Impaired renal function affects clinical outcomes and management of patients with heart failure.

AIMS: Inpatients with heart failure and renal impairment have poor outcomes and variable quality of care. We investigate treatment practice and outcomes in an unselected real-world cohort using historical creatinine measurements. METHODS AND RESULTS: Admissions between 1/4/2013 and 30/4/2015 diagnosed at discharge with heart failure were retrospectively analysed. Stages of chronic kidney disease (CKD) and acute kidney injury (AKI) were calculated from creatinine at discharge and 3-12 months before admission. We identified 1056 admissions of 851 patients (mean age 76 years, 56% Caucasian, 36% with diabetes mellitus, 54% with ischaemic heart disease, and 57% with valvular heart disease). CKD was common; 36%-Stage 3a/b, 11%-Stage 4/5; patients were older, more often diabetic, with higher potassium, lower haemoglobin, and more oedema but similar prevalence of left ventricular systolic dysfunction (LVSD) compared patients with Stages 0-2. AKI was present in 17.0% (10.4%-Stage 1, 3.7%-Stage 2, and 2.9%-Stage 3); these had higher potassium and lower haemoglobin than patients with no AKI. Length of stay was longer in Stage 4/5 CKD [11 days; P = 0.008] and AKI [13 days; P = 0.006]. Mortality was higher with Stage 4/5 CKD (13.8% compared with 7.7% for Stages 0-2 CKD (P = 0.036)] and increased with AKI (5%-no AKI, 20.9%-Stage 1, 35.9%-Stage 2, and 48.4%-Stage 3; P < 0.001). Adjusted for age, diabetes, and LVSD, both AKI and Stage 4/5 CKD were independent predictors of in-hospital mortality. In survivors with LVSD, the discharge prescription of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased with progressive CKD, [84%-no-mild, 59%-moderate, and 36%-severe CKD; P < 0.001]; this was not purely explained by hyperkalaemia. CONCLUSIONS: Inpatients with heart failure and renal impairment, acute and chronic, failed to receive recommended therapy and had poor outcomes

The renin‐angiotensin‐aldosterone system and its suppression

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/1/jvim15454-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/2/jvim15454-sup-0002-figures.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/3/jvim15454-sup-0005-TableS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/4/jvim15454-sup-0004-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/5/jvim15454-sup-0007-TableS5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/6/jvim15454_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/7/jvim15454.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/8/jvim15454-sup-0006-TableS4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148403/9/jvim15454-sup-0003-TableS1.pd

Update on anti-coagulation in atrial fibrillation

Atrial fibrillation (AF), the most common clinically relevant arrhythmia, affects 2.2 million individuals in the USA and 4.5 million in Europe, resulting in significant morbidity and mortality. Pharmacotherapy aimed at controlling both heart rate and rhythm is employed to relieve AF symptoms, though debate continues about which approach is preferable. AF prevalence rises with age from 0.4% to 1% in the general population to 11% in those aged >70 years. AF is associated with a pro-thrombotic state and other comorbidities; age, hypertension, heart failure and diabetes mellitus all play a key role in AF pathogenesis. Anti-coagulation is essential for stroke prevention in patients with AF and is recommended for patients with one or more risk factors for stroke. Used within the recommended therapeutic range, warfarin and other vitamin K antagonists decrease the incidence of stroke and mortality in AF patients. Warfarin remains under-used, however, because of the perceived high risk of haemorrhage, narrow therapeutic window and need for regular monitoring. Several novel anti-coagulants show promise in AF-related stroke prevention. In particular, the novel, oral, direct thrombin inhibitor, dabigatran etexilate, recently licensed by the US Food and Drug Administration (FDA) and Health Canada has shown improved efficacy and safety compared with warfarin for stroke prevention in AF, and has the potential to replace warfarin in this indication. The increasing number of new therapeutic options, including improved anti-arrhythmic agents, novel anti-coagulants and more accessible ablation techniques, are likely to deliver better care for AF patients in the near future

RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome

AIMS: To establish the safety, tolerability and most promising regimen of darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of ischaemic events in acute coronary syndrome (ACS). METHODS: In a 26-week, multi-centre, double-blind, randomized, parallel-group study, 1279 patients with recent high-risk non-ST-segment or ST-segment elevation ACS received one of six darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary outcome was incidence of major or clinically relevant non-major bleeding events. The main efficacy outcome was a composite of death, stroke, myocardial infarction, systemic thromboembolism, and severe recurrent ischaemia. RESULTS: Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled HR: 2.275; 95% CI: 1.13–4.60, P = 0.022). Using placebo as reference (bleeding rate 3.1%), there was a dose–response relationship (P = 0.009) for increased bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg daily, respectively), which was statistically significant for 30 mg b.i.d. (P = 0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg dose arms) in efficacy event rates with darexaban, but the study was underpowered for efficacy. Darexaban showed good tolerability without signs of liver toxicity. CONCLUSIONS: Darexaban when added to dual antiplatelet therapy after ACS produces an expected dose-related two- to four-fold increase in bleeding, with no other safety concerns but no signal of efficacy. Establishing the potential of low-dose darexaban in preventing major cardiac events after ACS requires a large phase III trial. ClinicalTrials.gov Identifier: NCT0099429

Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia in clinical practise and its prevalence is increasing. Over the last 25 years, flecainide has been used extensively worldwide, and its capacity to reduce AF symptoms and provide long-term restoration of sinus rhythm (SR) has been well documented. The increased mortality seen in patients treated with flecainide in the Cardiac Arrhythmia Suppression Trial (CAST) study, published in 1991, still deters many clinicians from using flecainide, denying many new AF patients a valuable treatment option. There is now a body of evidence that clearly demonstrates that flecainide has a favourable safety profile in AF patients without significant left ventricular disease or coronary heart disease. As a result of this evidence, flecainide is now recommended as one of the first-line treatment options for restoring and maintaining SR in patients with AF under current treatment guidelines. The objective of this article is to review the literature pertaining to the pharmacological characteristics, safety and efficacy of flecainide, and to place this drug in the context of current therapeutic management strategies for AF

The genetic basis of hypertrophic cardiomyopathy in cats and humans

Mutations in genes that encode for muscle sarcomeric proteins have been identified in humans and two breeds of domestic cats with hypertrophic cardiomyopathy (HCM). This article reviews the history, genetics, and pathogenesis of HCM in the two species in order to give veterinarians a perspective on the genetics of HCM. Hypertrophic cardiomyopathy in people is a genetic disease that has been called a disease of the sarcomere because the preponderance of mutations identified that cause HCM are in genes that encode for sarcomeric proteins (Maron and Maron, 2013). Sarcomeres are the basic contractile units of muscle and thus sarcomeric proteins are responsible for the strength, speed, and extent of muscle contraction. In people with HCM, the two most common genes affected by HCM mutations are the myosin heavy chain gene (MYH7), the gene that encodes for the motor protein β-myosin heavy chain (the sarcomeric protein that splits ATP to generate force), and the cardiac myosin binding protein-C gene (MYBPC3), a gene that encodes for the closely related structural and regulatory protein, cardiac myosin binding protein-C (cMyBP-C). To date, the two mutations linked to HCM in domestic cats (one each in Maine Coon and Ragdoll breeds) also occur in MYBPC3 (Meurs et al., 2005, 2007). This is a review of the genetics of HCM in both humans and domestic cats that focuses on the aspects of human genetics that are germane to veterinarians and on all aspects of feline HCM genetics