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Biomedical subjects

P A Poole-Wilson

Publications and source records attributed to P A Poole-Wilson.

At least 19 recordsLinked to original sources
PubMed2003

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

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.

Aged↗
PubMed2003

The therapeutic potential of new insights into myocardial excitation-contraction coupling.

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.

Anti-Arrhythmia Agents↗
PubMed2002

Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina.

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.

Angina Pectoris↗
PubMed2002

Measurement of left ventricular volume after anterior myocardial infarction: comparison of magnetic resonance imaging, echocardiography, and radionuclide ventriculography.

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.

Echocardiography↗
PubMed2002

Hospitalization of patients with heart failure: a population-based study.

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.

Age Factors↗
PubMed2002

NICE: guessing is not guidance. National Institute for Clinical Excellence.

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.

Arrhythmias, Cardiac↗
PubMed2001

Peripheral chemoreceptor hypersensitivity: an ominous sign in patients with chronic heart failure.

BACKGROUND: Peripheral chemoreceptor hypersensitivity is a feature of abnormal cardiorespiratory reflex control in chronic heart failure (CHF) and may contribute to sympathetic overactivity, attenuated baroreflex sensitivity (BRS), and excessive ventilation during exercise. We studied whether augmented peripheral chemosensitivity carries independent prognostic significance. METHODS AND RESULTS: We assessed peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalation of pure nitrogen) and BRS (phenylephrine and spectral methods) in 80 consecutive CHF patients (age 58+/-9 years; left ventricular ejection fraction [LVEF] 24+/-12%; peak oxygen consumption [peak VO(2)] 18+/-7 mL(-1). min(-1)). CHF patients demonstrated augmented peripheral chemosensitivity and decreased BRS (all P<0.01 versus reference values). During follow-up (median 41 months, >3 years in all survivors), 37 patients died. High peripheral chemosensitivity (>0.72 L. min(-1). %SaO(2)(-1)) predicted impaired survival (hazard ratio 3.2, 95% CI 1.6 to 6.0, P=0.0006). In the 27 patients (34%) with high peripheral chemosensitivity, 3-year survival was 41% (95% CI 22% to 60%) compared with 77% (66% to 89%) in 53 patients with normal chemosensitivity (P=0.0002). In multivariate analyses, augmented chemosensitivity independently predicted death (hazard ratio 2.8, 95% CI 1.5 to 5.5, adjusted for age, peak VO(2), and VE/VCO(2) [P=0.002]; hazard ratio 2.6, 95% CI 1.3 to 5.1, adjusted for age, LVEF, and peak VO(2) [P=0.008]). Depressed BRS was related to unfavorable prognosis in univariate analysis (P=0.05) but not in multivariate analyses. CONCLUSIONS: Hypersensitivity of the peripheral chemoreceptors independently predicts adverse prognosis in ambulatory patients with CHF. This hyperactive excitatory reflex, through its inhibitory effect on the baroreflex, may be the reason for the previously observed prognostic association of the latter.

Aged↗
PubMed2001

Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis.

BACKGROUND: In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (VE/VCO(2)) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and VE/VCO(2)and investigated the prognostic value of (VE/VCO(2)) in CHF patients with preserved exercise tolerance. METHODS AND RESULTS: Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (PEAK VO(2)) >/=18 mL. kg(-1). min(-1) (age 56 years; left ventricular ejection fraction 28%; peak VO(2) 23.5 mL. kg(-1). min(-1)). Hypoxic and hypercapnic chemosensitivity (n=38), heart rate variability (n=34), baroreflex sensitivity (n=20), and ergoreflex activity (n=20) were also assessed. We identified 40 patients (33%) with high VE/VCO(2) (ie, >34.0). During follow-up (49+/-22 months, >3 years in all survivors), 34 patients died (3-year survival 81%). High VE/VCO(2) (hazard ratio 4.3, P<0.0001) but not peak f1.gif" BORDER="0">O(2) (P=0.7) predicted mortality. In patients with high VE/VCO(2), 3-year survival was 57%, compared with 93% in patients with normal VE/VCO(2) P<0.0001). Patients with high VE/VCO(2) demonstrated impaired reflex control, as evidenced by augmented peripheral (P=0.01) and central (P=0.0006) chemosensitivity, depressed low-frequency component of heart rate variability (P<0.0001) and baroreflex sensitivity (P=0.03), and overactive ergoreceptors (P=0.003) compared with patients with normal VE/VCO(2). CONCLUSIONS: In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which VO(2) does not.

Chronic Disease↗
PubMed2001

Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.

Aged↗
PubMed2001

Implications of recent heart failure trials for patients with hypertension.

There are two major reasons why hypertension is an important risk factor for heart failure. The first is that an elevated blood pressure increases the wall stress in the left ventricle. The second is that hypertension, in a complex manner, contributes to the development of atheromatous vascular disease. Among the more common causes of heart failure are the sequelae of coronary heart disease. The treatment of hypertension modifies the progression to heart failure and the occurrence of coronary events. In patients who have heart failure, hypotension rather than hypertension is a predictor of a poor outcome, likely because low blood pressure is a consequence of damage to the myocardium. The clinical message is that hypertension should be treated aggressively. Where heart failure is a likely outcome, or where hypertension occurs in the presence of heart failure, there is a strong case for using drugs that have been shown to be beneficial in the treatment of both hypertension and heart failure.

Clinical Trials as Topic↗
PubMed2001

The underreporting of results and possible mechanisms of 'negative' drug trials in patients with chronic heart failure.

Large drug trials have become very important to determine which drugs should be used in the treatment of patients with chronic heart failure (CHF). When these trials showed "positive" results, publication of the data soon followed, leading to a substantial impact on prescription patterns. In the case of "negative" results, many times they were not published, or were reported as an abstract or as short paper disclosing only the main findings. In this article we will discuss some of these trials that were conducted in the last 10 years, since we believe they may provide insight into the pathophysiology and treatment options in CHF.

Bosentan↗
PubMed2001

Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.

OBJECTIVES: We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment. BACKGROUND: Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable. METHODS: Biochemical markers of the GH-insulin-like growth factor-I (IGF-I) axis were compared in 21 cachectic patients with CHF, 51 noncachectic patients and 26 healthy control subjects. In separate studies, the predictive value of baseline biochemical variables for the IGF-I response to GH treatment was analyzed. RESULTS: Cachectic patients showed an increase of total GH and immunologically intact GH (p < or = 0.0002) and a decrease of GH-binding protein (BP) (p = 0.005), IGF-BP3 (p = 0.01) and IGF-I (p = 0.06), compared with noncachectic patients. Similar changes were found when the cachectic group was compared with the control group. No differences were found between noncachectic patients and control subjects. Levels of GH-BP correlated with the IGF-I/GH ratio in all subgroups (all p < or = 0.002). Baseline GH-BP levels were related to the increase of IGF-I levels in response to GH treatment in patients with CHF after 24 h (r = 0.83, p = 0.005; n = 9; study 2), 44 days (r = 0.52, p = 0.007; n = 25; study 3) and 96 days (r = 0.54, p = 0.006; n = 24; study 3). CONCLUSIONS: Most cachectic and some noncachectic patients with CHF show features of acquired GH resistance. The principal predictors of the biochemical features of GH resistance and of the poor biochemical response to short-term and longer-term GH treatment are GH-BP plasma levels. The presence of GH resistance is potentially a major factor determining the response to GH therapy in patients with CHF.

Biomarkers↗
PubMed2001

Coronary artery disease as the cause of incident heart failure in the population.

AIMS: New approaches in the treatment of ischaemic left ventricular dysfunction, including revascularization, make it increasingly important to identify heart failure cases resulting from coronary artery disease. Without angiography these cases may be missed. We investigated the frequency of coronary artery disease in incident cases of heart failure in the population. METHODS AND RESULTS: We identified all incident cases of heart failure in a population of 292 000 in South London, U.K. by monitoring patients admitted to hospital and through a rapid access heart failure clinic. The presence and severity of coronary artery disease was identified by coronary angiography in patients under 75 years. Myocardial perfusion scanning was used to elucidate the aetiological significance of the coronary artery disease and identify hibernating myocardium. Three hundred and thirty-two cases of new heart failure were identified over 15 months. One hundred and thirty-six cases were under 75 years and angiography was undertaken in 99/136 (73%). Coronary artery disease was the aetiology in 71/136 (52%). In 18 of these 71 cases (25%), the aetiology was not recognised to be due to coronary artery disease prior to angiography, including eight cases with hibernating myocardium. CONCLUSION: Coronary artery disease is the cause of 52% (95% CI 43-61%) of incident heart failure in the general population under 75 years. Clinical assessment without angiography under-estimates the proportion of patients with coronary artery disease, and fails to identify those patients who may benefit from revascularization.

Adult↗
PubMed2001

Cardiovascular critical event pathways for the progression of heart failure; a report from the ATLAS study.

AIMS: To determine the sequence of critical cardiovascular events in the progression of heart failure, and whether aetiology or high-dose vs low-dose lisinopril affected these pathways. METHODS AND RESULTS: This was a post-hoc investigation of the ATLAS database, which comprised 3164 patients with chronic heart failure, randomized to low- (2.5-5.0 mg. day(-1)) or high-dose (32.5-35.0 mg. day(-1)) lisinopril, followed up for a median of 46 months. Two-thirds (64.3%) of patients had heart failure attributed to ischaemic heart disease. During the study, most patients (61.1%) had at least one cardiovascular hospitalization and 42.5% of all patients died: most deaths (88.2%) were cardiovascular. Nearly half (49.7%) of the cardiovascular deaths were considered sudden and 45.2% of cardiovascular deaths occurred as the first cardiovascular event. A third (30.2%) of deaths resulted from heart failure and were generally preceded by hospitalization, either for heart failure (85.5%), myocardial ischaemic events (21.7%) or arrhythmias (18.0%). Compared with low-dose, high-dose lisinopril was associated with a lower risk of death or hospitalization for any reason (P=0.002) and death or hospitalization with worsening heart failure (P<0.001). High-dose lisinopril delayed the time to all-cause mortality and hospitalization for chronic heart failure by 7.1 months. CONCLUSIONS: Vascular and arrhythmic events may not only be important precipitants of sudden death, but were also seen to contribute to the progression of heart failure. A reduction in vascular events, as well as benefits on ventricular remodelling, could account for the decrease in death or hospitalization with high-dose lisinopril.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

First permanent implant of the Jarvik 2000 Heart.

BACKGROUND: Heart failure is a major public-health concern. Quality and duration of life on maximum medical therapy are poor. The availability of donor hearts is severely limited, therefore an alternative approach is necessary. We have explored the use of a new type of left-ventricular assist device intended as a long-term solution to end-stage heart failure. METHODS: As part of a prospective clinical trial, we implanted the first permanent Jarvik 2000 Heart--an intraventricular device with an innovative power delivery system--into a 61-year-old man (New York Heart Association functional class IV) with dilated cardiomyopathy. We assessed the effect of this left-ventricular assist device on both native heart function and the symptoms and systemic characteristics of heart failure. FINDINGS: The Jarvik 2000 Heart sustained the patient's circulation, and was practical and user-friendly. After 6 weeks, exercise tolerance, myocardial function, and end-organ function improved. Symptoms of heart failure have resolved, and continuous decreased pulse-pressure perfusion has had no adverse effects in the short term. There has been no significant haemolysis and no device-related complications. The skull-mounted pedestal is unobtrusive and has healed well. CONCLUSIONS: The initial success of this procedure raises the possibility of a new treatment for end-stage heart failure. In the longer term, its role will be determined by mechanical reliability.

Blood Pressure↗
PubMed2000

Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial.

BACKGROUND: Sudden unexpected death frequently occurs in chronic heart failure. The importance of acute coronary events in triggering sudden death (SD) is unclear. METHODS AND RESULTS: We evaluated at autopsy the prevalence of acute coronary findings (coronary thrombus, ruptured plaque, or myocardial infarction [MI]) and their relation to SD. Autopsy results in 171 patients in the randomized ATLAS trial were reviewed. The prevalence of acute coronary findings was 33%: in 54% of patients with significant coronary artery disease (CAD) who died suddenly, 32% who died of myocardial failure, but in non-CAD patients, they were present in only 5% and 10% respectively. The percentage of patients classified as dying of MI was 28% in the autopsy group versus 4% in the nonautopsied group (P<0.0001). Of the autopsied group with acute MI, 97% (31 of 32 patients) with SD and 40% (6 of 15 patients) with myocardial failure did not have the MI diagnosed during life. When undiagnosed MI was classified as "sudden unexpected" or "myocardial failure" from clinical information only, the distribution of death causes was similar in the autopsy and nonautopsied groups. CONCLUSIONS: Acute coronary findings are frequent and usually not clinically diagnosed in heart failure patients with CAD, particularly in those dying suddenly, suggesting the importance of acute coronary events as a trigger for SD in this setting.

Acute Disease↗