Roxy Senior

Myocardial Iodine-123 Meta-Iodobenzylguanidine Imaging and Cardiac Events in Heart Failure: Results of the Prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) Study

OBJECTIVES The ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study prospectively evaluated iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) imaging for identifying symptomatic heart failure (HF) patients most likely to experience cardiac events. BACKGROUND Single-center studies have demonstrated the poorer prognosis of HF patients with reduced (123)I-mIBG myocardial uptake, but these observations have not been validated in large multicenter trials. METHODS A total of 961 subjects with New York Heart Association (NYHA) functional class II/III HF and left ventricular ejection fraction (LVEF) < or =35% were studied. Subjects underwent (123)I-mIBG myocardial imaging (sympathetic neuronal integrity quantified as the heart/mediastinum uptake ratio [H/M] on 4-h delayed planar images) and myocardial perfusion imaging and were then followed up for up to 2 years. Time to first occurrence of NYHA functional class progression, potentially life-threatening arrhythmic event, or cardiac death was compared with H/M (either in relation to estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses using clinical, laboratory, and imaging data were also performed. RESULTS A total of 237 subjects (25%) experienced events (median follow-up 17 months). The hazard ratio for H/M > or =1.60 was 0.40 (p < 0.001); the hazard ratio for continuous H/M was 0.22 (p < 0.001). Two-year event rate was 15% for H/M > or =1.60 and 37% for H/M <1.60; hazard ratios for individual event categories were as follows: HF progression, 0.49 (p = 0.002); arrhythmic events, 0.37 (p = 0.02); and cardiac death, 0.14 (p = 0.006). Significant contributors to the multivariable model were H/M, LVEF, B-type natriuretic peptide, and NYHA functional class. (123)I-mIBG imaging also provided additional discrimination in analyses of interactions between B-type natriuretic peptide, LVEF, and H/M. CONCLUSIONS ADMIRE-HF provides prospective validation of the independent prognostic value of (123)I-mIBG scintigraphy in assessment of patients with HF. (Meta-Iodobenzylguanidine Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126425; Meta-Iodobenzylguanidine [123I-mIBG] Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126438).

Intravenous Myocardial Contrast Echocardiography Predicts Recovery of Dysynergic Myocardium Early After Acute Myocardial Infarction

OBJECTIVES We aimed to ascertain whether triggered intravenous myocardial contrast echocardiography (MCE) can predict functional recovery in patients with acute myocardial infarction (AMI) and to determine the optimal triggering interval in this setting. BACKGROUND Detection of myocardial viability early after AMI has both therapeutic and prognostic implications. Myocardial contrast echocardiography using intracoronary injections of contrast can detect viable myocardium, but there is little data on the use of recently developed intravenous MCE techniques for this purpose. METHODS Ninety-six patients with recent AMI (4.8 +/- 1.7 days) underwent echocardiography at baseline and six months later or three months after revascularization to determine regional function (score 1 = normal to 3 = akinetic). Myocardial contrast echocardiography was performed at baseline using intravenous injections of Optison. Triggering intervals of 1:1 (early) and 1:10 (delayed) cardiac cycles were used. Segments were deemed viable if they demonstrated homogeneous contrast opacification. RESULTS Of 400 akinetic segments at baseline, 109 (27%) improved during the follow-up period, and 375 (94%) were adequately visualized with MCE, of which 59 (16%) were homogeneously opacified by early and 125 (33%) by delayed MCE (negative predictive value for recovery of contractile function 74% and 84%, positive predictive value 29% and 47%, respectively). Independent predictors of functional recovery were delayed MCE (odds ratio [OR]: 4.0, p < 0.001), revascularization (OR: 6.0, p < 0.001), and log creatine kinase (OR: 0.5, p = 0.03). However, the presence or absence of >90% stenosis of the infarct-related artery did not influence the ability of triggered MCE to predict functional recovery. CONCLUSIONS Intravenous delayed triggered MCE can independently detect myocardial viability early after AMI.

Beneficial Effects of Intravenous and Oral Carvedilol Treatment in Acute Myocardial Infarction A Placebo-Controlled, Randomized Trial

BACKGROUND Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.

Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys™ 1010 and 2010 analysers

The Elecsys NT‐proBNP assay is based on two polyclonal antibodies directed at residues 1–21 and 39–50 of the NT‐proBNP molecule. Analytical performance was assessed using NCCLS protocol EP‐5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7–1.6 (1010) and 1.2–1.5 (2010) and between run CV 5.3–6.7 (1010) and 4.4–5.0 (2010). In the multicentre evaluation within run CV was 1.0–2.5% with total imprecision 1.5–2.5% and between labs imprecision 3.8–4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x−0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 °C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT‐proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT‐proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT‐proBNP values increased with age and were higher in women than men.

The Heart Failure Revascularisation Trial (HEART)

Revascularization is frequently advocated to improve ventricular function and prognosis for patients with heart failure due to coronary artery disease, especially when there is evidence of extensive myocardial viability.

Increased left atrial volume index is an independent predictor of raised serum natriuretic peptide in patients with suspected heart failure but normal left ventricular ejection fraction : Implication for diagnosis of diastolic heart failure

Left atrial volume index (LAVI) is increasingly recognised as a relatively load‐independent marker of left ventricular (LV) filling pressures. We assessed the capacity of LAVI to predict LV diastolic dysfunction in comparison with N‐terminal pro B‐type natriuretic peptide (NTproBNP) in patients with suspected heart failure and a normal ejection fraction (EF).

The heart failure revascularisation trial (HEART): rationale, design and methodology.

Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial.

Synergistic value of simultaneous stress dobutamine sestamibi single-photon-emission computerized tomography and echocardiography in the detection of coronary artery disease

The relative value of exercise electrocardiography, simultaneous dobutamine technetium 99m-sestamibi (MIBI) single-photon-emission computerized tomography (SPECT), and echocardiography were evaluated for the diagnosis of coronary artery disease in patients with chest pain. Sixty-one consecutive patients underwent exercise electrocardiography and simultaneous graded dobutamine echocardiography and MIBI imaging. All patients underwent coronary arteriography. The exercise electrocardiogram was found to be a poor predictor of coronary artery disease (p not significant). Individually, MIBI SPECT and echocardiography were significantly predictive of coronary artery disease (p < 0.001). According to logistic regression analysis, the combined imaging modalities significantly increased the prediction of coronary artery disease for any vessel (p < 0.001), for multiple vessels (p < 0.001), and for the left anterior descending (p < 0.001), for right coronary artery (p < 0.001), and for left circumflex arteries (p < 0.01), compared with either MIBI SPECT or echocardiography alone. The results suggest a synergism in the detection of coronary artery disease when MIBI SPECT and echocardiography are combined during dobutamine stress.

Racial variation in cardiovascular morbidity and mortality in essential hypertension.

OBJECTIVES To perform a longitudinal comparison of morbidity and mortality among white, south Asian and Afro-Caribbean hypertensive patients in relation to baseline demographic characteristics and clinic and ambulatory blood pressure variables. DESIGN Observational follow up study. SETTING District general hospital and community setting in Harrow, England. PATIENTS 528 white, 106 south Asian, and 54 Afro-Caribbean subjects with essential hypertension who had undergone 24 hour ambulatory intra-arterial blood pressure monitoring. INTERVENTIONS Follow up for assessment of all cause morbidity and mortality over a mean (SD) of 9.2 (4.1) years. MAIN OUTCOME MEASURES Non-cardiovascular death, coronary death, cerebrovascular death, peripheral vascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation. RESULTS South Asians had the highest all cause event rate of 3.46, compared with 2.50 (NS) and 0.90 (p = 0.002) events/100 patient-years for whites and Afro-Caribbeans, respectively. This was because of an excess of coronary events (2.86v 1.32 events/100 patient-years in south Asians v whites, respectively; p = 0.002). Age (p < 0.001), sex (p < 0.001), race (south Asians : whites, hazard ratio 1.79; p = 0.008), diabetes (p = 0.05), previous history of cardiovascular disease (p < 0.001), and 24 hour ambulatory systolic blood pressure (p = 0.006) were independent predictors of time to a first event. Clinic blood pressure did not provide additional prognostic information. CONCLUSIONS South Asian origin was an independent predictor of all cause events, mainly because of an excess of coronary events in this group. Ambulatory but not clinic blood pressure was of additional value in predicting subsequent morbidity and mortality.

Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care.

AIMS The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards. METHODS AND RESULTS Data were obtained from 5508 patients from 10 studies in the UK, New Zealand, Europe, and USA. All have had NT-proBNP analysis and echocardiography. The median age was 62 years (range 18-100 years) with a prevalence of reduced left ventricular systolic function (left ventricular ejection fraction < or =40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. When looking at different age groups, AUC was highest (0.95) for <50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for >75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were: <50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and >75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%. A decision value of 400 ng/L for all ages gave much lower sensitivities. CONCLUSION In a large population of patients in primary care, the use of age-stratified NT-proBNP decision limits considerably improves performance over current standards, with an excellent NPV for exclusion of reduced left ventricular systolic function.