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Biomedical subjects

P Poole-Wilson

Publications and source records attributed to P Poole-Wilson.

At least 19 recordsLinked to original sources

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time.

BACKGROUND: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO(2)) 3-9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO(2) and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. METHODS AND RESULTS: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO(2) by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = -0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO(2) from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO(2). No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. CONCLUSIONS: In eligible patients, resynchronisation can acutely augment peak VO(2), possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO(2).

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[Adherence to guidelines in CHF therapy in Germany].

BACKGROUND AND OBJECTIVE: The MAHLER survey examined the impact of the European guidelines for the treatment of chronic heart failure (CHF). Especially, the trial addressed the question whether adherence to treatment guidelines leads to a reduction in the rate of CHF and cardiovascular (CV) hospitalization. The present sub-study presents the Germany specific data of the MAHLER study and compares the results with the results in other European countries. PATIENTS AND METHOD: The gobal adherence index (GAI) shows the proportion of correctly prescribed heart failure medications per patient. Class adherence indicators for angiotensin-converting enzyme (AC)-inhibitors, beta-blockers, spironolactone, diuretics and cardiac glycosides and general adherence indicators (GAI3 adherence to first three classes of heart failure medications, GAI5 adherence to five classes) were constructed. In the German sub-study, 251 patient were included, who were seen by 21 cardiologists in private practice (mean age 68,6 + 10,4 years; 173 man, 78 woman; 158 NYHA II; 91 NYHA III, 2 NYHA IV). RESULTS: Mean adherence to CHF therapy guidelines was 63 % for GAI3, 62 % for GAI5. Compared to the other MAHLER-study countries, Germany was on place two and three concerning GAI3 and GAI5, respectively. Strong adherence to treatment guidelines in Germany led to a reduction of CHF and CV hospitalization rate by 40 % (p < 0.033). Thus, the German data confirm the results of the international study indicating that a good GAI3 performance is an independent predictor of time to hospitalization. Hitherto, the relative risk for hospitalization was higher for CHF patients in Germany than for patients in all other European countries. CONCLUSIONS: In Germany like in other European countries, guideline adherence for CHF therapy leads to a reduction in hospitalization rate.

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Current evidence supporting the role of diuretics in heart failure: a meta analysis of randomised controlled trials.

OBJECTIVE: To summarise the current evidence from randomised controlled trials for diuretics in patients with congestive heart failure (CHF). DATA SOURCES: English-language randomised controlled trials and review papers referenced in Medline, Embase between 1966 and 1999. General literature review of pertinent journals was carried out and reference lists of papers were inspected. REVIEW METHOD STUDY DESIGN: Meta-analysis of randomised controlled trials of diuretic therapy in patients with CHF. STUDY SELECTION: Studies were included if they were randomised comparisons of loop or thiazide diuretics and control, or one diuretic and another active agent (e.g. ACE inhibitors, ibopamine and digoxin). DATA ABSTRACTION: Using a standardised protocol, two reviewers independently abstracted the data and assessed the methodological quality of each paper. DATA SYNTHESIS: The odds ratio (OR) of treated group compared with control was estimated for each end-point outcome and plotted against each other using the fixed-effects model. THE MAIN OUTCOME MEASURES: The primary outcomes of our analysis were effects of diuretics on mortality and morbidity. RESULTS: Eighteen trials met our criteria and were eligible for analysis, involving 928 patients. Eight trials were placebo-controlled. We analysed the data for mortality and for worsening heart failure. A further ten trials compared diuretics against other agents such as ACE inhibitors, ibopamine, and digoxin. Mortality data were available in three of the placebo-controlled trials (n=221); the mortality rate was lower for patients treated with diuretics than for control [the odds ratio for death, 0.25; 95% confidence intervals (CI), 0.07-0.84; P=0.03]. Admissions for worsening heart failure in the four small trials (n=448) showed an odds ratio of 0.31 (95% CI 0.15-0.62; P=0.001). In six studies of diuretics compared to active control, diuretics significantly improved exercise capacity in patients with CHF [OR: 0.37; CI: 0.10-0.64, P=0.007]. CONCLUSION: Compared to active control, diuretics appear to reduce the risk of worsening disease and improve exercise capacity. The available data from small studies show that in CHF conventional diuretics reduce the risk of death and worsening heart failure compared to placebo.

Diuretics↗

Effects of losartan versus captopril on mortality in patients with symptomatic heart failure: rationale, design, and baseline characteristics of patients in the Losartan Heart Failure Survival Study--ELITE II.

BACKGROUND: In the Evaluation of Losartan in the Elderly (ELITE) heart failure study, a survival benefit (primarily because of a reduction in sudden deaths) was observed in symptomatic patients treated with losartan compared with captopril. METHODS AND RESULTS: The Losartan Heart Failure Survival Study--ELITE II (currently ongoing) is a double-blind, randomized clinical trial being conducted in 45 countries at 288 sites. ELITE II formally tests the hypotheses that losartan, compared with captopril, will reduce all-cause mortality (primary end point) and sudden cardiac death and/or resuscitated cardiac arrest (secondary end point). In addition, all-cause mortality and/or hospitalizations and cardiovascular mortality and/or hospitalizations will be evaluated. The trial has 90% power to detect a 25% treatment difference in all-cause mortality (event driven, 510 deaths). Substudies are examining quality of life, health care resource utilization, and mechanisms related to the reduction in sudden death. During recruitment (June 1997 to May 1998), 3,152 patients aged 60 years or older (mean age, 71.6 years), with New York Heart Association classes II (51%), III (44%), and IV (5%), and left ventricular ejection fraction of 40% or less (mean, 31%) were randomized to receive either 12.5 mg of losartan, titrated as tolerated to 50 mg once daily, or 12.5 mg of captopril, titrated as tolerated to 50 mg thrice daily. Randomization was stratified by clinical site and for baseline beta-blocker use. CONCLUSION: The ELITE II study will further define the role of losartan in the treatment of patients with symptomatic heart failure relative to the angiotensin-converting enzyme inhibitor captopril, an agent from a class currently considered standard treatment for this disease.

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Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.

Alterations of autonomic nervous control of cardiac function have been described in syndrome X. The characteristics, however, of the autonomic control of the cardiovascular system in patients with syndrome X have not been adequately studied; thus, the aim of the present study was to investigate the role of baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group included 12 patients with syndrome X, 12 age- and sex-matched control patients with coronary artery disease, and 12 age- and sex-matched controls with no evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. Sympathovagal balance was assessed by using heart rate variability in the time and frequency domain and measuring plasma norepinephrine at rest and during incremental bicycle exercise. Baroreceptor sensitivity was significantly reduced in syndrome X compared with that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02). This was associated with a significantly lower percentage of adjacent normal RR intervals that differ by >50 ms, lower root-mean-square of the difference of adjacent RR intervals, and lower logarithmic value of the high-frequency component in patients with syndrome X compared with normal subjects. A nonsignificant trend toward lower baroreceptor sensitivity was found in patients with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/- 1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high-frequency ratio was also observed in patients with syndrome X than in both control groups. No difference was detected in norepinephrine levels either at rest or during exercise or in the exercise-induced norepinephrine increase between the 3 groups. No difference was also observed between ischemic patients and normal subjects in either baroreceptor sensitivity or heart rate variability measurements. A significant correlation (r = 0.80, p < 0.01) was found between baroreceptor sensitivity and the high-frequency component in normal controls but not for other measurements of autonomic function in the 3 groups. In conclusion, patients with syndrome X have an altered autonomic control of the cardiovascular system characterized by impaired baroreceptor sensitivity and reduced heart rate variability. Abnormal autonomic regulation of the cardiovascular system may be of pathophysiologic importance in syndrome X.

Baroreflex↗

Quantitation of left ventricular volumes and ejection fraction in post-infarction patients from biplane and single plane two-dimensional echocardiograms. A prospective longitudinal study of 371 patients.

AIMS: To determine whether left ventricular volumes and ejection fractions calculated from single plane two-dimensional echocardiograms using the algorithm (0.85A2L) correlate with those calculated using the biplane Simpson's method, and whether small changes in volumes and ejection fraction occurring post-infarction could be detected from single-plane as well as from biplane two-dimensional echocardiograms. METHODS AND RESULTS: Serial two-dimensional echocardiograms were obtained in 371 patients from the DEFIANT II trial a mean of 2 days, 1 week and 6 months post-infarction. Single plane volumes from the apical four chamber and apical long axis correlated closely with biplane Simpson's left ventricular volumes. Both single-plane left ventricular volumes significantly over-estimated biplane Simpson's volumes. Biplane Simpson's ejection fractions were consistently slightly under-estimated from the single-plane images. Differences between biplane Simpson's and single-plane volumes increased independently with increasing left ventricular size and distortion. The small changes in left ventricular volumes and ejection fraction over time were as reliably detected from single plane as from biplane images. CONCLUSION: Single-plane left ventricular volumes over-estimate biplane Simpson's volumes and under-estimate ejection fraction, and these discrepancies are amplified in dilated hearts with abnormal shape.

Adult↗