Clinical trials update from the American College of Cardiology 2007: ALPHA, EVEREST, FUSION II, VALIDD, PARR-2, REMODEL, SPICE, COURAGE, COACH, REMADHE, pro-BNP for the evaluation of dyspnoea and THIS-diet

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 March 2007. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. The ALPHA study suggested that patients with heart failure (HF) due to idiopathic dilated cardiomyopathy who have a negative T-wave alternans test have a good prognosis and are unlikely to benefit from ICD therapy. EVEREST provides some evidence of short-term symptom benefit of tolvaptan in patients with acute decompensated HF but no clinically important long-term benefit. FUSION II failed to show a benefit of nesiritide in patients with chronic decompensated HF. Reducing blood pressure in hypertensive patients improved diastolic dysfunction in VALIDD. Eplerenone did not improve left ventricular remodelling in mild to moderate chronic HF. Selecting HF patients for revascularisation using FDG-PET imaging did not significantly improve outcome. Crataegus extract added to standard HF therapy did not reduce morbidity or mortality in SPICE. The COURAGE study, conducted in patients without HF or major cardiac dysfunction, showed that PCI did not reduce cardiac morbidity or mortality and can be safely deferred in patients with stable coronary disease on optimal medical therapy. The COACH study failed to show that HF nurse-intervention could reduce hospitalisations but did show trends to lower mortality, especially amongst patients with reduced ejection fraction; however, the smaller REMADHE study suggested striking benefits on morbidity and mortality. A large study of BNP provided additional information on its ability to distinguish cardiac and pulmonary breathlessness. The importance of dietary intervention in post-MI patients was highlighted by the findings of THIS-diet study.     

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.     

Clinical trials update from the European Society of Cardiology Heart Failure Meeting 2010: TRIDENT 1, BENEFICIAL,CUPID, RFA‐HF,MUSIC, DUEL,handheld BNP,phrenic nerve stimulation,CHAMPION and CABG with CRT study

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention and treatment of heart failure (HF) presented at the annual meeting of the Heart Failure Association of the European Society of Cardiology held in Berlin. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Tonapofylline failed to show efficacy and was associated with an approximately 1% increased risk of seizures in patients with acute decompensated heart failure (ADHF) and renal dysfunction in TRIDENT. Results from BENEFICIAL do not support the use of alagebrium, an advanced glycation end‐product breaker, in clinically stable patients with relatively mild HF symptoms. CUPID showed encouraging preliminary results for augmentation of SERCA2a enzyme activity by gene transfection in patients with severe HF. The RFA‐HF study did not provide convincing evidence for the use of radiofrequency ablation for atrial fibrillation but was underpowered. A wearable, multi‐sensor patch showed potential for detecting impending HF decompensation in MUSIC. A comparison of low‐intensity oral diuretic therapy in patients hospitalized with ADHF suggested that torasemide was superior to furosemide in DUEL. The use of point‐of‐care B‐type natriuretic peptide and echocardiography failed to improve the rate of correct HF diagnosis in primary care. Phrenic nerve stimulation improved symptoms of sleep apnoea in a small study of patients with HF and central sleep apnoea. The use of a novel implantable pulmonary artery pressure monitoring system to guide patient management improved outcomes in the CHAMPION study. A study to evaluate a combined coronary artery bypass grafting (CABG) and epicardial cardiac resynchronization therapy implantation procedure reduced mortality compared with CABG alone.     

Ethical Challenges of Deactivation of Cardiac Devices in Advanced Heart Failure

More than 23 million adults worldwide have heart failure (HF). Although survival after heart failure diagnosis has improved over time, mortality from heart failure remains high. At the end of life, the chronic HF patient often becomes increasingly symptomatic, and may have other life-limiting comorbidities as well. Multiple trials have shown a clear mortality benefit with the use of implantable cardioverter defibrillators (ICDs) in patients with cardiomyopathy and ventricular arrhythmia. However, patients who have an ICD may be denied the chance of a sudden cardiac death, and instead are committed to a slower terminal decline, with frequent DC shocks that can be painful and decrease the quality of life, greatly contributing to their distress and that of their families during this period. While patients with ICDs are routinely counseled with regard to the benefits of ICDs, they have a poor understanding of the options for device deactivation and related ethical and legal implications. Deactivating an ICD or not performing a generator change is both legal and ethical, and is supported by guidelines from both sides of the Atlantic. Patient autonomy is paramount, and no patient is committed to any therapy that they no longer wish to receive. Left ventricular assist devices (LVADs) were initially used as bridge in patients awaiting heart transplantation, but they are currently implanted as destination therapy (DT) in patients with end-stage heart failure who have failed to respond to optimal medical therapy and who are ineligible for cardiac transplantation. The decision-making process for initiation and deactivation of LVAD is becoming more and more ethically and clinically challenging, particularly for elderly patients.     

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. The TIME‐CHF study failed to show that BNP guided therapy was superior to usual care in patients with heart failure. The BACH study suggested that a new biomarker, MR‐proANP, was as good as BNP for the diagnosis of heart failure in patients presenting with breathlessness. Ivabradine failed to reduce the incidence of cardiovascular events in patients with coronary artery disease and left ventricular systolic dysfunction in the BEAUTIFUL study, but patients with higher heart rates might have benefited. In GISSI‐HF, n–3 PUFA reduced mortality and cardiovascular hospitalisation by a small amount compared to placebo in patients with chronic heart failure, but rosuvastatin had no effect on clinical outcomes. In the HOME‐HF study, telemonitoring support failed to reduce the time to first re‐hospitalisation or death, or days alive and out of hospital, compared with usual care.     

Clinical trials update from the American College of Cardiology meeting 2010: DOSE,ASPIRE, CONNECT,STICH, STOP‐AF,CABANA, RACE II,EVEREST II,ACCORD, and NAVIGATOR

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the annual meeting of the American College of Cardiology held in March 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from DOSE suggest that giving diuretics using a high‐dose, bolus strategy may be better than using lower doses or a continuous infusion for patients with acute decompensated heart failure. In the ASPIRE study, addition of aliskiren to standard therapy failed to attenuate left ventricular remodelling in post‐MI patients and was associated with more adverse events. In CONNECT, remote monitoring reduced the time from CRT‐D‐ or ICD‐detected events to clinical decision and this was associated with fewer clinic visits and shorter hospitalizations. An analysis from STICH testing the effects of surgical ventricular reconstruction showed no benefit in the sub‐group of patients who achieved a greater reduction in LV volume. STOP‐AF and CABANA did not provide convincing evidence of the effectiveness or safety of catheter ablation for the treatment of AF. RACE II suggests that lenient heart rate control might be as effective as strict rate control in patients with permanent atrial fibrillation. In EVEREST II, a catheter‐based mitral valve repair procedure using the MitraClip® system had similar efficacy to traditional surgery but with fewer short‐term adverse effects. Valsartan reduced progression to diabetes in patients with impaired glucose tolerance but had no effect on cardiovascular events in NAVIGATOR. In ACCORD, strict blood pressure control failed to reduce the risk of overall cardiovascular events in high‐risk diabetic patients.     

Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE

This article provides information and a commentary on trials presented at the European Society of Cardiology meeting held in September 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. In the CARE-HF extension study, the benefits of cardiac resynchronisation therapy (CRT) observed in the original study were maintained over an increased follow-up period. A study of oral enoximone (25-50 mg t.i.d.) in advanced heart failure (ESSENTIAL) showed limited benefit compared to placebo. The CIBIS-III study showed that heart failure therapy could be safely initiated with bisoprolol followed by the addition of enalapril. A subcutaneous ICD system (S-ICD) showed potential as an alternative to a transvenous ICD. In the ISSUE-2 study, an implantable loop recorder was used to guide therapy in patients with recurrent syncope. The selective endothelin antagonist sitaxsentan improved 6-MWT and functional class in patients with pulmonary arterial hypertension in the STRIDE-2 study. In SOFA, fish oil had no beneficial effect on the incidence of life-threatening arrhythmias in patients with an ICD. In IMAGINE, quinapril showed no benefit when administered to patients following CABG. Perindopril reduced cardiac remodelling in post-MI patients with normal LV function in PREAMI. SIRIUS-II showed encouraging results for the use of intravenous ularitide in symptomatic decompensated chronic heart failure. The ACTIVE W study of warfarin versus aspirin plus clopidogrel in atrial fibrillation has been stopped due to superiority of warfarin.     

Clinical trials update from Heart Rhythm 2007 and Heart Failure 2007: CARISMA, PREPARE, DAVID II, SAVE-PACE, PROTECT and AREA-IN-CHF

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at Heart Rhythm 2007 organised by the Heart Rhythm Society which was held in Denver, USA and Heart Failure 2007 organised by the Heart Failure Association of the European Society of Cardiology which was held in Hamburg, Germany. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. The CARISMA study suggests that non-invasive screening tests may help to identify post-MI patients who may benefit from ICD therapy. Data from the PREPARE study show that more conservative ICD programming can reduce morbidity at the cost of an increased risk of arrhythmic syncope. DAVID II indicates that atrial pacing may be a safe alternative to ventricular back-up pacing in patients with left ventricular dysfunction and standard indications for an ICD. The incidence of persistent atrial fibrillation in patients with sinus node disease in SAVE-PACE was reduced by dual chamber minimal ventricular pacing compared to conventional dual chamber pacing. The pilot phase of the PROTECT studies confirmed 30 mg as the dose of the selective A1 adenosine receptor antagonist KW-3902 to be used in pivotal studies. AREA-IN-CHF failed to show a beneficial effect of canrenone on LV volumes compared to placebo however some beneficial effects on secondary clinical endpoints were observed.     

Current role of device therapy to reduce sudden cardiac death in heart failure

Sudden cardiac death (SCD) continues to be a major contributor to mortality in patients with heart failure (HF) despite recent advances in medical therapy. Device therapy, including the implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), serves as an adjunct in reducing HF mortality. Several clinical trials support the prophylactic use of the ICD in reducing mortality in certain HF populations and have established the clinical benefits of CRT in advanced HF. More recently, the Comparison of Medical Therapy Pacing and Defibrillation in Heart Failure trial was the first study to demonstrate a survival benefit of CRT alone or in conjunction with an ICD. This article reviews the most pertinent data regarding the role of device therapy in reducing SCD in HF and addresses future challenges faced by device manufacturers and clinicians.     

Clinical trials update from the American College of Cardiology meeting: CARE-HF and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF, VERITAS, CANPAP, PEECH and PREMIER

This article provides information and a commentary on landmark trials presented at the American College of Cardiology meeting held in March 2005, relevant to the pathophysiology, prevention and treatment of heart failure. All reports should be considered as preliminary data, as analyses may change in the final publication. CARE-HF showed that Cardiac Re-synchronisation Therapy, administered in addition to expert pharmacological management, reduced all cause mortality and CV hospitalisation in patients with moderate or severe heart failure and cardiac dyssynchrony. The Women's Health Study showed no benefit of vitamin E supplementation or aspirin in the primary prevention of CV disease. The TNT study showed that reducing LDL cholesterol to levels lower than currently recommended, produced a 22% reduction in the incidence of major cardiovascular events. In COMPASS, an implantable device that continuously monitors intra-cardiac pressures was shown to be safe and to improve care in patients with chronic heart failure. Tezosentan failed to show benefit in patients with acute heart failure in the VERITAS study. The CANPAP study failed to show a benefit of continuous positive airway pressure on mortality and heart transplantation in heart failure patients with central sleep apnoea. EECP therapy improved exercise capacity but had no effect on peak VO2 in heart failure patients in the PEECH study. In the PREMIER study the matrix metalloproteinase inhibitor PG-116800 failed to prevent LV remodelling following myocardial infarction.     

Impact of upgrade to cardiac resynchronization therapy on ventricular arrhythmia frequency in patients with implantable cardioverter-defibrillators.

OBJECTIVES: This study compared cardiac resynchronization therapy's (CRT) impact on ventricular tachyarrhythmia susceptibility in patients who, due to worsening heart failure (HF) symptoms, underwent a replacement of a conventional implantable cardioverter-defibrillator (ICD) with a CRT-ICD. BACKGROUND: Cardiac resynchronization therapy is an effective addition to conventional treatment of HF in many patients with left ventricular systolic dysfunction. However, whether CRT-induced improvements in HF status also reduce susceptibility to life-threatening arrhythmias is less certain. METHODS: Clinical and ICD electrogram data were evaluated in 18 consecutive ICD patients who underwent an upgrade to CRT-ICD. Pharmacologic HF therapy was not altered during follow-up. The definition of ventricular tachycardia (VT) and ventricular fibrillation (VF) for each patient was as determined by device programming. Statistical comparisons used paired t tests. RESULTS: Findings were recorded during two time periods: 47 +/- 21 months (range 24 to 70 months) before and 14 +/- 2 months (range 9 to 18 months) after CRT upgrade. At time of upgrade, patient age was 69 +/- 11 years and ejection fraction was 21 +/- 8%. Before CRT the frequency of VT, VF, and appropriate ICD shocks was 0.31 +/- 1.23, 0.047 +/- 0.083, and 0.048 +/- 0.085 episodes/month/patient, respectively. After CRT-ICD, VT and VF arrhythmia burdens and frequency of shocks were respectively 0.13 +/- 0.56, 0.001 +/- 0.004, and 0.003 +/- 0.016 episodes/month/patient (p = 0.59, 0.03, and 0.05 vs. pre-CRT). CONCLUSIONS: Arrhythmia frequency and number of appropriate ICD treatments were reduced after upgrade to CRT-ICD for HF treatment. Thus, apart from hemodynamic benefits, CRT may also ameliorate ventricular tachyarrhythmia susceptibility in HF patients.     

Heart failure and cognitive impairment: Challenges and opportunities

As populations age, heart failure (HF) is becoming increasingly common, and in addition to a high burden of morbidity and mortality, HF has an enormous financial impact. Though disproportionately affected by HF, the elderly are less likely to receive recommended therapies, in part because clinical trials of HF therapy have ignored outcomes of importance to this population, including impaired cognitive function (ICF). HF is associated with ICF, manifested primarily as delirium in hospitalized patients, or as mild cognitive impairment or dementia in otherwise stable outpatients. This association is likely the result of shared risk factors, as well as perfusion and rheological abnormalities that occur in patients with HF. Evidence suggests that these abnormalities may be partially reversible with standard HF therapy. The clinical consequences of ICF in HF patients are significant. Clinicians should consider becoming familiar with screening instruments for ICF, including delirium and dementia, in order to identify patients at risk of nonadherence to HF therapy and related adverse consequences. Preliminary evidence suggests that optimal HF therapy in elderly patients may preserve or even improve cognitive function, though the impact on related outcomes remains to be determined.     

Neurohormonal Intervention to Reduce Sudden Cardiac Death in Heart Failure: What is the Optimal Pharmacologic Strategy?

Sudden cardiac death (SCD) accounts for up to 50% of deaths in patients with heart failure (HF), depending on severity of symptomatic impairment and left ventricular dysfunction. Neurohormonal therapy directed at the renin-angiotensin-aldosterone system may reduce the propensity to SCD through improved hemodynamic responsiveness, reduced sympathetic tone in the myocardium and inhibition of cardiac remodelling. Angiotensin converting enzyme (ACE) inhibitors reduce overall mortality in chronic HF, the greatest benefit appearing to arises from reduction of HF progression rather than SCD. In HF patients who experience myocardial infarction (MI) reduced incidence in SCD may make a more marked contribution to the mortality benefits of ACE inhibition. Addition of beta-blocker therapy to ACE inhibition has consistently resulted in a reduction in SCD in patients with either mild-to-moderate or severe HF, and in the presence or absence of MI; the reduction in SCD is of the order of one-third versus placebo. Aldosterone blockade reduces the risk of SCD in advanced chronic heart failure (when added to ACE inhibitor) and in HF associated with acute MI (when given in addition to both ACE inhibitor and beta blocker). The evidence base suggests that for maximal SCD risk reduction in HF, beta-blocker therapy is advisable in combination with standard ACE inhibitor therapy, with addition of aldosterone blockade to this regimen for particular groups of heart failure patients.     

Neurohormonal intervention to reduce sudden cardiac death in heart failure: what is the optimal pharmacologic strategy?

Sudden cardiac death (SCD) accounts for up to 50% of deaths in patients with heart failure (HF), depending on severity of symptomatic impairment and left ventricular dysfunction. Neurohormonal therapy directed at the renin-angiotensin-aldosterone system may reduce the propensity to SCD through improved hemodynamic responsiveness, reduced sympathetic tone in the myocardium and inhibition of cardiac remodelling. Angiotensin converting enzyme (ACE) inhibitors reduce overall mortality in chronic HF, the greatest benefit appearing to arises from reduction of HF progression rather than SCD. In HF patients who experience myocardial infarction (MI) reduced incidence in SCD may make a more marked contribution to the mortality benefits of ACE inhibition. Addition of beta-blocker therapy to ACE inhibition has consistently resulted in a reduction in SCD in patients with either mild-to-moderate or severe HF, and in the presence or absence of MI; the reduction in SCD is of the order of one-third versus placebo. Aldosterone blockade reduces the risk of SCD in advanced chronic heart failure (when added to ACE inhibitor) and in HF associated with acute MI (when given in addition to both ACE inhibitor and beta blocker). The evidence base suggests that for maximal SCD risk reduction in HF, beta-blocker therapy is advisable in combination with standard ACE inhibitor therapy, with addition of aldosterone blockade to this regimen for particular groups of heart failure patients.     

Cardiac resynchronisation may reduce all-cause mortality: meta-analysis of preliminary COMPANION data with CONTAK-CD, InSync ICD, MIRACLE and MUSTIC

Landmark trials have demonstrated that biventricular pacing (also called cardiac resynchronisation therapy or CRT) in chronic heart failure due to left ventricular dysfunction improves symptomatic status, exercise capacity and quality of life. Yet critically, all-cause mortality has not been demonstrated to be reduced in any of the four randomised controlled trials with mortality data (CONTAK-CD, InSync implantable-cardioverter defibrillator (ICD), MIRACLE and MUSTIC). With the much larger COMPANION study now terminated, however, the currently available pooled data from all five trials shows a significant reduction in all-cause mortality, odds ratio (OR), 0.74: 95% confidence interval (CI) 0.56-0.97. This may now establish biventricular pacing as a standard therapy for a specific subset of patients with chronic heart failure and LBBB.     

Current status of implantable cardioverter-defibrillator therapy in heart failure

Sudden cardiac arrest is one of the leading causes of death in patients with heart failure (HF). The implantable cardioverter-defibrillator (ICD) is the only evidence-based treatment strategy for patients who have survived a life-threatening ventricular arrhythmic event. Randomized clinical trials have shown that specific subsets of HF patients with ischemic and nonischemic dilated cardiomyopathy benefit from ICD therapy for primary prevention of sudden cardiac arrest. Cardiac resynchronization therapy has become the device-based therapy of choice for improving symptoms and survival in severe HF patients with evidence of ventricular dyssynchrony. This review summarizes the current status of ICD therapy in treating HF patients based on randomized clinical trials and current practice guidelines.     

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. Rosuvastatin did not reduce mortality compared to placebo in patients with heart failure and left ventricular systolic dysfunction due to ischaemic heart disease in the CORONA study. Results of RethinQ provide equivocal evidence of benefit from CRT in patients with heart failure, echocardiographic dyssynchrony and QRS interval <130 ms. In the MASCOT study, the addition of atrial overdrive pacing did not reduce the incidence of permanent atrial fibrillation in patients receiving CRT. The AF-CHF study failed to show a benefit of rhythm control over rate control in patients with heart failure and atrial fibrillation. Self-management skills training and education had no benefit on the combined outcome of death or heart failure hospitalisation, compared with education alone in heart failure patients in the HART study. Microvolt T-wave alternans testing failed to identify patients at increased risk of life-threatening ventricular arrhythmias in the MASTER study. POISE suggests that initiating metoprolol therapy shortly prior to non-cardiac surgery increases the risk of hypotension, stroke and death, despite reducing the risk of myocardial infarction. Three trials of stem cell therapy in post-MI patients gave conflicting results.     

The Role of EP-Guided Therapy in Ventricular Arrhythmias: Beta-Blockers,Sotalol, and ICD's

Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 2—4%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy.Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit.Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients.The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on tolerability and compliance of the beta-blocking therapy in patients with low ejection fraction. In this study will be useful to optimize therapy in patients at high risk of sudden death     

Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF,COMPARE, MOMENTUM,thyroid hormone analogue study,HF-ACTION,I-PRESERVE, β-interferon study,BACH, and ATHENA

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.     

Successful treatment of heart failure with devices requires collaboration

Implanted biventricular pacemakers (cardiac resynchronisation therapy, CRT) with or without implantable cardioverter defibrillators (ICD) improve survival and morbidity in some patients with chronic heart failure (CHF) who are optimally treated with pharmacologic agents according to current guidelines. Correspondingly, ICDs improve survival. However, there is only limited evidence for device treatment in certain patient subgroups, such as the impact of ICD on outcomes in patients with reduced ejection fraction in New York Heart Association (NYHA) Class I or IV heart failure. Similarly, limited evidence exists for CRT in patients with only modest QRS prolongation or only modestly reduced ejection fraction. Despite evidence for a beneficial effect of device therapy in CHF, only a minority of eligible patients are currently offered these options. Multiple reasons contribute to the underuse of these potentially life‐saving therapies. A lack of adherence to guidelines by health care professionals is an important barrier. Clearly, efforts should be made to improve the standard of care and to familiarise all physicians involved in managing CHF patients with the indications and potential efficacy of these devices. Increased collaboration between structured heart failure care and pacemaker clinics as well as between electrophysiologists, heart failure clinicians, and primary care physicians is required. Such team collaborations should lead to improved care with reduced mortality and morbidity and increased cost effectiveness. Treatment strategy should be based on a structured approach tailored to local practice and national priorities.