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In the emergency setting, shortness of breath is a frequent presenting complaint to physicians worldwide. The differential diagnosis is often broad and requires careful analysis of investigations to reach the correct diagnosis. The authors present a case of acute heart failure with a number of unusual presenting features that suggested an uncommon aetiology.

Background: Glycated haemoglobin (HbA1c) is an indicator of average blood glucose concentrations over the preceding 3 months, is simpler to perform than either a fasting glucose or glucose tolerance test and is associated with a worse prognosis in some clinical settings. However, its relationship to survival in patients with suspected heart failure has not been studied., Methods: Patients referred to a community-based heart failure clinic with suspected heart failure had a comprehensive assessment including the measurement of HbA1c. For this analysis, patients with DM or who started diabetic medication in the subsequent 12 months, which might influence HbA1c, were excluded., Findings: Of 970 non-diabetic patients referred between 2001 and 2004, the median age was 72 years (range 25 to 96 years), 56% were men, 45% had left ventricular ejection fraction (LVEF) 6% (upper reference limit). Among patients with LVEF 6.7% (n = 68) compared with those with HbA1c 45% (HR 1.44, p = 0.36 after adjustment)., Interpretation: The abrupt increase in mortality with HbA1c may make it a useful risk stratification tool in non-diabetic patients with LVEF

Background: Atrial fibrillation (AF) and heart failure (HF) often coexist. The aim was to investigate whether restoring sinus rhythm (SR) could improve cardiac function, symptoms, exercise capacity and quality of life (QoL) in patients with chronic heart failure., Methods: Patients with HF and persistent AF receiving guideline-recommended treatments, including anticoagulants, were eligible for the study. Patients were randomised to either rhythm (treated with amiodarone for at least 3 months prior to attempting biphasic external cardioversion and continued amiodarone long-term if SR was restored) or rate control. Anticoagulants were continued throughout the study regardless of rhythm, unless contraindications developed. Both groups were treated with beta blockers and/or digoxin to reduce the heart rate to <80 bpm at rest and <110 bpm after walking. Symptoms, walk distance (6-minute corridor walk test, 6MWT), QoL and cardiac function were assessed at baseline and 1 year., Results: 61 patients with HF and persistent AF (median duration 14 months (IQR 5 to 32)) were randomly assigned to a rate or rhythm control strategy. Of patients assigned to rhythm control (n = 30), 66% were in SR at 1 year, and 90% of those assigned to rate control (n = 31) achieved the heart rate target. At 1 year, NYHA class (p = 0.424) and 6MWT distance (p = 0.342) were similar between groups but patients assigned to rhythm control had improved LV function (p = 0.014), NT-proBNP concentration (p = 0.046) and QoL (p = 0.019) compared with those assigned to rate control. Greatest improvement was seen in patients in whom SR was maintained., Conclusion: Restoring SR in patients with AF and heart failure may improve QoL and LV function when compared with a strategy of rate control.

Background: It is unclear whether age-related increases in N-terminal pro-brain natriuretic peptide (NT-proBNP) represent a normal physiological process-possibly affecting the prognostic power-of NT-proBNP-or reflect age-related subclinical pathological changes., Objective: To determine the effect of age on the short-term prognostic value of NT-proBNP in patients with chronic heart failure (CHF)., Design: Prospective observational study with inclusion and matching of consecutive patients aged >65 years (mean (SD) 73.1 (6.0) years) to patients <65 years (53.7 (8.6) years) with respect to NT-proBNP, New York Heart Association stage, sex and aetiology of CHF (final n = 443)., Setting: University hospital outpatient departments in the UK and Germany., Patients: Chronic stable heart failure due to systolic left ventricular dysfunction., Intervention: None., Outcome Measure: All-cause mortality., Results: In both age groups, NT-proBNP was a significant univariate predictor of mortality, and independent of age, sex and other established risk markers. The prognostic information given by NT-proBNP was comparable between the two groups, as reflected by the 1-year mortality of 9% in both groups. The prognostic accuracy of NT-proBNP as judged by the area under the receiver operating characteristics curve for the prediction of 1-year mortality was comparable for elderly and younger patients (0.67 vs 0.71; p = 0.09)., Conclusion: NT-proBNP reflects disease severity in elderly and younger patients alike. In patients with chronic stable heart failure, the NT-proBNP value carries the same 1-year prognostic information regardless of the age of the patient.

Background: Epidemiological studies suggest that "diastolic heart failure" (DHF) is common and has a prognosis similar to that of systolic heart failure (SHF). We wanted to assess whether patients with breathlessness who were being treated for DHF had objective evidence of cardiac impairment and exercise limitation., Methods: Consecutive patients with a clinical diagnosis of chronic heart failure completed a standardised 6-minute walk test (6-MWT) and underwent an echocardiographic examination to determine the presence of major structural heart disease (MSHD). N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured to determine degree of cardiac pathology., Results: 568 patients were identified with SHF (75.7% males) and 104 with DHF (54.7% males). They were compared with 400 healthy controls (matched with DHF group for age, sex and body mass index (BMI)). Controls (median (interquartile range); 43 (20-62) pmol/l)) and DHF patients (27 (13-67) pmol/l) had significantly lower NT-proBNP levels compared to SHF patients (178 (82-422) pmol/l). There was no difference in NT-proBNP levels between controls and DHF patients (p = 0.348). There was no correlation between BMI and NT-proBNP in either DHF (r(2) = 0.03; p = 0.287) or SHF (r(2) = 0.02; p = 0.346) patients. Both SHF and DHF patients reported similar degrees of breathlessness. 6-MWT distance (p = 0.973) was similar between SHF and DHF patients. DHF patients had a higher BMI (p<0.0001)., Conclusion: Patients being treated for a clinical diagnosis of DHF have the same self-reported symptoms and 6-MWT performance as patients with SHF, yet have normal NT-proBNP levels. Their perception of their symptoms is out of proportion to their evidence of cardiac pathology.

Objectives: This study evaluated gender differences in clinical characteristics, treatment and outcome among patients with heart failure, and to what extent these differences are due to age and differences in left ventricular (LV) function. Although gender differences are observed among heart failure patients, few studies have been adequately powered to investigate these differences., Methods: A total of 8914 (out of 10 701) patients (47% women) from the Euro Heart Survey on Heart Failure with confirmed diagnosis of heart failure were included in the analyses., Results: Women were older (74.7 vs 68.3 years, p<0.001), and less often had evidence of coronary artery disease (56% vs 66%, age-adjusted odds ratio (OR) 0.62; 95% CI 0.57 to 0.68). Women were more likely to have hypertension, diabetes, or valvular heart disease. Fewer women had an investigation of LV function (59% vs 74%, age-adjusted OR 0.67; 95% CI 0.61 to 0.74), and, among those investigated, fewer had moderate/severe left ventricular systolic dysfunction (44% vs 71%, age-adjusted OR 0.35; 95% CI 0.32 to 0.39). Drugs with a documented impact on survival, that is ACE-inhibitors and beta-blockers, were given less often to women, even in the adjusted analysis (OR 0.72; 95% CI 0.61 to 0.86 and OR 0.76; 95% CI 0.65 to 0.89, respectively). 12-week mortality was similar for men and women., Conclusions: Fewer women had an assessment of LV function, but, when investigated, women had better ventricular function. Women were less often treated with evidence-based drugs, even after adjustment for age and important clinical characteristics. Clinicians need to be aware of deficiencies in the treatment of women with heart failure and measures should be taken to rectify them.

Background: Cardiac resynchronisation therapy (CRT) improves symptoms and prognosis in patients with heart failure and cardiac dyssynchrony. Guidelines from the National Institute of Health and Clinical Excellence in the United Kingdom recommend CRT for patients with recent or persistent moderate or severe symptoms of heart failure. This analysis investigated whether the severity of symptoms was an important determinant of the prognostic benefits of CRT., Methods: In CARE-HF, patients with left ventricular ejection fraction < or =35% and markers of cardiac dyssynchrony who were, in the investigators' opinion, in New York Heart Association (NYHA) class III/IV were randomly assigned to pharmacological treatment alone or with addition of CRT. This analysis investigated whether the severity of symptoms reported by patients, using Likert Scales from the EuroHeart Failure Questionnaire and self-assessed NYHA class, influenced prognosis and the response to CRT., Results: Of 813 patients, 175 (21.5%) assessed themselves to be in NYHA class I or II. These patients also reported less severe symptoms and better quality of life than patients who assessed themselves to be in NYHA class III or IV. No statistical interaction was observed between the severity of symptoms assessed in several ways and the benefits of CRT on morbidity and mortality., Conclusions: The severity of symptoms was not an important determinant of the prognostic effects of CRT in patients with moderate or severe LVSD and markers of dyssynchrony in the CARE-HF study. This finding requires confirmation in an adequately powered prospective randomised controlled trial in patients with milder symptoms.

Objectives: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure., Design: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006., Setting: Acute NHS trusts in England, Wales and Northern Ireland., Main Outcome Measures: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge., Results: 176/177 (99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), beta-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, beta-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care., Conclusion: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and beta-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care.

Objectives: To establish the prevalence of preserved left ventricular (LV) systolic function (PSF) in 435 consecutive symptomatic patients referred to a heart failure clinic and to examine their ventilatory response to exercise when compared with 134 control volunteers., Methods: 216 (50%) patients had systolic heart failure (SHF) (ejection fraction < 45%). 51 (11%) had an immediately apparent alternative causes of breathlessness and 168 (39%), with no obvious other cause of breathlessness, were divided into those with PSF and diastolic dysfunction (DD) (PSF(DD); n = 113 or 26% of referrals) and those without DD (PSF(N); n = 55 or 13% of referrals). The controls were divided into those with (C(DD); n = 32) and those without (C(N); n = 102) echocardiographic evidence of DD., Results: Patients with SHF had lower peak oxygen consumption (pVo(2)), steeper slope of minute ventilation (Ve) to carbon dioxide production, lower exercise time and shorter 6 min walk test than PSF patients and controls. PSF(DD) patients had lower pVo(2), exercise time and 6 min walk test than C(DD), although their echocardiograms were not different. Exercise capacity did not differ between PSF(DD) and PSF(N) patients. The slope relating Ve to symptoms (Borg/Ve slope) was less steep in those with SHF than in PSF(DD) (0.17 (0.04) v 0.20 (0.08), p < 0.05) and in PSF(N) (0.19 (0.10), p < 0.05), implying greater symptoms of breathlessness for a given level of Ve. Both PSF groups had a steeper slope than C(DD) (0.14 (0.09), p < 0.05 for both comparisons)., Conclusions: Patients with PSF have exercise tolerance intermediate between that of patients with SHF and controls. Exercise tolerance is similar in PSF(DD) and PSF(N). Both groups have worse exercise tolerance than C(DD). PSF(DD) and PSF(N) patients seem to experience a greater awareness of Ve than C(DD) and patients with SHF.

Objective: To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction., Methods: 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging., Results: During a median follow up of 32 months (range 24-38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p = 0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p = 0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p = 0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p = 0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p = 0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p = 0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p = 0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p = 0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p = 0.016) emerged as independent predictors of outcome., Conclusions: In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.

Objective: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling., Methods: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment., Results: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ., Conclusion: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Objective: To establish the prevalence of chronotropic incompetence in a cohort of patients with chronic heart failure (CHF) taking modern medications for heart failure, and whether this affected exercise capacity and predicted prognosis., Methods: Heart rate response to exercise was examined in 237 patients with CHF in sinus rhythm, who were compared with 118 control volunteers. The percentage of maximum age predicted peak heart rate (%Max-PPHR) and percentage heart rate reserve (%HRR) were calculated, with a cut off of < 80% as the definition of chronotropic incompetence for both. Patients were followed up for an average (SD) of 2.8 (9) years. Mortality was related to peak oxygen consumption (pVo2), and the presence or absence of chronotropic incompetence., Results: %Max-PPHR < 80% identified 103 (43%) and %HRR < 80% identified 170 patients (72%) as having chronotropic incompetence. Chronotropic incompetence was more common in patients taking beta blockers than in those not taking beta blockers as assessed by both methods (80 (49%) v 23 (32%) by %Max-PPHR and 123 (75%) v 47 (64%) by %HRR, respectively). Patients with chronotropic incompetence by either method had a lower pVo2 than those without. These differences remained significant for both patients taking and not taking a beta blocker. %HRR, Max-PPHR%, and HRR were related to New York Heart Association class and correlated with pVo2. There was no difference in the slopes relating heart rate to pVo2 between patients with and those without chronotropic incompetence (6.1 (1.7) v 5.1 (1.8), p = 0.34). During an average 2.8 year follow up 40 patients (17%) died. In Cox proportional hazard models, pVo2 was the most powerful predictor of survival and neither measure of chronotropic incompetence independently predicted outcome., Conclusions: pVo2 is a powerful marker of prognosis for patients with CHF whether they are taking beta blockers or not. A low heart rate response to exercise in patients with CHF correlates with worse exercise tolerance but is unlikely to contribute to exercise impairment.

Objective: To determine the pattern of beta blocker prescribing over one year in a heart failure clinic with a structured approach towards initiation and dose titration and to give a real life perspective on beta blocker use, compliance, and target dose achievement., Methods: Data were retrospectively analysed on 513 consecutive patients regularly attending a community heart failure clinic over a year. Systolic dysfunction was determined from two dimensional echocardiography (left ventricular ejection fraction < or = 40%) and lung function was assessed by spirometry. All patients were considered for beta blocker initiation and dose up titration., Results: Within one year 157 patients died. 143 patients started beta blockers resulting in 315 (88%) patients taking beta blockers at one year; 38% were taking the target dose. 124 had evidence of airways obstruction at baseline, 100 (81%) of whom were taking beta blockers at one year. Forced expiratory volume in one second (1.1 v 1.5 l, p < 0.01) and forced vital capacity (2.3 v 2.5 l/min, p = 0.2) were not reduced in patients with airways obstruction who received beta blockers. Daily doses of beta blockers at one year did not differ statistically between patients with obstructive and patients with non-obstructive spirometry results. 12 patients discontinued beta blockers and 14 required dose reduction due to side effects., Conclusion: The majority of patients with heart failure and obstructive airways disease can safely tolerate low dose initiation and gradual up titration of beta blockers.

Robust epidemiological data on the incidence of myocardial infarction (MI) are hard to find, but synthesis of data from a number of sources indicates that the average hospital in the UK should admit about two patients with a first MI and one recurrent MI per 1000 population per year. Possibly the most relevant data on the incidence, prevalence, and persistence of post-MI heart failure can be derived from the TRACE study. Most patients will develop heart failure or major left ventricular systolic dysfunction (LVSD) at some time after an MI, most commonly during the index admission. In up to 20% of cases this will be transient, but such patients still have a poor prognosis. There is likely to be around one patient discharged per thousand population per year with heart failure or major LVSD after an acute MI. It is important to organise care structures to ensure that patients with post-MI heart failure and LVSD are identified and managed appropriately.

Objective: To examine the relation between longitudinal left ventricular function assessed by tissue Doppler imaging (TDi) and exercise capacity in heart failure., Subjects: 153 patients with chronic heart failure from left ventricular systolic dysfunction (ejection fraction < 45%) and 87 age and sex matched controls., Methods: Echocardiography was used to measure conventional indices of left ventricular systolic function. TDi was used to assess left and right ventricular longitudinal function by measuring mitral and lateral tricuspid annular velocities during the cardiac cycle. Velocities measured at each point were the systolic peak (S(m)) and the diastolic troughs (E(m) and A(m)), corresponding to passive and active (atrial) left ventricular filling. Each patient also underwent treadmill exercise testing with metabolic gas exchange measurements., Results: Left and right ventricular TDi velocities were greater in controls than in patients. Left ventricular ejection fraction (LVEF) correlated with S(m) (r = 0.30, p = 0.0005), but not with E(m), A(m), or the E(m)/A(m) ratio. There were no significant differences between New York Heart Association (NYHA) functional class for any of the TDi variables. Right ventricular indices were not related to exercise capacity. Systolic myocardial motion measured by TDi correlated more closely with peak oxygen consumption (pVO2) (r = 0.35, p < 0.0001) than LVEF (r = 0.21, p < 0.02). The E(m)/A(m) ratio was not correlated with pVO2. In multiple regression, S(m) was the only left ventricular TDi variable to predict exercise capacity independently (p < 0.05)., Conclusions: Exercise capacity and symptoms are poorly related to conventional measures of cardiac function and more closely correlated with indices of longitudinal left ventricular function as assessed by TDi.

Background: The ability of beta blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited., Objective: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease., Design: Randomised, double blind, placebo controlled study., Setting: Chronic stable heart failure., Patients and Intervention: 34 patients with chronic stable heart failure and left ventricular systolic function taking part in the CHRISTMAS trial (double blind carvedilol v placebo) underwent CMR before randomisation and after six months of treatment., Main Outcome Measure: Left ventricular remodelling at six months., Results: The carvedilol and placebo groups were well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESV(I)) and end diastolic volume index (EDV(I)) between the carvedilol and the placebo group (carvedilol -9 v placebo +3 ml/m2, p = 0.0004; carvedilol -8 v placebo 0 ml/m2, p = 0.05). The ejection fraction increased significantly between the groups (carvedilol +3% v placebo -2%, p = 0.003)., Conclusions: Treatment of chronic stable heart failure with carvedilol results in significant improvement in left ventricular volumes and function. These effects might contribute to the benefits of carvedilol on mortality and morbidity in patients with chronic heart failure.

Objective: To assess the influence of acute alpha and beta 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 alpha blocker and placebo, a beta blocker and a placebo, both an alpha blocker and a beta 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 < 0.0001) and a steeper slope relating ventilation to carbon dioxide production (VE/CO2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following alpha and beta blockade (p < 0.05) and the gradients of the slopes relating heart rate to oxygen consumption following the beta blocker were reduced (p < 0.05). Exercise time and peak ventilatory variables following beta or alpha blockers were unchanged. Ventilation was reduced during submaximal exercise following the active medications. Combined alpha and beta blockade produced the greatest difference (p < 0.005), but the alpha and beta blockers alone also reduced ventilation (p < 0.05). There was no difference in perceived exertion during exercise with any of the treatments., 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.

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 E was also examined., Results: Peak oxygen consumption (PVO2) (mean (SD)) was lower (19.7 (4.5) v 37.9 (8.6) ml/kg/min; p < 0001) and the ventilation to carbon dioxide production (VE/VCO2) slope was steeper (40.0 (6.5) v 26.0 (1.6); p < 0.0001) in patients with heart failure than in the control group. The patients reached the inflection point of the VE/VT slope sooner during exercise than the controls (271 (110) v 502 (196) seconds; p < 0.0001). Patients had a higher 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 PVO2 (r = 0.67; p < 0.0001). Despite having an increased sensation of breathlessness for a given E, patients were less symptomatic of 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 PVO2.

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 beta 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.