Biomarkers Of Myocardial Necrosis Research Articles

Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine

IntroductionCardiac troponins are sensitive and specific biomarkers of myocardial necrosis. We evaluated troponin, CK, and ECG abnormalities in patients with septic shock and compared the effect of vasopressin (VP) versus norepinephrine (NE) on troponin, CK, and ECGs.MethodsThis was a prospective substudy of a randomized trial. Adults with septic shock randomly received, blinded, a low-dose infusion of VP (0.01 to 0.03 U/min) or NE (5 to 15 μg/min) in addition to open-label vasopressors, titrated to maintain a mean blood pressure of 65 to 75 mm Hg. Troponin I/T, CK, and CK-MB were measured, and 12-lead ECGs were recorded before study drug, and 6 hours, 2 days, and 4 days after study-drug initiation. Two physician readers, blinded to patient data and drug, independently interpreted ECGs.ResultsWe enrolled 121 patients (median age, 63.9 years (interquartile range (IQR), 51.1 to 75.3), mean APACHE II 28.6 (SD 7.7)): 65 in the VP group and 56 in the NE group. At the four time points, 26%, 36%, 32%, and 21% of patients had troponin elevations, respectively. Baseline characteristics and outcomes were similar between patients with positive versus negative troponin levels. Troponin and CK levels and rates of ischemic ECG changes were similar in the VP and the NE groups. In multivariable analysis, only APACHE II was associated with 28-day mortality (OR, 1.07; 95% CI, 1.01 to 1.14; P = 0.033).ConclusionsTroponin elevation is common in adults with septic shock. We observed no significant differences in troponin, CK, and ECGs in patients treated with vasopressin and norepinephrine. Troponin elevation was not an independent predictor of mortality.Trial registrationControlled-trials.com ISRCTN94845869

2012 Late-Breaking Basic Science Oral Session

### Cardiac Myosin Binding Protein C is an Ultra-early and Cardiac-specific Biomarker of Myocardial Necrosis Diederik W Kuster1, Adriana Cardenas-Ospina2, Lawson Miller2, Christian Troidl3, Holger M Nef3, Christoph Liebetrau3, Mollmann Helge3, Karen S Pieper4, Kenneth W Mahaffey4, Neal S Kleiman5, Bruno D Stuyvers2, Ali J Marian6, Sakthivel Sadayappan1; 1Loyola Univ Chicago, Maywood, IL, 2Memorial Univ, St John’s, Canada, 3Kerckhoff Heart and Thorax Cntr, Bad Neuheim, Germany, 4Duke Univ Med Cntr, Durham, NC, 5The Methodist DeBakey Heart and Vascular Cntr, Houston, TX, 6Univ of Texas Health Sciences, Houston, TX Rationale: We recently demonstrated that proteolytic cleavage fragments of cardiac myosin binding protein-C (cMyBP-C) can be detected in the serum after myocardial infarction (MI) in a rat model and in patients with MI. The findings implied that serum cMyBP-C might be useful as cardiac-specific biomarker for MI. The release kinetics of cMyBP-C in the circulation post-MI remains to be elucidated. Objective: Determine the release kinetics of cMyBP-C as an ultra-early and cardiac-specific biomarker of myocardial necrosis. Method and Results: To determine the exact timing of cMyBP-C release in the bloodstream post-acute MI, left anterior descending (LAD) coronary artery was ligated in adult swine (n=6). ECG showed significant ST elevation. Infarct size represented 12.4 ± 1.9% of total ventricular mass. Blood samples were collected before and at predetermined time points between 30 min and 14 days after LAD ligation. Plasma cMyBP-C level was quantified using a highly sensitive and rapid sandwich enzyme-linked immunosorbent assay. Compared with baseline, cMyBP-C levels were increased in post-MI serum within 45 min (0.64 ± 0.52 ng/ml) after LAD ligation and declined after 16 hrs to the baseline level (0.01 ± 0.00 ng/ml). In contrast, cardiac troponin I (cTnI) level peaked after …

The prognosis of periprocedural myocardial infarction after percutaneous coronary interventions

An increase of biomarkers of myocardial necrosis is observed frequently after percutaneous coronary interventions (PCI) even when the procedure seems angiographically successful and otherwise uncomplicated. The recently updated Universal Definition of Myocardial infarction (MI) arbitrarily defined periprocedural MI (type 4a) by elevation of cardiac troponin (cTn) values >5 × the upper reference limit (URL) in patients with normal baseline values or a rise of cTn values >20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium. Most frequent causes of such event are side-branch closure and/or plaque microembolization. The present review is focused on the prognostic implication of periprocedural necrosis. The risk related to a PCI-induced MI is significantly lower as compared to a spontaneous event where a similar increase of biomarkers is detected. Moreover, although an association between CK-MB elevations and adverse prognosis after PCI has been documented, existing data do not support the statement that an isolated elevation of troponins after PCI is associated with an adverse prognosis after PCI; increased troponin levels before PCI seem far more predictive of future events than a peri-procedural itself. Caution should be paid in the interpretation of clinical trials using type 4a MI as a primary endpoint. Nevertheless, patients with periprocedural myocardial damage should be treated as a higher-risk cohort, carefully monitored and receive an intensified secondary prevention program.

Takotsubo Cardiomyopathy and Acute Ischemic Stroke

Takotsubo cardiomyopathy and acute ischemic stroke. The Takotsubo cardiomyopathy is characterized by transient left ventricle dysfunction, with apical ballooning in the absence of significant coronary stenosis, and may clinically mimic an acute myocardial infarction. The association between Takotsubo cardiomyopathy and several acute neurological conditions has been increasingly described. The authors present the case report of an acute stroke patient submitted to intravenous thrombolysis, whose EKG on admittance showed supra-ST deviation in DI, AVL and V2-V6 leads, with concomitant elevation of myocardial necrosis biomarkers. After intravenous thrombolysis, a cardiac catheterism was performed that showed apical ballooning and acinesia of the left ventricle with decreased ventricular function, with no significant coronaropathy. The cerebral MRI performed on the seventh day showed multiple acute infarctions in different vascular territories of the anterior and posterior circulations bilaterally. Transthoracic echocardiogram performed on the same day revealed normal ventricular function and myocardial kinetics supporting the diagnosis of Takotsubo cardiomyopathy. The patient was discharged on day 10, on hypocoagulation therapy. Takotsubo cardiomyopathy is a spontaneously reversible condition, mostly requiring supportive therapeutic measures. The acute left ventricle dysfunction characteristic of this syndrome is a potential mechanism for cardiac embolism. Acute ischemic stroke is a relatively rare but severe complication. According to this, hypocoagulant therapy must be considered especially until the ventricular function is fully recovered. doi: http://dx.doi.org/10.4021/jmc776w

Oral Fluid Analysis of Salivary Biomarkers of Acute Myocardial Necrosis

Oral Fluid Analysis of Salivary Biomarkers of Acute Myocardial Necrosis

The Biochemical Aspects of a Non–ST-Segment Elevation Acute Coronary Syndrome

The clinical course of an acute coronary syndrome can vary from relatively benign to potentially fatal. The biomarkers of myocardial necrosis relate to the amount of myocardial damage and are closely linked to a patient's prognosis. They are measured to help guide management decisions. Recent interest in myocardial neurohumoral mechanisms has identified the natriuretic peptides as strong prognostic biomarkers following an ischemic event. During an acute event they provide information regarding the area of myocardium at risk. The biomarkers of inflammation, such as C-reactive protein, are related to both the development of atherosclerosis and the risk of acute ischemic events. The mechanism characterizing the pathophysiology of the syndrome is represented by these cardiac biomarkers. Assessing combinations of pathobiologically diverse biomarkers may provide a better risk evaluation method and further dictate subsequent therapy.

Early phosphatemia changes in acute cardiac care patients

IntroductionThe significance of inorganic serum phosphate levels (Pi) in patients with acute coronary syndromes (ACS) in the reperfusion era is unknown, as well as its relation to biomarkers of myocardial necrosis. Our aim was to assess admission Pi and its dynamics in patients admitted to the intensive cardiac care unit (ICCU), with emphasis on patients with ST segment elevation myocardial infarction (STEMI). MethodsWe studied 192 patients admitted to the ICCU during a 4-month period. The first group included 92 patients with STEMI (STEMI group) treated by primary percutaneous coronary intervention (PCI). The second group consisted of 100 patients without ACS (non-ACS group). Normophosphatemia was defined as Pi 0.7–1.6mmol/l. Phosphatemia was measured at admission and then 6h and 12h later as well as troponin I. ResultsAdmission phosphatemia was lower in the STEMI group as compared to the non-ACS group (Pi 0.95mmol/l vs. 1.18mmol/l, p<0.001). Admission hypophosphatemia (Pi<0.7mmol/l) was more often present in the STEMI group than in the non-ACS group (21% vs. 4%, p=0.001). In all hypophosphatemic STEMI patients, serum Pi normalized itself within 6h without substitution. Admission hyperphosphatemia (Pi>1.6mmol/l) was more frequent in non-ACS group (6.5% STEMI pts. vs. 13% non-ACS pts.). In the STEMI group, admission phosphatemia did not correlate with peak troponin I. ConclusionWe conclude that patients with STEMI treated by primary PCI have lower Pi and more frequent transient hypophosphatemia at admission than acute cardiac care patients without acute coronary syndrome.

Serum complements and heart fatty acid binding protein in Bangladeshi patients with acute myocardial infarction

The complement system is activated following acute myocardial infarction (AMI). Heart fatty acid binding protein (H-FABP) is a sensitive early biomarker of myocardial necrosis that can be used to confirm...

Takotsubo Cardiomyopathy and Acute Ischemic Stroke

Takotsubo cardiomyopathy and acute ischemic stroke. The Takotsubo cardiomyopathy is characterized by transient left ventricle dysfunction, with apical ballooning in the absence of significant coronary stenosis, and may clinically mimic an acute myocardial infarction. The association between Takotsubo cardiomyopathy and several acute neurological conditions has been increasingly described. The authors present the case report of an acute stroke patient submitted to intravenous thrombolysis, whose EKG on admittance showed supra-ST deviation in DI, AVL and V2-V6 leads, with concomitant elevation of myocardial necrosis biomarkers. After intravenous thrombolysis, a cardiac catheterism was performed that showed apical ballooning and acinesia of the left ventricle with decreased ventricular function, with no significant coronaropathy. The cerebral MRI performed on the seventh day showed multiple acute infarctions in different vascular territories of the anterior and posterior circulations bilaterally. Transthoracic echocardiogram performed on the same day revealed normal ventricular function and myocardial kinetics supporting the diagnosis of Takotsubo cardiomyopathy. The patient was discharged on day 10, on hypocoagulation therapy. Takotsubo cardiomyopathy is a spontaneously reversible condition, mostly requiring supportive therapeutic measures. The acute left ventricle dysfunction characteristic of this syndrome is a potential mechanism for cardiac embolism. Acute ischemic stroke is a relatively rare but severe complication. According to this, hypocoagulant therapy must be considered especially until the ventricular function is fully recovered. J Med Cases. 2012;3(6):347-351 doi: https://doi.org/10.4021/jmc776w

Heart-type fatty acid binding protein and the diagnosis of acute coronary syndrome in the ED

BackgroundIn combination with cardiac troponin, heart-type fatty acid binding protein (h-FABP)—a biomarker of myocardial necrosis—offers the possibility of rapidly eliminating the diagnosis of acute myocardial infarction (AMI). ObjectiveThe main objective of this study was to assess the incremental value of h-FABP to cardiac troponin for a rapid elimination of AMI, according to the pretest probability (PTP) of AMI. MethodsIn consecutive patients presenting to emergency departments (ED) with chest pain less than 6 hours suggestive of AMI, h-FABP levels were measured, blinded to the ED physicians, who were asked to quote the PTP of AMI. The discharge diagnosis was adjudicated by 2 independent experts, blind to the h-FABP level. ResultsThree hundred seventeen patients (mean age of 57 years) were included in whom 149 had (47%) low, 117 (37%) moderate, and 51 (16%) high PTP. The final diagnosis was AMI in 45 patients (14%), including 16 STEMIs (5%). The negative predictive value for diagnostic elimination of AMI of an h-FABP less than 3 μg/L, combined with a negative cTnI was not higher than that of cardiac troponin I (cTnI) alone (96% [95% confidence interval, 93%-98%] vs 95% [93%-98%]), regardless of the PTP). Even in the low-PTP group, we did not demonstrate a significant improvement in negative predictive value with the addition of h-FABP, compare with that of cTnI alone (100% [97%-100%] vs 99% [96%-100%]). ConclusionIn triage of patients with chest pain, use of h-FABP does not provide useful additional information to cTnI for excluding the diagnosis of ST-elevation myocardial infarction and non–ST-elevation myocardial infarction diagnosis, whatever the PTP.

Comparison of the temporal release pattern of copeptin with conventional biomarkers in acute myocardial infarction

BackgroundEarly detection of acute myocardial infarction (AMI) using cardiac biomarkers of myocardial necrosis remains limited since these biomarkers do not rise within the first hours from onset of AMI. We aimed to compare the temporal release pattern of the C-terminal portion of provasopressin (copeptin) with conventional cardiac biomarkers, including creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT), and high-sensitivity cTnT (hs-cTnT), in patients with ST-elevation AMI.MethodsWe included 145 patients undergoing successful primary percutaneous coronary intervention (PCI) for a first ST-elevation AMI presenting within 12 h of symptom onset. Blood samples were taken on admission and at four time points within the first 24 h after PCI.ResultsIn contrast to all other markers, copeptin levels were already elevated on admission and were higher with a shorter time from symptom onset to reperfusion and lower systolic blood pressure. Copeptin levels peaked immediately after symptom onset at a maximum of 249 pmol/L and normalized within 10 h. In contrast, CK-MB, cTnT, and hs-cTnT peaked after 14 h from symptom onset at a maximum of 275 U/L, 5.75 μg/L, and 4.16 μg/L, respectively, and decreased more gradually.ConclusionsCopeptin has a distinct release pattern in patients with ST-elevation AMI, peaking within the first hour after symptom onset before conventional cardiac biomarkers and falling to normal ranges within the first day. Further studies are required to determine the exact role of copeptin in AMI suspects presenting within the first hours after symptom onset.

A New Angle on Classifying Coronary Artery Bifurcation Stenoses

ver the past 3 decades continued technological innovation has improved the safety and efficacy of percu taneous coronary intervention (PCI). Advances in guidewire, balloon, bare metal stent, and drug-eluting stent technologies have resulted in marked improvement in short term procedural success and in clinical cardiovascular outcomes for PCI patients. Despite the excellent results of PCI in simple lesions, significant challenges remain in the treatment of bifurcation stenoses, which currently account for approximately 20% of coronary interventions.1 Compared to singlevessel procedures, procedural success and clinical outcomes are significantly worse following bifurcation PCI, 2 and interventional cardiologists are challenged by suboptimal treatment strategies for bifurcation disease. Article p 299 Several different PCI techniques have been developed to treat coronary artery bifurcation stenoses. Culote, crush, T-stent, and kissing-stent, are the predominant bifurcation PCI techniques; 3 however, randomized studies have consistently demonstrated that a single-stent provisional strategy of stenting just the main branch (MB) has the best clinical outcomes compared to 2-stent techniques.4–8 Indeed, in studies comparing provisional MB stenting to a planned 2-stent strategy of stenting both branches, the 2-stent approach showed no major benefit in follow up angiographic stenosis or major adverse cardiovascular events, and was associated with significant periprocedural increases in myocardial necrosis bio markers, contrast utilization, and fluoroscopy time. 4 Despite best efforts to utilize a provisional strategy, modern investigations of drug-eluting stent bifurcation stenting demonstrate that bifurcations treated with a provisional strategy will frequently require balloon dilation and bail-out implantation of a second stent in the side branch (SB). 3 Importantly, the rates of bail-out SB stenting following a single-stent MB provisional strategy vary based on trial definitions for when a SB should be treated. In the CACTUS study, SB stenting was recommended following provisional single-stent MB PCI when the SB stenosis was greater than 50%.8 In CACTUS, 31% of the provisional single-stent-treated bifurcations required SB stenting. The Nordic bifurcation study, recommended balloon dilation only if the SB had less than Thrombolysis in Myocardial Infarction (TIMI)-3 flow, and recommended SB stenting only if the SB had TIMI-0 flow following balloon dilation. 4 Because of the higher tolerance for SB stenosis in the Nordic study, 32% of provisional single-stent-treated bifurcations were treated with SB balloon dilation, and only 4.3% were treated with bail-out SB stenting. In order to optimize treatment strategies for bifurcation stenosis, and to facilitate research on the efficacy of various bifurcation PCI techniques, several bifurcation classification strategies have been developed.9–12 These classification strate gies categorize bifurcation stenoses based on anatomic parameters that include stenotic involvement of MB and/or SB, size of the SB, and angulation of the SB. Experientially, these anatomic features strongly influence acute PCI success, mea sured by angiographic patency, residual stenosis of the MB or SB, and periprocedural myocardial infarction. Less is known about the impact of bifurcation stenosis anatomy or angle on clinical outcomes; however, it is certainly possible that the

Hospital discharge data for assessing myocardial infarction events and trends, and effects of diagnosis validation according to MONICA and AHA criteria

BackgroundAcute myocardial infarction (AMI; ICD9-CM 410*) is a leading cause of morbidity and mortality all over the world, and its community surveillance is essential to monitor variation in the occurrence...

Alterations in serum selenium levels and their relation to troponin I in acute myocardial infarction

Selenium (Se) is an essential trace element with antioxidant function. The aim of the present study was to estimate the alterations of Se serum level during the acute phase of myocardial infarction and its relation to biomarkers of myocardial necrosis. Serum Se levels were measured at admission and after 24h in 60 consecutive patients with acute coronary syndrome (both with and without ST elevation). Troponin I (TnI) was assessed at admission and then twice daily for 3days; patients with normal levels were excluded. Fifty-five patients with acute MI (positive TnI) were included into the analysis. During the first day of hospitalization, patients received standard therapy, including acetylsalicylic acid, clopidogrel, and heparin or enoxaparin; all underwent urgent coronary angiography and percutaneous intervention, when appropriate. Mean Se levels at baseline and 24h later were comparable (67.1±2.1 vs. 67.2±1.8μg/L, ns). Linear regression has shown significant correlation between baseline Se levels and peak TnI (y=3.4x-116, r (2)=0.13, P=0.008). Positive correlation was found also between the peak TnI and the difference from baseline to 24h (y=2.2x+115, r (2)=0.08, P=0.04). Moreover, close negative correlation was observed between baseline Se levels and the difference from baseline to 24h (y=-0.9x+62.7, r (2)=0.55, P<0.001). Our results have shown marked individual changes in Se levels during the acute phase of MI as well as correlation between Se levels and peak TnI. These results suggest that alterations in serum Se may be related to the extent of myocardial infarction.

A Timely Diagnosis of Myocardial Infarction

The diagnosis of acute myocardial infarction currently rests on the measurement of troponin, a biomarker of myocardial necrosis. Unfortunately, the current generation troponin assays detect troponin only 6-9 h after symptom onset. This can lead to a delay in diagnosis and also excessive resource utilization when triaging patients who, ultimately, have noncardiac causes of acute chest pain. For these reasons, there has been extensive research interest in biomarkers that can detect and rule out myocardial infarction early after symptom onset. These include markers of myocardial injury, such as myoglobin, heart-type fatty acid binding protein, glycogen phosphorylase BB; hemostatic markers, such as D-dimer; and finally, inflammatory markers, such as matrix metalloproteinase 9. Recently, highly sensitive troponin assays have reported an early sensitivity for myocardial infarction of greater than 95%, although at a cost of reduced specificity. The optimal strategy with which to use these novel biomarkers and highly sensitive troponins has yet to be determined, and interpretation of their results in light of thorough clinical assessment remains essential.

ST2 and mortality in non–ST-segment elevation acute coronary syndrome

ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.

Metastasis-Promoting protein S100A4 (MTS1) upregulates production of proinflammatory cytokines via TLR-4

<h3>Background</h3> Early triage is essential to improve outcome in patients with suspected Acute Myocardial Infarction (AMI). This study investigated whether cardiac myosin-binding protein C (cMyC), a novel biomarker of myocardial...

Glycoprotein VI for diagnosis of acute coronary syndrome when ECG is ambiguous

BackgroundThe purpose of the study was to test whether an elevated surface expression of platelet collagen receptor glycoprotein VI (GPVI) is an appropriate marker for the diagnosis of the acute coronary syndrome (ACS), especially when the electrocardiogram (ECG) is ambiguous. MethodsBetween 2007 to 2008, we consecutively evaluated 378 patients with ACS and ambiguous ECG on hospital admission. In all patients, GPVI surface expression was determined by flow cytometry. In addition, the myocardial necrosis markers troponin-I (Tn-I) and creatine kinase-MB (CKMB) were measured. ResultsWe found that in patients with ACS and unclear ECG in whom GPVI levels (mean fluorescence intensity (MFI) ≥18.6) were elevated, the relative risk for ACS was 2.6-fold enhanced. Binary logistic regression analysis revealed that an elevated platelet GPVI level is indicating an ACS independent of biomarkers of myocardial necrosis including Tn-I, creatine kinase (CK), CKMB (GPVI: p=0.011; Tn-I: p=0.180; CKMB: p=0.250; CK: p=0.127). Patients with evident T-wave inversion and/or ST-depression showed a strong association between ACS and GPVI expression. ConclusionsPlatelet GPVI surface expression is enhanced in patients with ACS with unclear ECG findings and is strongly associated with myocardial ischemia. Additional to the classical markers of myocardial necrosis Tn-I and CK, GPVI is an early biomarker for the diagnosis of ACS, especially when the ECG is ambiguous.

Abstract 5018: Soluble fms-like Tyrosine Kinase (sFLT1): A Biomarker of Endothelial Origin in Acute ST-segment Elevation Myocardial Infarction (STEMI)

In STEMI, early recognition improves clinical outcomes. Current biomarkers of myocardial necrosis are limited by poor sensitivity and specificity during the acute phase of coronary occlusion. sFLT1 is an endothelial-derived, hypoxia-inducible protein. We hypothesized that vascular occlusion induces early expression of sFLT1 in STEMI. Methods &amp; Results: In a prospective, observational study, serum sFLT1 levels were measured by ELISA in 30 patients with STEMI referred for emergent catheterization. Compared to 20 healthy, age-matched controls, sFLT1 levels were markedly increased at the time of presentation (11.7±2 vs 210.5±80 pg/mL, p&lt;0.0001), then substantially reduced within 24 hours of reperfusion (22.3±15 pg/mL, p&lt;0.0001). On admission, 100% of STEMI patients had elevated sFLT-1 levels (&gt;50pg/mL), whereas 73% and 64% had levels of CK-MB &gt;5ng/mL and Troponin-I &gt;1.0 ng/mL respectively. Two patients undergoing alcohol septal ablation were studied as positive controls. sFLT1 levels increased within 40 minutes of occlusion (27.8 vs 216.2 pg/mL, pre- vs post-ablation, p&lt;0.03). We also studied sFLT1 expression in a mouse model of myocardial infarction (MI). After 1 hour of left coronary ligation in 10-week old male wild-type mice (n=6/group), left ventricular sFLT1 mRNA levels were increased (p&lt;0.01 MI vs. sham), while aortic and lung mRNA expression were unchanged. Serum sFLT1 levels were also elevated in MI (170±71 vs 541±107pg/mL, sham vs. MI, p&lt;0.002). To explore the cellular origin of sFLT1, human coronary endothelial (HCE) and smooth muscle cells (HSMC) were rendered hypoxic. Within 1 hour, sFLT1 mRNA expression in HCE increased by 173±35% (p=0.03). By 12 hours, sFLT1 mRNA and protein expression in hypoxic HCE increased by 313±15% (p&lt;0.01) and 256±17% (p&lt;0.001) respectively. To simulate the effects of reperfusion on sFLT1 expression, HCE were exposed to 12 hours of hypoxia, then 6 hours of normoxia. After normoxic rescue, sFLT1 protein expression decreased by 36% (p&lt;0.01, vs hypoxic HCE). Hypoxia failed to induce sFLT1 mRNA or protein expression in HSMC. Conclusion: sFLT1 is a highly sensitive biomarker of vascular occlusion released by the endothelium during the acute phase of STEMI and may be an important new marker for acute ischemic syndromes. This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure

IntroductionInotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.MethodsTen patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25–0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand were performed at both time points.ResultsTroponin was elevated at baseline in all patients (mean 0.1259 ± 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 ± 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.ConclusionIn conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.