Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United Kingdom National Cancer Research Institute recommendations for monitoring.

More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.

Brain natriuretic peptide is stable in whole blood and can be measured using a simple rapid assay: implications for clinical practice.

OBJECTIVES: To compare the stability of brain natriuretic peptide (BNP) to that of N-terminal atrial natriuretic peptide (NT-ANP) in whole blood and plasma stored under different conditions. To compare a rapid, simple, direct (unextracted) BNP assay to a conventional assay using plasma extraction. DESIGN: Blinded, prospective, comparative study. SETTING: Tertiary referral cardiology department. SUBJECTS: Forty two subjects (24 men, 18 women) comprising 28 patients with left ventricular systolic dysfunction (LVSD) ranging from mild to severe and 14 healthy volunteers. MAIN OUTCOME MEASURES: Stability of NT-ANP and BNP when stored as whole blood or plasma at room temperature over three days. Reproducibility of measurements. RESULTS: BNP was stable in whole blood stored at room temperature for three days; mean change in concentration -7.4% (95% CI 0.6 to -14.8), (direct), -6.3% (5.0 to -16.4), (extracted); whereas a significant decline in BNP concentration was noted in plasma stored at room temperature; -23.2% (-13.7 to -31.6), (direct); -14.4% (-3.2 to -24.3), (extracted). By contrast a small nonsignificant rise in NT-ANP concentration was noted both in whole blood and plasma stored at room temperature for three days; whole blood +8.6% (+22.3 to -3.5), plasma +6.3%, (23.2 to -8.4). The reproducibility of the BNP measurements, and particularly the rapid, direct, measurement, was superior to that for NT-ANP. CONCLUSIONS: BNP is shown to be stable in whole blood for three days and can be measured using a rapid, simple assay. Routine assay of BNP is feasible in ordinary clinical practice and may be of value to general practitioners and hospital based physicians in the diagnosis and management of patients with LVSD. Samples can be sent to a central laboratory without special handling requirements.

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.

Importance of heart failure as a cause of death. Changing contribution to overall mortality and coronary heart disease mortality in Scotland 1979-1992.

AIMS: As heart failure is a syndrome arising from another condition, such as coronary heart disease, it is rarely officially coded as the underlying cause of death regardless of the cause recorded by the physician at the time of certification. We sought to assess the true contribution of heart failure to overall mortality and coronary heart disease mortality and to examine how this contribution has changed over time. METHODS AND RESULTS: We carried out a retrospective analysis of all death certificates in Scotland between 1979 and 1992 for which heart failure was coded as the underlying or a contributory cause of death. From a total of 833622 deaths in Scotland between 1979 and 1992, heart failure was coded as the underlying cause in only 1.5% (13695), but as a contributory cause in a further 14.3% (126073). In 1979, 28.5% of male and 40.4% of female deaths attributed to coronary heart disease (coded as the underlying cause of death) also had a coding for heart failure. In 1992 these percentages had risen significantly to 34.1% and 44.8%, respectively (both P<0.001). Mortality rates for heart failure as the underlying or contributory cause of death, standardized by age and sex, fell significantly over the period studied in all ages and in both sexes: by 31% in men and 41% in women <65 years and 15.8% in men and 5.1% in women > or =65 years, respectively (P<0.01 for all changes). CONCLUSIONS: Death from heart failure is substantially underestimated by official statistics. Furthermore, one third or more of deaths currently attributed to coronary heart disease may be related to heart failure and this proportion appears to be increasing. While the absolute numbers of deaths caused by heart failure remains constant, this study is the first to show that standardized mortality rates are declining.

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.

Biochemical detection of left-ventricular systolic dysfunction.

BACKGROUND: In previous studies on the use of natriuretic peptides to detect left-ventricular systolic dysfunction, a higher rate of cardiac disorders in the control groups than in the study groups could have led to bias. We investigated the effectiveness of plasma N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) concentrations to show left-ventricular systolic dysfunction in a random sample of the general population. METHODS: We randomly selected 2000 participants aged 25-74 years from family physicians' lists in Glasgow, UK. We sent all participants questionnaires. 1653 respondents underwent echocardiography and electrocardiography. We took a left-ventricular ejection fraction of 30% or less to show left-ventricular systolic dysfunction. NT-ANP and BNP were measured in plasma by RIAs. FINDINGS: 1252 participants had analysable electrocardiograms and echocardiograms, completed questionnaires, and available blood samples. Median concentrations of NT-ANP and BNP were significantly higher in participants with left-ventricular systolic dysfunction (2.8 ng/mL [IQR 1.8-4.6] and 24.0 pg/mL [18.0-33.0]) than in those without (1.3 ng/mL [0.9-1.8] and 7.7 pg/mL [3.4-13.0]; each p < 0.001). Among participants with left-ventricular systolic dysfunction, both symptomatic and asymptomatic subgroups had raised NT-ANP and BNP concentrations. A BNP concentration of 17.9 pg/mL or more gave a sensitivity of 77% and specificity of 87% in all participants, and 92% and 72% in participants aged 55 years or older. INTERPRETATION: Measurement of BNP could be a cost-effective method of screening for left-ventricular systolic dysfunction in the general population, especially if its use were targeted to individuals at high risk.