Prognostic value of cardiovascular screening in potential renal transplant recipients: a single-center prospective observational study.

We assessed the outcome of pretransplant cardiac assessment in a single center. Three hundred patients with end-stage renal disease underwent electrocardiogram, Bruce exercise testing (ETT) and ventricular assessment by cardiac MRI. Patients with high index of suspicion of coronary artery disease (CAD) underwent coronary angiography and percutaneous coronary intervention (PCI) if indicated. Two hundred and twenty-two patients were accepted onto the renal transplant waiting list; 80 patients were transplanted during the follow-up period and 60 died (7 following transplantation). Successful transplantation was associated with improved survival (mean survival 4.5 +/- 0.6 years vs. listed not transplanted 4.1 +/- 1.4 years vs. not listed 3.1 +/- 1.7 years; p < 0.001). Ninety-nine patients underwent coronary angiography; 65 had normal or low-grade CAD and 34 obstructive CAD. Seventeen patients (5.6%) were treated by PCI. There was no apparent survival difference between patients who underwent PCI or coronary artery bypass graft compared to those who underwent angiography without intervention or no angiography (p = 0.67). Factors associated with nonlisting for renal transplantation included burden of preexisting cardiovascular disease, poor exercise tolerance and severity of CAD. Pretransplant cardiovascular screening provides prognostic information and information that can be used to restrict access to transplantation. However, if the aim is to identify and treat CAD, the benefits are far from clear.

NHS heart failure survey: a survey of acute heart failure admissions in England, Wales and Northern Ireland.

OBJECTIVES: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure. DESIGN: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006. SETTING: Acute NHS trusts in England, Wales and Northern Ireland. MAIN OUTCOME MEASURES: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge. RESULTS: 176/177 (99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), beta-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, beta-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care. CONCLUSION: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and beta-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care.

Value of BNP to estimate cardiac risk in patients on cardioactive treatment in primary care.

UNLABELLED: Cardiac dysfunction may be suspected in patients with cardiovascular disease but identifying those with the highest risk is problematic. B-type natriuretic peptide (BNP) is a strong marker of heart failure in un-treated patients. This study evaluates a combined BNP and clinical algorithm for detecting cardiac dysfunction and the risk of death, in patients receiving cardioactive medication. METHODS: 459 stable general practice patients, who were taking typical heart failure drugs for any indication, were included. Echocardiography, ECG, and assay of NT-proANP and BNP (two methods) were performed. Regression models were used to identify items in a Risk Score to detect cardiac dysfunction. RESULTS: A Risk Score based on history of myocardial infarction (1 point), abnormal ECG (2 points), atrial fibrillation (1 point) and raised BNP (1-2 points) detected cardiac dysfunction with an AUC of ROC of 0.85. A Risk Score > or = 2 had a sensitivity of 90%, specificity of 58%, and positive and negative predictive values of 37% and 96%. Risk Score and LVEF<0.36 also predicted mortality. Abnormal BNP defined as either >100 pg/ml (Shionogi), or as age and sex related values, had similar predictive value. CONCLUSION: In patients on cardioactive medication, a structured Risk Score based on raised BNP, history of MI, atrial fibrillation and abnormal ECG was useful for identifying patients for immediate further examination and those who could be evaluated later.

B-type natriuretic peptide predicts cardiac morbidity and mortality after major surgery.

BACKGROUND: The objective of this study was to determine whether measurement of B-type natriuretic peptide (BNP) concentration before operation could be used to predict perioperative cardiac morbidity. METHODS: A prospective derivation study was performed in high-risk patients undergoing major non-cardiac surgery, with a subsequent validation study. A venous blood sample was taken the day before surgery for measurement of plasma BNP concentration. Screening for cardiac events (non-fatal myocardial infarction and cardiac death) was performed using clinical criteria, cardiac troponin I analysis and serial electrocardiography. RESULTS: Forty-one patients were recruited to the derivation cohort and 149 to the validation cohort. In the derivation cohort, the median (interquartile range) BNP concentration in the 11 patients who had a postoperative cardiac event was 210 (165-380) pg/ml, compared with 34.5 (14-70) pg/ml in those with no cardiac complications (P < 0.001). In the validation cohort, the median BNP concentration in the 15 patients who had a cardiac event was 351 (127-1034) pg/ml, compared with 30.5 (11-79.5) pg/ml in the remainder (P < 0.001). BNP concentration remained a significant outcome predictor in multivariable analysis (P < 0.001). Using receiver-operator curve analysis it was calculated that a BNP concentration of 108.5 pg/ml best predicted the likelihood of cardiac events, with a sensitivity and specificity of 87 per cent each. CONCLUSION: Preoperative serum BNP concentration predicted postoperative cardiac events in patients undergoing major non-cardiac surgery independently of other risk factors.

NT-proBNP can be used to detect right ventricular systolic dysfunction in pulmonary hypertension.

Right ventricular systolic dysfunction (RVSD) at baseline (pre-treatment) predicts early death in patients with pulmonary hypertension (PH). However, RVSD can only be detected reliably by prohibitively invasive or expensive techniques. N-terminal B-type natriuretic peptide concentration ([NT-proBNP]) correlates with RV function in PH; however, an [NT-proBNP] threshold that indicates RVSD in individual patients has not previously been determined. Twenty-five patients with PH (pulmonary arterial hypertension (n = 19) or chronic thromboembolic PH (n = 6)) underwent cardiovascular magnetic resonance (CMR) imaging and NT-proBNP measurement at baseline. [NT-proBNP] was correlated against RV dimensions and ejection fraction (RVEF) measured directly by CMR imaging. The ability of NT-proBNP to detect RVSD (defined as a CMR-derived RVEF >2 SDS below control values) was tested and predictors of [NT-proBNP] identified. [NT-proBNP] correlated negatively with RVEF. RVSD was present in nine out of 25 patients. An [NT-proBNP] threshold of 1,685 pg.mL(-1) was sensitive (100%) and specific (94%) in detecting RVSD. RVEF and RV mass index independently predicted [NT-proBNP]. In pulmonary hypertension, a baseline N-terminal B-type natriuretic peptide concentration of >1,685 ng.L(-1) suggests right ventricular systolic dysfunction, and thus an increased risk of early death. N-terminal B-type natriuretic peptide could prove useful as an objective, noninvasive means of identifying patients with pulmonary hypertension who have right ventricular systolic dysfunction at presentation.

Vascular function in patients with end-stage renal disease and/or coronary artery disease: a cardiac magnetic resonance imaging study.

Decreased arterial compliance in end-stage renal disease (ESRD) is associated with increased cardiovascular risk. Our aim was to examine aortic compliance in patients with ESRD using cardiac magnetic resonance imaging (MRI) and to compare these with patients with advanced atherosclerotic disease who are known to be at high cardiovascular risk. We examined a total of 83 subjects matched for age: 24 had ESRD and were on dialysis therapy for 3+/-6 years, 24 had severe coronary artery disease (CAD), 11 had both ESRD and CAD (4+/-5 years on dialysis therapy), and 24 healthy subjects with no evidence of CAD. Vascular and cardiac function was assessed using cardiac MRI. Aortic compliance was significantly reduced in patients with CAD compared to control subjects (11.3+/-6.3 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml x 10(-3)/mm Hg, P=0.009). Patients with ESRD also exhibited significantly reduced aortic compliance compared to healthy controls (12.4+/-5.8 ml x 10(-3)/mm Hg vs 15.6+/-6.0 ml 10(-3)/mm Hg, P=0.012), whereas there was no significant difference in aortic compliance between patients with CAD and ESRD. Even in the absence of symptomatic CAD, patients with ESRD have significantly reduced aortic compliance compared to normal subjects. Patients with ESRD have equivalent aortic compliance to patients with advanced CAD. These findings suggest that a significantly reduced aortic compliance is one of many mechanisms promoting premature cardiovascular events in patients with ESRD compared to age-matched controls from the general population.

Economic evaluation of the impact of nicorandil in angina (IONA) trial.

OBJECTIVE: To estimate the net cost of adding nicorandil to usual treatment for patients with angina and to compare this with indicators of health benefit. DESIGN: Cost effectiveness analysis. SETTING: Based on results of the IONA (impact of nicorandil on angina) trial. PATIENTS: Patients with angina fulfilling the entry criteria for the IONA trial. INTERVENTIONS: In one arm of the trial nicorandil was added to existing antianginal treatment and compared with existing treatment alone. MAIN OUTCOME MEASURES: Costs were for use of hospital resources (for cardiovascular, cerebrovascular, and gastrointestinal reasons), nicorandil, and care after hospital discharge. Benefits were assessed in three ways: (1) IONA trial primary outcome (coronary heart disease (CHD) death, non-fatal myocardial infarction, or hospital admission for cardiac chest pain); (2) acute coronary syndrome (CHD death, non-fatal myocardial infarction, or unstable angina); and (3) event-free survivors at the end of the trial. RESULTS: The net cost for each additional IONA trial end point averted was -5 pounds sterling (-7 euros). The net cost for each case of acute coronary syndrome averted was -8 pounds sterling (-12 euros). The net cost for each event-free survivor was -5 pounds sterling (-7 euros). These figures are based on gastrointestinal events that were judged definitely or probably related to nicorandil. When all gastrointestinal events were included these three ratios rose to 567 pounds sterling (835 euros), 886 pounds sterling (1305 euros), and 516 pounds sterling (760 euros), respectively. CONCLUSIONS: A substantial amount of the additional cost of nicorandil is offset by reduced use of hospital services. The limited comparisons possible with other CHD interventions suggest that nicorandil compares favourably.

Redefinition of uremic cardiomyopathy by contrast-enhanced cardiac magnetic resonance imaging.

Patients with end stage renal failure (ESRF) have an increased risk of premature cardiovascular disease. Left ventricular (LV) abnormalities, so called 'uremic cardiomyopathy', are associated with poorer outcome. Cardiac magnetic resonance imaging (CMR) accurately defines LV dimensions and identifies underlying myocardial pathology. We studied the relationship between LV function and myocardial pathology in ESRF patients with CMR. A total of 134 patients with ESRF underwent CMR. LV function was assessed with further images acquired after gadolinium-diethylentriaminepentaacetic acid (DTPA). The presence of myocardial fibrosis was indicated by late gadolinium enhancement (LGE). Two main myocardial pathologies were identified. A total of 19 patients (14.2%) displayed 'subendocardial LGE' representing myocardial infarction, which was associated with conventional cardiovascular risk factors including a history of ischemic heart disease (IHD) (P < 0.001), hypercholesterolemia (P < 0.05), and diabetes (P < 0.01). Patients with subendocardial LGE had greater LV mass (P < 0.05), LV dilation (P < 0.01), and LV systolic dysfunction (P < 0.001) compared to patients with no evidence of LGE. The second pattern, 'diffuse LGE', seen in 19 patients (14.2%) appeared to represent regional areas of diffuse myocardial fibrosis. Diffuse LGE was associated with greater LV mass compared to patients without LGE (P < 0.01) but not systolic dysfunction. In total, 28.4% of all patients exhibited evidence of myocardial fibrosis demonstrated by LGE. In contrast to published literature describing three forms of uremic cardiomyopathy - left ventricular hypertrophy (LVH), dilation, and systolic dysfunction, we have shown that LVH is the predominant cardiomyopathy specific to uremia, while LV dilation and systolic dysfunction are due to underlying (possibly silent) ischemic heart disease.

Should pre-operative troponin be a standard requirement in patients undergoing major lower extremity amputation?

OBJECTIVES: The objective of this study was to ascertain the benefit of routine pre-operative cardiac troponin I (cTnI) measurement in patients undergoing major lower extremity amputation for critical limb ischaemia. DESIGN: This was a prospective, blinded observational study. METHODS: All patients scheduled for lower extremity amputation, without evidence of unstable coronary artery disease were recruited prospectively over a period of 1 year. In addition to routine pre-operative evaluation, a blood sample was taken for measurement of serum cTnI. Post-operative screening was conducted for cardiac events with patients followed up to 6 weeks. RESULTS: Ten of the 44 patients included suffered a non-fatal myocardial infarction or died from a cardiac cause post-operatively. A rise in pre-operative cTnI was associated with a very poor outcome (two cardiac deaths and one post-operative myocardial infarction) and was the only significant predictor of post-operative cardiac events. CONCLUSION: Routine pre-operative cTnI measurement may be of use to identify patients at high risk of cardiac complication who would benefit from optimization of cardiac status or in whom surgery could be deferred.

Comparison of the dual receptor endothelin antagonist enrasentan with enalapril in asymptomatic left ventricular systolic dysfunction: a cardiovascular magnetic resonance study.

OBJECTIVE: To compare the effect of the dual endothelin A/B receptor antagonist enrasentan with enalapril on left ventricular (LV) remodelling. METHODS: Multicentre, randomised, double blind, parallel group study of 72 asymptomatic patients with LV dysfunction. Patients received enrasentan (60-90 mg/day) or enalapril (10-20 mg/day). The primary end point was the change in LV end diastolic volume index (EDVI) after six months' treatment. RESULTS: LV EDVI increased with enrasentan but decreased with enalapril (3.9 (1.8) v -3.4 (1.4) ml/m2, p = 0.001). Enrasentan increased resting cardiac index compared with enalapril (0.11 (0.07) v -0.10 (0.07) l/m2, p = 0.04), as well as LV mass index (0.67 (1.6) v -3.6 (1.6) g/m2, p = 0.04). Other variables were comparable between groups. Enalapril lowered brain natriuretic peptide more than enrasentan (-19.3 (9.4) v -5.8 (6.9) pg/ml, p = 0.005). Noradrenaline (norepinephrine) (p = 0.02) increased more with enrasentan than with enalapril. Enrasentan was associated with more serious adverse events compared with enalapril (six (16.7%) patients v one (2.8%), p = 0.02); the rate of progression of heart failure did not differ. CONCLUSION: In asymptomatic patients with LV dysfunction, LV EDVI increased over six months with enrasentan compared with enalapril treatment, with adverse neurohormonal effects. This suggests that enrasentan at a dose of 60-90 mg/day over six months causes adverse ventricular remodelling despite an increase in the resting cardiac index.

Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol.

AIMS/HYPOTHESIS: Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. MATERIALS AND METHODS: RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1-9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of < or = 7.0%. If confirmed HbA1c rises to > or = 8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. RESULTS: Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). CONCLUSIONS/INTERPRETATION: The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.

Heart failure post-myocardial infarction: a review of the issues.

In most patients with heart failure due to left ventricular systolic dysfunction, the underlying cause is coronary heart disease. To reduce progression to heart failure in a patient with acute myocardial infarction, it is important to achieve the earliest possible reperfusion, whether by thrombolysis or primary percutaneous coronary intervention. Every patient with acute myocardial infarction should have an assessment of their left ventricular function, the potential for reversibility should be considered, and reversible ischaemia should be identified. Left ventricular dysfunction does not only occur with ST segment elevation myocardial infarction but is also commonly associated with non-ST segment elevation myocardial infarction. Secondary prevention is crucial and this requires long term commitment by the patient and the health care system. Heart failure and left ventricular dysfunction are treatable but require a multidisciplinary, integrated network approach.

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.

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.

The value of routine non-invasive tests to predict clinical outcome in stable angina.

BACKGROUND: Chronic stable angina is a common condition, but considerable differences exist in the likelihood of acute coronary events such as CHD death, non-fatal myocardial infarction (MI) and unstable angina between individual patients. Effective risk prediction is necessary for optimum management. The aim of this study was to identify clinical features and non-invasive test parameters associated with high risk of these coronary events in stable angina and compose a clinically useful model to predict adverse outcomes in this population. METHODS: Six hundred and eighty-two patients with stable angina and a positive exercise test (1mm ST depression) from the Total Ischaemic Burden European Trial (TIBET) study, were studied. Resting ECG, exercise tolerance testing and echocardiography were performed at baseline, off anti-anginal therapy. The patients were then randomised to treatment with atenolol, nifedipine or a combination of both. Clinical follow up continued for an average of 2 years (range 1-3 years). RESULTS AND CONCLUSIONS: Prior MI or prior CABG were the clinical parameters associated with adverse outcome in patients with stable angina and a positive exercise test. On the ECG, left ventricular hypertrophy was predictive, and on echocardiogram, increased left ventricular dimensions were predictive of adverse events. When combined with time to ischaemia on exercise testing in a simple clinically applicable table these factors could be used to predict of 2 year probability of events for an individual patient.