Showing papers by "John G.F. Cleland published in 2003"

The EuroHeart Failure survey programme-- a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis.

Abstract: The European Society of Cardiology (ESC) has published guidelines for the investigation of patients with suspected heart failure and, if the diagnosis is proven, their subsequent management. Hospitalisation provides a key point of care at which time diagnosis and treatment may be refined to improve outcome for a group of patients with a high morbidity and mortality. However, little international data exists to describe the features and management of such patients. Accordingly, the EuroHeart Failure survey was conducted to ascertain if appropriate tests were being performed with which to confirm or refute a diagnosis of heart failure and how this influenced subsequent management. Methods The survey screened consecutive deaths and discharges during 2000-2001 predominantly from medical wards over a 6-week period in 115 hospitals from 24 countries belonging to the ESC, to identify patients with known or suspected heart failure. Results A total of 46,788 deaths and discharges were screened from which 11,327 (24%) patients were enrolled with suspected or confirmed heart failure. Forty-seven percent of those enrolled were women. Fifty-one percent of women and 30% of men were aged >75 years. Eighty-three percent of patients had a diagnosis of heart failure made on or prior to the index admission. Heart failure was the principal reason for admission in 40%. The great majority of patients (>90%) had had an ECG, chest X-ray, haemoglobin and electrolytes measured as recommended in ESC guidelines, but only 66% had ever had an echocardiogram. Left ventricular ejection fraction had been measured in 57% of men and 41% of women, usually by echocardiography (84%) and was <40% in 51% of men but only in 28% of women. Forty-five percent of women and 22% of men were reported to have normal left ventricular systolic function by qualitative echocardiographic assessment. A substantial proportion of patients had alternative explanations for heart failure other than left ventricular systolic or diastolic dysfunction, including valve disease. Within 12 weeks of discharge, 24% of patients had been readmitted. A total of 1408 of 10,434 (13.5%) patients died between admission and 12 weeks follow-up. Conclusions Known or suspected heart failure comprises a large proportion of admissions to medical wards and such patients are at high risk of early readmission and death. Many of the basic investigations recommended by the ESC were usually carried out, although it is not clear whether this was by design or part of a general routine for all patients being admitted regardless of diagnosis. The investigation most specific for patients with suspected heart failure (echocardiography) was performed less frequently, suggesting that the diagnosis of heart failure is still relatively neglected. Most men but a minority of women who underwent investigation of cardiac function had evidence of moderate or severe left ventricular dysfunction, the main target of current advances in the treatment of heart failure. Considerable diagnostic uncertainty remains for many patients with suspected heart failure, even after echocardiography, which must be resolved in order to target existing and new therapies and services effectively. (C) 2003 Published by Elsevier Science Ltd on behalf of The European Society of Cardiology.

The EuroHeart Failure Survey programme--a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.

Abstract: Background National surveys suggest that treatment of heart failure in daily practice differs from guidelines and is characterized by underuse of recommended medications. Accordingly, the Euro Heart Failure Survey was conducted to ascertain how patients hospitalized for heart failure are managed in Europe and if national variations occur in the treatment of this condition. Methods The survey screened discharge summaries of 11 304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment. Results Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age 70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70. Conclusion Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.

A systematic review of telemonitoring for the management of heart failure.

Abstract: Background: Telemonitoring allows a clinician to monitor, on a daily basis, physiological variables measured by patients at home. This provides a means to keep patients with heart failure under close supervision, which could reduce the rate of admission to hospital and accelerate discharge. Objective: To review the literature on the application of telemedicine in the management of heart failure. Methods: A literature search was conducted on studies involving telemonitoring and heart failure between 1966 and 2002 using Medline, Embase, Cochrane Library and Journal of Telemedicine and Telecare. Results: Eighteen observational studies and six randomised controlled trials involving telemonitoring and heart failure were identified. Observational studies suggest that telemonitoring; used either alone or as part of a multidisciplinary care program, reduce hospital bed-days occupancy. Patient acceptance of and compliance with telemonitoring was high. Two randomised controlled trials suggest that telemonitoring of vital signs and symptoms facilitate early detection of deterioration and reduce readmission rates and length of hospital stay in patients with heart failure. One study also showed a reduction in readmission charges. One substantial randomised controlled study showed a significant reduction in mortality at 6 months by monitoring weight and symptoms in patients with heart failure; however, no difference was observed in readmission rates. Another randomised study comparing video-consultation performed as part of a home health care programme for patients with a variety of diagnoses, suggested a reduction in the costs of hospital care, which offset the cost of video-consultation. Patients with heart failure were not reported separately. One randomised study showed no difference in outcomes between the telemonitoring group and the standard care group. Conclusion: Telemonitoring might have an important role as part of a strategy for the delivery of effective health care for patients with heart failure. Adequately powered multicentre, randomised controlled trials are required to further evaluate the potential benefits and cost-effectiveness of this intervention.

Longitudinal ventricular function: normal values of atrioventricular annular and myocardial velocities measured with quantitative two-dimensional color Doppler tissue imaging.

Abstract: Objective Quantitative 2-dimensional color Doppler tissue imaging is a new method to reveal impairment of left ventricular (LV) and right ventricular (RV) longitudinal function, which is a potential marker of early myocardial disease. The aim of this study was to obtain normal values for atrioventricular annular and regional myocardial velocities using this method. Methods A total of 123 healthy patients (age range: 22 to 89 years) underwent echocardiography including color Doppler tissue imaging using a scanner (Vivid 5, GE Vingmed, Horten, Norway) with postprocessing analysis (Echopac 6.3, GE Vingmed). Regional myocardial velocities were measured at 12 LV segments in 3 apical views and 2 segments of the free RV wall. Mitral annular velocities from 6 sites, and tricuspid annular velocities at its lateral site, were also assessed. At each site, systolic (S m ), early diastolic (E m ), and late diastolic (A m ) velocities were measured, and the E m /A m ratio was calculated. Results Patients were classified into 4 groups aged 20 to 39, 40 to 59, 60 to 79, and ≥80 years. Mitral annular velocity and regional LV myocardial S m and E m progressively decreased with age. A m , whereas low in the youngest age group, increased significantly in patients more than 40 years of age. The E m /A m ratio gradually declined with aging. There were no differences between age groups in S m measured at the tricuspid annulus and free RV wall, but the pattern of age-related changes of diastolic velocities and E m /A m ratio was the same as in the LV. Slight but significant sex-related differences were observed in middle-aged groups. The intraobserver and interobserver reproducibility was highest for atrioventricular annular velocities. Conclusions A progressive decrease in S m reveals a decline in longitudinal systolic LV function with age, whereas systolic RV function remains unaffected. Atrioventricular annular velocity and regional E m decrease with aging in both ventricles, suggesting a deterioration in the diastolic properties of the myocardium, whereas A m increases from middle age implying a compensatory augmentation of atrial function. The study results can be used as reference data for the quantitative assessment of longitudinal LV and RV function in patients with cardiac disease.

The prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in a typical regional pacemaker population

Abstract: Aims To assess the prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in the chronically paced population. Methods and Results Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001). Conclusions Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on ‘optimal’ therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.

Mode of death in heart failure: findings from the ATLAS trial

Abstract: Objective: To investigate markers that predict modes of death in patients with chronic heart failure. Design: Randomised, double blind, three period, comparative, parallel group study (ATLAS, assessment of treatment with lisinopril and survival). Patients: 3164 patients with mild, moderate, or severe chronic heart failure (New York Heart Association functional class II–IV). Interventions: High dose (32.5 or 35 mg) or low dose (2.5 or 5 mg) lisinopril once daily for a median of 46 months. Main outcome measures: All cause mortality, cardiovascular mortality, sudden death, and chronic heart failure death related to prognostic factors using competing risks analysis. Mode of death was classified by trialists and by an independent end point committee. Results: Age, male sex, pre-existing ischaemic heart disease, increasing heart rate, creatinine concentration, and certain drugs taken at randomisation were markers of increased risk of all cause mortality and cardiovascular death. There were risk markers for sudden death that were different from the risk markers for death from chronic heart failure. Low systolic blood pressure at baseline, raised creatinine, reduced serum sodium or haemoglobin, and increased heart rate were associated with chronic heart failure death. Use of β blockers or antiarrhythmic agents (mainly amiodarone) was associated with a reduced risk of sudden death, whereas long acting nitrates and previous use of angiotensin converting enzyme inhibitors were markers for increased risk. Conclusions: The use of competing risks analysis on the data from the ATLAS study has identified variables associated with certain modes of death in heart failure patients. This approach to analysing outcomes may make it possible to predict which patients might benefit most from particular therapeutic interventions.

Effect of age and sex on left atrial morphology and function.

Abstract: Aims: Left atrial function is abnormal in a wide range of cardiac diseases. This study was designed to assess the effects of normal ageing and sex on left atrial morphology and function. Methods and Results: Echocardiography was performed in 123 subjects (age 5719 years, range 22 to 89 years, 59 women) with no evidence of cardiovascular disease. M-mode derived left atrial size, B-mode derived left atrial maximal and minimal volumes, and the volume at onset of atrial systole (P-volume) were measured. Left atrial filling, active and passive emptying volumes and ejections fractions, and expansion index were calculated. Subjects were divided into four groups according to age. Left atrial diameter increased with age, with significantly smaller left atrial size in younger subjects. The oldest subjects had significantly higher (P<0·05) left atrial minimal, maximal and P-volume indices. Filling volume index was highest in the oldest subjects (21·95·6 ml/m 2 ). Passive emptying volume index was the lowest in those of middle age (10·52·8 ml/m 2 ). Active emptying volume index progressively increased with age (P<0·001). Left atrial expansion index and active emptying fraction were not different between the age groups. There was significant difference in passive emptying fraction (P<0·001) with highest values in the youngest (44·77·3%) and lowest values in the oldest subjects (33·65·4%). Conclusions: Age- and sex-related reference values of echocardiographic indices of left atrial morphology and function are reported. Ageing is associated with left atrial dilatation. Left atrial conduit function deteriorates with age while reservoir and pump function are maintained. Left atrial anteroposterior diameter is smaller in women than in men, but overall left atrial function is not influenced by sex. (Eur J Echocardiography 2003; 4: 36–42)

The heart failure revascularisation trial (HEART): Rationale, design and methodology

Abstract: Background: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. Aims To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. Methods: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. Results: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. Conclusion: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure: an analysis based on the international LIDO trial

Abstract: Background: Levosimendan, a novel calcium sensitiser, improves cardiac performance and symptoms without increasing oxygen consumption, and decreases the mortality of patients with low-output heart failure. Aims: To estimate the cost-effectiveness of intravenous treatment with levosimendan compared with dobutamine in patients with severe low-output heart failure. Methods: This economic evaluation was based on a European clinical trial (LIDO), in which 203 patients with severe heart failure randomly received a 24 h infusion with either levosimendan or dobutamine. Survival and resource utilisation data were collected for 6 months; survival was extrapolated assuming a mean additional lifetime of 3 years based on data from the Cooperative North Scandinavian Enalapril Survival Study trial. Costs were based on study drug usage and hospitalisation in the 6-month follow-up. A sensitivity analysis on dosage of drug and duration of survival was performed. Results: The mean survival over 6 months was 157±52 days in the levosimendan group and 139±64 days in the dobutamine group (P<0.01). When extrapolated up to 3 years, the gain in life expectancy was estimated at 0.35 years (discounted at 3%). Levosimendan increased the mean cost per patient by €1108, which was entirely due to the cost of the study drug. The incremental cost per life-year saved (LYS) was €3205 at the European level; in the individual countries the cost per LYS ranged between €3091 and €3331. The result was robust in the sensitivity analysis. Conclusions: Although the patients in the levosimendan group were alive for more days and thus at risk of hospitalisation for longer, there was no increase in hospitalisation or hospitalisation costs with levosimendan treatment. The cost per LYS using levosimendan compares favourably with other cost-effectiveness analyses in cardiology.

Update of clinical trials from the American College of Cardiology 2003. EPHESUS, SPORTIF‐III, ASCOT, COMPANION, UK‐PACE and T‐wave alternans

Abstract: The American College of Cardiology provided much useful new information to inform those who care for patients with heart failure about what they should and should not adopt into current clinical practice. The EPHESUS trial suggests a much wider role for aldosterone antagonists for the management of heart failure and left ventricular systolic dysfunction. SPORTIF-III indicates we may have a safer, simpler warfarin substitute soon. ASCOT reinforces the potential futility of statin therapy unless it is well targeted. The results of the COMPANION study investigating cardiac resynchronisation devices and implantable defibrillators were encouraging but inconclusive and/or hard to interpret. UK-PACE again questions the use of dual chamber pacing. T-wave alternans is an interesting experimental technique that may be useful in selecting which patients need an implantable defibrillator, although the technology needs testing in an appropriate patient population.

Cardiovascular prophylaxis with aspirin: costs of supply and management of upper gastrointestinal and renal toxicity.

Abstract: Aims To determine the cost to the NHS of prescribed low-dose aspirin. Methods This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. Results Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional £49.86 per year (pragmatic analysis) made up of £1.96 for aspirin tablets (4%), £5.49 for dispensing costs (11%), £24.60 for UGI complications (49%) and £17.81 for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (£2.66 for UGI complications and £2.92 for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between £62 500 (primary prevention, pragmatic analysis) and £867 (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. Conclusions Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects.

Left Ventricular Ejection Fraction and Volumes from Gated Blood-Pool SPECT: Comparison with Planar Gated Blood-Pool Imaging and Assessment of Repeatability in Patients with Heart Failure

Abstract: Gated blood-pool SPECT (GBPS) has several potential advantages over planar radionuclide ventriculography (PRNV), including the possibility of greater repeatability of left ventricular ejection fraction (LVEF) and the noninvasive calculation of left ventricular end-systolic volume and left ventricular end-diastolic volume (LVEDV). The aim of this study was to assess the repeatability of LVEF and LVEDV from GBPS and to compare LVEF with those from PRNV. Methods: Fifty patients underwent PRNV and GBPS, 23 of whom also had repeated studies in the same session. GPBS studies were processed using the Cedars Sinai Quantitative Blood-Pool SPECT (QBS) software that automatically calculates LVEF and LVEDV. Automatic processing with QBS was successful in 70% of the GBPS studies, with the remaining studies processed using the manual option in QBS. All PRNV studies were processed using a manual processing technique. Results: Comparison of LVEF from PRNV and GBPS yielded a correlation coefficient of 0.80. Bland–Altman analysis demonstrated a mean difference of 0.74% ± 7.62% (mean ± SD) between LVEF from the 2 techniques. The 95% limits of agreement are therefore −14.50% to +15.98%. The correlation between repeated measurements was 0.87 for GBPS and 0.95 for PRNV. Bland–Altman analysis revealed poorer repeatability for GBPS (95% limits of agreement, −9.63% to +14.97% vs. −4.66% to +5.92%; P = 0.003). The mean LVEDV was 198 ± 94 mL, with a mean difference of 9 ± 47 mL between repeated measurements. The 95% limits of agreement are therefore −85 to +103 mL. Conclusion: GBPS provides a less repeatable measurement of LVEF than PRNV. Repeatability of LVEDV measurements from GBPS is poor.

Pattern of ventilation during exercise in chronic heart failure

Abstract: Objective: To determine the pattern of the abnormal ventilatory response in heart failure and how it relates to symptoms by looking at tidal volume (Vt) and frequency ( f ) during exercise. Methods: 45 patients with heart failure and 21 controls underwent maximal treadmill based exercise testing with metabolic gas exchange analysis. The relation of ventilation (VE) to Vt was plotted to look for an inflection point where Vt failed to increase further. The slope of the relation before this inflection point was documented. Time to the inflection point, Vt, and f at the inflection point were recorded. The relation of symptom scores to f and VE was also examined. Results: Peak oxygen consumption (PVo 2 ) (mean (SD)) was lower (19.7 (4.5) v 37.9 (8.6) ml/kg/min; p 2 ) slope was steeper (40.0 (6.5) v 26.0 (1.6); p v 502 (196) seconds; p f and a smaller Vt at that point and throughout exercise until the peak where f was the same for patients and controls. Vt at the inflection point correlated with PVo 2 ( r = 0.67; p f than controls. Conclusions: Patients with heart failure breathe at a higher f throughout exercise, reaching an apparent maximal Vt earlier. The Vt at an inflection point on the VE/Vt slope predicts PVo 2 .

The effects of α and β blockade on ventilatory responses to exercise in chronic heart failure

Abstract: Objective: To assess the influence of acute α and β blockade on ventilation and symptoms of breathlessness during exercise in patients with chronic heart failure and in controls. Methods: 11 patients with chronic heart failure and 11 control subjects underwent repeated exercise testing with metabolic gas exchange after random, double blind administration of either an α blocker and placebo, a β blocker and a placebo, both an α blocker and a β blocker, or double placebo. Results: Patients had a lower peak oxygen consumption (mean (SD) 20.7 (4.9) v 37.6 (9.6) ml/kg/min, p 2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following α and β blockade (p Conclusion: Acute sympathetic inhibition can reduce submaximal ventilation during exercise in patients with heart failure and control subjects, suggesting that autonomic nervous system activation has an important role in the abnormal ventilatory response to exercise in chronic heart failure.

Clinical trials update from the European Society of Cardiology: CHARM, BASEL, EUROPA and ESTEEM.

Abstract: This article contains a series of reports on recent research developments in the field of heart failure. Reports of key presentations made at the European Society of Cardiology meeting, held in Vienna, Austria, between 30 August and 3 September 2003 are reported. In the CHARM study, candesartan reduced cardiovascular deaths and hospital admissions for heart failure, both in patients who were already taking an ACE-inhibitor and in those who were ACE intolerant. However, results in patients with preserved left ventricular function were less conclusive. The BASEL study supports the use of B-type natriuretic peptide testing to confirm the diagnosis of heart failure in patients presenting with acute dyspnoea. In EUROPA, the largest ever study of secondary prevention of coronary artery disease, long-term treatment with perindopril reduced the incidence of cardiovascular death, myocardial infarction (MI) and cardiac arrest. The ESTEEM study showed that the oral thrombin inhibitor ximelagatran plus aspirin was more effective than aspirin alone in the prophylaxis of major cardiovascular events following MI.

High- versus low-dose angiotensin converting enzyme inhibitor therapy in the treatment of heart failure: an economic analysis of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial

Abstract: Background Angiotensin-converting enzyme (ACE) inhibitors reduce heart failure death and hospitalization. Prescribed doses often are lower than randomized clinical trial (RCT) targets and practice guideline recommendations. Objective To assess the cost-effectiveness of high- versus low-dose ACE inhibitor therapy in the ATLAS trial. Study design A 19-nation RCT of high-dose (32.5-35.0 mg/day) versus low-dose (2.5-5.0 mg/day) lisinopril in 3164 patients with class II-IV heart failure and left ventricular ejection fraction Methods Data on clinical outcomes and major cost events (hospitalizations and drug utilization) were collected prospectively. Hospital costs were estimated using Medicare and representative managed care diagnosis-related group reimbursement rates. ACE inhibitor drug costs were estimated using US average wholesale prices. Costs were discounted at 3% annually. Results Patients in the high-dose lisinopril group had fewer hospitalizations (1.98 vs 2.22, P = .014) and hospital days (18.28 vs 22.22, P = .002), especially heart failure hospitalizations (0.64 vs 0.80, P = .006) and heart failure hospital days (6.02 vs 7.45, P = .028) compared with the low-dose group. The high-dose lisinopril group also had lower heart failure hospital costs (dollars 5114 vs dollars 6361, P = .006) but higher ACE inhibitor drug costs (dollars 1368 vs dollars 855, P = .0001). Total hospital and drug costs were similar between high- and low-dose lisinopril groups (mean difference dollars -875, 95% CI dollars -2613 to dollars 884). Sensitivity analyses confirmed these findings. Conclusions Cost savings from fewer heart failure hospitalizations offset higher ACE inhibitor costs in the high-dose group. The improved clinical outcomes were achieved without increased treatment costs.

Multi-chamber pacing: a perfect solution for cardiac mechanical dyssynchrony?

Abstract: See doi:10.1016/S1095-668X(02)00475-Xfor the article to which this editorial refers. When the heart fails, it becomes less efficient, as myocardial energy consumption rises without a corresponding increase in cardiac output. There are many possible reasons for this decline in cardiac efficiency (Fig. 1). Recently, because of the potential value of multi-site pacing, interest has focused on mechanical dyssynchrony, which encompasses a complex array of problems that often coexist in varying degrees along with ‘functional’ mitral regurgitation.1–3 Fig. 1 Some mechanisms of heart failure causation and progression (usually multiple mechanisms operating simultaneously conspire to cause progression of heart failure). It is likely that mechanical dyssynchrony is common, although precisely how common is unclear, and will depend on the definition and the tools used to measure it. The presence and severity of cardiac dyssynchrony can be assessed directly using imaging techniques or indirectly by measuring time-intervals from a standard 12-lead echocardiography (ECG). ECG is the current method of choice owing to its wide availability, high temporal resolution and its ability to assess flow across the valves, although diagnostic criteria for cardiac dyssynchrony are still being refined.4 In the meantime, studies on relatively small numbers of patients have suggested that patients who have a QRS width ≥150ms very often have evidence of major inter- and intra-ventricular dyssynchrony on imaging.5 A high, but as yet uncertain, proportion of patients with QRS 120–150ms will also fulfil current echocardiographic criteria for ventricular dyssynchrony.6,7 Approximately, one in every four patients with heart failure secondary to left ventricular systolic dysfunction (LVSD) will have a QRS width >120ms on their surface ECG.8 The PR interval may be a useful marker for atrio-ventricular dyssynchrony,1 but <5% of patients with heart failure and LVSD will have a PR interval ≥220ms.8–11 Mechanical dyssynchrony and the possibility of …

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

Abstract: 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 European Society of Cardiology Heart Failure meeting: COMET, COMPANION, Tezosentan and SHAPE.

Abstract: 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 Strasbourg, France are described. The COMET study showed a 17% relative risk reduction in all-cause mortality with carvedilol compared with metoprolol tartrate. The COMPANION study, as previously reported, showed encouraging results for the use of cardiac resynchronisation and implantable defibrillator therapy in patients with heart failure, but further evidence is awaited. The results of a study on tezosentan suggest that lower doses of this endothelin antagonist may be clinically more effective with fewer adverse effects compared with higher doses. The SHAPE survey of heart failure awareness in Europe identified a need for further heart failure education amongst the public, patients, their carers and primary care physicians.

Ongoing trials of cardiac resynchronisation.

Abstract: Heart failure is an increasingly common and debilitating condition for which pharmacological therapy has, so far, provided only partial relief. Despite medical therapy the overall prognosis remains poor with high rates of sudden death and death from progressive heart failure. Device based therapies offer considerable promise both for the relief of symptoms and for improving prognosis. Cardiac resynchronisation therapy (CRT) has already been shown to improve the symptoms of heart failure when optimal pharmacological therapy (including aggressive diuretic therapy, ACE inhibitors, b-blockers and spironolactone) has failed. Two large trials (CARE-HF and COMPANION) are currently investigating the effects of CRT on morbidity and mortality in patients with heart failure and sinus rhythm who have left ventricular systolic dysfunction and ventricular dyssynchrony. A series of small and medium sized studies are assessing the effects of CRT in patients similar to the above but who also have atrial fibrillation. Other potential indications for CRT that are being explored include heart failure due to left ventricular diastolic function and for the prevention of iatrogenic dyssynchrony caused by conventional pacing. The MADIT-II study suggests a small benefit from routine implantation of defibrillators in patients with heart failure who have a markedly depressed ( 150 msec, an ECG marker for cardiac dyssynchrony. The COMPANION trial will not only assess the effects of CRT alone but also the effects of a combined CRT and defibrillator device. Premature over-interpretation of the limited amount of existing data threatens to undermine the evidence that will form the basis of future guidelines and funding decisions. Those involved in trials have an ethical duty to minimise device implantation into patients who have been randomised to the control group (cross-overs). Doctors may have difficulty explaining to patients why they implanted a CRT device should the current trials not show benefit. Patients should be warned that CRT is still an experimental therapy that has not yet been proven to alter outcome substantially.