Carbimazole-induced lupus.

We describe the case of a 50-year-old lady admitted with a 3-week history of dyspnoea and left-sided pleuritic pain associated with pleural effusion. This common clinical picture nevertheless gave rise to a significant diagnostic challenge. The medical history included a diagnosis of thyrotoxicosis made 6 months previously that was being treated with carbimazole by her general practitioner. Key-investigation results were as follows: (1) pleural fluid was sterile and exudative, with no malignant cells, (2) erythrocyte sedimentation rate, C reactive protein and D-dimer were raised, (3) antinuclear antibody, anti-dsDNA and antihistone antibodies were newly positive, (4) imaging revealed a large left ventricular mass consistent with thrombus in the absence of evidence of a myocardial infarction. Based on the above investigations we hypothesised that carbimazole had induced systemic lupus erythematosus, manifesting as serositis resulting in an exudative pleural effusion and a proinflammatory/prothrombotic state. Carbimazole was stopped. The patient's pleural effusion completely resolved and she remains asymptomatic.

Complication of etanercept treatment for rheumatoid arthritis--purulent pericarditis caused by a commensal organism.

The patient presented with increasing fatigue and dyspnoea. The patient had medical history of rheumatoid arthritis for which she had been taking methotrexate for the past 15 years and etanercept for the past 6 years. Initial diagnosis was cardiac failure but further investigation by echocardiogram revealed a large pericardial effusion. Empirical piperacillin-tazobactam was started due to moderately raised inflammatory markers. Four hundred millilitre of frank pus was aspirated from the pericardial sac and antimicrobial treatment was changed to meropenem. Gram positive cocci were seen in the initial Gram stain, but conventional cultures remained negative. However, 16S ribosomal RNA gene sequencing of the pus sample detected the presence of Parvimonas micra genome. Reaccumulation of the effusion required further drainage where again P micra was detected by 16S ribosomal RNA gene sequencing. Two weeks of meropenem was completed followed by treatment with benzylpenicillin and metronidazole.

Plasma indices of angiogenesis in rheumatoid disease: relationship to cardiovascular risk factors and cardiac function.

INTRODUCTION: Rheumatoid Disease (RD) is associated with increased rates of cardiovascular disease (CVD). Angiogenesis is central to RD, and well-recognized in CVD. We hypothesised that plasma levels of two indices associated with angiogenesis, vascular endothelial growth factor (VEGF) and angiogenin, would be higher among RD patients compared to healthy controls (HC), would relate to CVD risk factors, calculated 10-year coronary heart disease (CHD) and stroke risk scores. METHODS: 144 clinic patients with established RD and 63 HC were recruited in a cross-sectional study. RD patients were grouped according to the presence (RD-CVD, n=73 or absence (non-CVD RD; n=71) of CVD risk factors. Angiogenin and VEGF levels were quantified by ELISA. RESULTS: There were no significant differences for VEGF or angiogenin, between RD-CVD, non-CVD RD and HC groups (p=NS). Calculated risks for both CHD (p=0.017) and stroke (p=0.016) were higher when RD-CVD was compared to non-CVD RD and HC. Upon multivariate analysis, methotrexate use (p=0.006) and prior mycocardial infarction (MI) (p=0.034) were associated with higher angiogenin levels; body mass index (BMI) (p=0.034) and presence of RD (p=0.029) itself predicted lower levels. For RD patients, serum creatinine (p<0.001) and CRP levels, VEGF levels, and NSAID/COX2 inhibitor use (all p<0.05) were independently associated with CHD risk; plasma VEGF and serum creatinine levels were independently associated with stroke risk (p<0.05). CONCLUSIONS: Although levels of angiogenin were not significantly different between HC and RD patients, RD may have some influence on their variation. Methotrexate use and prior MI predicted higher angiogenin levels, whilst levels of VEGF were negatively associated with 10-year CHD and stroke risk.

Markers of thrombosis and hemostasis in acute coronary syndromes: relationship to increased heart rate and reduced heart-rate variability.

BACKGROUND: Acute coronary syndromes (ACS) are characterized by abnormal heart-rate variability (HRV) and biomarkers of endothelial damage and thrombosis. HYPOTHESIS: We hypothesized an association between these factors in patients with ACS. METHODS: We studied 99 patients with ACS measuring HRV and plasma markers of endothelial damage/dysfunction (von Willebrand factor, vWF) and thrombosis/hemostasis (soluble P-selectin (s-Psel); CD(40)-ligand (CD(40)-L); D-dimer). HRV and plasma indices were compared to age- and gender-matched controls. Measures were repeated at 4 months in a subset. vWF, s-Psel and D-Dimer levels were raised compared to control. RESULTS: HRV indices were reduced (mean RR, SDNN, SDNNi, RMSSD, Triangular index, LF and HF). There were weak correlations between mean RR and s-Psel (R = - 0.234, p = 0.023) and D-dimer (R = - 0.219, p = 0.041). At 4-month follow-up, significant correlations were between mean RR and CD(40)L (R = - 0.414, p = 0.008) and D-dimer (R = - 0.363, p = 0.012). On multivariate logistic regression analysis statin use (p = 0.046) was the only independent predictor of acute s-Psel levels. Age (p = 0.004) and mean RR interval (p = 0.01) were independent predictors of D-dimer levels at follow-up. CONCLUSIONS: Abnormal HRV is associated with markers of hemostasis and thrombosis in ACS, and present both in the acute and rehabilitation phases.

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: relationship to cardiovascular co-morbidity.

BACKGROUND: Rheumatoid Disease (RD) is associated with ischaemic heart disease (IHD). We sought to investigate whether abnormalities of endothelial function and platelet activation in patients with established RD were related to co-morbid cardiovascular risk factors. METHODS: In a cross-sectional study, RD patients with no cardiac risk factors and normal cardiac function (RD, n=73), those with cardiovascular disease or risk factors and normal cardiac function (RD-risk, n=59), and those with left ventricular systolic dysfunction (RD-LVSD, n=21) were recruited, and compared to healthy controls (HC, n=76). Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction), soluble E-selectin (sE-sel, a marker of endothelial activation), and soluble P-selectin (sP-sel, an index of platelet activation) were studied. RESULTS: Plasma levels of vWF and sP-sel (but not sE-sel) were significantly higher among 153 RD patients compared to controls (p=0.002 and p<0.001, respectively). Levels of vWF progressively rose with increasing cardiovascular risk across the four subgroups (p for trend<0.001). Previous IHD was independently associated with vWF levels, and diabetes mellitus (DM) was similarly associated with all three markers. RD itself and beta-blocker use were associated with sP-sel. CONCLUSION: Plasma levels of vWF and sP-sel are higher among RD patients. Levels of vWF were particularly influenced by cardiac risk factor status, and associated with known IHD and DM.

Effects of white European, African Caribbean and South Asian ethnicity on homocysteine levels in patients with systolic heart failure.

BACKGROUND: Patients with heart failure of any cause have elevated homocysteine compared to healthy controls. A number of studies in the UK and other western countries have documented higher levels of homocysteine among South Asian than among White European or African Caribbean subjects both in health and in disease, and have suggested that dietary deficiency of folate is the main cause for the difference. METHODS: Plasma homocysteine, vitamin B(12), and folate levels were measured in a multiethnic UK heart failure clinic population (n=112), and compared to matched control subjects (n=131). RESULTS: Plasma homocysteine levels were significantly higher in heart failure patients than controls (p<0.001), a result that was consistent across all ethnic groups. There was no difference in homocysteine levels by ethnic group in either patients (p=0.898) or controls (p=0.368). There was no significant difference in levels of folate or B(12) among patients or controls. Using a stepwise linear regression model, homocysteine levels in patients and controls were independently associated with age (p<0.001), vitamin B(12) (p<0.001), folate (p<0.001) and healthy control status (p<0.001), but not with gender, ethnicity, diabetes status, smoking status or BNP levels. CONCLUSION: This study does not provide evidence of ethnic differences in homocysteine levels between White European, South Asian, and African Caribbean subjects with systolic heart failure. The lack of difference in levels of folate or B(12) among patients or controls, suggests that homocysteine levels - and differences previously seen between South Asians and other ethnic groups - may be driven by dietary factors.

Evaluation of B-type natriuretic peptide for validation of a heart failure register in primary care.

BACKGROUND: Diagnosing heart failure and left ventricular systolic dysfunction is difficult on clinical grounds alone. We sought to determine the accuracy of a heart failure register in a single primary care practice, and to examine the usefulness of b-type (or brain) natriuretic peptide (BNP) assay for this purpose. METHODS: A register validation audit in a single general practice in the UK was carried out. Of 217 patients on the heart failure register, 56 of 61 patients who had not been previously investigated underwent 12-lead electrocardiography and echocardiography within the practice site. Plasma was obtained for BNP assay from 45 subjects, and its performance in identifying echocardiographic abnormalities consistent with heart failure was assessed by analysing area under receiver operator characteristic (ROC) curves. RESULTS: 30/217 were found to have no evidence to suggest heart failure on notes review and were probably incorrectly coded. 70/112 who were previously investigated were confirmed to have heart failure. Of those not previously investigated, 24/56 (42.9%) who attended for the study had echocardiographic left ventricular systolic dysfunction. A further 8 (14.3%) had normal systolic function, but had left ventricular hypertrophy or significant valve disease. Overall, echocardiographic features consistent with heart failure were found in only 102/203 (50.2%). BNP was poor at discriminating those with and without systolic dysfunction (area under ROC curve 0.612), and those with and without any significant echocardiographic abnormality (area under ROC curve 0.723). CONCLUSION: In this practice, half of the registered patients did not have significant cardiac dysfunction. On-site echocardiography identifies patients who can be removed from the heart failure register. The use of BNP assay to determine which patients require echocardiography is not supported by these data.

Left ventricular systolic dysfunction in rheumatoid disease: an unrecognized burden?

OBJECTIVES: This study sought to ascertain whether left ventricular systolic dysfunction (LVSD) is more common among clinic patients with rheumatoid disease (RD) compared with the general population, and to assess the diagnostic utility of brain natriuretic peptide (BNP). BACKGROUND: Patients with RD are at increased risk of ischemic heart disease. However, there are few large echocardiographic studies identifying cardiac dysfunction in RD. We hypothesized that LVSD would be more prevalent in RD patients than in the general population. METHODS: A total of 226 hospital out-patients with RD (65% women) underwent clinical evaluation, electrocardiography (ECG), echocardiography, and plasma BNP assay (218 patients). Prevalence of LVSD was compared with local population estimates. RESULTS: Definite LVSD (left ventricular ejection fraction <40%) occurred in 5.3% of the RD group: standardized prevalence ratio, 3.20; 95% confidence interval, 1.65 to 5.59. Median BNP values were higher in patients with LVSD compared with those without: 16.6 pmol/l versus 8.5 pmol/l, p < 0.005, although values between the two groups overlapped. One in nine patients with an abnormal ECG had definite LVSD. CONCLUSIONS: Definite LVSD was three times more common in RD patients than in the general population. Given the prognostic benefits of treating LVSD, echocardiographic screening of RD patients with an abnormal ECG may be worthwhile.

Rheumatoid disease and ischaemic heart disease: insights from pathophysiology and vascular biology.

Rheumatoid disease (RD) is a multisystem inflammatory disorder, which is associated with an increased cardiovascular mortality, thought to be due to ischaemic heart disease (IHD). The precise mechanisms causing increased IHD in RD are unclear. However, there is increasing recognition that atherosclerosis is another chronic inflammatory condition, which shares several pathophysiological features with RD. For example, endothelial damage/dysfunction, platelet activation, hypercoagulability and angiogenesis are well-recognised in both disease processes. Furthermore, RD may influence traditional risk factors such as dyslipidaemia. Although the exact reasons for the increased ischaemic burden are unclear, physicians should place a high priority upon reducing cardiovascular risk in sufferers of RD. This review summarises factors that might contribute to the pathogenesis of IHD in RD. Discussion will focus upon features shared by atherosclerotic and rheumatoid processes, as well as possible interactions between RD and conventional IHD risk factors.

Rheumatoid disease and the heart: from epidemiology to echocardiography.

Rheumatoid disease (RD) is a common chronic inflammatory condition associated with progressive joint destruction. Sufferers of RD experience reduced life expectancy, reflected in the increased standardised mortality rates reported in several studies over the last 50 years. Most studies indicate that the increased mortality affecting this population is mainly due to cardio-vascular disease. Epidemiological data have revealed an increased risk of developing ischaemic heart disease and heart failure in RD. The increased risk of ischaemic heart disease may result from traditional risk factors but data suggest that RD may confer risk independently. Although pericardial involvement, valvopathy and myocarditis are the most well-recognised cardiac manifestations of RD, and constitute a rheumatoid heart disease, these features are relatively benign. The current prevalence of rheumatoid heart disease in the era of early administration of disease-modifying therapy requires evaluation.

Drug development and the importance of ethnicity: lessons from heart failure management and implications for hypertension.

Heart failure is a common condition, associated with both poor prognosis and poor quality of life. In contrast to all other cardiovascular diseases, the prevalence of heart failure is increasing in the western world, and is likely to continue to do so as the population ages. In the UK, a significant proportion of patients with heart failure come from South Asian and African Caribbean ethnic groups. A large body of evidence exists that there may be epidemiological and pathophysiological differences between patients with heart failure from different ethnic groups. Treatments such as ACE inhibitors, which are now part of standard heart failure therapy, have an evidence base consisting of trials in patients of almost exclusively white ethnicity. Such treatments may not be equally effective in patients from other ethnic groups. This review will discuss the current evidence for heart failure management with respect to ethnicity, and consider the implications for future drug development and implications for antihypertensive therapy.

Heart failure--the importance of ethnicity.

Heart failure is a major public health problem in the Western world. Aetiological factors involved in its development include hypertension, diabetes, and ischaemic heart disease--all of which differ in prevalence, and possibly mechanism, between patients of differing ethnicity. Unfortunately, epidemiological and therapeutic trials have involved almost exclusively white populations, and evidence from these trials cannot necessarily be assumed to be generalisable to populations that include high proportions of patients from other ethnic origins. This review will discuss the mechanistic and therapeutic differences that exist in heart failure between those of European origin, and patients from the major ethnic minority groups of the UK.

An 8-year follow-up study of acute admissions with heart failure in a multiethnic population.

In 1994, we reported a cross-sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short-term (in-patient) mortality. We analysed long-term mortality data for this original survey cohort after 8 years' follow-up. At 8 years' follow-up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non-Europeans (log rank test, P=0.0705). The non-European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta-blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta-blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow-up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.

Congestive heart failure and Virchow's triad: a neglected association.

Congestive heart failure (CHF) is associated with significant morbidity and mortality. In particular, patients with CHF have a high risk of venous thromboembolism and stroke, as well as recurrent ischaemia and infarction. However, in large heart failure trials, such thrombotic complications have often been regarded as less important end points than total mortality or readmission to hospital. In addition, a high proportion of mortality in CHF is due to sudden cardiac death (SCD). Although it was long thought that SCD was due to malignant arrhythmias, current evidence suggests that thrombosis also has a significant part to play. Thrombosis in CHF may therefore be a much more significant problem than is generally appreciated. CHF is associated with abnormalities of flow (low cardiac output, dilated cardiac chambers), vessel wall (endothelial dysfunction), and abnormalities of blood constituents (abnormalities of platelets and haemorrheology). Thus it fulfills all of Virchow's triad of characteristics of a prothrombotic state. In view of these findings, antithrombotic therapy ought to provide a substantial morbidity and mortality benefit to patients with CHF. However, current data is conflicting, and comes from non-randomised, retrospective analyses of major heart failure trials, and a few randomised trials of anticoagulants in CHF that are more than 50 years old. Prospective trials of warfarin and antiplatelet agents in CHF are in progress. Measures to identify patients at highest risk of thrombosis may help to guide treatment. Further study into the relationships between such markers and the severity of heart failure, the value of such markers in predicting thrombotic complications in CHF, and the effect of treatments, is therefore needed.