N-terminal brain natriuretic peptide is predictive of death after cardiac transplantation.
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Biomarkers↗
Biomedical subjects
T A McDonagh
Publications and source records attributed to T A McDonagh.
The prognostic use of right heart catheterization data in patients with advanced heart failure: how relevant are invasive procedures in the risk stratification of advanced heart failure in the era of neurohormones?
BACKGROUND: Right heart catheterization long has been a routine investigation in advanced heart failure, and its measurements have been linked variably to prognosis. However, in the modern era, newer potential markers of prognosis are coming to light. This study reconsiders the use of right heart catheterization data and compares their use to that of N-terminal pro-brain natriuretic peptide (NT-proBNP), a neurohormone linked with prognosis in chronic heart failure. METHODS: We assessed prospectively the prognostic potential of baseline right heart catheterization data in 97 consecutive patients with advanced heart failure referred to the Scottish Cardiopulmonary Transplant Unit for consideration of cardiac transplantation. Patients underwent baseline routine investigation, including right heart catheterization and blood draws for NT-proBNP analysis. Patients were observed for a median of 370 days. RESULTS: The primary end-point of all-cause mortality was reached in 17 patients (17.5%), and the secondary end-point of all-cause mortality or urgent cardiac transplantation was reached in 21 (21.6%) patients. Univariate predictors of all-cause mortality included pulmonary artery systolic pressure (PASP), pulmonary artery wedge pressure (PAWP), and NT-proBNP concentration greater than their median values. Univariate predictors of the secondary end-point included right atrial pressure, PASP, PAWP, and NT-proBNP concentration greater than their median values, and left ventricular ejection fraction, cardiac output, and cardiac index less than their median values. In multivariate analyses, however, only NT-proBNP concentration remained an independent predictor of all-cause mortality. Both NT-proBNP concentration and PAWP were independent predictors of all-cause mortality and of the need for urgent cardiac transplantation. CONCLUSION: Baseline data from routine right heart catheterization are of limited prognostic use in advanced heart failure. A baseline NT-proBNP concentration is a superior, non-invasive method of risk stratification in this era of measuring neurohormones.
Cardiac Catheterization↗
Lessons from the management of chronic heart failure.
In seeking to implement evidence based medicine for the patient with heart failure occurring after a myocardial infarction (MI), much can be learnt from the long road to delivery of best care for the patient with chronic heart failure (CHF) caused by left ventricular systolic dysfunction. Both patient groups are part of the same cardiovascular continuum. A mass of evidence has accrued for the beneficial effects of angiotensin converting enzyme inhibitors, beta blockers, and aldosterone antagonists on both morbidity and mortality across a wide spectrum of patient severity. This evidence has informed the development of management guidelines, although registry data showed that uptake of treatments remained low, leading to research focused on how heart failure care could be delivered more effectively. This has resulted in a range of heart failure management programmes, many of which have been shown to reduce hospital admission rates and to improve adherence with treatments. Multidisciplinary heart failure management programmes that span primary and secondary care are now considered a routine "standard" to be aspired to in delivering effective CHF care. Applying such an approach to the care of the post-MI heart failure patient should be equally important.
Adrenergic beta-Antagonists↗
NT-proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies.
Many studies have shown that the B-type natriuretic peptides (BNP and NT-proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut-point resulting in numerous different values for both BNP and NT-proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT-proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT-proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT-proBNP for the detection of 'heart failure' was 0.85 and 0.69 for LVD. NT-proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT-proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT-proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT-proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT-proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT-proBNP merely indicates the presence of 'cardio-renal distress' and should prompt referral for further investigation.
Adult↗
N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure.
AIMS: The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2 and the HFSS. METHODS AND RESULTS: We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (chi2=6.03, P=0.01) and the combined endpoint of all cause mortality or urgent CTx (chi2 =12.68, P=0.0004). LVEF, VO2 and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study. CONCLUSION: A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2 or HFSS.
Adolescent↗
Importance of beta blockade in the treatment of advanced heart failure.
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Adrenergic beta-Antagonists↗
The prevalence of haemochromatosis gene mutations in the West of Scotland and their relation to ischaemic heart disease.
OBJECTIVES: Excess iron stores have been postulated to enhance the risk of ischaemic heart disease. This study aims to determine whether the two major mutations of the haemochromatosis (HFE) gene (C282Y and H63D) are associated with ischaemic heart disease (IHD) or myocardial infarction (MI). DESIGN: Cross sectional case-control study. SETTING: The geographical area studied by the MONICA (monitoring trends and determinants in cardiovascular disease) heart attack register for North Glasgow in Scotland, UK. PATIENTS: 1009 control subjects chosen at random from general practitioner registers were studied. Additionally, 924 subjects who had survived a first MI sustained between 1985 and 1992 were identified from the MONICA register. MAIN OUTCOME MEASURES: C282Y and H63D mutations, previous MI, and presence or absence of IHD. RESULTS: Mutant gene prevalences in the whole control population were as follows: C282Y: homozygote 0.9%, heterozygote 17.7%; H63D: homozygote 2.1%, heterozygote 25.5%; and compound heterozygote: 2.4%. Analysis by chi(2) test and logistic regression analysis did not identify any significant difference in genotype prevalence between normal control, IHD control, and MI survivor groups. CONCLUSIONS: The C282Y homozygote and heterozygote prevalences are among the highest reported worldwide. No association between IHD or MI and HFE genotype was identified. However, these results need to be interpreted in the light of the cross sectional case-control nature of the study.
Aged↗
Morphine for the relief of breathlessness in patients with chronic heart failure--a pilot study.
BACKGROUND: Chronic heart failure (CHF) patients can experience significant breathlessness despite maximum medication for their heart failure. Morphine has long been used to relieve symptoms in acute failure, but there is little evidence about this potentially useful palliative therapy in CHF. AIMS: To determine the efficacy of morphine for the relief of breathlessness in patients with CHF. METHOD: Ten out-patients with NYHA III/IV CHF entered a randomised, double-blind, placebo controlled, crossover pilot study. The active arm was 4 days of 5 mg oral morphine four times daily (2.5 mg morphine if creatinine > 200 micromol/l). There were 2 days wash-out between active and placebo arms. RESULTS: 6/10 patients indicated that morphine improved their breathlessness. On morphine, the median breathlessness score fell by 23 mm (P = 0.022) by day 2. The improvement was maintained. Sedation scores increased until day 3 (P = 0.013), reducing on day 4. Four patients developed constipation (P = 0.026). On placebo, there was no significant difference in breathlessness or sedation. One patient had constipation. There were no significant differences in either arm in nausea, quality of life scores, blood pressure, pulse, respiratory rate, or catecholamines. Brain natriuretic peptide fell in both arms; significantly in the morphine arm. CONCLUSION: Morphine relieves breathlessness due to CHF. A larger study is indicated.
Administration, Oral↗
Randomised controlled trial of continuous positive airway pressure and standard oxygen therapy in acute pulmonary oedema; effects on plasma brain natriuretic peptide concentrations.
AIMS: The study aim was to compare the effects of continuous positive airway pressure (CPAP) on clinical outcomes and plasma neurohormonal concentrations in patients with acute pulmonary oedema. METHODS AND RESULTS: In addition to standard therapy, 58 consecutive patients were randomized to receive 60% inhaled oxygen with or without CPAP at 7.5 cmH(2)O pressure. Clinical variables, symptoms and oxygenation were monitored and plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) concentrations estimated at 0, 1, 6 and 24 h. CPAP was associated with less breathlessness at 1 h (P<0.001), no treatment failures and more rapid resolution in respiratory rate (P<0.001), heart rate (P<0.001) and acidosis (P<0.005). Length of hospital stay was similar but there was a trend for a reduction in overall hospital mortality in the CPAP group (0.10>P>0.05). Plasma BNP concentrations rose progressively (P<0.001) before falling below admission concentrations at 24 h. Plasma neurohumoral concentrations were unaffected by CPAP treatment but were elevated in patients who died or had acute myocardial infarction. CONCLUSION: CPAP produces a more rapid clinical and symptomatic improvement in patients with acute pulmonary oedema, particularly within the first hour. CPAP is a useful adjunctive treatment in the early management of acute heart failure.
Acute Disease↗
Screening for left ventricular dysfunction: a step too far?
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Adult↗
Randomised controlled trial of specialist nurse intervention in heart failure.
OBJECTIVES: To determine whether specialist nurse intervention improves outcome in patients with chronic heart failure. DESIGN: Randomised controlled trial. SETTING: Acute medical admissions unit in a teaching hospital. PARTICIPANTS: 165 patients admitted with heart failure due to left ventricular systolic dysfunction. The intervention started before discharge and continued thereafter with home visits for up to 1 year. MAIN OUTCOME MEASURES: Time to first event analysis of death from all causes or readmission to hospital with worsening heart failure. RESULTS: 31 patients (37%) in the intervention group died or were readmitted with heart failure compared with 45 (53%) in the usual care group (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96). Compared with usual care, patients in the intervention group had fewer readmissions for any reason (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051). CONCLUSIONS: Specially trained nurses can improve the outcome of patients admitted to hospital with heart failure.
Aged↗
Validation of an echocardiographic wall motion index in heart failure due to ischaemic heart disease.
AIMS: The echocardiographic assessment of left ventricular ejection fraction (LVEF) by geometric methods is limited in many patients because of inadequate views and also in the presence of regional wall motion abnormalities due to ischaemic heart disease (IHD). This study aimed to examine the application of a wall motion index (WMI) method, using a nine-segment LV model in patients with chronic heart failure (CHF) due to IHD. METHODS AND RESULTS: Echocardiography was performed in 71 consecutive subjects with CHF due to IHD. WMI could be derived in 70 subjects (99%). The inter-observer variability (repeatability coefficient) of WMI was 0.66, i.e. LVEF+/-20%. In 66 subjects, LVEF was measured, within 4 weeks, using radionuclide ventriculography (RNV-EF). The inter-observer variability of RNV-EF was +/-3.1%. Using the mean of two observations for each method, the Bland-Altman range of agreement for LVEF was 26% (+/-13%). CONCLUSION: WMI is a widely applicable echocardiographic method for assessing LV systolic function and has moderate agreement with RNV-EF. Unlike RNV-EF, however, WMI is not likely to be a suitable method for the measurement of small, but prognostically important, changes in LV function that may occur in CHF.
Aged↗
Platelet and cardiac function in Darier's disease.
ATP2A2, the gene that is abnormal in Darier's disease, encodes SERCA2, a calcium pump that is expressed in many tissues. The wide expression of SERCA2 might suggest that ATP2A2 mutations would cause a multisystem disease. There is however, no evidence of consistent extracutaneous manifestations of Darier's disease. We have conducted preliminary studies in patients with Darier's disease, in two extracutaneous systems in which SERCA2 is known to be important, in order to investigate whether subtle defects have been overlooked. We found no evidence for altered cardiac function in 10 patients using two-dimensional, colour and Doppler echocardiography. There were no consistent defects in platelet function in 12 patients, using bleeding time and aggregation studies. We conclude that the skin is sensitive to defects in SERCA2 function to which other systems appear robust.
Adult↗
ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.
BACKGROUND: Persistent activation of the renin-angiotensin-aldosterone-system (RAAS) is known to occur in patients with chronic heart failure (CHF) despite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone. METHODS: Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were randomly assigned in a double-blind manner to receive either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF) as measured by radionuclide ventriculography, and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects. RESULTS: There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo. A trend toward an increase in plasma renin activity was noted with eprosartan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged. CONCLUSIONS: When added to an ACE inhibitor, eprosartan reduced arterial pressure without increasing heart rate. There was no change in LVEF after 2 months of therapy with eprosartan.
Acrylates↗
Left ventricular dysfunction, natriuretic peptides, and mortality in an urban population.
OBJECTIVE: To report the mortality of left ventricular systolic dysfunction (LVD), assessed objectively by echocardiography, and its association with natriuretic peptide hormones in a random sample of 1640 men and women aged 25-74 years from a geographical, urban population. METHODS: Left ventricular function was measured by echocardiography in 1640 attendees studied in 1992-3. LVD was defined as a left ventricular ejection fraction (LVEF) </= 30%. Plasma concentrations of N-terminal atrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP) were measured by standard radioimmunoassays. Mortality was documented at four years. RESULTS: The four year all cause mortality rate in the whole cohort was 4.9% (80 deaths). It was 21% (nine deaths) in those with an LVEF </= 30% and 4% in those whose LVEF was > 30% (p < 0.001). The median (interquartile range) BNP concentration in those who died was 16.9 pg/ml (8.8-27) and 7.8 pg/ml (3.4-13) in survivors (p < 0.0001). Similarly, N-ANP had a median concentration of 2.35 ng/ml (1.32-3.36) in those with a fatal outcome and 1.27 ng/ml (0.9-2.0) in those alive at four years (p < 0.0001). Subjects with an LVEF </= 40% also had a significant mortality rate of 17% if they also had a BNP concentration >/= 17.9 pg/ml compared with 6.8% if their BNP was below this concentration (p = 0.013). Multivariate analysis revealed the independent predictors of four year all cause mortality to be increasing age (p < 0.001), a BNP concentration >/= 17.9 pg/ml (p = 0.006), the presence of ischaemic heart disease (p = 0.03), and male sex (p = 0.04). CONCLUSIONS: LVD is associated with a considerable mortality rate in this population. BNP also independently predicts outcome. In addition to its role as a diagnostic aid in chronic heart failure and LVD, it provides prognostic information and clarifies the meaning of a given degree of LVD.
Adult↗
Asymptomatic left ventricular dysfunction in the community.
The syndrome of chronic heart failure (CHF) is usually attributable to left ventricular dysfunction (LVD), which is most commonly systolic in nature. Many patients who go on to develop heart failure pass through a phase in which they have significant systolic dysfunction but lack clinical symptoms and signs: so-called asymptomatic LVD (ALVD). Treatment of this asymptomatic phase with angiotensin-converting enzyme inhibitors can delay the progression to CHF and ameliorate its substantial morbidity and mortality. This article reviews the epidemiology of ALVD. ALVD is at least as prevalent as CHF, is mainly caused by ischemic heart disease, significantly impairs effort capacity, reduces quality of life, and is associated with a substantial mortality rate. As such, it would appear to satisfy many of the criteria required to screen for a disease. The natriuretic peptide hormones (atrial natriuretic peptide and brain natriuretic peptide ) are elevated in subjects with ALVD. BNP, in particular, has acceptable accuracy to detect LVD in the general population. In particular, it has a high negative predictive value meaning a low concentration makes the presence of significant LVD highly unlikely. As such it has the potential to be a cost-effective means of filtering subjects suspected of having LVD and allowing more appropriate use of tertiary referrals for specialist assessment and detailed echocardiography.
Disease Progression↗
Titration of vasodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentration: randomized comparison of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy.
BACKGROUND: Most patients with chronic heart failure (CHF) receive the same dose of angiotensin-converting enzyme (ACE) inhibitors because there is currently no measure of treatment efficacy. We sought to determine whether titration of vasodilator therapy according to plasma brain natriuretic peptide (BNP) concentration may be of value in the individual optimization of vasodilator therapy in CHF. METHODS AND RESULTS: Twenty patients with mild to moderate CHF receiving stable conventional therapy including an ACE inhibitor were randomly assigned to titration of ACE inhibitor dosage according to serial measurement of plasma BNP concentration (BNP group) or optimal empirical ACE inhibitor therapy (clinical group) for 8 weeks. Only the BNP-driven approach was associated with significant reductions in plasma BNP concentration throughout the duration of the study and a significantly greater suppression when compared with empiric therapy after 4 weeks [-42.1% (-58.2, -19.7) vs -12.0% (-31.8, 13.8), P =.03]. Both treatment strategies were well tolerated and associated with favorable neurohormonal and hemodynamic effects; however, in comparison between groups, mean heart rate fell (P =.02) and plasma renin activity rose (P =.03) in the BNP group when compared with the clinical group. CONCLUSIONS: Plasma BNP concentration may be chronically reduced by tailored vasodilator therapy in CHF. Furthermore, titration of vasodilator therapy according to plasma BNP was associated with more profound inhibition of the renin-angiotensin-aldosterone system and significant fall in heart rate when compared with empiric therapy.
Aged↗
The Lys198Asn polymorphism in the endothelin-1 gene is associated with blood pressure in overweight people.
There is accumulating evidence that endothelin-1 plays an important role in vascular pathophysiology. Our objective was to examine whether molecular variations at the endothelin-1 locus were involved in susceptibility to myocardial infarction and variation in blood pressure. The entire coding sequence and 1.4 kb of the 5' flanking region were screened. Five polymorphisms were detected, which were genotyped in the ECTIM (Etude Cas-Témoin de l'Infarctus du Myocarde) Study, a multicenter study comparing 648 male patients who had survived a myocardial infarction and 760 population-based controls. The polymorphisms were not associated with myocardial infarction, nor did they contribute to blood pressure levels in the population at large. However, a G/T polymorphism predicting an Lys/Asn change (ET1/C198) strongly interacted (P<0.001) with body mass index in the determination of blood pressure levels. There was a steeper increase of blood pressure with body mass index in carriers of the T allele than in GG homozygotes. As a consequence, the T allele was associated with an increase of blood pressure in overweight subjects (body mass index >/=26 kg/m2), while no significant effect was observed in lean subjects (body mass index <26 kg/m2). To determine whether this finding could be replicated, the ET1/C198 was genotyped in the Glasgow Heart Scan Study, a population-based study including 619 men and 663 women. Subjects homozygous for the T allele had higher resting blood pressure levels than others (P<0.05). A similar interaction between the T allele and body mass index was observed on the maximum blood pressure achieved during a treadmill exercise test (P<0.001). In conclusion, results from 2 independent studies suggest that the ET1/C198 polymorphism is associated with blood pressure levels in overweight people.
Adult↗