Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study

OBJECTIVES: We sought to determine the predictors of heart failure (HF) development in long-term survivors of myocardial infarction (MI). BACKGROUND: Modern strategies of acute MI care have resulted in an increasing proportion of survivors at heightened risk of future non-fatal events, including HF. METHODS: We assessed the risk of developing HF in 3860 stable MI patients without a previous history of HF, who were enrolled in the Cholesterol And Recurrent Events (CARE) trial a median of 10 months post MI. Baseline characteristics of patients who did or did not develop HF during the five years of observation were assessed. RESULTS: A total of 243 patients (6.3%) developed HF in a linear pattern at a rate of 1.3%/year. Heart failure development markedly increased the risk of death (hazard ratio 10.2, 95% confidence interval 7.7 to 13.5). Fifty-seven patients (23.5%) who developed HF had a recurrent MI between enrollment and the onset of HF, increasing the risk fivefold. The most important predictors of HF were age and left ventricular ejection fraction. Other predictors included diabetes, history of hypertension, previous MI, and baseline heart rate. Moderate exercise three or more times per week was independently associated with a 30% lower risk of HF. CONCLUSIONS: Heart failure post MI occurs in a time-dependent fashion, which is usually not a direct consequence of a detectable interim MI. Patients who experience late-onset HF have a 10-fold increased risk of death compared with other MI survivors. Baseline characteristics can risk stratify patients at high risk of subsequent HF.     

Predictors of the first heart failure hospitalization in patients who are stable survivors of myocardial infarction complicated by pulmonary congestion and/or left ventricular dysfunction: a VALIANT study.

AIMS: We sought to assess the incidence of and prognostic factors for heart failure (HF) hospitalization among survivors of high-risk acute myocardial infarction (MI). METHODS AND RESULTS: We assessed the risk of an initial hospitalization for HF in 11 040 stable MI patients (no major non-fatal cardiovascular events or deaths within 45 days of randomization) without a prior history of HF enrolled in the VALIANT trial. Multivariable models were developed to identify independent predictors of HF and HF or cardiovascular death. Of 11 040 stable post-MI patients, 1139 (10.3%) developed HF during the median 25-month follow-up at a rate of approximately 3.4% per year. Most patients, 824 (72.3%), did not have a symptomatic recurrent MI between randomization and the onset of HF. The most important predictors of HF were older age, antecedent diabetes, prior MI before index MI, and reduced renal function. HF markedly increased the risk of death [HR(hazard ratio) 8.22; 95% CI(confidence interval), 7.49-9.01]. CONCLUSION: HF post high risk-MI occurs in a time-dependent fashion and is usually not directly related to re-infarction. Patients who experience HF beyond the acute phase have increased mortality. Long-term survivors of high-risk MI should be followed closely and treated aggressively beyond the acute MI period.     

The impact of morbid events on survival following hospitalization for complicated myocardial infarction

BACKGROUND: Little is known about the importance of morbid events with respect to longer term survival following MI hospital discharge. AIMS: Establish the risk of death associated with morbid events following initial discharge from MI hospitalization. METHODS: We examined the rates of morbid events (reinfarction, stroke/TIA, revascularization, heart failure (HF) hospitalization, cardiovascular hospitalization and all-cause hospitalization) and the relationships of these events to subsequent death in patients who survived the initial hospitalization for MI (n = 5301) in the OPTIMAAL trial. Events were classified as Early (< or = 30 days post discharge) and Late (> 30 days post discharge) for an average of 2.7 years follow-up. RESULTS: Death rates were higher in the Early period (0.20 deaths/patient year) than in the Late period (0.05 deaths/patient year). Once a morbid event, excluding revascularization, occurred, the acute hazard ratios (HR, determined by Cox regression) for death on the day of event were higher than at time periods following the event and were highest for reinfarction and stroke/TIA. The acute HRs for death for all 6 morbid events were especially high for events occurring during the Late period. The highest chronic HR for death was associated with HF and all-cause hospitalizations. By contrast, the chronic HR for death from revascularization in both the Early (HR = 0.3) and Late (HR = 0.4) period indicated reduced risk. CONCLUSIONS: The results document event rates following hospitalization for MI, provide quantification of the associated risk for death, and may be useful in designing clinical trials. The serious morbid events examined may serve as potential surrogate endpoints in long-term studies and identify patients that should be targeted for aggressive management.     

Management of post-myocardial infarction patients with left ventricular systolic dysfunction

After a myocardial infarction (MI), patients are at risk for reinfarction, heart failure (HF), and sudden death. This risk is much higher in patients with left ventricular systolic dysfunction (LVSD). Although post-MI patients with LVSD have an even greater risk of mortality and morbidity, they had been generally excluded from clinical trials. This article reviews recent clinical trials that included post-MI patients with LVSD with or without signs and symptoms of HF. These trials have defined the benefits of pharmacologic management and device therapy in patients who survive an MI in the presence of LVSD.     

The timing of development and subsequent clinical course of heart failure after a myocardial infarction.

AIMS: Myocardial infarction (MI) is a common cause of heart failure (HF), which may develop early and persist or resolve, or develop late. The cumulative incidence, persistence, and resolution of HF after MI are poorly described. The aim of this study is to describe the natural history and prognosis of HF after an MI. METHODS AND RESULTS: Patients with a death or discharge diagnosis of MI in 1998 were identified from records of hospitals providing services to a local community of 600 000 people. Records were scrutinized to identify the development of HF, defined as signs and symptoms consistent with that diagnosis and treated with loop diuretics. HF was considered to have resolved if diuretics could be stopped without recurrent symptoms. Totally, 896 patients were identified of whom 54% had died by December 2005. During the index admission, 199 (22.2%) patients died, many with HF, and a further 182 (20.3%) patients developed HF that persisted until discharge, of whom 121 died subsequent to discharge. Of 74 patients with transient HF that resolved before discharge, 41 had recurrent HF and 38 died during follow-up. After discharge, 145 (33%) patients developed HF for the first time, of whom 76 died during follow-up. Overall, of 281 deaths occurring after discharge, 235 (83.6%) were amongst inpatients who first developed HF. CONCLUSION: The development of HF precedes death in most patients who die in the short- or long-term following an MI. Prevention of HF, predominantly by reducing the extent of myocardial damage and recurrent MI, and subsequent management could have a substantial impact on prognosis.     

Impact of nonfatal myocardial infarction on outcomes in patients with advanced heart failure and the effect of bucindolol therapy

We sought to identify the clinical characteristics and outcomes of patients who had advanced heart failure and nonfatal myocardial infarction (MI) in the beta-Blocker Evaluation of Survival Trial (BEST) and to investigate whether bucindolol alters the risk of developing nonfatal MI. Of the 2,708 patients enrolled in the study, 142 had suspected MI and 69 had confirmed MI; there were 860 deaths overall. The rate of nonfatal MI in the BEST was low over the 4.1 years of follow-up (4.8% had suspected events and 2.4% had adjudicated events) and was similar to that in high-risk populations. Cox's proportional hazard model with 23 prespecified candidate variables associated advanced age, heart failure symptoms, male gender, ischemic etiology, diabetes, and hypertension with nonfatal MI or cardiovascular death. The 2-year mortality rate was 56% for the cohort that had suspected nonfatal MI versus 30% for the cohort that did not (p = 0.01). Likewise, the risk of hospitalization for congestive heart failure was twofold greater. Beta-blocker therapy with bucindolol resulted in a 52% decrease in suspected nonfatal MI (2.9% vs 5.5%, p = 0.001). In conclusion, nonfatal MI occurs at low rates but increases the risks for mortality and hospitalization in patients who have advanced heart failure. Beta-blocker therapy with bucindolol appears to attenuate the risk of nonfatal MI in this population.     

Predictors of 90-day outcome in patients stabilized after acute coronary syndromes.

AIMS: We investigated predictors of 90-day risk among patients surviving the early period after an acute coronary syndrome (ACS). METHODS AND RESULTS: The study population included 15 904 stabilized ST-segment elevation or non-ST-segment elevation ACS patients randomized in SYMPHONY and 2nd SYMPHONY. We developed risk models for death, death or myocardial infarction (MI), and death, MI, or severe recurrent ischaemia (SRI) using Cox proportional-hazards techniques. Demographic, history, and pre-randomization clinical and medication variables were tested. Validation techniques included development of individual trial models, backward elimination and bootstrapping. Of 118 variables, 17 independently predicted mortality. The strongest associations included greater age (chi(2)=31.1), higher randomization heart rate (chi(2)=27.4), and heart failure (HF) variables (HF between qualifying event and randomization, chi(2)=21.8; history of HF, chi(2)=12.2). Higher creatinine clearance (chi(2)=17.7) and percutaneous coronary intervention between qualifying event and randomization (chi(2)=11.1) most strongly predicted lower risk. Similar characteristics entered the double and triple composite models, but HF variables and age less strongly predicted these end-points. CONCLUSIONS: In patients stabilized after ACS, those at highest risk over the next 90 days can be identified. Typical clinical markers are better at identifying risk of death than non-fatal MI or SRI. Novel risk markers are needed for these outcomes.     

Gender Differences in the Pathophysiology, Clinical Presentation, and Outcomes of Ischemic Heart Failure

Despite advances in the treatment of acute myocardial infarction (MI), heart failure (HF) remains a frequent acute and long-term outcome of ischemic heart disease (IHD). In response to acute coronary ischemia, women are relatively protected from apoptosis, and experience less adverse cardiac remodeling than men, frequently resulting in preservation of left ventricular size and ejection fraction. Despite these advantages, women are at increased risk for HF- complicating acute MI when compared with men. However, women with HF retain a survival advantage over men with HF, including a decreased risk of sudden death. Sex-specific treatment of HF has been hindered by historical under-representation of women in clinical trials, though recent work has suggested that women may have a differential response to some therapies such as cardiac resynchronization. This review highlights the sex differences in the pathophysiology, clinical presentation and outcomes of ischemic heart failure and discusses key areas worthy of further investigation.     

Association of QRS duration and outcomes after myocardial infarction: the VALIANT trial.

BACKGROUND: Prolongation of the QRS duration has been shown to be associated with adverse outcomes among heart failure (HF) patients. The association of QRS duration with clinical outcomes in the post-myocardial infarction (MI) setting is less well defined. OBJECTIVES: To assess the prognostic significance of QRS duration prolongation on initial electrocardiogram after acute MI. METHODS: QRS duration was measured in 403 patients with MI complicated by left ventricular dysfunction, signs or symptoms of HF, or both, who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echo study. The cohort was divided into quartiles of QRS duration (<75 ms, 75-88 ms, 89-108 ms, >108 ms). The number of clinical events were determined and compared across the groups. RESULTS: Increasing QRS duration is associated with a higher incidence of HF, sudden death (SD), and cardiovascular (CV) death (P-trend <0.05) but not with stroke or recurrent MI. The univariate relative risks for HF, SD, and CV death with increasing QRS duration quartiles were 1.31 (95% CI, 1.06-1.64), 1.57 (95% CI, 1.03-2.40), and 1.31 (95% CI, 1.03-1.66), respectively, but QRS duration did not remain independently predictive of adverse outcome after adjusting for the 10 most predictive baseline covariates. Baseline end-diastolic and end-systolic volumes were larger and ejection fraction was lower in the higher QRS quartile groups. CONCLUSIONS: Prolonged QRS duration, even within the normal range, is associated with larger ventricular volumes, reduced systolic function, and an increased risk for development of HF, SD, and CV death after MI but appears to be a marker, rather than an independent predictor, for increased risk.     

Usefulness of right ventricular fractional area change to predict death, heart failure, and stroke following myocardial infarction (from the VALIANT ECHO Study)

Severe right ventricular dysfunction independent of left ventricular ejection fraction increased the risk of heart failure (HF) and death after myocardial infarction (MI). The association between right ventricular function and other clinical outcomes after MI was less clear. Two-dimensional echocardiograms were obtained in 605 patients with left ventricular dysfunction and/or clinical/radiologic evidence of HF from the VALIANT echocardiographic substudy (mean 5.0 +/- 2.5 days after MI). Clinical outcomes included all-cause mortality, cardiovascular (CV) death, sudden death, HF, and stroke. Baseline right ventricular function was measured in 522 patients using right ventricular fractional area change (RVFAC) and was related to clinical outcomes. Mean RVFAC was 41.9 +/- 4.3% (range 19.2% to 53.1%). The incidence of clinical events increased with decreasing RVFAC. After adjusting for 11 covariates, including age, ejection fraction, and Killip's classification, decreased RVFAC was independently associated with increased risk of all-cause mortality (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.31 to 1.98), CV death (HR 1.62, 95% CI 1.30 to 2.01), sudden death (HR 1.79, 95% CI 1.26 to 2.54), HF (HR 1.48, 95% CI 1.17 to 1.86), and stroke (HR 2.95, 95% CI 1.76 to 4.95), but not recurrent MI. Each 5% decrease in baseline RVFAC was associated with a 1.53 (95% CI 1.24 to 1.88) increased risk of fatal and nonfatal CV outcomes. In conclusion, decreased right ventricular systolic function is a major risk factor for death, sudden death, HF, and stroke after MI.     

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.     

Novel biomarkers for cardiovascular risk prediction

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high- sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well vali?dated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.     

Previously known and newly diagnosed atrial fibrillation: a major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction

AIMS: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). METHODS: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. RESULTS: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03-1.52; p=0.03) for prior AF and 1.32 (1.20-1.45; p<0.0001) for current AF. HR for major CV events was 1.15 (0.98-1.35; p=0.08) and 1.21 (1.12-1.31; p<0.0001). CONCLUSION: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD.     

An international perspective on heart failure and left ventricular systolic dysfunction complicating myocardial infarction: the VALIANT registry.

AIMS: We analysed the contemporary incidence, outcomes, and predictors of heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) before discharge in patients with acute myocardial infarction (MI). The baseline presence of HF or LVSD, or its development during hospitalisation, increases short- and long-term risk after MI, yet its incidence, predictors, and outcomes have not been well described in a large, international, general MI population. METHODS AND RESULTS: The VALIANT registry included 5573 consecutive MI patients at 84 hospitals in nine countries from 1999 to 2001. A multivariable logistic survival model was constructed using baseline variables to determine the adjusted mortality risk for those with in-hospital HF and/or LVSD. Baseline variables were also tested for associations with in-hospital HF and/or LVSD. Of the 5566 patients analysed, 42% had HF and/or LVSD during hospitalisation. Their in-hospital mortality rate was 13.0% compared with 2.3% for those without HF and/or without LVSD. After adjustment for other baseline risk factors, in-hospital HF and/or LVSD carried a hazard ratio for in-hospital mortality of 4.12 (95% confidence interval: 3.08-5.56). Patients with HF and/or LVSD also had disproportionately higher rates of other cardiovascular events. CONCLUSIONS: HF and/or LVSD is common in the general contemporary MI population and precedes 80.3% of all in-hospital deaths after MI. Survivors of early MI-associated HF and/or LVSD have more complications, longer hospitalisations, and are more likely to die during hospitalisation. Although baseline variables can identify MI patients at highest risk for HF and/or LVSD, such patients are less likely to receive indicated procedures and medical therapies.     

Cardiac imaging to identify patients at risk for developing heart failure after myocardial infarction

The development of heart failure (HF) after acute myocardial infarction (MI) is recognized as a major complication that leads to a significant increase in morbidity and mortality. Given the availability of effective treatments for improving both quality of life and survival for patients at increased risk for developing HF after MI, early identification of these individuals is critical. Noninvasive cardiac imaging offers a detailed characterization of two important pathophysiological processes related to the development of HF post-MI: left ventricular (LV) remodeling and LV functional recovery. Cardiovascular MRI has recently emerged as the preferred noninvasive imaging modality because of its ability to provide the most comprehensive and informative evaluation of these processes. In addition to allowing for an accurate and reproducible longitudinal follow-up of LV volumes and mass, MRI also offers information on infarct size, the presence of microvascular obstruction, and the transmural extent of infarct scar, all of which are valuable parameters that can assist in identifying patients at risk for developing HF after MI.     

Severity of heart failure, treatments, and outcomes after fibrinolysis in patients with ST-elevation myocardial infarction.

AIMS: To define the clinical characteristics, co-morbidities, treatment, and clinical outcomes of patients with varying degrees of heart failure (HF) complicating ST-elevation myocardial infarction (STEMI), and to identify patients at high risk for HF following fibrinolysis. METHODS AND RESULTS: 15,078 STEMI patients enrolled in a worldwide fibrinolytic trial (InTIME-II) were categorised into one of four hierarchical, mutually exclusive groups of HF: shock (n = 719, 5%); severe HF (n = 1082, 7%); mild HF (n = 1619, 11%); no HF (n = 11,658, 77%). In a multivariable model, anterior MI (OR 1.8, 95% CI [1.6; 1.9]), age > or = 65 (OR 1.8 [1.6; 2.0]), prior HF (OR 3.3 [2.6; 4.2]), and creatinine clearance < 60 mL/min (OR 1.8 [1.6; 2.1]) were the four most powerful correlates of HF. Although 30-day mortality was sixfold higher for patients with HF (18.9% vs. 3.1%, P < 0.0001), these patients were less likely to undergo angiography (30% vs. 40%, P < 0.0001) and revascularisation (19% vs. 25%, P , 0.0001), than patients without HF. Likewise, angiotensin-inhibitors and beta-blockers were not optimally utilised in patients with HF following MI. CONCLUSIONS: During the index admission following fibrinolysis 23% of patients had HF. Despite a higher risk profile, patients with more severe HF were treated less aggressively than patients without HF.     

Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice

BACKGROUND: Tissue kallikrein (TK) is a major kinin-releasing enzyme present in arteries. TK is involved in cardioprotection in the setting of acute myocardial ischaemia but its role in post-ischaemic heart failure (HF), a major cause of delayed mortality after myocardial infarction (MI), is unknown. AIM: To determine whether TK deficiency in the mouse influences survival and cardiac remodelling after MI. METHODS: MI was induced in 10 week-old male TK-deficient mice and wild-type littermates. Survival was assessed up to 14 months. Cardiac morphological and functional parameters were serially measured by echocardiography. In another experiment, myocardial capillary density and NOS content were evaluated at 3 months. RESULTS: Infarct size was similar in both genotypes. MI resulted in severe cardiac dysfunction. Up to 12 months after MI, TK(-/-) mice displayed an increased mortality rate (P<0.05, relative risk of death=3.41) and aggravation of left ventricular hypertrophy and dilatation by comparison with TK(+/+) (+18% and +27% respectively, both P<0.05). NOS1 and NOS3 were abnormally regulated in the heart of TK(-/-) mice after MI. CONCLUSIONS: TK exerts a protective role in HF in mice. Coronary effects are probably involved. As partial genetic deficiency in TK activity occurs in humans, TK-deficient subjects may be at increased risk of mortality in HF.     

Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction

BACKGROUND/AIMS: Studies of the prognostic importance of QRS duration in patients with heart failure (HF) have shown conflicting results and few studies have estimated the importance after myocardial infarction (MI). METHODS: The Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study randomised 3028 patients to dofetilide (class III antiarrhythmic) or placebo. The study consisted of two almost identical trials conducted simultaneously. One trial included 1518 patients with chronic HF and the other trial 1510 patients with a recent MI. All patients had left ventricular dysfunction. Dofetilide did not influence mortality in either trial. QRS duration was systematically measured at randomisation and was available in 2972 patients. RESULTS: Over a 10 year observation period 1037 (70%) patients in the MI study and 1324 (87%) in the HF study died. In the MI study, risk of death increased 6% for each 10 ms increase in QRS duration (HR=1.06/10 ms increase in QRS (CI=1.04-1.09), p<0.0001) whereas QRS duration had no influence in the HF study after multivariable adjustment. The difference between HF and MI was significant (p<0.0004 for interaction). CONCLUSION: QRS duration predicts death in patients with left ventricular dysfunction who have suffered MI. In patients with HF QRS duration is not predictive of mortality.