Stephen D. Robb

The index of microcirculatory resistance measured acutely predicts the extent and severity of myocardial infarction in patients with ST-segment elevation myocardial infarction.

OBJECTIVES This study investigated the relationship between the index of microcirculatory resistance (IMR) with myocardial injury and microvascular obstruction (MVO) assessed by contrast-enhanced cardiac magnetic resonance (ceCMR) imaging in a broad range of ST-segment elevation myocardial infarction (STEMI) patients undergoing emergency percutaneous coronary intervention (PCI). BACKGROUND Contrast-enhanced cardiac magnetic resonance imaging is the gold standard for assessment of microvascular obstruction (MVO), left ventricular (LV) ejection fraction, and infarct volumes in ST-segment elevation myocardial infarction (STEMI). However, ceCMR is not available acutely. The index of microcirculatory resistance is a simple invasive measure of microvascular function available at the time of emergency PCI. We investigated the relationship between IMR with myocardial injury and MVO assessed by ceCMR in STEMI patients undergoing emergency PCI. METHODS Fifty-seven patients with STEMI were included and 53 (93%) and 47 (82%) patients had complete ceCMR scans 2 days and 3 months following MI, respectively. Microvascular obstruction was defined as a dark core of hypoenhancement within the area of hyperenhanced infarct tissue 10 to 15 min following intravenous gadolinium (0.1 mmol/kg). RESULTS The median IMR (interquartile range [IQR]) was 35 (24 to 63) U. Twenty-seven patients (46%) had MVO. We found that IMR (median [IQR]) was higher in patients with MVO (38 [29 to 55] U) than in patients without MVO (27 [18 to 36] U); p = 0.003). The index of microcirculatory resistance was a negative multivariable predictor of LV ejection fraction, (p < or = 0.001) and infarct volume (p = 0.01) on the ceCMR scan 2 days after MI, and IMR was a multivariable predictor of LV ejection fraction (p = 0.028) and infarct volume (p = 0.048) at 3 months. CONCLUSIONS The index of microcirculatory resistance measured acutely was higher in patients with MVO on ceCMR, and IMR independently predicted LV function and infarct volume. This easily measured physiological parameter provides important prognostic information at the time of emergency PCI.

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 non-significant 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.

Effects of P-Selectin Antagonist Inclacumab in Patients Undergoing Coronary Artery Bypass Graft Surgery: SELECT-CABG Trial.

Despite unprecedented advances over the last few decades, saphenous vein graft (SVG) failure remains a major concern following coronary artery bypass graft (CABG) surgery [(1)][1], and since contemporary treatment options are limited in these patients, there is an unmet need for novel therapeutic

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.

129 Myocardial salvage during primary PCI can be predicted in the Cath lab

Objectives This study investigated the relationship between the index of microcirculatory resistance (IMR) and myocardial salvage as determined by T2-weighted and contrast-enhanced cardiac magnetic resonance (CMR) imaging in patients undergoing primary percutaneous coronary intervention (pPCI) for ST elevation myocardial infarction (STEMI). Background IMR is a simple invasive measure of microvascular function available at the time of pPCI. T2-weighted non-contrast CMR can reveal myocardial oedema, and in the post-infarct population this represents the ischaemic area at risk (AAR). Contrast-enhanced CMR delineates the area of myocardial infarction. The volume of myocardium within the AAR, but not contained within the infarct area is salvaged myocardium. Methods 108 patients with STEMI underwent invasive coronary physiology measurements during pPCI and had a subsequent CMR scan at a median of 19 h post pPCI. Short axis non-contrast T2-weighted images were acquired and delayed enhancement imaging was performed following administration of intravenous gadolinium (0.1 mmol/kg). AAR was determined and myocardial salvage was calculated as AAR—infarct area. Results IMR was 29 (21), AAR 32% (13%) and myocardial salvage 6% (9%)—all mean (SD). Spearman rank correlation between IMR and AAR was 0.27 (p 0.02) and between IMR and salvage was −0.31 (p 0.01). IMR was also a multivariate predictor of AAR (p 0.01) and a negative multivariate predictor of myocardial salvage (p 0.02). Conclusions IMR measured acutely correlates with AAR and correlates negatively with myocardial salvage as determined by MRI.

119 Chronic change in BNP after myocardial infarction adds no additional prognostic information over that gained from a once-off assessment of BNP

Elevated B-type natriuretic peptide (BNP) has been shown to be strongly predictive of adverse outcome following myocardial infarction (MI). Chronic change in BNP after MI is less well studied and it is not known whether this adds any additional prognostic information Method In 1995, individuals who had sustained an index myocardial infarction in the preceeding were invited to attend the Western Infirmary, Glasgow to undergo screening; this included blood sampling, medical history and echocardiography. BNP levels were also assessed. A second round of screening was subsequently performed in 1998. All deaths up to 31 December 2006 were collated from the General Register Office for Scotland. Results Four hundred and eighty-one patients had BNP levels measured in both the 1995 and 1998 screening. Baseline median (IQR) BNP was 33.0 (51.8) pg/ml. Baseline BNP, was strongly predictive of outcome; the quartile with the highest BNP level had adjusted HR for all cause mortality of 3.15 (1.78–5.58) compared to the lowest quartile. Absolute change (Ä) in BNP between the screening visits was normally distributed with a mean change of +25.3±100.4 pg/ml, and ranged from −233 to+1151 pg/ml. There was no significant relationship between baseline BNP and subsequent Ä BNP; baseline log BNP did not correlate with Ä BNP (r=0.035, p=0.479). ÄBNP added no further prognostic information; the quartile with the highest change (mean change +114.2±162.9 pg/ml) was not predictive of outcome compared to the lowest quartile change (mean change −36.3±38.4) with an adjusted HR of 1.17 (0.68–2.00) for all cause mortality. Crude mortality was slightly higher in this group (30% vs 22%, p=ns), but not significantly so. Conclusion BNP is a strong predictor of adverse outcome, even when assessed many years after MI. However, direct comparison of BNP measurements taken many years apart adds no further prognostic information, even if there are marked increases or decreases in levels.

BAS/BSCR39 Circulating chemical and cellular injury/repair responses are linked to cardiac dysfunction and remodelling in human myocardial infarction

Background Endogenous regenerative pathways may contribute to cardiovascular repair following ischaemic injury. Based on recent results in experimental studies, we investigated candidate endogenous chemical and cellular injury/repair responses in human myocardial infarction (MI). Methods Circulating injury (eg, platelets) and repair (circulating CD34+ progenitor cells, serum vascular endothelial growth factor (VEGF) and thymosin β4, and urine acetyl-Ser-Asp-Lys-Pro (AcSDKP)) responses were quantified 2 days and 3 months after acute MI. Progenitor cells in whole blood were quantified using flow cytometry, and cytokines were measured by immunoassay. An automated analyser was used for haematological measurements. Invasive measures of coronary artery microvascular resistance and collateral supply were measured acutely using coronary thermodilution techniques. Cardiac function and remodelling were quantified by magnetic resonance imaging. Results 35 consecutive patients with MI (mean±SD age 58%±10 years) were included. AcSDKP measured 2 days post-MI negatively predicted left ventricular ejection fraction (R2=0.43; p=0.024) and positively predicted left ventricular end-systolic volume index (R2=0.56; p=0.011) at 3 months. At follow-up, CD34+ count negatively predicted myocardial infarct mass (R2=0.29; p=0.015) and left ventricular end-systolic volume index (R2=0.20; p=0.02). In multivariable analyses, haemoglobin concentration measured 2 days post-MI negatively predicted coronary collateral supply (p=0.006), whereas red cell distribution width (p=0.004) and platelet count (p=0.0001) positively predicted coronary collateral supply. Serum VEGF at 3 months and change in VEGF were negative multivariable predictors of left ventricular end-diastolic volume index at 3 months (p=0.021 and p=0.006, respectively). Conclusion Circulating chemical and cellular responses participate in myocardial injury and repair and represent targets for therapeutic development.