Usefulness of serial assessment of B-type natriuretic peptide, troponin I, and C-reactive protein to predict left ventricular remodeling after acute myocardial infarction (from the REVE-2 study)

Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death. However, LV remodeling is difficult to predict, and limited information is available on the association of cardiac biomarkers with LV remodeling. Our aim was to study the association of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein with LV remodeling after MI. We designed a prospective multicenter study including 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 months and 1 year after MI; quantitative analysis was performed at a core echocardiographic laboratory. Blood samples for determination of BNP, cTnI, and C-reactive protein levels were obtained at hospital discharge and the 1-month, 3-month, and 1-year follow up visits. One-year echocardiographic follow-up was obtained in 226 patients. End-diastolic volume increased from 52.3 ± 13.8 ml/m(2) at baseline to 62.3 ± 18.4 ml/m(2) at 1 year (p <0.0001); LV remodeling (>20% increase in end-diastolic volume) was observed in 87 patients (38%). At baseline, we found significant univariate relations between LV remodeling and the 3 biomarkers. During follow-up, high BNP levels and persistently detectable levels of cTnI were associated with LV remodeling. In multivariate analysis, none of the 3 biomarkers at baseline was independently predictive of LV remodeling. In contrast, during follow-up, high BNP and positive cTnI were independently associated with LV remodeling. In conclusion, circulating cardiac biomarkers may reflect pathophysiologic processes implicated in LV remodeling after MI. Determination of BNP and cTnI during follow-up can help refine risk stratification.     

Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction

Abstract: As experimental studies suggest that melatonin is cardioprotective after myocardial infarction (MI), this study sought to investigate the relationships between circulating levels of melatonin and left ventricular (LV) remodelling in patients after acute MI. This prospective study included 161 patients (age 61 ± 3 yr; 78% men) undergoing primary percutaneous coronary intervention who were assessed echocardiographically at hospital discharge (day 3–7) and at 12 months. LV remodelling was defined as >20% increase in LV end‐diastolic volume at 12‐month follow‐up compared with baseline. Serum melatonin concentrations were measured at admission, during the light period. Twenty‐four patients showed LV remodelling, and 137 had no evidence of LV remodelling. Patients with LV remodelling had lower levels of melatonin at study entry [9.96 (8.28–11.03) versus 16.74 (13.77–19.59) pg/mL, respectively; P < 0.0001]. Multivariate analysis showed that melatonin levels (OR = 2.10, CI 95% 1.547–2.870, P < 0.001) were an independent predictor of LV remodelling at 12‐month follow‐up. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.959 (CI 95% 0.93–0.98; P < 0.0001). To our knowledge, this is the first study to show the relationship between melatonin and LV remodelling during the chronic phase post‐MI.     

Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function

OBJECTIVES: We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI). BACKGROUND: The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion. METHODS: We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS: The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001) and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS: Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.     

Plasma C-reactive protein predicts left ventricular remodeling and function after a first acute anterior wall myocardial infarction treated with coronary angioplasty: comparison with brain natriuretic peptide

BACKGROUND: C-reactive protein (CRP) directly participates in the myocardial injury of acute myocardial infarction (MI). Although high plasma CRP levels in the acute phase strongly indicate a poor early clinical outcome of patients with MI, the impact of CRP levels on late left ventricular (LV) function and remodeling, which are closely associated with long-term prognosis, remains unknown. HYPOTHESIS: Acute plasma CRP levels may predict late LV function and remodeling after MI. METHODS: We prospectively studied 12 consecutive patients with a first acute anterior MI recanalized by angioplasty. We measured plasma CRP levels on Days 0, 1, 2, 3, 4, and 7, and calculated the area under the curve (AUC). We also measured plasma brain natriuretic peptide (BNP) levels on Day 3 as the referential indicator of LV dysfunction and late LV remodeling. Late LV indices were independently assessed on a left ventriculogram obtained at 5.3 months to estimate the extent of LV remodeling. RESULTS: Plasma CRP reached its peak at Day 2.8 (8.68+/-4.57 mg/dl). On linear regression analysis, the AUC of CRP (35.21+/-19.33 mg/dl x day) correlated positively with BNP (316.5+/-418.6 pg/ml) (r = 0.646, p = 0.023). The AUC of CRP, peak CRP, and BNP correlated significantly with late LV indices. Among these, the AUC of CRP showed the best correlation with end-diastolic volume index (r = 0.765, p = 0.004), end-systolic volume index (r = 0.907, p < 0.001), and ejection fraction (r = -0.862, p < 0.001). CONCLUSIONS: Patients with high plasma CRP levels may be at risk for late LV dysfunction and remodeling; theoretically, their long-term prognosis may be poor. Measuring plasma CRP levels may provide valuable information for long-term risk stratification after MI.     

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.     

Cardiac remodelling in the era of aggressive medical therapy: does it still exist?

AIM: To delineate the natural history of left ventricular remodelling following large anterior myocardial infarction (MI), in the era of aggressive medical therapy. METHODS: Seventeen selected patients underwent cardiovascular magnetic resonance (CMR) at 2 weeks and 1, 3, 6 and 12 months post infarction. RESULTS: There was a significant increase in left ventricular (LV) end-diastolic volume index (EDVI) and LV ESVI from 2 weeks to 1 month (P<0.05) but no significant change thereafter. The LV ejection fraction (EF) decreased from 2 weeks to 1 month (P<0.05) and then increased over the year (P=0.02). Throughout the study period the sphericity index increased. There was a significant and progressive decrease in LV mass index over the year, which was associated with a decrease in wall thickness at both the infarct and non-infarct sites. Independent predictors of an early increase in LVESVI were increasing age, increasing CK-MB and not receiving treatment with a statin. CONCLUSION: This study delineates the natural history of left ventricular remodelling in the modern medical era in those patients who have suffered a large anterior MI. Classical remodelling occurred up to 1 month, but thereafter was attenuated. These findings would suggest that remodelling is not as prevalent in the modern era, and that combined medical management with thrombolysis, ACEi, beta-blockers and statins may strongly influence the development of this remodelling.     

Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction.

AIMS: Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling. METHODS AND RESULTS: Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8+/-0.6 mm in MI vs. 3.6+/-0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7+/-3.8% in MI vs. 10.5+/-2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration. CONCLUSION: Atrial fibrosis caused by chronic CHF is reduced by spironolactone.     

Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction

Background

Recent studies have suggested that the microRNAs miR-133a and miR-423-5p may serve as useful biomarkers in patients with left ventricular (LV) heart failure or with LV remodeling after myocardial infarction (MI). These results were however obtained in small series of patients and control subjects were used as reference groups. Whether these microRNAs may be indicators of the degree of LV remodeling after MI is unknown.

Methods

246 patients with a first anterior Q-wave MI were included. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI and analyzed at a core laboratory. We investigated the temporal profile (baseline, 1, 3 and 12 months) of circulating miR-133a and miR-423-5p and their relations with cardiac biomarkers (B-type natriuretic peptide, C-reactive protein, and cardiac troponin I) and LV remodeling during the 1 year follow-up.

Results

There were time-dependent changes in the levels of circulating miR-133a and miR-423-5p with significant increase of miR-133a at 12 months compared to 3 months and significant increase of miR-423-5p at 1, 3, and 12 months compared to baseline. However, miR-133a and miR-423-5p were not associated with indices of LV function and LV remodeling serially assessed during a 1 year period after an acute anterior MI, nor with B-type natriuretic peptide.

Conclusions

Circulating levels of miR-133a and miR-423-5p are not useful biomarkers of LV remodeling after MI.     

Serial echocardiographic assessment of the left ventricular function after direct PCI

BACKGROUND: Acute myocardial infarction (AMI) causes remodelling of the left ventricle (LV). Restoration of patency of an infarct-related artery by percutaneous coronary interventions (PCI) may prevent or inhibit cardiac remodelling. AIM: To assess LV contractility and function by serial echocardiographic examinations. METHODS: The study group consisted of 61 patients (47 males, mean age 60+/-10 years) with acute MI treated with direct PCI. Echocardiography was performed 6-8 days after PCI, and 1, 6 and 12 months thereafter. RESULTS: LV ejection fraction increased significantly at the end of the first month in comparison with the baseline examination whereas EF values obtained after 6 months and after 1 year were not significantly different. Wall motion score index showed a significant improvement after one month, whereas it did not show any further improvement when measured after 6 or 12 months after AMI. The baseline LV end-diastolic diameter was 49+/-6 mm and did not change after one or 6 months, whereas it increased significantly 12 months after AMI. The baseline LV end-systolic diameter was 37+/-5 mm. At the one-month and six-month examinations it was similar to the baseline values but increased significantly to 38+/-6 mm after one year. CONCLUSIONS: These results confirm the beneficial effects of PCI-induced infarct-related artery patency on LV remodelling after AMI.     

Patterns of post-MI left ventricular volume changes - clinical implications

BACKGROUND: Left ventricular (LV) enlargement - the main discriminant of postinfarction remodelling - is dynamic and not necessarily progressive. The magnitude of the remodelling process is directly proportional to infarct size (IS), although it is significantly influenced by other factors. AIM: To assess the clinical implications of different patterns of LV volume changes in 1-year echocardiographic follow-up after myocardial infarction (MI) and to determine early predictors of adverse remodelling. METHODS: The study group consisted of 132 patients (pts) (mean age 55.7+/-12 years) with their first MI (STEMI) (67% pts treated with fibrinolysis). In the consecutive ECHO examinations (S1, first day; S2, at discharge; S3, 6 months; and S4, one year after MI) the following parameters were assessed: WMSI, EDVI, ESVI, LVEF, LV sphericity index (WSF), index of infarct expansion (EXP), restrictive pattern of mitral flow (RP), grade of mitral regurgitation (MR). The criterion of significant LV dilatation was EDVI > or =85 ml/m2 and/or DEDVI > or =20% between two succeeding ECHO. At S3 pts were classified into groups: group 1 with no LV dilatation (n=68), group 2 with early transient LV dilatation (S1 and/or S2) (n=26), group 3 with progressive (S1 - S2 - S3) LV dilatation (n=28). The prognostic value of the following parameters was assessed: anterior infarct location, Q-wave MI, Killip-Kimball class ?2, lack of noninvasive assessed reperfusion R(-), EXP(+), CK > or =3000 IU, WMSIS2 > or =1.5, EDVIS2 > or=80 ml/m2, ESVIS2 > or =40 ml/m2, EFS2 <45%, RPS2 and baseline LV hypertrophy (S1). RESULTS: Patients in group 3 had significantly larger IS (WMSI) than in group 1 (p <0.01) and group 2 (p <0.05). Infarct expansion was found only in group 3. One year after MI in group 3 compared to groups 1 and 2 adverse remodelling was observed: lower EFS4 (p <0.001), more spherical LV (WSFS4) (p <0.001), higher rate of MRS4 > or =2 (p <0.001) and RPS4 (p <0.001). Within each group LVEFS1-S4 was stable in one-year follow-up. In group 3 incidence of heart failure (HF) was significantly higher than in groups 1 and 2 (respectively 57 vs. 2 vs. 4%; p <0.001). Cardiac death (CD) was observed only in group 3 (25% of pts). Increased EDVI > or =80 ml/m2 at discharge was the most powerful independent predictor of progressive LV dilatation. Large IS (CK >/=3000 IU and/or WMSI > or =1.5) was not an independent predictor of adverse remodelling. CONCLUSIONS: 1) During the first 6 months after MI the progression of LV dilatation was a useful sign identifying adverse remodelling, even in the absence of LVEF evolutionary changes. Progressive LV dilatation was associated with more spherical LV and higher rate of MR > or =2 degrees . 2) Patients with progressive LV were at higher risks of HF and CD in one-year follow-up. 3) Increased EDVI > or =80 ml/m2 at discharge was the most powerful independent predictor of adverse postinfarction remodelling. Large IS was not an independent predictor. 4) Echocardiographic monitoring after MI is of great clinical importance - it enables pts at higher risk of HF and CD to be identified.     

A proteomic study of the effects of ramipril on post-infarction left ventricular remodelling in the rabbit

OBJECTIVES: In this study, we used a proteomic approach to investigate the potential proteins regulated by ramipril in post-infarction left ventricular remodelling in the rabbit. METHODS AND RESULTS: Myocardial infarction (MI) was induced in male New Zealand White rabbits (2.5-3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were either left untreated (MI group) or were treated daily for one month with 0.1 mg/kg wt of ramipril (ramipril group), then sacrificed. One month of ramipril treatment resulted in a significant improvement in the LV ejection fraction (LVEF) and a decrease in hydroxyproline content. The protein profiles of LV tissue showed that ramipril caused upregulation of glutathione peroxidase, superoxide dismutase (SOD), and heart-type fatty acid binding-protein (h-FABP) and downregulation of HSP27 and cyclophilin A. Ramipril treatment caused an increase in catalase, glutathione peroxidase, and SOD activity in the LV tissue. Oxidized glutathione levels and the GSSG/GSH ratio in the heart tissue were lower in the ramipril group than in the MI group. CONCLUSIONS: Ramipril increased antioxidative protein expression and enzyme activity, which could partly explain the role of ramipril in attenuating LV remodelling. In addition, the present study identifies several potential protein targets which may help to explain the mechanism by which ramipril exerts its effect in post-infarction LV remodelling in the rabbit.     

Plasma matrix metalloproteinase-9 and left ventricular remodelling after acute myocardial infarction in man: a prospective cohort study.

AIM: To describe temporal profiles of plasma matrix metalloproteinases (MMP-2 and MMP-9), and their relationship with echocardiographic (Echo) parameters of left ventricular (LV) function and remodelling, after acute myocardial infarction (AMI) in man. METHODS AND RESULTS: Plasma MMP-2 and MMP-9 were assayed at intervals (0-12, 12-24, 24-48, 48-72, 72-96, and > 96 h) in 91 patients with AMI (ST-elevation/non-ST-elevation 77/24; 73% male; 40% anterior site) and on a single occasion in 172 age- and sex-matched control subjects with stable coronary artery disease. Echo assessment of LV volumes, LV ejection fraction (LVEF), and wall motion index score were assessed before discharge and at follow-up (median 176, range 138-262 days) for patients and on a single occassion in controls. Plasma MMP-2 was similar at all times after AMI, elevated when compared with control (P = 0.005-0.001) and unrelated to LV function or volume during index admission or at follow-up. Maximal MMP-9 was seen at 0-12 h and was elevated when compared with control (P = 0.002) followed by fall to a plateau. Both maximal and plateau MMP-9 concentration correlated with white blood cell (WBC, P = 0.023 to < 0.001) and neutrophil count (P = 0.014 to < 0.001). Maximal MMP-9 had independent predictive value for lower LVEF (P = 0.004) during admission and for greater change in LV end-diastolic volume between admission and follow-up (R = 0.3, P = 0.016). In contrast, higher plateau levels of MMP-9 were associated with relative preservation of LV function (increasing LVEF, P = 0.002; decreasing WMIS, P = 0.009) and less change in end-systolic volume and end-diastolic volumes after discharge (P = 0.001 and 0.024, respectively). CONCLUSION: Both MMP-9 and MMP-2 are elevated following AMI. The biphasic profile of plasma MMP-9 is related to LV remodelling and function following AMI in man. Higher early levels of MMP-9 associate with the extent of LV remodelling and circulating WBC levels. In contrast, higher plateau levels later after AMI are associated with relative preservation of LV function. Temporal profile, rather than absolute magnitude, of MMP-9 activity appears to be important for LV remodelling after AMI.     

Left atrial remodelling in patients with myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: the VALIANT Echo Study

Aims: To assess the relationship between left atrial (LA) size andoutcome after high-risk myocardial infarction (MI) and to studydynamic changes in LA size during long-term follow-up. Methods and results: The VALIANT Echocardiography study prospectively enrolled 610patients with left ventricular (LV) dysfunction, heart failure(HF), or both following MI. We assessed LA volume indexed tobody surface area (LAVi) at baseline, 1 month, and 20 monthsafter MI. Baseline LAVi was an independent predictor of all-causedeath or HF hospitalization (P = 0.004). In patients who survivedto 20 months, LAVi increased a mean of 3.00 ± 7.08 mL/m²from baseline. Hypertension, lower estimated glomerular filtrationrate, and LV mass were the only baseline independent predictorsof LA remodelling. Changes in LA size were related to worseningin MR and increasing in LV volumes. LA enlargement during thefirst month was significantly greater in patients who subsequentlydied or were hospitalized for HF than in patients without events. Conclusion: Baseline LA size is an independent predictor of death or HFhospitalization following high-risk MI. Moreover, LA remodellingduring the first month after infarction is associated with adverseoutcome.     

Myocardial damage and left ventricular dysfunction in patients with and without persistent negative T waves after Q-wave anterior myocardial infarction

Persistent T-wave inversions during the chronic stage of Q-wave myocardial infarction (MI) indicate the presence of a transmural infarction with a fibrotic layer pathologically. The aim of the present study was to examine the relation between left ventricular (LV) damage and changes in polarity of the T waves from the acute to chronic phase in patients with Q-wave anterior wall MI. We studied 140 patients with persistent T-wave inversions in leads with Q waves (negative T-wave group) and 158 patients with positive T waves (positive T-wave group) at 12 months after anterior MI. In the positive T-wave group, the precordial T waves reverted from a negative to a positive morphology < 3 months after MI in 21 patients (3 M-positive T-wave subgroup), 3 to 6 months in 52 patients (6 M-positive T-wave subgroup), and 6 to 12 months in 75 patients (12 M-positive T-wave subgroup). Ten patients had persistent positive T waves without initial T-wave inversion (persistent positive T-wave group). Wall motion index and LV dimension were higher and the wall thickness for the infarct area and LV ejection fraction were lower in the negative T-wave than in the positive T-wave groups, except the persistent positive T-wave group in the chronic stage (p < 0.0001). Wall motion in the infarcted area improved over the course of 1 year in the 3 M-, 6 M-, and 12 M-positive T-wave subgroups (p < 0.0001), but not in the persistent positive T-wave group. Among the patients with T-wave inversions after admission, those who had persistent negative T waves after 12 months had worse LV function. In patients with initial T-wave inversion, earlier normalization of the precordial T waves was associated with greater improvement in LV function. Patients with persistent positive T waves without initial negative T waves had poorer recovery of LV function than patients with persistent negative T waves. We conclude that the presence of inverted T waves in leads with abnormal Q waves 12 months after MI and the time required for T-wave normalization can be used to assess the degree of LV dysfunction.     

Role of aldosterone in mid- and long-term left ventricular remodelling after acute myocardial infarction: The REMI study

Aims

Whether aldosterone levels after myocardial infarction (MI) are associated with mid- and long-term left ventricular (LV) remodelling in the era of systematic use of renin–angiotensin system inhibitors is uncertain. We prospectively investigated the relationship between aldosterone levels and mid- and long-term LV remodelling in patients with acute MI.

Methods and results

Plasma aldosterone was measured in 119 patients successfully treated by primary percutaneous coronary angioplasty for a first acute ST-elevation MI (STEMI) 2–4 days after the acute event. LV volumes were assessed by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the same timeframe and 6 months later. LV assessment was repeated by TTE 3–9 years after MI (n = 80). The median aldosterone level at baseline was 23.1 [16.8; 33.1] pg/ml. In the multivariable model, higher post-MI aldosterone concentration was significantly associated with more pronounced increase in LV end-diastolic volume index (TTE: β ± standard error [SE]: 0.113 ± 0.046, p = 0.015; CMR: β ± SE: 0.098 ± 0.040, p = 0.015) and LV end-systolic volume index (TTE: β ± SE: 0.083 ± 0.030, p = 0.008; CMR: β ± SE: 0.064 ± 0.032, p = 0.048) at 6-month follow-up, regardless of the method of assessment. This result was consistent also in patients with a LV ejection fraction (LVEF) >40%. The association between baseline plasma aldosterone and adverse LV remodelling did not persist at the 3–9-year follow-up evaluation.

Conclusion

Aldosterone concentration in the acute phase was associated with adverse LV remodelling in the medium term, even in the subgroup of patients with LVEF >40%, suggesting a potential role of the mineralocorticoid system in post-MI adverse remodelling. Plasma aldosterone was no longer associated with LV remodelling in the long term (NCT01109225).     

Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention

Abstract. Ørn S, Ueland T, Manhenke C, Sandanger Ø, Godang K, Yndestad A, Mollnes TE, Dickstein K, Aukrust P (Stavanger University Hospital, Stavanger; Oslo University Hospital Rikshospitalet; University of Bergen, Bergen; University of Oslo; Oslo; Norway). Increased interleukin‐1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention. J Intern Med 2012; 272: 267–276. Objectives. To assess the relationship between interleukin (IL)‐1‐related molecules, infarct size and left ventricular (LV) remodelling following acute myocardial infarction (MI). Methods. Forty‐two patients with first‐time diagnosis of ST segment elevation MI (STEMI), with a single occluded vessel successfully revascularized by primary percutaneous coronary intervention (PCI), were recruited to this observational study conducted at a university teaching hospital and followed for 1 year. Main outcome measures. Plasma levels of IL‐1β, IL‐1 receptor antagonist (IL‐1Ra), IL‐18 and caspase‐1 were analysed before and 2 days, 1 week and 2 months after PCI. Serial cardiac magnetic resonance imaging (CMR) was used for the assessment of infarct size and LV remodelling. CMR findings at 1 year was the primary outcome variable. Results. Univariate analysis showed that IL‐1‐related mediators were strongly (IL‐1 β), moderately (caspase‐1) and weakly (IL‐1Ra) associated with impaired myocardial function and noninfarct mass, but not infarct size, 1 year after reperfused STEMI. In multivariate analyses, troponin T predicted LV ejection fraction (LVEF), infarct size and LV end‐diastolic (LVEDVi) and end‐systolic volume index (LVESVi). However, significant additional variance was explained by IL‐1β, IL‐18 and caspase‐1. IL‐1β levels at 2 months, IL‐18 at 2 days and pre‐PCI caspase‐1 were predictors of LVEF. Caspase‐1 and in particular IL‐1β at 2 days were the only predictors of noninfarct mass. IL‐1β and IL‐18 at 2 days were predictors of LVEDVi, whilst pre‐PCI levels of IL‐1β contributed to prediction of LVESVi. By contrast, pro‐B‐type natriuretic peptide, C‐reactive protein, IL‐6 and transforming growth factor‐β1 (TGF‐β1) had no or only a weak (TGF‐β1) association with these CMR parameters in multivariate analyses. Conclusions. IL‐1β levels after STEMI were strongly associated with impaired myocardial function and noninfarct LV mass after 1 year, suggesting a potential role for IL‐1β as a predictor of maladaptive myocardial remodelling following reperfused MI.     

首发急性ST段抬高性心肌梗死患者早期B型利钠肽水平与左室重构的关系

目的 探讨首发急性ST段抬高性心肌梗死患者心肌梗死发作24小时血浆B型利钠肽（BNP）水平与心肌梗死后6个月左窒重构的相关性.方法 选择首发急性ST段抬高性心肌梗死患者70例,发病后12小时之内均成功接受急诊经皮冠状动脉介入治疗.采用荧光测定法测定患者心梗急性发作24小时（早期）、第30天及6个月时血浆BNP水平;超声心动图测定左室舒张未期容积、左室收缩未期容积并计算左室射血分数.随访6个月,观察心梗后早期BNP水平与心梗后6个月左室重构的关系.结果 27%的患者发生了左室重构,左室重构组患者早期及随访30天、6个月血浆BNP水平均明显高于无左室重构组患者.在校正了年龄、高血压病、糖尿病、心梗部位、E峰减速时间及左室射血分数等影响左室重构的因素后,心梗后早期血浆BNP水平与心梗后6个月左室重构独立相关.结论 早期测定血浆BNP水平有助于评价首发急性ST段抬高性心肌梗死患者急诊冠脉介入术后左心室重构,对判断预后有一定价值.     

Left ventricular mass predicts heart failure not related to previous myocardial infarction: the Cardiovascular Health Study.

AIMS: The relationship of left ventricular hypertrophy (LVH) to incident heart failure (HF) not attributable to myocardial infarction (MI) has not been defined. We assessed whether LVH is an independent predictor of MI-independent HF. METHODS AND RESULTS: LVH was assessed by echocardiographic LV mass index (in g/m2.7) and excess of LV mass (eLVM, in % of the observed value) relative to the amount predicted by sex, stroke work, and height, using a prognostically validated equation in 2078 participants of Cardiovascular Health Study without prevalent MI and normal systolic function. Increasing eLVM was associated with progressively increasing left atrial dimension and concentric geometry, decreasing systolic (P < 0.0001), and diastolic function (P < 0.04). After adjustment for age, sex, obesity, diabetes, hypertension, and antihypertensive therapy, and accounting for by incident MI, hazard of HF increased by 1% for each 1% increase in eLVM and by 3% for each g/m2.7 increase in LV mass index (both P < 0.0001). The results were confirmed when also C-reactive protein and measures of systolic (endocardial shortening) and diastolic function (categories of E/A ratio) were added to the Cox models. CONCLUSION: In an elderly population, LVH, measured as LV mass index or eLVM is an independent predictor of incident HF not related to prevalent or incident MI.     

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.