of RAAS inhibitors, testing renal function is mandatory; a decline in renal function of 30% or more can be acceptable. During intercurrent illness, there is no evidence that stopping RAAS inhibitor is beneficial, but if potassium rises above 6.0 mmol/L, or creatinine rises more than 30%, RAAS inhibitors should be temporarily withheld. In patients with fluid retention, high doses of diuretic are needed and a decline in renal function is not an indication to reduce diuretic dose: if the patient remains congested, more diuretics are required. If a patient is hypovolaemic, diuretics should be stopped or withheld temporarily. Towards end of life, consider stopping RAAS inhibitors. RAAS inhibition has no known prognostic benefit in heart failure with preserved ejection fraction. Efforts should be made to initiate, titrate and maintain patients with HFrEF on RAAS inhibitor treatment, whether during intercurrent illness or worsening heart failure.
To assess the frequency of chronic kidney disease (CKD), define the associated demographics, and evaluate its association with use of evidence-based drug therapy in a contemporary global study of ...patients with stable coronary artery disease.
22,272 patients from the ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) were included. Baseline estimated glomerular filtration rate (eGFR) was calculated (CKD-Epidemiology Collaboration formula) and patients categorised according to CKD stage: >89, 60-89, 45-59 and <45 mL/min/1.73 m2.
Mean (SD) age was 63.9±10.4 years, 77.3% were male, 61.8% had a history of myocardial infarction, 71.9% hypertension, 30.4% diabetes and 75.4% dyslipidaemia. Chronic kidney disease (eGFR<60 mL/min/1.73 m2) was seen in 22.1% of the cohort (6.9% with eGFR<45 mL/min/1.73 m2); lower eGFR was associated with increasing age, female sex, cardiovascular risk factors, overt vascular disease, other comorbidities and higher systolic but lower diastolic blood pressure. High use of secondary prevention was seen across all CKD stages (overall 93.4% lipid-lowering drugs, 95.3% antiplatelets, 75.9% beta-blockers). The proportion of patients taking statins was lower in patients with CKD. Antiplatelet use was significantly lower in patients with CKD whereas oral anticoagulant use was higher. Angiotensin-converting enzyme inhibitor use was lower (52.0% overall) and inversely related to declining eGFR, whereas angiotensin-receptor blockers were more frequently prescribed in patients with reduced eGFR.
Chronic kidney disease is common in patients with stable coronary artery disease and is associated with comorbidities. Whilst use of individual evidence-based medications for secondary prevention was high across all CKD categories, there remains an opportunity to improve the proportion who take all three classes of preventive therapies. Angiotensin-converting enzyme inhibitors were used less frequently in lower eGRF categories. Surprisingly the reverse was seen for angiotensin-receptor blockers. Further evaluation is required to fully understand these associations. The CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) Registry is registered in the ISRCTN registry of clinical trials with the number ISRCTN43070564. http://www.controlled-trials.com/ISRCTN43070564.
Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery ...disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain.
For patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves symptoms, ...exercise capacity and may in the following 12 months, reduce hospitalisations for heart failure. The Effectiveness of
nt
avenous ir
treat
ent versus standard care in p
tie
ts with heart failure and iron deficiency (IRONMAN) trial evaluated whether the benefits of intravenous iron persist in the longer term and impact on morbidity and mortality.
IRONMAN is a prospective, randomised, open-label, blinded endpoint (PROBE) event-driven trial. Patients aged ≥18 years with HFrEF (LVEF ≤45%) and evidence of iron deficiency (ferritin <100 µg/L and/or TSAT <20%) were enrolled if they had either a current or recent hospitalisation for heart failure or elevated plasma concentrations of a natriuretic peptide. Participants were randomised to receive, or not to receive, intravenous ferric derisomaltose in addition to guideline-recommended therapy for HFrEF. Every 4 months, intravenous iron was administered if either ferritin was <100 µg/L or, provided ferritin was ≤400 µg/L, TSAT was <25%. The primary endpoint is a composite of total hospitalisations for heart failure and cardiovascular death. Hospitalisation and deaths due to infection are safety endpoints.
Trial recruitment was completed across 70 UK hospital sites in October 2021. Participants were followed until the end of March 2022. We plan to report the results by November 2022.
IRONMAN will determine whether repeated doses of intravenous ferric derisomaltose are beneficial and safe for the long-term treatment of a broad range of patients with HFrEF and iron deficiency.
NCT02642562.
Introduction
Intravenous (IV) iron is the preferred treatment for patients with iron deficiency anemia (IDA) who require rapid replenishment of iron stores or in whom oral iron is not tolerated or ...effective. Data from two large-scale randomized controlled trials (RCTs) have recently been published reporting the incidence of adjudicated cardiovascular events after ferric derisomaltose (FDI) and iron sucrose (IS). The objective was to calculate the relative incidence of cardiovascular events with FDI and IS, and to conduct an indirect comparison with ferric carboxymaltose (FCM) based on previously published studies of cardiovascular risk.
Methods
RCTs reporting the incidence of blindly adjudicated cardiovascular events in IDA patients treated with IV iron were identified by systematic literature review (SLR). Pairwise random effects meta-analyses of FDI versus IS, and FCM versus IS were conducted for the pre-specified adjudicated composite cardiovascular endpoint of: death due to any cause, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmia, and protocol-defined hypertensive and hypotensive events. Analyses were also conducted for the composite endpoint excluding blood pressure events. Meta-analysis results were combined in an adjusted indirect comparison to provide an indirect estimate of cardiovascular risk with FDI versus FCM.
Results
The SLR retrieved 694 unique articles, of which four were RCTs reporting the incidence of the composite cardiovascular endpoint; two studies comparing FCM (
N
= 1529) with IS (
N
= 1505), and two studies comparing FDI (
N
= 2008) with IS (
N
= 1000). The odds ratios of the composite CV endpoint were 0.59 (95% confidence interval: 0.39–0.90) for FDI versus IS, 1.12 (95% CI 0.90–1.40) for FCM versus IS, and the indirect OR for FDI versus FCM was 0.53 (95% CI 0.33–0.85).
Conclusions
Pooling data from four large-scale RCTs suggested that FDI was associated with significantly lower incidence of cardiovascular adverse events compared to both FCM and IS.
British Society of Heart Failure Chaggar, Parminder; Squire, Iain; Kalra, Paul R
European heart journal,
08/2018, Letnik:
39, Številka:
30
Journal Article
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