Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the European Society of Cardiology Heart Failure Update meeting, held in Wroclaw, Poland, in June 2004 are reported. The SHAPE study identified a need to educate general practitioners (GPs) in order to optimise treatment of heart failure in primary care. BRING-UP 2 VAS showed that cognitive impairment is very common in elderly heart failure patients and that these patients require specialist care. Carvedilol was shown to be well tolerated and effective in elderly heart failure patients in the observational COLA II study. In the FOSIDIAL study of patients with end-stage renal disease, fosinopril showed no benefit over placebo in reducing the incidence of cardiovascular events in these high-risk patients. The BETACAR study showed that carvedilol and metoprolol produced a similar effect on left ventricular ejection fraction (+13.1% and +12.0%, respectively). Revised mortality data for the CASINO study and a meta-analysis of the effects of cardiac resynchronisation therapy on mortality in the light of the recently published COMPANION study are reported.     

Clinical trials update from the American Heart Association meeting: ACORN-CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A-HeFT, GEMINI, vitamin E meta-analysis, ESCAPE, CARP, and SCD-HeFT cost-effectiveness study

This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African-American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.     

Cardiac resynchronisation as a rescue therapy in patients with catecholamine-dependent overt heart failure: results from a short and mid-term study

BACKGROUND: Cardiac resynchronisation therapy (CRT) is a validated treatment for heart failure (HF) patients in NYHA class III-IV despite optimal medical therapy. We aimed to assess the beneficial effects of CRT in patients with catecholamine-dependent overt HF (CDOHF). METHODS: We studied 20 CDOHF patients who had undergone CRT implantation. Patients had a mean baseline QRS duration of 174+/-25 ms and/or echocardiographic asynchrony, and LVEF of 18+/-3%. Mean follow-up was 18+/-12 months. Dependence on catecholamine agents was defined as the inability to stop or reduce drug infusion without re-occurrence of hypotension, low urine output and hypoxaemia. RESULTS: After CRT implantation, catecholamine agents were mostly withdrawn within 2 days and blood pressure, urine output and BNP rapidly improved within 24 h. During follow-up, survival rates were 85% at 3 months, 80% at 6 months and 55% at 18 months. Among the 9 deaths, 5 were related to overt HF, 3 to sudden cardiac death and 1 to non-cardiac death. LVEF improved from 18+/-3% to 21+/-4% three months after CRT implantation. CONCLUSION: "Rescue" CRT implantation in CDOHF patients allowed a rapid and successful catecholamine weaning in all studied patients. Furthermore, this immediate beneficial effect is sustained for more than one year in surviving patients.     

Clinical trials update from the European Society of Cardiology Congress 2007: 3CPO, ALOFT, PROSPECT and statins for heart failure

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 Congress 2007. Unpublished reports should be considered as preliminary data, as analyses may change in the final publication. In the 3CPO study, non-invasive ventilation produced a more rapid resolution of symptoms in patients hospitalised with acute cardiogenic pulmonary oedema; but had no effect on survival, compared to standard oxygen therapy. The ALOFT study showed that the selective oral renin inhibitor aliskiren reduces plasma BNP levels and is well tolerated in patients with heart failure receiving ACE inhibitors or ARBs, although the study was not powered to show clinical benefit. In the PROSPECT study, no echocardiographic measure of mechanical dyssynchrony was identified that was useful for identifying patients more or less likely to respond to CRT. Low dose atorvastatin reduced the incidence of sudden cardiac death in a small placebo controlled study of patients with advanced chronic heart failure.     

Clinical trials update from the American Heart Association meeting: PROSPER,DIAL, home care monitoring trials,immune modulation therapy,COMPANION and anaemia in heart failure

This article continues a series of reports on research developments of particular interest to those involved in the management of patients with heart failure. Summaries of the following trials, reported at the 75th Scientific Sessions of the American Heart Association held in Chicago, Illinois between 17th and 20th November 2002 are included: PROSPER; DIAL; home care monitoring trials; immune modulation therapy; COMPANION; and anaemia in heart failure.     

Clinical trials update from the American College of Cardiology Meeting 2011: STICH, NorthStar, TARGET, and EVEREST II

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 American College of Cardiology meeting held in New Orleans in 2011. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The STICH trial failed to show a benefit of revascularization on all‐cause mortality in patients with HF and coronary artery disease; however, cardiovascular deaths were reduced compared with medical therapy alone. Results from the NorthStar study suggest that patients with clinically stable systolic HF, who are on optimal medical therapy, including those with elevated amino‐terminal B‐type natriuretic peptide levels, may not benefit from long‐term follow‐up in an HF clinic. Results from the TARGET study demonstrate that targeted left ventricular lead placement using speckle tracking echocardiography is feasible in patients undergoing implantation of a cardiac resynchronization therapy device and is associated with an enhanced response. Two‐year follow‐up data from EVEREST II show that although a catheter‐based mitral valve repair procedure using the MitraClip^® system was less effective at reducing mitral regurgitation than conventional surgery, similar improvements in clinical outcomes were observed with fewer short‐term adverse events.     

Clinical trials update: highlights of the scientific sessions of the American Heart Association year 2000: Val HeFT, COPERNICUS, MERIT, CIBIS-II, BEST, AMIOVIRT, V-MAC, BREATHE, HEAT, MIRACL, FLORIDA, VIVA and the first human cardiac skeletal muscle myoblast transfer for heart failure

This article continues a series of reports summarising recent research developments pertinent to the topic of heart failure. This is a summary of presentations made at scientific sessions of the American Heart Association in November 2000. Clinical studies of particular interest to people caring for patients with heart failure include Val-HeFT, AMIOVIRT and V-MAC. New data from beta-blockers trials are reviewed, highlights from some important developments in post-infarction care, including MIRACL and FLORIDA, discussed and results of some early studies of gene therapy reported.     

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.     

Clinical trials update from the European Society of Cardiology Heart Failure meeting and the American College of Cardiology: darbepoetin alfa study, ECHOS, and ASCOT-BPLA

This article provides information and a commentary on landmark trials presented at the European Society of Cardiology Heart Failure meeting held in June 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. The erythropoiesis stimulating protein, darbepoetin alfa, increased haemoglobin levels, improved quality of life and showed a trend for improved exercise duration in anaemic patients with symptomatic chronic heart failure. In the ECHOS study, the selective dopamine agonist nolomirole (CHF1035) showed no benefit in heart failure patients. Preliminary results of the ASCOT-BPLA study, which were reported at the American College of Cardiology meeting in March 2005, showed that in hypertensive patients, treatment with a calcium antagonist plus an ACE inhibitor was more effective at reducing cardiovascular outcomes than atenolol plus a diuretic.     

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 European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902

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 heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.     

Clinical trials update from the European Society of Cardiology: CARMEN,EARTH, OPTIMAAL,ACE, TEN-HMS,MAGIC, SOLVD-X and PATH-CHF II

This article continues a series of reports on research developments related to the field of heart failure. Reports of presentations made at the Hot Line sessions of the European Society of Cardiology XXIV Congress held in Berlin, Germany, between 31 August and 4 September 2002 are included. Summaries of the results of the following trials are presented: CARMEN, EARTH, OPTIMAAL, ACE, TEN-HMS, MAGIC, SOLVD-X and PATH-CHF II.     

Clinical Trials Update: CAPRICORN, COPERNICUS, MIRACLE, STAF, RITZ-2, RECOVER and RENAISSANCE and cachexia and cholesterol in heart failure. Highlights of the Scientific Sessions of the American College of Cardiology, 2001

This is a synopsis of presentations made at the American College of Cardiology (ACC) in 2001 summarising recent research developments relating to heart failure. Clinical studies of particular interest to physicians with an interest in heart failure and its prevention are reviewed. The COPERNICUS trial lends further support to the use of the beta-blocker, carvedilol, in severe heart failure and the CAPRICORN trial to its use in patients with post-infarction left ventricular systolic dysfunction. The MIRACLE study reinforces the evidence from three smaller trials that cardiac resynchronisation therapy is an effective treatment for the relief of symptoms in patients with severe heart failure and cardiac dyssynchrony. The STAF trial casts further doubt on the wisdom of cardioversion as a routine strategy for the management of chronic atrial fibrillation. The RITZ-2 trial suggests that an intravenous, non-selective endothelin antagonist is effective in improving haemodynamics and symptoms and possibly in reducing morbidity in severe heart failure. Observational studies in heart failure suggest that a moderate excess of body fat and elevated blood cholesterol may be desirable in patients with heart failure, challenging the current non-evidenced-based vogue for cholesterol lowering therapy in heart failure. The RENAISSANCE and RECOVER outcome studies of etanercept, a tumour necrosis factor (TNF) receptor analogue that blocks the effect of TNF, were stopped because of lack of evidence of benefit shortly after the ACC.     

Canadian Cardiovascular Society Consensus Conference guidelines on heart failure, update 2009: Diagnosis and management of right-sided heart failure, myocarditis, device therapy and recent important clinical trials

The Canadian Cardiovascular Society published a comprehensive set of recommendations on the diagnosis and management of heart failure in January 2006. Based on feedback obtained through a national program of heart failure workshops and through active solicitation of stakeholders, several topics were identified because of their importance to the practicing clinician. Topics chosen for the present update include best practices for the diagnosis and management of right-sided heart failure, myocarditis and device therapy, and a review of recent important or landmark clinical trials. These recommendations were developed using the structured approach for the review and assessment of evidence adopted and previously described by the Society. The present update has been written from a clinical perspective to provide a user-friendly and practical approach. Specific clinical questions that are addressed include: What is right-sided heart failure and how should one approach the diagnostic work-up? What other clinical entities may masquerade as this nebulous condition and how can we tell them apart? When should we be concerned about the presence of myocarditis and how quickly should patients with this condition be referred to an experienced centre? Among the myriad of recently published landmark clinical trials, which ones will impact our standards of clinical care? The goals are to aid physicians and other health care providers to optimally treat heart failure patients, resulting in a measurable impact on patient health and clinical outcomes in Canada.     

Clinical trials update from the American College of Cardiology: Darbepoetin alfa, ASTEROID, UNIVERSE, paediatric carvedilol, UNLOAD and ICELAND

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 55th Annual Scientific Session held in March 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. Darbepoetin alfa increased haemoglobin levels in heart failure patients and improved some aspects of quality of life compared to placebo. In the ASTEROID study rosuvastatin significantly reduced LDL-cholesterol levels and induced regression of atherosclerosis in patients with CAD. Rosuvastatin also produced a significant reduction in LDL-cholesterol levels in heart failure patients in the UNIVERSE study, but had no effect on left ventricular remodelling compared to placebo. The paediatric carvedilol study failed to show a benefit of carvedilol in children with heart failure. Ultrafiltration produced a greater weight and fluid loss than intravenous diuretics in heart failure patients with volume overload in the UNLOAD study but did not exert a greater improvement in breathlessness; however, ultrafiltration did reduce readmission rates. The ICELAND MI study showed that CMR imaging was more sensitive than ECG or clinical criteria for detecting myocardial infarction.     

Clinical trials update from the European Society of Cardiology Meeting 2010: SHIFT, PEARL-HF, STAR-heart, and HEBE-III

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 European Society of Cardiology held in Stockholm in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. The SHIFT study supports the use of ivabradine in patients with HF due to left ventricular systolic dysfunction and resting sinus rhythm rate ≥70 b.p.m. despite treatment with beta-blockers or where beta-blockers are contra-indicated. Results from PEARL-HF suggest that the potassium binding polymer RLY5016 may be useful for both prevention and treatment of hyperkalaemia in HF patients with or without concomitant chronic kidney disease. The STAR-heart study provides encouraging observational data about the potential for intracoronary stem cell transplantation in patients with HF. Results from HEBE-III showed no effect of erythropoietin on ejection fraction measured 6 weeks post-MI; although there were fewer cardiovascular events in patients assigned to erythropoietin, the study was too small to provide conclusive evidence of effect.     

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.     

心脏再同步化与常规治疗对心力衰竭患者心房颤动影响的比较

目的探讨心脏再同步化(CRT)与常规治疗对心力衰竭(简称心衰)患者心房颤动(简称房颤)的影响。方法选择行CRT、CRTD治疗的患者,作为CRT组。选择同期心衰行常规药物治疗的患者,作为对照组。比较两组患者治疗后,阵发性房颤、永久性房颤的发生率,以及房颤患者的预后差异。结果:①对照组房颤的发生率较CRT组高(阵发性房颤9/46 vs 5/47;永久性房颤24/46 vs 11/47,P均<0.05)。②常规药物治疗下房颤患者的死亡率高于窦性心律患者(P<0.05)。结论 CRT治疗后,房颤发生率较低,房颤并心衰患者的死亡率亦降低,CRT组心衰临床症状明显改善,心功能提高,运动耐量增加,生活质量提高。     

Clinical trials update from the European Society of Cardiology heart failure meeting 2009: CHANCE,B‐Convinced,CHAT, CIBIS‐ELD,and Signal‐HF

This paper provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the Heart Failure Association of the European Society of Cardiology held in Nice. The CHANCE study showed a substantial reduction in morbidity and mortality in a randomized controlled trial (RCT) of a multidisciplinary management programme for patients with chronic heart failure in Russia. Data from the B‐Convinced study, also an RCT, suggest that continuation of beta‐blocker (BB) therapy in patients hospitalized with worsening heart failure may be associated with improved outcomes when compared with treatment discontinuation. The CHAT study suggests that telephone support can improve prognosis in heart failure patients living in remote rural locations. CIBIS‐ELD showed that titration of BBs to target doses in older patients with heart failure is more difficult; but tolerance levels were similar for bisoprolol and carvedilol. Signal‐HF randomized elderly heart failure patients to treatment guided by NT‐proBNP levels or usual care, and showed no effect of NT‐proBNP‐guided treatment on outcomes.