Relationship of long-term prognosis to MMP and TIMP polymorphisms in patients after ST elevation myocardial infarction.

The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.

The value of novel invasive hemodynamic parameters added to the TIMI risk score for short-term prognosis assessment in patients with ST segment elevation myocardial infarction.

BACKGROUND: We compared the prognostic capacity of conventional and novel invasive parameters derived from the slope of the preload recruitable stroke work relationship (PRSW) in STEMI patients and assessed their contribution to the TIMI risk score. METHODS: Left ventricular end-diastolic pressure (EDP), ejection fraction (EF), pressure adjusted maximum rate of pressure change in the left ventricle (dP/dt/P), aortic systolic pressure to EDP ratio (SBP/EDP) and end-diastolic volume adjusted stroke work (EW), derived from the slope of the PRSW relationship, were obtained during the emergency cardiac catheterization in 523 STEMI patients. The predictive power of the analyzed parameters for 30-day and 1-year mortality was evaluated using C-statistics and reclassification analysis was adopted to assess the improvement in TIMI score. RESULTS: The highest area under the curve (AUC) values for 30-day mortality were observed for EW (0.872(95% confidence interval 0.801-0.943)), SBP/EDP (0.843(0.758-0.928)) and EF (0.833(0.735-0.931)); p<0.001 for all values. For 1-year mortality the best predictive value was found for EW (0.806(0.724-0.887) and EF (0.793(0.703-0.883)); p<0.001 for both. The addition of EDP, SBP/EDP ratio and EW to TIMI score significantly increased the AUC according to De Long's test. For 30-day mortality, increased discriminative power following addition to the TIMI score was observed for EW and SBP/EDP (Integrated Discrimination Improvement was 0.086(0.033-0.140), p=0.002 and 0.078(0.028-0.128), p=0.002, respectively). CONCLUSIONS: EW and SBP/EDP are prognostic markers with high predictive value for 30-day and 1-year mortality. Both parameters, easily obtained during emergency catheterization, improve the discriminatory capacity of the TIMI score for 30-day mortality.

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). DESIGN: Prospective observational cohort study. SETTING: One university/tertiary centre. PARTICIPANTS: A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. PRIMARY OUTCOME: 1-year mortality. SECONDARY OUTCOMES: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. STATISTICAL METHODS: Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). RESULTS: The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%. CONCLUSIONS: The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

GRACE Score among Six Risk Scoring Systems (CADILLAC, PAMI, TIMI, Dynamic TIMI, Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction.

AIM: To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients. METHODS AND RESULTS: A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores--the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE--showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73-0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80-0.83). CONCLUSIONS: All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.

Prognostic value of pentraxin-3 level in patients with STEMI and its relationship with heart failure and markers of oxidative stress.

OBJECTIVE: Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). METHODS: Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. RESULTS: ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2'-deoxyguanosine, and nitrite/nitrate. CONCLUSIONS: Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year.

Unstable angina pectoris prior to ST elevation myocardial infarction in patients treated with primary percutaneous coronary intervention has no influence on prognosis.

BACKGROUND: Pre-infarction unstable angina pectoris (UAP) can be considered ischemic preconditioning. The aim of this study was to compare short and long term outcomes in patients with or without pre-infarction UAP and ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS: 593 patients with STEMI (388 without and 205 with UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin, endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were assessed. Echocardiography was undertaken on the fourth day after MI and after 12 months. The median follow-up was 37 months. RESULTS: We found no significant differences in sex, age or risk factors for atherosclerosis between the UAP and non-UAP group. As the median time from the onset of chest pain to admission was significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a propensity score to obtain comparable matched groups for use in further analyses. The levels of NT-proBNP were significantly higher on admission and after 24 hours in the UAP group. Left ventricular functions according to invasive and echocardiographic parameters were entirely comparable at hospitalization and after 12 months. No differences were found in severity index of acute heart failure during hospitalization. The incidence of major acute coronary events during follow-up was comparable for the groups. CONCLUSIONS: In patients with STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical effect during hospitalization or during long-term follow-up.

Association of circulating levels of RANTES and -403G/A promoter polymorphism to acute heart failure after STEMI and to cardiogenic shock.

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.

[Dynamics of interleukin 6 levels in the patients with cardiogenic and septic shock and in a control group of patients with uncomplicated AMI]. / Dynamika hladiny interleukinu 6 u pacientu v septickém a kardiogenním soku a u pacientu s akutním infarktem myokardu s elevacemi ST.

INTRODUCTION: Cardiogenic shock (CS) is the leading cause of mortality in patients with acute myocardial infarction (AMI). Inflammatory response seems to be common response in patients with AMI, especially those with CS. We have therefore conducted a study to determine diagnostic and prognostic utility of interleukin 6 (IL6) levels in the cohort of patients with cardiogenic and septic shock (SS) and in a control group of patients with uncomplicated AMI. METHODS: In this prospective study 71 patients fulfilled the inclusion criteria: 30 patients with cardiogenic shock, 21 patients with septic shock and 20 patients with ST elevation myocardial infarction (STEMI). Plasma levels of IL6 were measured at 8 time points. The main endpoint was 3 month mortality. RESULTS: We have shown that the highest IL6 levels during the first week were recorded in patients with septic shock with peak value at admission. The maximum level of IL6 was detected between 12 to 24 hours after the onset of MI among patients with cardiogenic shock. According to Receiver operating characteristic (ROC) statistics levels of IL6 > 357 pg/ml at admission (AUC 0.730, p = 0.031) were typical for patients with CS in comparison with control group of STEMI patients. Values of IL6 > 1 237 pg/ml at admission and > 1 071 pg/ml at 24 hours (after admission?) were typical for thouse in septic shock in comparison with CS patients. We found only a non-significant trend of IL6 for the prediction of mortality in the cohort of CS patients for levels 1 854 pg/ml (AUC 0.769, p = 0.066) sampled 12 hours after admission. There was no association of plasma levels of IL6 with mortality in septic shock patients. CONCLUSIONS: Patients with cardiogenic shock demonstrated more pronounced cytokine response as evidenced by increased levels of IL6 compared to patients with uncomplicated STEMI. Levels of IL6 peaked in SS patients at admission, in CS patients 12-24 hours after admission. In daily clinical practice routine measurement of IL6 levels for prediction of prognosis both in cardiogenic and septic shock are of little value mainly due to significant interindividual variability of IL6 values.

The association between levels of tissue inhibitor of metalloproteinase-1 with acute heart failure and left ventricular dysfunction in patients with ST elevation myocardial infarction treated by primary percutaneous coronary intervention.

AIMS: Tissue inhibitors of metalloproteinase (TIMPs) bind to active matrix metalloproteinase (MMPs), and thereby inhibit their proteolytic activity. We investigated the role of polymorphisms in the gene for TIMP-1 and serum levels of TIMP-1 in association with postmyocardial infarction (MI), left ventricular (LV) dysfunction, and symptoms of acute heart failure (AHF) in patients treated with primary percutaneous coronary intervention. METHODS: In total, 556 patients with STEMI were evaluated. Levels of TIMP-1 were measured at admission and 24 h after MI onset. The TIMP-1 exon 5 SNP rs4898 (F124F with T>C) located at X chromosome was assayed. RESULTS: TIMP-1 levels were higher for men with AHF as well as for men with LV dysfunction (ejection fraction [EF]<40%). According to multivariate analysis, the TIMP-1 level was a factor with an independent negative relationship to EF and AHF in men. An independent relationship between exon 5 TIMP-1 gene polymorphism and EF, AHF or TIMP-1 level was not documented. CONCLUSION: These results provide evidence that a higher level of circulating TIMP-1 is independently associated with worse EF and AHF.

ACE gene insertion/deletion polymorphism has a mild influence on the acute development of left ventricular dysfunction in patients with ST elevation myocardial infarction treated with primary PCI.

BACKGROUND: We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI). METHODS: A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI. RESULTS: In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥ 55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]). CONCLUSIONS: These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.