Damien Cullington

Heart rate achieved or beta‐blocker dose in patients with chronic heart failure: which is the better target?

To investigate whether the mortality of patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD) is more strongly related to beta‐blocker dose or to heart rate. It is known that beta‐blockers reduce mortality in patients with CHF and LVSD, but the primary mechanism of action is uncertain.

Clinical trials update from Heart Rhythm 2008 and Heart Failure 2008: ATHENA, URGENT, INH study, HEART and CK-1827452.

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the Heart Rhythm Society meeting in San Francisco, USA and the Heart Failure Association meeting of the European Society of Cardiology which was held in Milan, Italy in June 2008. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication.

Is Heart Rate Important for Patients With Heart Failure in Atrial Fibrillation

OBJECTIVES This study sought to investigate the relationship between resting ventricular rate and mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) who were in sinus rhythm (SR) or atrial fibrillation (AF). BACKGROUND Slower heart rates are associated with better survival in patients with CHF in SR, but it is not clear whether this is true for those in AF. METHODS We assessed 2,039 outpatients with CHF and LVEF ≤50% undergoing baseline assessment, of whom 24% (n = 488) were in AF; and 841 outpatients reassessed after attempted treatment optimization at 1 year, of whom 22% (n = 184) were in AF. Cox proportional hazards models were used to assess the relationships between heart rate and survival in patients with CHF and AF or sinus rhythm. We analyzed heart rate and rhythm data recorded at the baseline review and after 1-year follow-up. Proportional hazards assumptions were checked by Schoenfeld and Martingale residuals. RESULTS The median survival for those in AF was 6.1 years (interquartile range [IQR]: 5.3 to 6.9 years) and 7.3 years (IQR: 6.5 to 8.1 years) for those in SR. In univariable analysis, patients with AF had a worse survival (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.08 to 1.47; p = 0.003) but after covariate adjustment, survival rates were similar. After adjusting Cox regression models, there was no association between heart rate (per 10 beats/min increments) and survival in patients with AF before (HR: 0.94, 95% CI: 0.88 to 1.00, p = 0.07) or after (HR: 1.00, 95% CI: 0.99 to 1.00, p = 0.84) therapy optimization. For patients in SR, higher heart rates were associated with worse survival, both before (HR: 1.10, 95% CI: 1.05 to 1.15, p <0.0001) and after (HR: 1.13, 95% CI: 1.03 to 1.24, p = 0.008) therapy optimization. CONCLUSIONS In patients with CHF and a reduced LVEF, slower resting ventricular rate is associated with better survival for patients in SR but not for those with AF.

Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American Heart Association 2007. These should be considered as preliminary data, as analyses may change in the final publication.

Clinical trials update from the American College of Cardiology 2009: ADMIRE-HF, PRIMA, STICH, REVERSE, IRIS, partial ventricular support, FIX-HF-5, vagal stimulation, REVIVAL-3, pre-RELAX-AHF, ACTIVE-A, HF-ACTION, JUPITER, AURORA, and OMEGA

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the American College of Cardiology meeting in 2009. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. 123I‐mIBG myocardial scintigraphy was a good predictor of mortality in patients with heart failure in ADMIRE‐HF. In PRIMA, use of individualized target NT‐proBNP levels failed to improve outcomes compared with usual care in patients hospitalized with symptomatic heart failure. In the STICH trial, additional ventricular reconstruction surgery failed to improve outcomes in patients with ischaemic heart failure undergoing CABG. Cardiac resynchronization therapy may modify disease progression in patients with mild heart failure, according to data from REVERSE. Implantation of a defibrillator early after MI in high‐risk patients in the IRIS study failed to improve outcomes compared with usual care. Cardiac contractility modulation showed some beneficial effects on symptoms and exercise capacity in the unblinded FIX‐HF‐5 study. Data from pre‐RELAX‐AHF show that relaxin may have potential as a treatment for acute heart failure. HF‐ACTION showed that patients who complied with an exercise training regime achieved a better outcome, although this may be confounded by the ability of patients with a good prognosis to exercise for longer.

Limited role for ivabradine in the treatment of chronic heart failure

Objective To quantify the proportion of patients attending a community heart failure clinic with left ventricular systolic impairment who might be suitable for ivabradine therapy. Background High resting heart rate is an important and potentially modifiable risk factor in patients with heart failure. The SHIFT study suggested that ivabradine was beneficial when added to conventional treatment including a β-blocker in heart failure patients in sinus rhythm whose resting heart rates remained 70 beats per minute (bpm) or greater and who had worse than moderate left ventricular impairment. Methods and Results The primary cohort included 2211 patients with a left ventricular ejection fraction (LVEF) of 50% or less. Patients were seen at baseline, then reviewed at 4 and 12 months. ‘Suitability’ for ivabradine was assessed as: LVEF 35% or less, sinus rhythm and a resting heart rate of 70 bpm or greater. The proportion of patients who were ‘suitable’ for ivabradine therapy fell from 19.4% (n=429) at baseline, to 14.1% (n=185) at 4 months and finally 9% (n=82) by the 12-month clinic visit. The proportion fell to 5.3% (n=48) if only patients with New York Heart Association class I symptoms and/or no β-blocker therapy were excluded. Conclusions After uptitration of heart failure medications, the number of patients ‘suitable’ for ivabradine therapy was small. First and foremost, β-blocker therapy should be commenced and titrated. The decision to add ivabradine should be made after allowing adequate time to uptitrate conventional medical therapy.

Clinical trials update from the American College of Cardiology 2008: Carisma, Trends, meta-analysis of Cox-2 studies, Hat, on-Target, Hyvet, Accomplish, Momentum, Protect, Horizon-hf and Reverse

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the American College of Cardiology. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication.

Clinical trials update from European Society of Cardiology meeting 2008: TIME‐CHF, BACH, BEAUTIFUL, GISSI‐HF, and HOME‐HF

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the European Society of Cardiology meeting which was held in Munich, Germany from 30th August to 3rd September 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication.

Cardiac resynchronization therapy: dyssynchrony imaging from a heart failure perspective.

Purpose of review To review the evidence for and against imaging as a means of selecting patients for cardiac resynchronization therapy (CRT). Recent findings There is no evidence that either the QRS interval on the surface ECG or dyssynchrony measured by imaging is of any practical value in predicting the clinical response to CRT in patients with a dilated and dysfunctional left ventricle. Careful assessment of the patient, so that therapy can be logically aligned with treatment goals, such as improving symptoms or prognosis, is the only useful method for selecting patients. Simple clinical evaluation may be as effective as, or more effective than, more complex assessments in predicting treatment benefits. Patients with a low blood pressure and moderate functional mitral regurgitation might benefit more, in absolute terms, from CRT. The benefits of adding a defibrillator to CRT are modest and, for many patients, uncertain. Summary Echocardiography, which was supposed to facilitate the introduction of CRT, may have become the greatest barrier to its appropriate implementation. Cardiac dyssynchrony, measured by echocardiography prior to implantation, may not be the substrate for the effects of CRT.

Clinical trials update from the European Society of Cardiology Meeting 2011: ARISTOTLE, SMART-AV: QLV substudy, SHIFT: echocardiography and quality of life substudies, European CRT Survey, and Basic Science Update.

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the European Society of Cardiology meeting held in Paris, France in August 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from ARISTOTLE suggest that apixaban is more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Electrical dyssynchrony, measured by the time from onset of electrical activity on the surface ECG to activation of myocardium by intrinsic conduction at the pacing site (QLV), was a strong and independent predictor of improvement in ventricular function after cardiac resynchronization therapy (CRT) in an observational analysis of a subgroup of patients from the SMART‐AV study. Subgroup analyses from SHIFT suggest that heart rate reduction with ivabradine causes favourable left ventricular remodelling and improves quality of life in patients with symptomatic systolic heart failure and an increased heart rate. The European CRT Survey reported outcome data.