Circulating stromelysin-1 (MMP-3): a novel predictor of LV dysfunction, remodelling and all-cause mortality after acute myocardial infarction

INTRODUCTION: Changes to cardiac matrix are central to ventricular remodelling after acute MI and matrix metalloproteinase expression is implicated in this process. We investigated the temporal profile of MMP-3 and its relationship to LV dysfunction and prognosis following AMI. METHODS: We studied 382 patients with AMI. Plasma MMP-3 was measured at 0-12, 12-24 h and for subsequent 24 h periods during admission. LV function (LVEF) was assessed by echocardiography pre-discharge and at a median of 148 days and clinical endpoints at a median of 313 days. RESULTS: MMP-3 peaked prior to discharge thus pre-discharge levels were used in analyses. MMP-3 was associated with patient age (p<0.001), creatinine (p<0.001) and was higher in males (p<0.001) and hypertensives (p<0.001). MMP-3 inversely correlated with LVEF at follow-up (p=0.043), was higher in subjects with LVEF <40% (p=0.017) and in subjects with increasing EDV (p=0.017) or ESV (p=0.007) compared to those in whom volumes fell between visits. In the 58 patients reaching the endpoint of death or heart failure, MMP-3 was higher (p<0.001). On Kaplan-Meier analysis, subjects with levels above optimum cut off identified via ROC curves were more likely to suffer a clinical event (p=0.037). CONCLUSION: MMP-3 is associated with left ventricular dysfunction, adverse left ventricular remodelling and prognosis after AMI.     

Obstructive sleep apnoea inhibits the recovery of left ventricular function in patients with acute myocardial infarction.

AIMS: It has been suggested that obstructive sleep apnoea syndrome (OSA) may be a direct cause of left ventricular (LV) systolic dysfunction. This study was designed to examine our hypothesis that OSA inhibits the recovery of LV function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Our 86 consecutive first-AMI patients underwent primary percutaneous coronary intervention (PCI). All patients underwent polysomnography and OSA was defined as an apnoea-hypoapnoea index (AHI) > or =15 events/h, of which more than 50% were obstructive. Left ventriculograms immediately after PCI and at 21 days were used to evaluate LV ejection fraction (LVEF), LV end-diastolic volume index, and regional wall motion (RWM) within the infarct area. OSA was observed in 37 patients (43%). All three indices of LV function after primary PCI were comparable between the two groups. Increases in LVEF and RWM during admission were significantly lower in OSA patients than those without OSA (delta LVEF: -0.3+/-9.6 vs. 7.4+/-7.2%, P < 0.001; delta RWM: 0.26+/-1.04 SD/chord vs. 1.16+/-1.20 SD/chord, P = 0.002). Multiple regression analysis showed that AHI correlated negatively with delta LVEF and delta RWM. CONCLUSION: The novel finding is that OSA may inhibit the recovery of LV function in patients with AMI.     

Increased serum matrix metalloproteinase-1 concentration predicts advanced left ventricular remodeling in patients with acute myocardial infarction.

The left ventricular ejection fraction (LVEF) is one of the major prognostic factors after acute myocardial infarction (AMI) and matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for extracellular collagen degradation and remodeling. The present study investigated whether the concentration of serum MMP-1 was associated with the LVEF after AMI. Blood was sampled on admission, and at 24 h, 3 days, 7 days, 2 weeks and 4 weeks in 24 patients with their first AMI. Left ventriculography was performed 4 weeks after the onset of AMI and the LVEF was calculated by center line method. MMP-1 concentrations were higher at 7 days and at 2 weeks than on admission (p<0.001), and at 7 days (r=-0.655, p=0.0005) and at 2 weeks (r=-0.636, p=0.0008) were negatively correlated with the LVEF. The patients with AMI were divided into high and low LVEF groups according to the results of left ventriculography. Although there were no differences in the clinical characteristics between the 2 LVEF groups, the MMP-1 concentrations at 24 h (p<0.01), 7 days (p<0.01) and 2 weeks (p<0.05) were lower in the high LVEF group than in low LVEF group. A high concentration of MMP-1 at the subacute phase after AMI predicts advanced left ventricular remodeling.     

Serum C-reactive protein elevation in left ventricular remodeling after acute myocardial infarction--role of neurohormones and cytokines

BACKGROUND: We previously reported that increased peak serum C-reactive protein (CRP) level after acute myocardial infarction (AMI) was a major predictor of cardiac rupture and long-term outcome. The aim of this study was to clarify the role of serum CRP elevation as a possible marker of left ventricular (LV) remodeling after AMI. METHODS: We prospectively studied 31 patients who underwent primary angioplasty for a first anterior Q-wave AMI. Peak serum CRP level was determined by serial measurements after admission. LV volume and the plasma levels of various neurohormones and cytokines were measured on admission, and 2 weeks and 6 months after AMI. RESULTS: Patients with higher peak CRP levels (above the median) had a greater increase in LV end-diastolic volume during 2 weeks after AMI (+21+/-14 vs. +5+/-6 ml/m(2), P=0.001) and a lower ejection fraction (45+/-11 vs. 53+/-7%, P=0.02) than those with lower CRP levels, associated with a higher incidence of pump failure, atrial fibrillation, and LV aneurysm. Plasma levels of norepinephrine, brain natriuretic peptide, and interleukin-6 2 weeks after AMI were higher in the high CRP group than in the low CRP group. CONCLUSIONS: Increased peak serum CRP level was associated with a greater increase in LV volume after anterior AMI. Plasma norepinephrine and interleukin-6 levels were increased in patients with higher CRP levels, suggesting a possible role of sympathetic activation and enhanced immune response in the development of LV remodeling after AMI.     

Circulating white blood cell count correlates with left ventricular indices independently of the extent of risk area for myocardial infarction after successful reperfusion

OBJECTIVE: To test the hypothesis that the circulating white blood cell (WBC) and neutrophil counts are related to left ventricular (LV) indices in patients with the same risk area for acute myocardial infarction (AMI), we examined 100 consecutive AMI patients who had the culprit lesion at segment 6 according to the American Heart Association classification and who underwent successful direct coronary angioplasty. METHODS AND RESULTS: The LV ejection fraction (LVEF), end-systolic volume (LVESVI) and end-diastolic volume index (LVEDVI) were obtained by left ventriculography performed 4 weeks after AMI onset. Univariate analysis disclosed that the counts of WBC and neutrophils on admission, and the maximal WBC count correlated negatively with LVEF (r = -0.46, p < 0.001; r = -0.54, p < 0.001 and r = -0.40, p < 0.001, respectively) and positively with LVESVI (r = 0.43, p < 0.001; r = 0.55, p < 0.001, and r = 0.30, p < 0.01, respectively). The counts of WBC and neutrophils on admission also correlated with LVEDVI (r = 0.28, p < 0.01 and r = 0.41, p < 0.001, respectively). Multivariate analysis with other clinical and angiographic factors revealed that the counts of WBC and neutrophils on admission correlated with LVEF (partial correlation coefficient, r = -0.37, p < 0.001 and r = -0.52, p < 0.001, respectively), with LVESVI (r = 0.34, p < 0.01 and r = 0.56, p < 0.001, respectively) and with LVEDVI (r = 0.28, p < 0.01 and r = 0.44, p < 0.001, respectively). The maximal WBC count also correlated with LVEF and LVESVI (r = -0.40, p < 0.001 and r = 0.21, p < 0.05, respectively). CONCLUSION: The present study revealed that the circulating WBC count correlated with function and volume of the successfully reperfused LV after AMI in patients with the same risk area for AMI, indicating that the WBC count needs to be taken into consideration as an independent factor affecting the LV indices.     

Stress hyperglycaemia is an independent predictor of left ventricular remodelling after first anterior myocardial infarction in non-diabetic patients.

AIMS: Stress hyperglycaemia (SH) is associated with adverse outcome in patients with acute myocardial infarction (MI) but the mechanisms underlying this association are unknown. Our hypothesis was that SH on admission for acute MI may be associated with left ventricular (LV) remodelling. METHODS AND RESULTS: We analysed LV remodelling in 162 non-diabetic patients with anterior MI. SH was defined as a glycaemia on admission >or=7 mmol/L. Systematic echocardiographic follow-up was performed at 3 months and 1 year after MI. The changes in end-diastolic volume (EDV) and end-systolic volume (ESV) from baseline to 1 year were 11.4 +/- 16.5 and 6.4 +/- 12.4 ml/m(2), respectively, in patients with SH vs. 1.9 +/- 11.1 and 0.2 +/- 8.5 ml/m(2), respectively, in patients without SH (both P < 0.0001). When LV remodelling was defined as a >20% increase in EDV, it was observed in 46% patients in the SH group vs. 19% patients in the no SH group (P = 0.0008). By multivariable analysis, baseline wall motion score index (P = 0.001) and SH (P = 0.009) were independently associated with changes in EDV. SH was an independent predictor of LV remodelling [adjusted OR: 3.22 (1.31-7.94)]. CONCLUSION: SH is a major and independent predictor of LV remodelling after anterior MI in non-diabetic patients.     

Cardioprotective effects of magnesium sulfate in patients undergoing primary coronary angioplasty for acute myocardial infarction.

BACKGROUND: Experimental evidence indicates that magnesium sulfate may have potential cardioprotective properties as an adjunct to coronary reperfusion. The present study was designed to examine the hypothesis that magnesium might have beneficial effects on left ventricular (LV) function and coronary microvascular function in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study population of 180 consecutive patients with a first AMI (anterior or inferior) underwent successful primary coronary intervention. Patients were randomized to treatment with either intravenous magnesium (magnesium group, n=89) or normal saline (control group, n=91). Pre-discharge left ventriculograms were used to assess LV ejection fraction (LVEF), regional wall motion (RWM) within the infarct-zone and LV end-diastolic volume index. The Doppler guidewire was used to assess coronary flow velocity reserve (CFVR) as an index of coronary microvascular function. Magnesium group subjects showed significantly better LV systolic function (LVEF 63+/-9% vs 55+/-13%, p<0.001; RWM: -1.01+/-1.29 SD/chord vs -1.65+/-1.11 SD/chord, p=0.004), significantly smaller LV end-diastolic volume index (63+/-17 ml/m(2) vs 76+/-20 ml/m(2), p<0.001), and significantly higher CFVR (2.95+/-0.76 vs 2.50+/-0.99, p=0.023) than controls. CONCLUSION: Magnesium sulfate as an adjunct to primary coronary intervention shows favorable functional outcomes in patients with AMI.     

Baseline Doppler parameters are useful predictors of chronic left ventricular reduction in size by cardiac resynchronization therapy.

AIMS: The identification of responders to cardiac resynchronization therapy (CRT) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains difficult. We aimed to define the predictive value of conventional Doppler parameters. METHODS AND RESULTS: In 73 patients (65 +/- 9 years, 51 male, 36 ischaemic, 37 non-ischaemic cardiomyopathy, QRS 167 +/- 31 ms, LVEF 23 +/- 6%) with LBBB, a CRT device was implanted. LV pre-ejection interval (PEI), interventricular mechanical delay (IVMD), LV filling time (FT), and myocardial performance index (MPI) were assessed at baseline and on optimized CRT. Left ventricular end-diastolic diameter (EDD) was obtained at baseline and after 10.6 +/- 6.7 months. end-diastolic diameter diminished from 66.3 +/- 8.1 to 59.9 +/- 9.6 mm (P < 0.001). Initial LVPEI (r = 0.41, P < 0.001), baseline IVMD (r = 0.34, P = 0.003), acute LVPEI shortening (r = 0.33, P = 0.006), and baseline LVEDD (r = 0.32, P = 0.007) correlated with LVEDD reduction. An LVPEI > or =140 ms had a 82% accuracy to predict long-term LVEDD reduction (sensitivity 86%, specificity 67%, positive and negative predictive values 91 and 56%, respectively). Multivariate analysis solely revealed baseline LVPEI as predictor of LVEDD reduction. FT and MPI correlated only with their respective improvements. CONCLUSION: Left ventricular pre-ejection interval and IVMD predict favourable LV remodelling on CRT. The additional application of tissue Doppler parameters may further increase specificity and negative predictive value.     

Tissue plasminogen activator antigen predicts medium-term left ventricular end-systolic volume after acute myocardial infarction

Von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) predict adverse cardiovascular outcome following acute myocardial infarction (AMI) and are weakly associated with pre-discharge left ventricular ejection fraction (LVEF). We examined the relationships between VWF, t-PA antigen, matrix metalloproteinase (MMP)-2,-3, and -9, and B-type natriuretic peptide (BNP), and their predictive effect on serial change in LV volumes in a cohort of patients admitted with AMI. Plasma VWF, t-PA antigen, MMP-2,-3,-9, and BNP were measured at a mean 46 h after AMI in 100 patients (mean age 58.9 ± 12 years, 77% male) with depressed LVEF. Cardiac magnetic resonance (CMR) imaging was then performed. Biomarker measurement and CMR were repeated at 12 and 24 weeks. Plasma concentrations of VWF, BNP and MMP-9 were elevated while t-PA antigen concentration was at the upper limits of normal; over 24 weeks VWF, t-PA antigen, MMP-9 and BNP decreased significantly. Baseline VWF correlated with BNP (r = 0.35, P < 0.001) and MMP-3 (r = 0.24, P = 0.019) as did t-PA antigen (r = 0.27, P = 0.007 for BNP; r = 0.40, P < 0.001 for MMP-3). t-PA antigen, VWF, MMP-3 and BNP were univariate predictors of LV end-systolic volume at 24 weeks; tPA antigen and BNP remained significant independent predictors on multivariate analysis. t-PA antigen and VWF are related to medium-term LV volumes after AMI, and to MMP-3. This novel link between the coagulation-fibrinolysis system and matrix turnover merits further study in understanding the pathophysiology of adverse ventricular remodeling after AMI.     

Circulating level of gelatinase activity predicts ventricular remodeling in patients with acute myocardial infarction

BACKGROUND: Matrix metalloproteinase (MMP) plays an important role in the development of ventricular remodeling in an animal model of acute myocardial infarction (AMI). We examined whether circulating MMP activity can predict left ventricular (LV) remodeling after AMI in humans. METHODS: We measured the circulating level of MMP-2 and MMP-9 activities (gelatinase activity) at 14 days after the onset of AMI by gelatin zymography in 52 consecutive patients (age 62+/-2). All patients underwent direct PTCA and stenting at an acute stage, and were treated subsequently with losartan or enalapril. Biplane left ventriculography was performed at admission, and 2 weeks and 6 months after the onset of AMI. RESULTS: We expressed gelatinolysis activity as the ratio to MMP-2 standard. Mean gelatinase activity was 0.721+/-0.013. We divided patients into two groups, groups with gelatinolysis activity <0.72 (low group, n=27) and >0.72 (high group, n=25). Either change in LV end-diastolic volume index (LVEDVI, ml/m(2)) or end-systolic volume index (LVESVI, ml/m(2)) from admission to 2 weeks was not different between the two groups. Changes in both LVEDVI and LVESVI from 2 weeks to 6 months were greater in high gelatinolysis activity group than those in low activity group. Moreover, circulating level of gelatinolysis activity was positively correlated with changes in LVEDVI and LVESVI from 2 weeks to 6 months. CONCLUSION: These results demonstrate that circulating level of gelatinase activity can predict LV remodeling after AMI. Inhibition of gelatinase activity at the acute phase may be a therapeutic strategy for the prevention of remodeling after AMI.     

Impact of prodromal angina pectoris and white blood cell count on outcome of patients with acute myocardial infarction

BACKGROUND: Elevation of white blood cell (WBC) count at admission is associated with adverse outcome after acute myocardial infarction (AMI). Prodromal angina, by the mechanism of ischemic preconditioning, improves left ventricular (LV) function and survival after reperfusion therapy in patients with AMI. Recent experimental studies have reported that preconditioning has anti-inflammatory effect. METHODS: This study consisted of 598 patients with first anterior wall AMI who underwent coronary angiography within 12 h after symptom onset. WBC count was measured at the time of hospital admission. Prodromal angina was defined as angina occurring within 24 h before the onset of AMI. Serial measurements of LV ejection fraction (EF) were obtained before reperfusion therapy and before discharge in 421 patients (71%). RESULTS: High WBC count (>10.2 x 103/mm3, n=297) was associated with higher 30-day mortality (8% vs. 4%, p=0.02) and lower predischarge LVEF (51+/-15% vs. 57+/-14%, p<0.001), although there was no significant difference in acute LVEF (47+/-10% vs. 49+/-11%, p=0.07). High WBC count was an independent predictor of 30-day mortality (p=0.009) and predischarge LVEF (p=0.002). Prodromal angina was associated with lower 30-day mortality (3% vs. 7%, p=0.02) and preserved predischarge LVEF (57+/-15% vs. 53+/-14%, p=0.006). Patients with prodromal angina had lower WBC count (10.0+/-3.3 x 10(3)/mm3 vs. 11.0+/-3.9 x 10(3)/mm3, p=0.001) and prodromal angina was an independent predictor of WBC count (p<0.001). CONCLUSIONS: Elevation of WBC count and lack of prodromal angina were associated with impaired LV function and mortality after reperfusion in patients with AMI. Prodromal angina might have contributed to favorable outcome after AMI through its anti-inflammatory effect.     

Prediction of remote left ventricular volumes and functions after acute myocardial infarction with successful coronary intervention.

BACKGROUND: The scintigraphic perfusion defect size (DS) at 1 week after acute myocardial infarction (AMI) predicts remote left ventricular (LV) volumes and LV ejection fraction (LVEF). The present study examined whether LV volumes and LVEF 6 months after AMI may be better predicted by the combination of LV volumes and LVEF just after reperfusion, and DS at 1 week, after AMI in patients with Thrombolysis In Myocardial Infarction (TIMI) grade III reperfusion by percutaneous coronary intervention. METHODS AND RESULTS: In 48 patients with AMI and TIMI grade III reperfusion, quantitative gated SPECT (QGS) was performed just after reperfusion, and at 1 week and 6 months after AMI. LV end-diastolic volume index decreased (108+/-8 to 93+/-6 ml/m(2), p<0.05) and LVEF increased (44+/-3 to 50+/-2%, p<0.05) 6 months after AMI. In addition, they were better predicted by a combination of LV volumes and LVEF just after reperfusion and DS at 1 week after AMI. CONCLUSIONS: In AMI with TIMI grade III reperfusion, LV volumes and LVEF at 6 months after MI correlate with the values obtained just after reperfusion. Myocardial perfusion imaging combined with QGS at reperfusion may predict these late-phase parameters.     

Plasma matrix metalloproteinase-9 level is correlated with left ventricular volumes and ejection fraction in patients with heart failure

BackgroundMatrix metalloproteinases (MMPs) can alter myocardial extracellular matrix and thereby contribute to adverse ventricular remodeling in progressive heart failure (HF). We hypothesized that increased plasma MMP levels correlate with increased left ventricular (LV) volumes and reduced LV ejection fraction (LVEF) in patients with HF.Methods and ResultsIn the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, patients with symptomatic HF and LVEF <0.40 were randomized to receive various combinations of therapies with candesartan, enalapril, and metoprolol CR. Left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and LVEF were determined by radionuclide angiography at baseline and at Week 43. Baseline and Week 43 plasma MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in 184 patients in this substudy. At baseline, plasma MMP-9 correlated positively with ESV (Spearman's rank correlation coefficient ρ = 0.17, P = .02) and negatively with LVEF (ρ = –0.18, P = .01). After 43 weeks, LVEF, EDV, and ESV increased significantly (all P < .01); MMP-2 level increased (P = .01), but MMP-9 and TIMP-1 levels did not change significantly overall in the study population. Temporal changes in MMP-9 level were inversely correlated with changes in LVEF (ρ = –0.16, P = .04). In multivariable analysis adjusting for clinical characteristics and treatment, a smaller proportional change in MMP-9 level after 43 weeks (below versus above median) predicted a concurrent improvement in LVEF (odds ratio = 2.35, 95% CI 1.24–4.46; P < .01). Similar relationships for MMP-2 and TIMP-1 were not observed.ConclusionsElevated plasma MMP-9 levels correlated with lower LVEF and higher ESV, whereas increasing MMP-9 levels are associated with a concurrent deterioration of LV function. These findings suggest that monitoring of plasma markers of myocardial matrix remodeling may provide important prognostic information with respect to ongoing adverse LV remodeling in HF patients.     

Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients

Matrix metalloproteinases (MMPs) are involved in cardiac remodelling. We examined whether MMP-2 genetic polymorphisms are associated with hypertension and left ventricular (LV) remodelling in hypertensive patients. We studied 160 hypertensive patients and 123 healthy controls. Echocardiography was performed in all patients and the C(-1306)T (rs243865) and C(-735)T (rs 2285053) MMP-2 polymorphisms were analysed. Haplo.stats analysis was used to evaluate whether MMP-2 haplotypes are associated with hypertension and with extremes in LV mass index (LVMI). Multiple linear regression analysis was performed to assess whether MMP-2 genotypes or haplotypes affect LVMI and other echocardiography parameters. The C(-1306)T 'CC' genotype was associated with reduced LVMI and LV end-diastolic diameter (EDD) (P=0.0365 and P=0.0438, respectively). The haplotype 'C, C' was associated with reduced LVMI and EDD (P=0.0278 and P=0.0322, respectively). The comparison of upper and lower extremes of the LVMI phenotype showed that the 'C, C' haplotype was more common in the lower LVMI group (P=0.0060), whereas the 'T, C' haplotype was more common in the higher quartile of LVMI (P=0.0187), and this haplotype was associated with increased risk of higher LVMI values (odds ratio=3.5121, 95% confidence interval=1.3193-9.3494). The findings suggest that MMP-2 polymorphisms affect hypertension-induced LV remodelling.     

Early validation study of 64-slice multidetector computed tomography for the assessment of myocardial viability and the prediction of left ventricular remodelling after acute myocardial infarction.

AIMS: We aim to validate the ability of multidetector computed tomography (MDCT) for assessing myocardial viability and predicting left ventricular (LV) remodelling after acute myocardial infarction (AMI). METHODS AND RESULTS: In 52 consecutive patients with first AMI, 64-slice MDCT without iodine re-injection was performed immediately following coronary stenting. Electrocardiogram-gated thallium-201 single-photon emission tomography was performed using QGS programs within 5 days and 6 months after onset. Among the 52 patients, 18 patients (Group A) showed transmural contrast-delayed enhancement on MDCT images, 20 patients (Group B) showed subendocardial contrast-delayed enhancement, and 14 patients (Group C) had no contrast-delayed enhancement. In the acute phase, peak creatine kinase-MB [497 (189-744), 182 (90-358), 85 (40-204) IU/mL, respectively, P = 0.0004] was significantly higher in Group A, while the incidence of myocardial blush grade 3 (22, 67, 75%, respectively, P = 0.001) and LV ejection fraction (41 +/- 7, 53 +/- 12, 62 +/- 11%, respectively, P < 0.0001) were significantly lower in Group A. During the 6-month period, LV remodelling (P = 0.001) and the number of rehospitalization for heart failure (P = 0.0017) were more significantly observed in Group A. CONCLUSION: Myocardial contrast-delayed enhancement patterns provide promising information regarding myocardial viability, LV remodelling, and prognosis in AMI.     

Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function.

AIMS: Recent data suggest that the administration of bone marrow-derived stem cells (BMSC) might improve myocardial perfusion and left ventricular (LV) function after acute myocardial infarction (AMI). The aim of this study was to assess spontaneous mobilization of BMSC expressing the haematopoietic and endothelial progenitor cell-associated antigen CD34+ after AMI and its relation to post-infarction remodelling. METHODS AND RESULTS: Peripheral blood concentration of CD34+ BMSC was measured by flow cytometry in 54 patients with AMI, 26 patients with chronic stable angina (CSA), and 43 normal healthy subjects. In patients with AMI, LV function was measured by 2D-echocardiography. Eighteen AMI patients were reassessed at 1 year. BMSC concentration was higher in patients with AMI (mean peak value: 7.04+/-6.27 cells/microL), than in patients with CSA (3.80+/-2.12 cells/microL, P=0.036) and in healthy controls (1.87+/-1.52 cells/microL, P<0.001). At multivariable analysis statin use (P<0.001), primary percutaneous intervention (P=0.048) and anterior AMI (P=0.05) were the only independent predictors of increased BMSC mobilization after AMI. In the 28 patients without subsequent acute coronary events reassessed at 1 year follow-up, CD34+ cell concentration was an independent predictor of global and regional improvement of LV function (r=0.52, P=0.004 and r=-0.41, P=0.03, respectively). CONCLUSION: AMI is followed by enhanced spontaneous mobilization of BMSC, in particular, in patients on statin therapy and following a primary percutaneous intervention. More importantly persistent spontaneous mobilization of BMSC might contribute to determine a more favourable post-AMI remodelling.     

Is glycated haemoglobin a sensitive index to identify left ventricular dysfunction two months after acute myocardial infarction in normotensive subjects?

BACKGROUND: Glycated haemoglobin concentration (HbA1c) is a marker of glucose metabolism. Glucose intolerance is associated with a high incidence of left ventricular (LV) dysfunction after acute myocardial infarction (AMI). This study was carried out in order to relate HbA1c to LV function two months following AMI in 171 normotensive patients who were not previously known to have had diabetes mellitus. METHODS: Oral glucose tolerance test (GTT) and HbA1c. Echo and Doppler-cardiography were used to measure the E/A (peak velocity of the early filling/atrial contraction waves) at rest and at peak isometric exercise (IME), deceleration time (DT) of E wave, LV ejection fraction (LVEF), LV mass index and diastolic LV function. RESULTS: GTT was diabetic in 20, impaired in 35 and normal in 116 subjects. HbA1c was >6.0% (cut off level for high risk subjects) in 76 patients (67%) with impaired relaxation (E/A<1) during IME and in 30 patients (27%) with restrictive LV filling (identified by E/A=1-2, DT<140 ms). The sensitivity and specificity of HbA1c to predict underlying impaired LV relaxation were 68% and 37%, respectively, and to predict restrictive LV filling were 27% and 98%, respectively. Whereas in univariate analysis, DT.3 was linearly related to HbA1c only (p=0.0002), multiple regression analysis showed that HbA1c was related to LVEF, DT and E/A but not to LVH, LVMI, smoking habit, age, gender and creatinine kinase level during admission for AMI. CONCLUSION: At 2 months after admission for AMI, HbA1c is related to systolic and diastolic LV function but not to LVMI or LVH. HbA1c is a sensitive predictor of impaired relaxation but highly specific to rule out underlying non-restrictive LV filling.     

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

AIMS: To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. METHODS: Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. RESULTS: At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). CONCLUSIONS: Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.     

Course of the radionuclide left ventricular ejection fraction at rest and during exercise in surgically treated asymptomatic chronic aortic insufficiency

In order to preserve left ventricular (LV) function, aortic valve replacement may be contemplated in asymptomatic patients with aortic regurgitation when LV dilatation and dysfunction are not too advanced. Our study involved 10 asymptomatic patients with severe, isolated and pure aortic regurgitation. Before, and 6 months after the operation, the LV ejection fraction (LVEF) was measured at rest and during exercise on an ergometric bicycle by radionuclide angiography (multigated technique). Mean preoperative values were: age 52 +/- 14 years; cardiothoracic ratio 0.55 +/- 0.04; end-diastolic LV diameter 69 +/- 9 mm; end systolic LV diameter 47 +/- 7 mm; LV fibre shortening fraction 0.31 +/- 0.03; LVEF 0.55 +/- 0.10 at rest and 0.41 +/- 0.13 at exercise. After surgery, the cardiothoracic ratio value (0.51 +/- 0.03) and the LVEF value at rest (0.60 +/- 0.07) were not significantly different from the corresponding preoperative values, but the LVEF value during exercise was significantly increased (0.58 +/- 0.11, p less than 0.001). Among the 9 patients who before surgery showed a fall in LVEF at exercise, after surgery 5 had a rise (group B) and 4 had a fall (group A) in LVEF at exercise. Before surgery, group A patients had greater LV diameters than group B patients: end-diastolic diameter 76 +/- 6 mm vs 63 +/- 9 mm; end-systolic diameter 53 +/- 4 mm vs 43 +/- 7 mm (p = 0.07). These diameters were the only variables that predicted the postoperative changes in LVEF at exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinogen and C-reactive protein on admission as markers of final infarct size after primary angioplasty for acute myocardial infarction.

BACKGROUND: In acute myocardial infarction (AMI) treated conservatively or with thrombolysis, marked increases of C-reactive protein (CRP) and fibrinogen have been observed. No data are however available concerning a possible relation between CRP and fibrinogen levels on admission and markers of infarct size after obtaining thrombolysis in myocardial infarction (TIMI) flow III by primary angioplasty. METHODS: We studied 34 patients with a first AMI (29 men, mean age 54+/-11 years) who were treated with primary angioplasty (TIMI flow III in all patients, no concomitant treatment with glycoprotein IIb-IIIa antagonists) within 6 h of onset of pain. CRP and fibrinogen levels on admission were determined and related to the following markers of infarct size: peak creatine kinase MB (CKMB) levels, radionuclide left ventricular ejection fraction (LVEF) at discharge and thallium-201 single-photon emission computed tomography (SPECT) infarct size at 1 month. RESULTS: Median CRP levels were 0.4 mg/dl (range 0.09-3 mg/dl), median fibrinogen levels 412 mg/dl (range 198-679 mg/dl), mean CKMB was 178+/-151 U/l, mean LVEF 52+/-8% and mean thallium-201 infarct size 7+/-6%. Although CRP levels were related to fibrinogen levels on admission (r=0.56, P=0.002), only fibrinogen levels were related to markers of infarct size (r=0.58, P=0.001 for CKMB, r=-0.44, P=0.01 for LVEF and r=0.64, P=0.001 for thallium-201 infarct size). No relation was found between CRP or fibrinogen levels on admission and the extent of coronary artery disease or the myocardial area at risk. In multiple regression analysis, the relation between fibrinogen and markers of infarct size was independent of CRP levels and the duration of pain on admission. CONCLUSIONS: These findings indicate a relation between fibrinogen levels on admission and myocardial infarct size in patients treated with primary angioplasty for AMI. This relation seems to be independent of CRP levels and the duration of pain on admission. If confirmed in larger patient populations, fibrinogen levels on admission could have an important value for risk stratification and more aggressive reduction of infarct size in patients who are treated with primary angioplasty.