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9. Lip, G. Y. H. et al. Bleeding risk assessment and management in atrial ﬁbrillation patients: executive summary of a position document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb. Haemostat. 106, 997–1011 (2011). 10. Lip, G. Y. The role of aspirin for stroke prevention in atrial fibrillation. Nat. Rev. Cardiol. 8, 602–606 (2011).
HEART FAILURE IN 2011
Heart failure therapy—technology to the fore
John J. V. McMurray
Studies published in 2011 in the field of heart failure have reinforced the benefit of cardiac resynchronization therapy in patients with mild symptoms and confirmed the value of left ventricular assist devices and CABG surgery in selected patients. Conversely, the efficacy of nesiritide in acute heart failure has been questioned.
McMurray, J. J. V. Nat. Rev. Cardiol. 9, 73–74 (2012); doi:10.1038/nrcardio.2011.212
Although many interesting studies on epidemiology, pathophysiology, and biomarkers in heart failure (HF) were published in 2011, my focus in this article is on treatments that are available for use and can make an impact in everyday practice. Five important studies, covering device and drug therapy, and surgery in patients with HF will be discussed. In August 2011, a follow-up report from MADIT-CRT1 reinforced the impressive effect of cardiac resynchronization therapy (CRT) on outcomes among patients with HF, even in those with mild symptoms. The investigators showed that CRT plus a defibrillator, compared with a defibrillator alone, reduced the risk of a first episode of worsening HF by 46% (P <0.001) and, importantly, also reduced the risk of subsequent episodes by 38% (P = 0.003). Because patients experiencing a first episode of worsening HF were at a substantially elevated risk of a further event, the absolute reduction in risk of subsequent episodes with CRT was large (from 72 to 44 events per 100 patient years of follow-up). The benefit was greatest in patients with left bundle branch block. In addition, a 19-fold increase in mortality risk was reported in patients experiencing a second episode of worsening HF.1 These findings are important for several reasons. Clearly, worsening of HF is extremely unpleasant for patients and usually leads to hospital admission with major consequences (economic and otherwise) for health-care systems, and is associated with an increased risk of death.1 These findings also highlight the limitations of the conventional ‘time to first-event’ analysis of
NATURE REVIEWS | CARDIOLOGY
trials, in which recurrent events that are frequent and of great clinical significance than first HF events are ignored. A report from INTERMACS 2 also reinforced the impressive technological progress made with left ventricular assist devices (LVADs). In a post-approval study required by the FDA, outcomes in the first 169 consecutive patients receiving a HeartMate II® (Thoratec Corporation, Pleasanton, CA, USA) device as a bridge-to-transplant were compared with those in 169 patients receiving different LVADs for the same indication over the same time period. The proportion of patients transplanted, recovered, or receiving continuing LVAD support at 6 months was 91% in the HeartMate II® group and 80% in the comparator group (85% and 70%,
respectively, at 1 year). These excellent outcomes from ‘real-world’ practice at 77 centers in the USA are consistent with the findings of the pivotal, randomized HeartMate II® trial,3 which showed that this continuousflow device was superior to the comparator pulsatile-flow device. Monitoring devices are currently of immense interest in HF research and the findings of the CHAMPION study 4 were notable. This moderate-sized trial showed that a small, implantable hemodynamic monitor improved outcomes in patients with NYHA class III HF who had been hospitalized for HF in the previous year and were optimally treated. The monitor was placed transvenously in a pulmonary artery branch and allowed wireless noninvasive measurement of pulmonary artery pressure. Physicians in the control group and patients in both groups did not have knowledge of pressure measurements; however, site investigators, the trial principal investigators, and sponsor (CardioMEMS, Atlanta, GA, USA) employees had access to pressure measurements and these were used to adjust therapy. Addition of nitrates and hydralazine and adjustment of diuretic therapy, including use of intravenous diuretics, were more frequent in the intervention group. The primary outcome was the rate of HF hospitalization over 6 months; 83 hospitalizations occurred among 55 of the 270 patients in the intervention group, compared with 120 among 80 of the 280 patients in the control group (rate 0.31 vs 0.44; HR 0.70, 95% CI 0.60–0.84, P <0.0001). In absolute terms, 12.5 fewer hospitalization events per 100 patients occurred over
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Med. Cardiol. HR 0. with intriguing proof-of-concept data in patients. 3. 1695–1701 (2011). Peterson. and no indication for revascularization (that is. Coll. 126 University Place. I would like to mention an important study relevant to the holistic care of patients with HF. there was an initial mortality excess in the surgery group and benefit from surgery was not apparent until after approximately 2 years of follow-up. 8. 676–683 (2011). Effect of nesiritide in patients with acute decompensated heart failure. G. et al. which is rapid and substantial. which was an independent predictor of all-cause mortality. 4 Although these results are impressive. audible patient alerts. et al. 57. I. D. Lancet 378. J. R. in carefully selected patients with systolic HF and coronary artery disease likely to survive for more than 2 years. 365. Intrathoracic impedance monitoring. Engl. C. Advanced heart failure treated with continuous-flow left ventricular assist device. 2241–2251 (2009).nature. 9. 6. J. See the article online for full details of the relationships. two-thirds had symptoms of angina. The primary end point was death from any cause. van Veldhuisen. E.ac. Cleland. 2. CA. Engl. However. 364. M. Am. T. J. et al. the trial has been criticized because of the active involvement of the sponsor in encouraging treatment changes in the intervention group. et al. N. Engl. crossover. Circulation 124. Peterson and colleagues10 looked at health literacy in 1. J. Coronary-artery bypass surgery in patients with left ventricular dysfunction. 1. N. The effects of the cardiac myosin activator. Velazquez. 7. although the patients were highly selected and atypically young (mean age 60 years) for the majority with HF. Am. Reduction of the risk of recurring heart failure events with cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).6 On balance. but substantial progress has yet to be made in the treatment of patients with preserved ejection fraction and those with acute decompensation. is a ‘first-in-class’ cardiac myosin activator.212 patients with a left ventricular ejection fraction <35%.7 which showed that nesiritide (recombinant human B-type natriuretic peptide) had only a small effect on dyspnea at 6 h and 24 h and no effect on mortality or worsening HF at 30 days.
www. 797–805 (2011). 58.6 In this study. et al. Pleasanton. CABG surgery may reduce cardiovascular mortality and morbidity6 ■ Nesiritide has a small and clinically insignificant effect on dyspnea and no effect on mortality or worsening HF in patients with acute HF7
6 months in the intervention group. Health literacy and outcomes among patients with heart failure. left main disease or Canadian Cardiovascular Class III angina or greater) were randomly assigned to receive medical therapy or CABG surgery. Med. 364. S. the positive findings of the CHAMPION trial4 contrasted strikingly with those of other studies. P = 0.uk
Competing interests The author declares associations with the following companies: Amgen and Johnson & Johnson/Scios. J. Slaughter. preoperative evaluation of myocardial viability did not help to identify patients who would benefit from revascularization. 361. J.72–1. interesting new drugs continue to be developed. such as the negative study DOT-HF5 in which an implantable intrathoracic impedance detection device was used. UK. N. 95% CI 0.
British Heart Foundation Cardiovascular Research Centre. The takehome message seems to be that. 1. omecamtiv mecarbil. Results of the post-US Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). 5. placebo-controlled. force-generating) state. 1719–1726 (2011). 32–43 (2011). et al. the STICH trial probably was a positive study. Glasgow G12 8TA. Coll. Goldenberg.10 These findings argue for testing of the effect of interventions thought to improve health literacy on outcomes in HF. 729–737 (2011). et al. Another study that raised as many questions as answers was the STICH trial. Nevertheless. how often do you have problems learning about your medical condition because of difficulty reading hospital materials. episodes of worsening heart failure (HF) in patients with systolic dysfunction and mild symptoms1 ■ Use of the HeartMate II®(Thoratec Corporation. Lancet 377. on cardiac function in systolic heart failure: a double-blind. M. coronary artery disease amenable to surgery. J. C. CABG surgery leads to reduced long-term mortality and morbidity compared with medical therapy alone. Med. and whether the benefit would be as substantial when used in ordinary practice has been questioned. et al. W. meaning that eight patients needed to be treated to prevent one hospitalization.12). 218 of the 610 patients assigned to surgery and 244 of the 602 patients allocated to medical therapy died (36% vs 41%. N. All rights reserved
. Felker. O’Connor. 1607–1616 (2011).com/nrcardio
© 2012 Macmillan Publishers Limited. and how confident are you filling out forms by yourself?
More than one in six patients showed a low level of health literacy. University of Glasgow. P . Starling. 658–666 (2011). Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. N. Over a median follow-up of 56 months. dose-ranging phase 2 trial. devices. john.494 patients with an emergency room visit or hospitalization with HF using three brief screening questions—how often do you have someone help you read hospital materials. which is thought to improve cardiac performance by increasing the rate of transition from the weak myosin-acting binding state to the strongly bound (that is. 2011 has been largely a year of consolidation for HF therapeutics.mcmurray@glasgow. J. G. as was all-cause mortality in an adjusted intention-to-treat analysis and in a per protocol analysis. Cardiol.8 Despite the lack of success with treatments for acute HF to date. M. This trial ended a long-running controversy about the safety and efficacy of nesiritide and highlighted the difficulty of demonstrating a benefit for novel therapies over and above that of conventional treatment with diuretics and nitrates. et al. Engl. 4.86. 1890–1898 (2011). but also subsequent. after taking account of other prognostic variables.04. USA) continuous-flow left ventricular assist device was associated with excellent 6-month and 12-month survival in a ’real-world’ registry study2 ■ Pharmacological intervention prompted by noninvasive pulmonary artery monitoring may reduce the risk of HF hospitalization in patients with moderately severe symptoms and previous admission for HF4 ■ In selected patients with ischemic systolic HF and a life expectancy of more than 2 years. 10. Abraham.YEAR IN REVIEW
■ Cardiac resynchronization therapy reduced not only the first. J. et al.9 Finally. and outcome in patients with heart failure. One of these. As in prior trials of CABG surgery. occurrence of the key secondary end points (cardiovascular death and death or cardiovascular hospitalization) was significantly less common in the surgical
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group. This agent increases the duration of systole without increasing heart rate or myocardial oxygen consumption. Diuretic strategies in patients with acute decompensated heart failure. The list of treatments that are ineffective in acute HF grew longer in 2011 with the publication of the results of ASCEND-HF. We have an array of effective drugs. Unexpectedly. and surgical procedures for patients with systolic HF. In summary. Med. JAMA 305. omecamtiv mercarbil.