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1.
Int J Cardiol ; 138(3): 317-9, 2010 Feb 04.
Article in English | MEDLINE | ID: mdl-18752859

ABSTRACT

Central sleep apnoea (CSA) occurs in up to 40% of patients with chronic heart failure (CHF). It is thought to be a consequence of CHF and is associated with an accelerated decline in cardiac function, and increased morbidity and mortality. The optimal treatment of CSA remains unclear. Resolution of CSA has been reported after cardiac transplantation. We report the first case of resolution of CSA 10 months following implantation of a permanent Jarvik 2000 left ventricular assist device (LVAD). The correction of CSA after implantation of the LVAD was associated with improvements in symptoms, exercise capacity, renal function, and increased arterial carbon dioxide levels at rest during wakefulness and also reduction in brain natriuretic peptide.


Subject(s)
Cardiomyopathy, Dilated/surgery , Heart Failure/surgery , Heart-Assist Devices , Sleep Apnea Syndromes/therapy , Cardiomyopathy, Dilated/complications , Heart Failure/complications , Humans , Male , Middle Aged , Sleep Apnea Syndromes/etiology
2.
Eur J Heart Fail ; 9(3): 243-50, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17030014

ABSTRACT

BACKGROUND: Sleep disordered breathing (SDB) is common in severe chronic heart failure (CHF) and is associated with increased morbidity and mortality. The prevalence of SDB in mild symptomatic CHF is unknown. AIM: The aim of this study was to determine the prevalence and characteristics of SDB in male patients with NYHA class II symptoms of CHF. METHODS AND RESULTS: 55 male patients with mild symptomatic CHF underwent assessment of quality of life, echocardiography, cardiopulmonary exercise, chemoreflex testing and polysomnography. 53% of the patients had SDB. 38% had central sleep apnoea (CSA) and 15% had obstructive sleep apnoea. SDB patients had steeper VE/VCO(2) slope [median (inter-quartile range) 31.1 (28-37) vs. 28.1 (27-30) respectively; p=0.04], enhanced chemoreflexes to carbon dioxide during wakefulness [mean+/-sd: 2.4+/-1.6 vs. 1.5+/-0.7 %VE Max/mmHg CO(2) respectively; p=0.03], and significantly higher levels of brain natriuretic peptide and endothelin-1 compared to patients without SDB. No differences in left ventricular ejection fraction, percent predicted peak oxygen uptake, or symptoms of SDB were observed. CONCLUSIONS: A high prevalence of SDB was found in men with mild symptomatic CHF. Patients with SDB could not be differentiated by symptoms or by routine cardiac assessment making clinical diagnosis of SDB in CHF difficult.


Subject(s)
Heart Failure/complications , Sleep Apnea, Central/physiopathology , Sleep Apnea, Obstructive/physiopathology , Ventricular Dysfunction, Left/complications , Aged , Cohort Studies , Exercise Test , Heart Failure/diagnostic imaging , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Quality of Life , Sleep Apnea, Central/epidemiology , Sleep Apnea, Obstructive/epidemiology , Statistics, Nonparametric , Ultrasonography , Ventricular Dysfunction, Left/physiopathology
3.
Heart ; 92(10): 1473-9, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16621882

ABSTRACT

OBJECTIVE: To determine whether, in acute non-ST elevation coronary syndrome, the benefit from early invasive coronary intervention compared with a conservative strategy of later symptom-guided intervention varies over time. METHODS: In RITA 3 (Randomised Intervention Trial of unstable Angina 3) patients were randomly assigned to coronary angiography (median 2 days after randomisation) and appropriate intervention (n = 895) or to a symptom-guided conservative strategy (n = 915). RESULTS: In the first week patients in both groups were at highest risk of death, myocardial infarction (MI) or refractory angina (incidence rate 40 times higher than in months 5-12 of follow up). There were 22 MIs and 6 deaths in the intervention group (largely due to procedure-related events, 14 MIs and 3 deaths) versus 17 MIs and 3 deaths in the conservative group. In the rest of the year there were an additional 12 versus 27 MIs, respectively (treatment-time interaction p = 0.021). Over one year in the intervention group there was a 43% reduction in refractory angina; 22% of patients underwent coronary artery bypass surgery and 35% underwent percutaneous coronary intervention only, which reduced refractory angina but provoked some early MIs; and 43% were still treated medically, mostly because of a favourable initial angiogram. CONCLUSION: Any intervention policy needs to recognise the high risk of events in the first week and the substantial minority of patients not needing intervention. Intervention may be best targeted at higher risk patients, as the early hazards of the procedure are then offset by reduced subsequent events.


Subject(s)
Angina, Unstable/therapy , Adult , Aged , Angina, Unstable/mortality , Coronary Artery Bypass , Female , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Recurrence , Risk Factors , Survival Analysis , Treatment Outcome
4.
Heart ; 92(4): 437-40, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16537755

ABSTRACT

The recently published guidelines by the European Society of Cardiology on the diagnosis and treatment of chronic heart failure are well worth reading, include important new recommendations and are reviewed here.


Subject(s)
Heart Failure/therapy , Practice Guidelines as Topic , Cardiovascular Agents/therapeutic use , Defibrillators, Implantable , Humans , Societies, Medical
5.
Eur Respir J ; 27(3): 571-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16507858

ABSTRACT

In patients with obstructive sleep apnoea (OSA), the very low frequency power spectral density index (VLFI) derived from analysis of heart rate correlates with the severity of obstructive apnoeas. VLFI is also associated with Cheyne-Stokes respiration/central sleep apnoea (CSR/CSA) in congestive heart failure (CHF). The present authors have tested the hypothesis that per cent VLFI, derived from a standard Holter ECG recording, can be used to detect the presence of OSA and CSR/CSA in patients with mild-to-moderate CHF. In total, 60 CHF patients underwent polysomnography with monitoring of heart rate. Data from 33 patients were analysed for per cent VLFI. Of the 60 patients, 27 were excluded due to atrial fibrillation, extensive pacing or frequent ventricular extra systoles. Receiver operator characteristic curves were constructed to establish the per cent VLFI that would optimally identify the presence or absence of sleep-disordered breathing. Using an apnoea-hypopnoea index>20 events.h-1 and setting the per cent VLFI at 2.23% yielded a sensitivity of 85%, specificity of 65%, positive predictive value of 61% and a negative predictive value of 87%. The latter increased to 100% when using an apnoea-hypopnoea cut-off of 30 events.h-1. In conclusion, these results suggest that spectral analysis of heart rate may be useful as a "rule-out test" for sleep-disordered breathing in patients with mild-to-moderate congestive heart failure.


Subject(s)
Heart Failure/physiopathology , Heart Rate , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/physiopathology , Female , Heart Failure/complications , Humans , Male , Middle Aged , Sleep Apnea Syndromes/complications
6.
Cochrane Database Syst Rev ; (1): CD003838, 2006 Jan 25.
Article in English | MEDLINE | ID: mdl-16437464

ABSTRACT

BACKGROUND: Chronic heart failure is a major cause of morbidity and mortality world-wide. Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief. The effects of diuretics on disease progression and survival remain unclear. OBJECTIVES: To assess the harms and benefits of diuretics for chronic heart failure SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 2 2004), MEDLINE 1966-2004, EMBASE 1980-2004 and HERDIN database. We hand searched pertinent journals and reference lists of papers were inspected. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: Only double-blinded randomised controlled trials of diuretic therapy comparing one diuretic with placebo, or one diuretic with another active agent (e.g. ACE inhibitors, digoxin) in patients with chronic heart failure were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted the data and assessed the eligibility and methodological quality of each trial. Extracted data were entered into the Review Manager 4.2 computer software, and analysed by determining the odds ratio for dichotomous data, and difference in means for continuous data, of the treated group compared with controls. The likelihood of heterogeneity of the study population was assessed by the Chi-square test. If there was no evidence of statistical heterogeneity and pooling of results was clinically appropriate, a combined estimate was obtained using the fixed-effects model. MAIN RESULTS: We included 14 trials (525 participants), 7 were placebo-controlled, and 7 compared diuretics against other agents such as ACE inhibitors or digoxin. We analysed the data for mortality and for worsening heart failure. Mortality data were available in 3 of the placebo-controlled trials (202 participants). Mortality was lower for participants treated with diuretics than for placebo, odds ratio (OR) for death 0.24, 95% confidence interval (CI) 0.07 to 0.83; P = 0.02. Admission for worsening heart failure was reduced in those taking diuretics in two trials (169 participants), OR 0.07 (95% CI 0.01 to 0.52; P = 0.01). In four trials comparing diuretics to active control (91 participants), diuretics improved exercise capacity in participants with CHF, difference in means WMD 0.72 , 95% CI 0.40 to 1.04; P < 0.0001. AUTHORS' CONCLUSIONS: The available data from several small trials show that in patients with chronic heart failure, conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo. Compared to active control, diuretics appear to improve exercise capacity.


Subject(s)
Diuretics/therapeutic use , Heart Failure/drug therapy , Humans , Randomized Controlled Trials as Topic
7.
Heart ; 92(5): 603-8, 2006 May.
Article in English | MEDLINE | ID: mdl-16159966

ABSTRACT

OBJECTIVE: To characterise patients who appear to fulfil the diagnosis of heart failure with preserved systolic function clinically, echocardiographically, and by concentrations of brain-type natriuretic peptide (BNP). METHODS: 102 new cases of heart failure were identified over 24 months in 213 patients referred to a rapid access heart failure clinic. Patients with heart failure and preserved systolic function with contemporary markers of diastolic function were assessed to evaluate their cardiac status further. RESULTS: Forty patients (39%) had an ejection fraction (EF) < 45% and 62 (61%) had an EF > or = 45%. Of these 62 patients, 30 (48%) fulfilled the case definition of diastolic heart failure. The remaining 32 (52%) had neither an EF < 45% nor abnormalities of diastolic function. Dobutamine stress echocardiography was performed on 26 (42%) patients with EF > or = 45%, which provided an alternative explanation for symptoms in 15 (58%) patients. Concentrations of BNP were higher in patients with diastolic abnormalities (mean (SEM) 101.4 (32.5) pg/ml v 58.4 (6.78) pg/ml, p = 0.042) and with no diastolic abnormalities (199 (37.9) pg/ml v 58.4 (6.78) pg/ml, p < 0.0001) than in patients with no heart failure. CONCLUSION: Among ambulatory patients presenting with suspected heart failure in the community 19% have systolic dysfunction, 14% have diastolic dysfunction, and 15% seemingly have heart failure with neither systolic nor diastolic dysfunction. A new understanding, including alternative parameters of diastolic function, seems to be necessary to classify patients with heart failure and preserved systolic function.


Subject(s)
Cardiac Output, Low/diagnosis , Heart Failure/diagnosis , Natriuretic Peptide, Brain/metabolism , Adult , Aged , Aged, 80 and over , Cardiac Output, Low/diagnostic imaging , Echocardiography, Stress , Female , Heart Failure/diagnostic imaging , Humans , Male , Middle Aged , Pilot Projects , Stroke Volume , Systole , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/diagnostic imaging
8.
Int J Cardiol ; 98(2): 299-306, 2005 Feb 15.
Article in English | MEDLINE | ID: mdl-15686782

ABSTRACT

OBJECTIVE: To evaluate whether the frequency of anginal attacks in medically treated patients with stable angina is related to the intensity of anti-anginal treatment, the clinical history and coronary anatomy. METHODS: Analysis of baseline data from the A Coronary disease Trial Investigating Outcome with Nifedipine GITS (ACTION) study, an ongoing placebo-controlled trial in 7669 patients with stable angina pectoris who require anti-anginal treatment. RESULTS: Prior to randomisation, 8% of 7669 patients had no anginal attacks, 63% had occasional, 22% had regular, 4% had frequent and 3% had daily attacks. Men (79% of all patients) and patients with a history of MI (51%) had less frequent anginal attacks (P<0.0001). The number of coronary angiograms ever performed (70% had at least one angiogram), the extent of angiographic coronary disease (32% of those who had angiography had more than two-vessel disease), a history of peripheral artery disease (12%), the number of anti-anginal drugs used (64% were prescribed two or more such medications) and a history of revascularisation (a history of coronary bypass surgery was present in 23% and of balloon dilatation in 26%) were each positively associated with anginal attack frequency. CONCLUSIONS: For the majority of patients with chronic stable angina not on a calcium-antagonist, medical treatment with other anti-anginal drugs is sufficient to control symptoms and only a minority of patients are refractory to medical treatment. Invasive treatments for chronic stable angina are only needed in a small proportion where symptoms persist.


Subject(s)
Angina Pectoris/drug therapy , Adult , Aged , Aged, 80 and over , Angioplasty, Balloon, Coronary , Cardiovascular Diseases/epidemiology , Coronary Angiography , Diabetic Angiopathies/therapy , Female , Humans , Male , Middle Aged , Multivariate Analysis , Risk Factors , Treatment Outcome
9.
Basic Res Cardiol ; 99(6): 382-91, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15365729

ABSTRACT

Cardiomyocytes derived from embryonic stem cells (ESCM) have potential both as an experimental model for investigating cardiac physiology and as a source for tissue repair. For both reasons it is important to characterise the responses of these cells, and one of the key modulators of contraction is the beta-adrenergic system. We therefore undertook a detailed study of the response of the spontaneous beating rate of ESCM to beta-adrenoceptor (betaAR) stimulation. Embryoid bodies (EBs) were generated from murine ES line E14Tg2a by the hanging drop method, followed by plating. Spontaneously beating areas were seen starting from 9-14 days after differentiation: the experiments described here were performed on EBs between developmental day 19 and 48. Beating cell layers were seeded with charcoal to allow tracking of movement by a video-edge detection system. Experiments were performed in physiological medium containing 1 mM Ca2+ at 37 degrees C. Isoprenaline (Iso) increased beating rate with an EC50 value of 52 nM. Iso (0.3 microM) increased basal rate from 67 +/- 7 beats per minute (bpm) to 138 +/- 18 bpm, P < 0.001, n = 22. At earlier developmental time points the response to Iso was not maintained through 5 min exposure; this spontaneous desensitisation only being observed before day 36. A repeat application of Iso after a wash period of 20 min produced reproducible effects on beating rate. Subtype dependence of the betaAR response was determined by comparing an initial response with a second in the presence of selective beta1- or beta2AR antagonists. In the presence of the specific beta1AR-blocker CGP 20712A (300 nM) the increase in rate with Iso was reduced from 207 +/- 42% of basal to 128 +/- 13%, P < 0.01. With the beta2AR-blocker ICI 118,551 (50 nM) there was no significant change in Iso response. Exposure to the muscarinic agonist, carbachol (10 microM), inhibited the increase in frequency mediated by isoprenaline, but had mixed stimulatory and inhibitory effects on basal rate. This study extends the characterisation of ESCM as a preparation for studying receptor pharmacology, and indicates that the beta1AR is the predominant subtype mediating increases in contraction rate in murine ESCM.


Subject(s)
Embryo, Mammalian/cytology , Heart/physiology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Receptors, Adrenergic, beta/metabolism , Stem Cells/cytology , Animals , Cell Differentiation , Cell Line , Cholinergic Agents/pharmacology , Heart/drug effects , Isoproterenol/pharmacology , Mice , Myocardial Contraction/drug effects , Myocytes, Cardiac/drug effects
10.
Eur Heart J ; 25(18): 1641-50, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15351164

ABSTRACT

AIMS: The RITA 3 trial randomized patients with non-ST-elevation myocardial infarction or unstable angina to strategies of early intervention (angiography followed by revascularization) or conservative care (ischaemia or symptom driven angiography). The aim of this analysis was to investigate the impact of gender on the effect of these two strategies. METHODS AND RESULTS: In total, 1810 patients (682 women and 1128 men) were randomized. The risk factor profile of women at presentation was markedly different to men. There was evidence that men benefited more from an early intervention strategy for death or non-fatal myocardial infarction at 1 year (adjusted odds ratios 0.63, 95% confidence interval 0.41-0.98 for men and 1.79, 95% confidence interval 0.95-3.35 for women; interaction p-value=0.007). Men who underwent the assigned angiogram were more likely to be put forward for coronary artery bypass surgery, even after allowing for differences in disease severity. CONCLUSION: An early intervention strategy resulted in a beneficial effect in men which was not seen in women although caution is needed in interpretation. Further research is needed to evaluate why women do not appear to benefit from early intervention and to identify treatments that improve the prognosis of women.


Subject(s)
Angina, Unstable/therapy , Angioplasty, Balloon, Coronary/statistics & numerical data , Myocardial Infarction/therapy , Female , Humans , Male , Middle Aged , Myocardial Revascularization , Risk Assessment , Risk Factors , Sex Factors , Survival Analysis , Treatment Outcome
11.
Am Heart J ; 148(1): 157-64, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15215806

ABSTRACT

BACKGROUND: Heart failure is commonly associated with vascular disease and a high rate of athero-thrombotic events, but the risks and benefits of antithrombotic therapy are unknown. METHODS: The current study was an open-label, randomized, controlled trial comparing no antithrombotic therapy, aspirin (300 mg/day), and warfarin (target international normalized ratio 2.5) in patients with heart failure and left ventricular systolic dysfunction requiring diuretic therapy. The primary objective was to demonstrate the feasibility and inform the design of a larger outcome study. The primary clinical outcome was death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: Two hundred seventy-nine patients were randomized and 627 patient-years exposure were accumulated over a mean follow-up time of 27 +/- 1 months. Twenty-six (26%), 29 (32%), and 23 (26%) patients randomized to no antithrombotic treatment, aspirin, and warfarin, respectively, reached the primary outcome (ns). There were trends to a worse outcome among those randomized to aspirin for a number of secondary outcomes. Significantly (P =.044) more patients randomized to aspirin were hospitalized for cardiovascular reasons, especially worsening heart failure. CONCLUSIONS: The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.


Subject(s)
Anticoagulants/therapeutic use , Aspirin/therapeutic use , Cardiomyopathy, Dilated/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Warfarin/therapeutic use , Aged , Anticoagulants/adverse effects , Aspirin/adverse effects , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/mortality , Feasibility Studies , Female , Hospitalization , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/prevention & control , Platelet Aggregation Inhibitors/adverse effects , Stroke/etiology , Stroke/prevention & control , Warfarin/adverse effects
13.
QJM ; 97(3): 133-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14976270

ABSTRACT

BACKGROUND: Carvedilol therapy reduces mortality in patients with chronic heart failure. Multi-centre studies suggest a low first dose failure rate and high levels of tolerability to carvedilol. Little is known, however, concerning the eligibility and tolerance to treatment with carvedilol within a district general hospital setting. AIM: To evaluate the eligibility and tolerance of patients with heart failure to carvedilol within a district general hospital. DESIGN: Prospective clinical audit analysis. METHODS: We assessed 100 heart failure patients eligibility to commence carvedilol therapy. In those who satisfied clinical criteria, we evaluated first dose failure rate, target dose achievement, reasons for intolerance, heart rate and blood pressure reduction and resource requirements over a six-month period. RESULTS: Of 100 patients, 16% had contra-indications to commence carvedilol and 22% were receiving a beta-blocker as part of their existing heart failure therapy. Although 62% satisfied eligibility criteria, 1% refused therapy, thus 61% were initiated on carvedilol. The first dose failure rate was 11.5% and 6.6% of patients achieved 'target dose'. Mean heart rate and systolic blood pressure reductions were 15 (SE 1.2)bpm and 17 (SE 1.7) mmHg, respectively. Resource requirements included 155 hours of work-time for a trained heart failure specialist nurse and doctor. CONCLUSIONS: In the general setting, eligible patients appear to display a high first dose failure rate, poor tolerance to higher doses and achievement of a 'target dose' of carvedilol. Responses to adrenergic blockade were similar to previously published data, irrespective of the final tolerated dose, suggesting that the concept of achieving a 'target dose' may not be clinically useful. Guidelines and treatment protocols for heart failure should reflect not only what is considered gold standard, but also what is practical in general hospitals.


Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Carbazoles/administration & dosage , Heart Failure/drug therapy , Propanolamines/administration & dosage , Adrenergic beta-Antagonists/therapeutic use , Adult , Aged , Aged, 80 and over , Blood Pressure/drug effects , Carbazoles/therapeutic use , Carvedilol , Dose-Response Relationship, Drug , Drug Tolerance , Female , Heart Failure/physiopathology , Heart Rate/drug effects , Hospitals, District , Hospitals, General , Humans , Male , Medical Audit , Middle Aged , Patient Selection , Propanolamines/therapeutic use , Prospective Studies , Treatment Failure
14.
Heart ; 89(4): 371-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12639859

ABSTRACT

The physiological mechanisms that link myocyte depolarisation and contraction are referred to collectively as excitation-contraction coupling. This important process uses calcium as a second messenger to convert electrical depolarisation of the myocyte sarcolemma into the coordinated contraction of the cell's internal myofilament apparatus. The inotropic properties of the cell are determined by the efficiency of this process and when this efficiency is lost contractile dysfunction and heart failure develop, along with a propensity for arrhythmias. Previous attempts to use positive inotropic drugs in the management of chronic heart failure have been disappointing. Such drugs have been associated with unacceptable side effects and worse morbidity and mortality outcomes, primarily through their non-specific amplification of intracellular cascade pathways that modify the cell's inotropic state. As a result of recent advances in our understanding of how excitation-contraction coupling works in both health and disease it may be possible to design more specifically targeted drug treatment that has the potential to avoid the detrimental effect of currently available drugs while at the same time improving the inotropic properties of the cell.


Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/therapy , Myocardial Contraction/physiology , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/etiology , Calcium/physiology , Calcium-Binding Proteins/antagonists & inhibitors , Calcium-Transporting ATPases/physiology , Drug Design , Heart Conduction System/physiology , Humans , Muscle Cells/physiology , Ryanodine Receptor Calcium Release Channel/drug effects , Ryanodine Receptor Calcium Release Channel/genetics , Ryanodine Receptor Calcium Release Channel/physiology , Sarcoplasmic Reticulum/physiology , Sarcoplasmic Reticulum Calcium-Transporting ATPases
15.
Heart ; 89(1): 42-8, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12482789

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 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.


Subject(s)
Heart Failure/mortality , Aged , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/mortality , Cause of Death , Creatinine/blood , Death, Sudden, Cardiac/etiology , Double-Blind Method , Female , Heart Failure/drug therapy , Heart Failure/physiopathology , Humans , Lisinopril/administration & dosage , Male , Middle Aged , Myocardial Ischemia/mortality , Risk Assessment , Risk Factors , Stroke Volume/physiology , Treatment Outcome
17.
Lancet ; 360(9335): 743-51, 2002 Sep 07.
Article in English | MEDLINE | ID: mdl-12241831

ABSTRACT

BACKGROUND: Current guidelines suggest that, for patients at moderate risk of death from unstable coronary-artery disease, either an interventional strategy (angiography followed by revascularisation) or a conservative strategy (ischaemia-driven or symptom-driven angiography) is appropriate. We aimed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients. METHODS: We did a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes (mean age 62 years, 38% women). Patients were assigned an early intervention or conservative strategy. The antithrombin agent in both groups was enoxaparin. The co-primary endpoints were a combined rate of death, non-fatal myocardial infarction, or refractory angina at 4 months; and a combined rate of death or non-fatal myocardial infarction at 1 year. Analysis was by intention to treat. FINDINGS: At 4 months, 86 (9.6%) of 895 patients in the intervention group had died or had a myocardial infarction or refractory angina, compared with 133 (14.5%) of 915 patients in the conservative group (risk ratio 0.66, 95% CI 0.51-0.85, p=0.001). This difference was mainly due to a halving of refractory angina in the intervention group. Death or myocardial infarction was similar in both treatment groups at 1 year (68 [7.6%] vs 76 [8.3%], respectively; risk ratio 0.91, 95% CI 0.67-1.25, p=0.58). Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy (p<0.0001). INTERPRETATION: In patients presenting with unstable coronary-artery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.


Subject(s)
Angina Pectoris/therapy , Cardiotonic Agents/therapeutic use , Coronary Artery Bypass , Coronary Disease/therapy , Myocardial Infarction/therapy , Angina Pectoris/etiology , Angina Pectoris/mortality , Atherectomy, Coronary , Coronary Angiography , Coronary Disease/complications , Coronary Disease/mortality , Endpoint Determination , Female , Humans , Male , Middle Aged , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Risk Factors , United Kingdom
18.
Int J Cardiovasc Imaging ; 18(2): 135-42, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12108909

ABSTRACT

We have compared echocardiography (echo) and radionuclide ventriculography (RNV) with magnetic resonance imaging (MRI) for the measurement of left ventricular (LV) volume and ejection fraction. Seventy asymptomatic patients were studied up to 12 days after first Q wave anterior myocardial infarction and again after 6 months. Each patient had LV volume measured by all three techniques within 24 hours of each other on each occasion. LV end-systolic and end-diastolic volume index (LVESVI and LVEDVI) and LV ejection fraction (LVEF) were measured using the modified Simpson formula (echo), a counts-based method (RNV), and a multislice area summation method (MRI). Radionuclide volumes were measured both with and without correction for attenuation of isotope. Echocardiography overestimated LV volume compared with MRI. Mean (SD) differences (echo-MRI) were: LVEDVI + 10.6 ml/m2 (16.8), LVESVI + 13.7 ml/m2 (12.9), LVEF -8.5% (11.2). RNV underestimated both volume and ejection fraction compared with MRI. Mean differences (RNV-MRI) were: LVEDVI -25.4 ml/m2 (23.8), LVESVI -5.0 ml/m2 (18.6), LVEF -13.8% (10.4). Variability in the difference between echo and MRI and between RNV and MRI was very similar for LVEF (coefficient of variation 23.9% echo, 22.2% RNV) but there was greater variability in the radionuclide than the echo measurements of absolute volume. Variability of the radionuclide measurements was reduced by not correcting for attenuation, and this finding may improve the radionuclide technique for serial measurements of percentage change in volume. Long-term inter-study reproducibility of MRI for LVEF (coefficient of reproducibility) was 10.9%, for echo it was 10.6%, and for RNV it was 14.6%. We conclude that measurements of LV volume depend on the method used and are not interchangeable. Echocardiography agrees more closely with MRI than RNV for the measurement of absolute volume, but the two techniques are similar for the measurement of LVEF.


Subject(s)
Echocardiography , Hypertrophy, Left Ventricular/diagnosis , Magnetic Resonance Imaging , Radionuclide Ventriculography , Female , Humans , Male , Middle Aged , Myocardial Infarction/complications , Reproducibility of Results , Stroke Volume
19.
Eur Heart J ; 23(11): 877-85, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12042009

ABSTRACT

AIMS: To describe the clinical course of heart failure in a population-based sample of incident cases, and to identify factors predicting hospitalization and mortality. METHODS AND RESULTS: Three hundred and thirty-two incident cases were identified over 15 months; 208 inpatients and 124 outpatients. Thirty-eight inpatients died during the first hospital admission (case fatality 18%) leaving 294 at risk of subsequent hospitalization. Over an average follow-up of 19 months, 173 cases were hospitalized on 311 occasions. Two hundred and twenty-four (72%) of these admissions were unplanned, with 51% due to worsening heart failure. One hundred and ten cases died over the same period. Cases diagnosed as an inpatient had 26 more admissions for worsening heart failure per 100 cases during follow-up (95% CI 9 to 44) compared to cases diagnosed as an outpatient, and also a higher mortality (hazard ratio 3.1 (95% CI 1.9 to 5.1)). Age was the only factor associated with an increased risk of hospitalization for worsening heart failure, but age, functional class and serum creatinine were predictive of mortality. CONCLUSIONS: New cases of heart failure are at high risk of subsequent hospitalization, especially during the first months after diagnosis. Whilst predicting which patients will be hospitalized is difficult, interventions designed to reduce hospitalizations for worsening heart failure should be targeted at elderly inpatients with a new diagnosis.


Subject(s)
Heart Failure/epidemiology , Hospitalization/statistics & numerical data , Age Factors , Cohort Studies , Female , Follow-Up Studies , Heart Failure/therapy , Humans , London/epidemiology , Male , Patient Readmission/statistics & numerical data , Risk Factors , Survival Analysis , Time Factors
20.
Heart ; 87(6): 510-2, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12010929

ABSTRACT

A preliminary assessment of the extent to which the National Institute for Clinical Excellence (NICE) has achieved its goals within cardiovascular medicine is presented. NICE is a government sponsored agency operating in the UK which attempts to assess the value of medical therapies, devices, and surgery for a wide range of medical and surgical problems. Its recommendations determine whether a particular therapy can be adopted in the National Health Service.


Subject(s)
Evidence-Based Medicine/standards , Heart Diseases/therapy , Practice Guidelines as Topic/standards , Technology Assessment, Biomedical/standards , Arrhythmias, Cardiac/therapy , Coronary Disease/drug therapy , Defibrillators, Implantable/standards , Humans , Platelet Glycoprotein GPIIb-IIIa Complex/therapeutic use , Stents
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