Peak Creatine kinase-MB Levels Research Articles

Circulating growth differentiation factor 11 exacerbates myocardial injury in mice and associates with increased infarct size in humans

Abstract Background The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a TGF-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing. Methods Young (3-4 months) and old (22-24 months) C57Bl/6 mice were subjected to either systemic recombinant GDF11 (rGDF11; 0.1 mg/kg BW daily) or control treatment over 30 days before myocardial ischaemia-reperfusion (I/R) injury was induced. Dissected hearts underwent in-depth profiling that ranged from histological workup and the assessment of inflammatory pathways to cardiomyocyte viability testing and IPA-guided -omics. Key regulatory mechanisms were studied in vitro using human adult stromal cardiac-specific mesenchymal cells (cMSCs) and HL-1 cardiomyocytes. By harnessing liquid chromatography–tandem mass spectrometry (LC-MS/MS), plasma levels of GDF11/MSTN were determined in prospectively recruited patients with MI and the independent association with myocardial infarct size was estimated using hierarchical regression models. Results In contrast to endogenous Mstn, myocardial Gdf11 mRNA expression levels declined upon ageing, and were further reduced following I/R injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by rGDF11 delivery prior to myocardial I/R augmented rather than reduced infarct size in mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. By applying a targeted transcriptomics approach on dissected hearts subjected to I/R, we identified the mesenchymal marker Nkx2-5 to be blunted upon rGDF11 supplementation, pointing toward a cMSC-mediated mechanism. Accordingly, human cMSCs exposed to high rGDF11 in vitro showed similar reductions in NKX2-5 expression levels, coinciding with diminished anti-apoptotic effects conferred by resident cMSCs on HL-1 cardiomyocytes. Finally, by harnessing a highly-specific LC–MS/MS based assay, we show that in patients with MI receiving contemporary management circulating GDF11 but not MSTN levels inclined with age. Moreover, circulating GDF11 emerged as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels. Notably, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event. Conclusions Our data challenge the initially reported rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice by impinging on the cardioprotective effects of resident cMSCs. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of endogenous cardioprotective mechanisms and thus poor outcomes post-MI.

Circulating GDF11 exacerbates myocardial injury in mice and associates with increased infarct size in humans.

The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing. In contrast to endogenous Mstn, myocardial Gdf11 declined during the course of ageing and was particularly reduced following ischaemia/reperfusion (I/R) injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by recombinant GDF11 delivery (0.1 mg/kg body weight over 30 days) prior to myocardial I/R augmented myocardial infarct size in C57BL/6 mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. While intrinsic cardioprotective signalling pathways remained unaffected by high circulating GDF11, targeted transcriptomics and immunomapping studies focusing on GDF11-associated downstream targets revealed attenuated Nkx2-5 expression confined to CD105-expressing cells, with pro-apoptotic activity, as assessed by caspase-3 levels, being particularly pronounced in adjacent cells, suggesting an indirect effect. By harnessing a highly specific and validated liquid chromatography-tandem mass spectrometry-based assay, we show that in prospectively recruited patients with MI circulating GDF11 but not MSTN levels incline with age. Moreover, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event, with circulating GDF11 emerging as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels. Our data challenge the initially reported heart rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice and humans alike. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of cardioprotective mechanisms and thus poor outcomes of elderly patients following acute MI.

Body fat percentage and infarct size in patients with non-ST segment elevation myocardial infarction.

Obesity is a global health problem that increases the risk of coronary artery disease (CAD). However in studies, it has been observed that when the disease develops, obese patients have a more favorable prognosis than leaner patients. This is called the "obesity paradox." This study aims to evaluate the effect of obesity assessed with body fat percentage (BFP) and relative fat mass (RFM) besides body mass index (BMI) on infarct size (IS) estimated from peak creatine kinase-MB (CK-MB) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Patients with a diagnosis of NSTEMI who underwent coronary angiography between January 2017 and January 2022 were retrospectively evaluated. Patients without available anthropometric data to calculate BMI, BFP, and RFM and serial CK-MB measurements were excluded from the study. BMI was calculated using weight(kg)/(height[m])2 formula. Patients were dichotomized as obese (BMI≥30 kg/m2) and non-obese (BMI<30 kg/m2) to compare baseline characteristics. BFP and RFM were calculated from anthropometric data. Linear regression analysis was performed to define predictors of IS. Final study population consisted of 748 NSTEMI patients (mean age was 59.3±11.2 years, 76.3% were men, 36.1% of the patients were obese). Obese patients were more likely to be female, hypertensive, and diabetic. Smoking was less frequently observed in obese patients. Peak CK-MB levels were similar among groups. Obese patients had higher in-hospital left ventricular ejection fraction, and less severe CAD was observed in coronary angiographies of these patients. Multivariable regression analysis identified diabetes mellitus, systolic blood pressure, white blood cell count, hemoglobin, and BFP (β=-4.8, 95% CI=-8.7; -0.3, p=0.03) as independent predictors of IS. Higher BFP is associated with smaller IS in NSTEMI patients. These findings support the obesity paradox in this patient group, but further, randomized controlled studies are required.

Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD).

BackgroundIntramyocardial edema and hemorrhage are key pathological mechanisms in the development of reperfusion‐related microvascular damage in ST‐segment–elevation myocardial infarction. These processes may be facilitated by abrupt restoration of intracoronary pressure and flow triggered by primary percutaneous coronary intervention. We investigated whether pressure‐controlled reperfusion via gradual reopening of the infarct‐related artery may limit microvascular injury in patients undergoing primary percutaneous coronary intervention.Methods and ResultsA total of 83 patients with ST‐segment–elevation myocardial infarction were assessed for eligibility and 53 who did not meet inclusion criteria were excluded. The remaining 30 patients with totally occluded infarct‐related artery were randomized to the pressure‐controlled reperfusion with delayed stenting (PCRDS) group (n=15) or standard primary percutaneous coronary intervention with immediate stenting (IS) group (n=15) (intention‐to‐treat population). Data from 5 patients in each arm were unsuitable to be included in the final analysis. Finally, 20 patients undergoing primary percutaneous coronary intervention who were randomly assigned to either IS (n=10) or PCRDS (n=10) were included. In the PCRDS arm, a 1.5‐mm balloon was used to achieve initial reperfusion with thrombolysis in myocardial infarction grade 3 flow and, subsequently, to control distal intracoronary pressure over a 30‐minute monitoring period (MP) until stenting was performed. In both study groups, continuous assessment of coronary hemodynamics with intracoronary pressure and Doppler flow velocity was performed, with a final measurement of zero flow pressure (primary end point of the study) at the end of a 60‐minute MP. There were no complications associated with IS or PCRDS. PCRDS effectively led to lower distal intracoronary pressures than IS over 30 minutes after reperfusion (71.2±9.37 mm Hg versus 90.13±12.09 mm Hg, P=0.001). Significant differences were noted between study arms in the microcirculatory response over MP. Microvascular perfusion progressively deteriorated in the IS group and at the end of MP, and hyperemic microvascular resistance was significantly higher in the IS arm as compared with the PCDRS arm (2.83±0.56 mm Hg.s.cm−1 versus 1.83±0.53 mm Hg.s.cm−1, P=0.001). The primary end point (zero flow pressure) was significantly lower in the PCRDS group than in the IS group (41.46±17.85 mm Hg versus 76.87±21.34 mm Hg, P=0.001). In the whole study group (n=20), reperfusion pressures measured at predefined stages in the early reperfusion period showed robust associations with zero flow pressure values measured at the end of the 1‐hour MP (immediately after reperfusion: r=0.782, P<0.001; at the 10th minute: r=0.796, P<0.001; and at the 20th minute: r=0.702, P=0.001) and peak creatine kinase MB level (immediately after reperfusion: r=0.653, P=0.002; at the 10th minute: r=0.597, P=0.007; and at the 20th minute: r=0.538, P=0.017). Enzymatic myocardial infarction size was lower in the PCRDS group than in the IS group with peak troponin T (5395±2991 ng/mL versus 8874±1927 ng/mL, P=0.006) and creatine kinase MB (163.6±93.4 IU/L versus 542.2±227.4 IU/L, P<0.001).ConclusionsIn patients with ST‐segment–elevation myocardial infarction, pressure‐controlled reperfusion of the culprit vessel by means of gradual reopening of the occluded infarct‐related artery (PCRDS) led to better‐preserved coronary microvascular integrity and smaller myocardial infarction size, without an increase in procedural complications, compared with IS.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02732080.

Effects of Intracoronary Pro-urokinase or Tirofiban on Coronary Flow During Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Multi-Center, Placebo-Controlled, Single-Blind, Randomized Clinical Trial.

Background: To determine whether intracoronary pro-urokinase or tirofiban improves myocardial reperfusion during primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI).Methods: The study included patients with acute STEMI presenting within 12 h of symptoms at 11 hospitals in China between November 2015 and July 2017. Patients were randomized to receive selective intracoronary infusion of recombinant pro-urokinase (20 mg), tirofiban (10 μg/kg), or saline (20 mL) proximal to the infarct-related lesion over a 3-min period before stent implantation during primary PCI. The primary outcome was final corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) after PCI.Results: This study included 345 patients. Initial angiography identified a high-grade thrombus (TIMI 4–5) in 80% of patients. Final CTFC after PCI was significantly lower in the pro-urokinase (P < 0.001) and tirofiban (P < 0.001) groups than in the saline group and similar between the pro-urokinase and tirofiban groups (P > 0.05). The pro-urokinase (P = 0.008) and tirofiban groups (P = 0.022) had more complete ST-segment resolution at 2 h and lower peak creatine kinase-MB levels after PCI than the saline group (P = 0.006 and P = 0.023). The 30-day incidence of major adverse cardiac events was 4.5% in the pro-urokinase group, 3.4% in the tirofiban group, and 2.6% in the saline group. The incidence of in-hospital TIMI major bleeding events was low and comparable between groups.Conclusions: Adjunctive intracoronary pro-urokinase or tirofiban given before stent implantation during primary PCI improves myocardial reperfusion without increasing the incidence of major bleeding events.

Efficacy of central extracorporeal life support for patients with fulminant myocarditis and cardiogenic shock.

OBJECTIVESFulminant myocarditis with cardiogenic shock requires extracorporeal life support (ECLS) and has poor outcomes. To improve outcomes, we have converted patients with severely impaired cardiac and multiorgan function from peripheral to central ECLS. In this study, we reviewed these patients’ clinical outcomes and investigated associated factors.METHODSWe retrospectively studied 70 consecutive patients with fulminant myocarditis under peripheral support from 2006 to 2020. Forty-eight patients underwent surgical conversion to central support, and the remaining patients continued peripheral support. The end point was survival and ventricular assist device-free survival.RESULTSMore severe pulmonary congestion and multiorgan failure were present in patients with central than peripheral support. Weaning from ECLS was achieved in 95% and 62% of patients with peripheral and central support, respectively. Five-year survival was not significantly different between patients with central and peripheral support (71.2% vs 87.5%, respectively; P = 0.15). However, the ventricular assist device-free survival rate was significantly higher in patients with central than peripheral support (82.2% vs 52.0%, respectively; P = 0.017). A peak creatine kinase-MB level of >180 IU/l, rhythm disturbance and aortic valve closure were detrimental to functional recovery in patients with central support.CONCLUSIONSConversion to central ECLS is feasible and safe in patients with fulminant myocarditis. Patients with severe myocardial injury as shown by a high creatine kinase-MB level, rhythm disturbance and aortic valve closure should be converted to a durable left ventricular assist device.

Early Differentiation of Stress Cardiomyopathy from Acute Anterior Wall Myocardial Using Changing Cardiac Enzyme Patterns.

BACKGROUNDMost patients with acute anterior wall ST elevation myocardial infarction (STEMI) or stress cardiomyopathy (SCMP) show elevations in cardiac enzymes that peak within 24 hours. The changing pattern of cardiac enzymes can be an early clue to the differentiation of anterior STEMI and SCMP.METHODSThis study was a retrospective analysis (matching cases and respective control subjects) performed at a single center. We compared 27 patients with SCMP and 30 patients with anterior STEMI. We used laboratory data included cardiac marker, such as the initial creatine kinase MB (CK-MB) fraction and troponin T (Tn-T), at admission and peak CK-MB and Tn-T at follow up.RESULTSThe mean age was 69.3 ± 14.1 years, and 38.6% of patients were female. The SCMP patients were older, more often female, and had lower left ventricular ejection fractions than the anterior STEMI patients. The initial CK-MB was higher in the anterior STEMI group than in the SCMP group. In contrast, the initial Tn-T level was not significantly different between the 2 groups. Peak CK-MB and Tn-T levels and change from initial levels were significantly greater in the anterior STEMI group than they were in the SCMP group. SCMP could be differentiated from anterior STEMI based on peak CK-MB > 46.65 ng/mL or Tn-T > 1.56 ng/mL.CONCLUSIONSFollow-up changes in cardiac enzymes can be an effective early tool for differentiating SCMP from anterior STEMI.

Daytime-Dependent Cardioprotection in Cardiac Surgery: A Large Propensity-matched Cohort Study

A recent article provided compelling evidence for a cardioprotective effect of afternoon compared with morning operation in patients undergoing aortic valve replacement. The present study sought to investigate any daytime-dependent effect on perioperative myocardial injury or clinical outcomes in a large cohort of patients undergoing elective cardiac surgery. The study identified all patients who underwent nonemergency aortic valve replacement and/or on-pump coronary artery bypass grafting at the Department of Cardiothoracic and Vascular Surgery of Aarhus University Hospital, Aarhus, Denmark between 1999 and 2018. Propensity-score matching was used to create adjusted cohorts for morning and afternoon operation. The primary end point was a composite of 30-day mortality and in-hospital acute myocardial infarction (major adverse cardiac events). Secondary end points were new-onset in-hospital atrial fibrillation, peak creatine kinase-MB levels, and up to 19 years of follow-up for all-cause mortality. The study identified 7148 patients who underwent either aortic valve replacement with or without coronary artery bypass grafting (n= 2806) or isolated coronary artery bypass grafting (n= 4342). Propensity-score matching resulted in comparable cohorts of morning and afternoon operation. The morning and afternoon operation cohorts had no differences in the rates of major adverse cardiac events after both procedures. Similarly, no daytime-dependent variation in the rate of new-onset in-hospital atrial fibrillation, long-term all-cause mortality, or peak creatine kinase-MB levels could be identified. In this large cohort study of Danish patients, who underwent either aortic valve replacement and/or coronary artery bypass grafting, the study identified no clinically relevant biorhythm for myocardial ischemia-reperfusion tolerance.

Meta-analysis of Nicorandil effectiveness on myocardial protection after percutaneous coronary intervention

BackgroundUsing the current meta-analysis as well as systematic review, to determine the curative effect of Nicorandil in comparison of no Nicorandil after elective percutaneous coronary intervention(PCI) on patients.MethodsPublished literatures were identified via a computerized literature search of CENTRAL, PubMed, Cochrane, Embase Databases of Systematic Reviews. A set of randomized trials evaluating Nicorandil in comparison of no Nicorandil administered following PCI in patients harboring coronary artery disease were included. Outcomes were revealed based on the following parameters: peak creatine kinase-MB (CK-MB) value, left ventricular ejection fraction (LVEF), peak troponin I (cTnI), and major adverse cardiovascular events (MACEs) per randomized patients.ResultsWe included a total of 14 RCTs involving 1864 subjects in the present review. According to this meta-analysis, LVEF was significantly improved in Nicorandil group; the peak CK-MB level and the incidence of adverse cardiovascular events were remarkably lower in Nicorandil group. Nicorandil and no Nicorandil administered group appeared to be equivalent with regards to cTnI.ConclusionsNicorandil is effective for patients undergoing elective PCI with coronary artery disease in terms of reducing the incidence of adverse cardiovascular events as well as improving heart function. Nicorandil may exert potential role as a valid and adjunctive therapy accompanied with PCI.

The Role of Bradykinin and Angiotensin Converting Enzyme Inhibitors in Myocardial Protection: A Review of Randomized Control Trials

Context: Bradykinin as a principal active agent of kallikrein-kinin can mediate the powerful cardioprotective mechanism. Both the bradykinin and angiotensin converting enzyme inhibitors (ACE-I) can stimulate this protective pathway through the B2 kinin receptors. We performed a systematic review to determine the effects of bradykinin on cardiac biomarkers and outcomes after surgery or coronary intervention. Evidence Acquisition: We searched the PubMed, Cochrane CENTRAL, and Scopus databases up to the end of August 2017. Only randomized controlled trials were included. Results: From a total of 1081 citations, 8 RCTs totaling 268 patients were included for review. Bradykinin could reduce the blood pressure and cause a slight increase in heart rate. But these changes were not significant in comparison to control groups. The major effect of bradykinin or ACE-I on cardiac biomarkers were related to creatine kinase-MB (CKMB). The ST-segment shift was much lower in patients treated with ACE-I as well as the ST-segment peak elevation. Conclusions: The remote ischemic preconditioning (RIPC) stimulus decreased expression of B1 and B2 kinin receptors and this suggested the role of kinins in cardioprotection. ST-segment shift could be reduced by administration of ACE-I before coronary interventions. In patients who were unresponsive to initial preconditioning ischemia, the infusion of intracoronary enalaprilat during the angioplasty could elicit adequate myocardial protection. The effect of bradykinin is dose dependent. Low doses of bradykinin prevent the increased leukocyte adhesion induced by ischemia reperfusion. High doses activate the bradykinin B2 receptors and lead to increase in leukocyte adhesion. The stimulation of kinin receptor pathway causes a reduction in infarct size, troponin T, peak CKMB levels, and edema of the myocardium. Considering the importance of bradykinin and ACE-I in cardiovascular interventions, further RCTs are required to determine the dosage and precise details of functional pathways of these agents.

Relation of coronary culprit lesion morphology determined by optical coherence tomography and cardiac outcomes to preinfarction angina in patients with acute myocardial infarction

BackgroundWhile preinfarction angina pectoris (pre-IA) is recognized as favorable effects on acute myocardial infarction (AMI), the detail has not been fully investigated. The aims of the current study were to clarify patient characteristics, lesion morphologies determined by optical coherence tomography (OCT), and cardiac outcomes related to pre-IA in patients with AMI. MethodsClinical data and outcomes were compared between AMI patients with pre-IA (pre-IA group, n = 507) and without pre-IA (non-pre-IA group, n = 653). Angiography and OCT findings were analyzed in patients with pre-intervention OCT and compared between groups of pre-IA (n = 219) and non-pre-IA (n = 269). ResultsST-segment elevation myocardial infarction (61% vs. 75%, p < 0.001) and cardiogenic shock (8% vs. 14%, p = 0.001) were less prevalent in pre-IA group. Peak creatine kinase-MB levels were lower in pre-IA group (median 83 IU/mL vs. 126 IU/mL, p < 0.001). In pre-intervention coronary angiography findings, initial TIMI flow grade 0/1 (43% vs. 56%, p = 0.019) and Rentrop collateral circulation 0/1 (69% vs. 79%, p = 0.018) were less frequently observed in pre-IA than in non-pre-IA patients. In post-thrombectomy OCT images, plaque rupture (39% vs. 56%, p = 0.003) and red thrombi (42% vs. 54%, p = 0.027) were also less frequently observed in pre-IA group. Kaplan–Meier estimate survival curves showed that cardiac death at 12-months was lower in pre-IA group than in non-pre-IA group (6.9% vs. 10.1%, p = 0.036). ConclusionsPatients with pre-IA had less severe AMI on admission, smaller infarction size, and more favorable long-term survival, which may be caused by difference of lesion morphology between patients with and without pre-IA.

Clinical impact of undersized- versus oversized-stenting approaches in ST-elevation myocardial infarction.

Primary percutaneous coronary intervention (PCI) is the standard treatment in patients with ST-elevation myocardial infarction (STEMI). However, some patients still develop ST re-elevation during PCI, resulting in further myocardial damage and a poor outcome. An undersized-stenting approach may prevent ST re-elevation. We aimed to determine the association between final stent area and ST re-elevation during primary PCI for STEMI. Overall, 102 consecutive STEMI patients who underwent primary PCI under integrated backscatter intravascular ultrasound guidance were enrolled. The stent-reference (SR) ratio was defined as the stent cross-sectional area (CSA) divided by the average CSA of the 5-mm proximal and distal reference lumens. The patients were divided into two groups according to the SR ratio: undersize group (SR<1.0, n=62) and oversize group (SR≥1.0, n=40). The incidences of ST re-elevation and total ST resolution (STR) were compared. The oversize group showed a higher incidence of ST re-elevation (32.5 vs. 9.7%, p=0.004) and a lower total STR (22.4±62.7 vs. 43.4±38.6%, p=0.04). After adjustment, the oversized-stenting approach was independently associated with ST re-elevation [odds ratio: 3.74, 95% confidence interval (CI) 1.27-12.1, p=0.02]. The peak creatine kinase-MB level was higher in the oversize group (341±259 vs. 242±208IU/l, p=0.04). The incidences of stent thrombosis and restenosis were similar between the two groups. An oversized-stenting approach in patients with STEMI was associated with a higher incidence of ST re-elevation and a lower total STR, resulting in increased myocardial damage.

Prediction of Infarct Transmurality From C-Reactive Protein Level and Mean Platelet Volume in Patients With ST-Elevation Myocardial Infarction: Comparison of the Predictive Values of Cardiac Enzymes.

High C-reactive protein (CRP) and mean platelet volume (MPV) levels are associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to evaluate the relationship between CRP level or MPV and infarct transmurality in patients with STEMI. We retrospectively reviewed CRP level, MPV, and infarct transmurality in 112 STEMI patients who were assessed with contrast-enhanced cardiac magnetic resonance imaging. When the cut-off peak CRP level and MPV were set at 2.35 mg/dl and 7.3 fl using receiver operating characteristic curves analysis, the sensitivity was 67.3/69.2% and specificity was 76.7/76.7% for differentiating between the groups with and those without transmural involvement. Peak CRP level, MPV, peak creatine kinase-MB (CK-MB) level, and peak high-sensitivity cardiac troponin T (hs-cTnT) level had comparable predictive values for transmural involvement (area under the curve, 0.749, 0.761, 0.680, and 0.696, respectively). High peak CRP level and MPV were independent predictors of transmural involvement after adjusting for the peak CK-MB level, peak hs-cTnT level, baseline thrombolysis in myocardial infarction flow grade, and left ventricular ejection fraction (odds ratio: 5.16/5.42, 95% confidence interval: 1.84-14.50/2.03-14.47, P = 0.002/0.001, respectively) in the logistic regression analysis. The results of this study show that peak CRP level and MPV are predictive markers for transmural involvement. Their predictive power for transmural involvement is independent of and comparable to that of peak CK-MB and hs-cTnT levels.

Level and value of interleukin-18 in patients with acute myocardial infarction undergoing primary coronary angioplasty

The prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) is currently unclear. Thus, the purpose of this study was to test whether the circulating IL-18 level can predict prognosis in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). A prospective cohort study was conducted with 267 consecutive patients with STEMI of onset <12 h who were undergoing primary PCI. Blood samples for plasma IL-18 level were collected in the catheterization laboratory following vascular puncture. The plasma IL-18 level was also evaluated in 25 healthy and 30 at-risk control subjects. The plasma level of IL-18 was significantly higher in acute myocardial infarction (AMI) patients than in both groups of control subjects (all P < 0.0001). Patients with high plasma IL-18 level (⩾560 pg/ml) had significantly higher peak creatine kinase-MB levels, higher incidence of cardiogenic shock upon presentation, significantly lower left ventricular ejection fraction (LVEF), lower successful reperfusion and significantly higher incidence of 30-day composite major adverse clinical events (MACE) (advanced congestive heart failure ⩾class 3 or 30-day mortality) than those patients with low plasma IL-18 level (<560 pg/ml) (all P < 0.0001). Multiple stepwise logistic regression analysis demonstrated that high plasma IL-18 level (⩾560 pg/ml) along with low LVEF (<50%) and cardiogenic shock were the most independent predictors of 30- day MACE ( P < 0.0001). In patients with STEMI, plasma IL-18 level is a major independent inflammatory predictor of 30-day MACE. Evaluation of circulating IL-18 might improve the prediction of unfavorable clinical outcomes following AMI.

Systemic hyperkalemia and mild hypothermia for valve surgery in patients with patent internal mammary artery graft

Myocardial protection is compromised in patients with a patent internal mammary artery (IMA) graft. We assessed the advantages of systemic hyperkalemia with mild hypothermia for valve surgery in patients with a patent IMA graft. Nine patients (mean age 71.5+/-7.0 years) with a patent IMA graft underwent valve surgery from May 2004 to July 2009. Of those, eight underwent aortic valve replacement and one mitral repair, with two double-valve surgery. Antegrade and retrograde blood cardioplegia were performed intermittently, and systemic potassium was given to all. The lowest bladder temperature was 27.2+/-2.4 degrees C, and the initial and peak systemic potassium levels were 6.8+/-1.4 and 8.0+/-1.6 mEq/l, respectively, while potassium at the end of the cardiopulmonary bypass procedure after sufficient modified ultrafiltration was reduced to 5.5+/-0.6 mEq/l. There was one hospital death due to ischemic colitis. Cardiac arrest was easily achieved in each patient without IMA or aortocoronary graft injury. The postoperative peak creatine kinase-MB level was 33+/-17 IU/l, with no ST changes seen in electrocardiogram findings or new asynergy seen in echocardiogram findings. Systemic hyperkalemia and mild hypothermia for valve surgery in patients with a patent IMA graft is a good option to reduce graft and myocardial injuries.

Prognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction

Although the prognostic significance of creatine kinase (CK) and creatine kinase-MB (CK-MB) after myocardial infarction has been established after thrombolysis or no reperfusion therapy, there is limited evidence of the prognostic importance after primary percutaneous coronary intervention (PCI). In this prospective, observational study, individual data from all patients who survived at least 2 days after primary PCI between 1991 and 2004 in our hospital were recorded. The association between enzymatic infarct size (examined by peak CK and peak CK-MB levels, each divided into tertiles) and both left ventricular ejection fraction (LVEF) and 1-year mortality was evaluated. In the study group of 4670 patients, mean peak CK was 2327 U/L (SD 2008) and mean peak CK-MB was 244 U/L (SD 208). Both increased CK and CK-MB were associated with a lower LVEF. A total of 252 patients (5.4%) died between 2 days and 1 year after admission. Both peak CK and peak CK-MB were higher in those who died. Particularly, patients in the highest tertile of either peak CK or peak CK-MB had increased mortality, whereas the differences between the lower tertiles were not significant. In 2738 patients, after multivariable analysis including LVEF, the hazard ratio for 1-year mortality in patients in the highest CK tertile was 2.28 (95% CI 1.32-3.91) and for CK-MB, 1.91 (95% CI 1.11-3.26), compared to those in the other tertiles. According to this large-scale study, peak CK and peak CK-MB are comparable independent predictors of LV function and 1-year mortality in patients after primary PCI.

Performance of Delayed-Enhancement Magnetic Resonance Imaging With Gadoversetamide Contrast for the Detection and Assessment of Myocardial Infarction

The identification and assessment of myocardial infarction (MI) are important for therapeutic and prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance of delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast for the detection of MI in an international, multicenter trial. Patients with their first MI were enrolled in an acute (< or = 16 days after MI; n=282) or chronic (17 days to 6 months; n=284) arm and then randomized to 1 of 4 doses of gadoversetamide: 0.05, 0.1, 0.2, or 0.3 mmol/kg. Standard delayed-enhancement MRI was performed before contrast (control) and 10 and 30 minutes after gadoversetamide. For blinded analysis, precontrast and postcontrast MRIs were randomized and then scored for enhanced regions by 3 independent readers not associated with the study. The infarct-related artery perfusion territory was scored from x-ray angiograms separately. In total, 566 scans were performed in 26 centers using commercially available scanners from all major US/European vendors. All scans were included in the analysis. The sensitivity of MRI for detecting MI increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 94% (chronic) after contrast compared with 11% before contrast. Likewise, the accuracy of MRI for identifying MI location (compared with infarct-related artery perfusion territory) increased with rising dose of gadoversetamide (P<0.0001), reaching 99% (acute) and 91% (chronic) after contrast compared with 9% before contrast. For gadoversetamide doses > or = 0.2 mmol/kg, 10- and 30-minute images provided equal performance, and peak creatine kinase-MB levels correlated with MRI infarct size (P<0.0001). Gadoversetamide-enhanced MRI using doses of > or = 0.2 mmol/kg is effective in the detection and assessment of both acute and chronic MI. This study represents the first multicenter trial designed to evaluate an imaging approach for detecting MI.

Myocardial enzyme release in totally endoscopic coronary artery bypass grafting on the arrested heart

Robotic totally endoscopic coronary artery bypass grafting enables coronary artery bypass grafting without sternotomy or thoracotomy. However, longer cardiopulmonary bypass and aortic endo-occlusion times are currently required compared with those of standard coronary artery bypass grafting operations. We investigated whether longer operation times affect the myocardial enzyme release and the postoperative course. From 2001 through 2006, 85 patients with a median age of 58 years (range, 31-76 years) underwent totally endoscopic coronary artery bypass grafting on the arrested heart by using the da Vinci telemanipulator and remote access perfusion through the femoral vessels (Estech or Heartport). The operations involved the left internal thoracic artery-left anterior descending coronary artery or diagonal branch (n = 74); right internal thoracic artery-right coronary artery (n = 2); double-vessel left internal thoracic artery-obtuse marginal branch/circumflex artery and right internal thoracic artery-left anterior descending coronary artery (n = 8); and double-vessel left internal thoracic artery-left anterior descending coronary artery and saphenous vein graft-right coronary artery (n = 1). Totally endoscopic coronary artery bypass grafting duration was 254 minutes (range, 178-710 minutes), cardiopulmonary bypass time was 114 minutes (range, 57-428 minutes), and aortic endo-occlusion time was 65 minutes (range, 28-230 minutes). The postoperative ventilation time was 8 hours (range, 0-278 hours), and the intensive care unit stay was 20 hours (range, 11-389 hours). The postoperative stay at our department was 6 days (range, 4-22 days), and we observed no hospital deaths in this series. Forty-five percent of the patients had an increased postoperative peak creatine kinase MB level, and 75% had an increased troponin T level. Postoperative peak creatine kinase MB levels significantly increased with totally endoscopic coronary artery bypass grafting duration (r = 0.588, P < .001), cardiopulmonary bypass time (r = 0.521, P < .001), and aortic endo-occlusion time (r = 0.400, P < .001) and translated into moderately prolonged intensive care unit stay (r = 0.432, P < .001) and ventilation time (r = 0.517, P < .001). Creatine kinase MB levels were not associated with sex, age, or EuroSCORE. The postoperative left ventricular ejection fraction did not differ significantly from the preoperative left ventricular ejection fraction. Myocardial protection can be established in arrested heart totally endoscopic coronary artery bypass grafting operations. An influence of increased myocardial enzyme release on postoperative ventilation time and intensive care unit stay is detectable but does not translate into an early mortality or a decrease in left ventricular ejection fraction.

Predictors of Periprocedural Creatine Kinase-Myocardial Band Elevation Complicating Elective Percutaneous Coronary Intervention

Limited data are available regarding the predictors of periprocedural creatine kinase-MB (CK-MB) isoenzyme increase after elective percutaneous coronary intervention (PCI) in the stenting era. We explored the predictors of periprocedural CK-MB increase in 882 consecutive patients with normal preprocedural CK-MB who underwent 919 angiographically successful elective PCIs with (n = 814) or without (n = 105) stenting. Patients were categorized into 3 groups based on their peak CK-MB levels after PCI: (1) normal CK-MB (n = 761), (2) minor CK-MB increase (CK-MB 1 to 3 times normal, n = 112), and (3) major CK-MB increase (CK-MB >3 times normal, n = 46). By logistic regression analysis, independent predictors for minor CK-MB increase included thrombus (odds ratio [OR] 5.09, p = 0.001), platelet IIb/IIIa antagonist use (OR 0.53, p <0.01), number of lesions treated (per additional lesion, OR 1.54, p <0.01), maximum balloon size (per millimeter increase, OR 1.57, p <0.05), American College of Cardiology/American Heart Association type C lesion (OR 1.68, p <0.05), sustained chest pain during procedure (OR 1.94, p <0.05), dissection (OR 2.05, p <0.05), and transient side branch occlusion (OR 4.54, p <0.05). Independent predictors for major CK-MB increase were chest pain at end of procedure (OR 9.66, p <0.001), type C lesion (OR 2.42, p <0.05), Canadian Cardiovascular Society angina class III to IV (OR 3.32, p <0.05), thrombus (OR 5.09, p = 0.001), and abrupt closure (OR 5.30, p <0.05). In conclusion, baseline clinical and angiographic characteristics and procedural complications were associated with minor and major CK-MB increases. Patients with chest pain at the end of the procedure were at the highest risk for major CK-MB increase.

Level and Value of Interleukin-18 in Patients With Acute Myocardial Infarction Undergoing Primary Coronary Angioplasty

The prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) is currently unclear. Thus, the purpose of this study was to test whether the circulating IL-18 level can predict prognosis in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). A prospective cohort study was conducted with 267 consecutive patients with STEMI of onset <12 h who were undergoing primary PCI. Blood samples for plasma IL-18 level were collected in the catheterization laboratory following vascular puncture. The plasma IL-18 level was also evaluated in 25 healthy and 30 at-risk control subjects. The plasma level of IL-18 was significantly higher in acute myocardial infarction (AMI) patients than in both groups of control subjects (all p<0.0001). Patients with high plasma IL-18 level (> or =560 pg/ml) had significantly higher peak creatine kinase-MB levels, higher incidence of cardiogenic shock upon presentation, significantly lower left ventricular ejection fraction (LVEF), lower successful reperfusion and significantly higher incidence of 30-day composite major adverse clinical events (MACE) (advanced congestive heart failure > or = class 3 or 30-day mortality) than those patients with low plasma IL-18 level (<560 pg/ml) (all p<0.0001). Multiple stepwise logistic regression analysis demonstrated that high plasma IL-18 level (> or =560 pg/ml) along with low LVEF (<50%) and cardiogenic shock were the most independent predictors of 30-day MACE (p<0.0001). In patients with STEMI, plasma IL-18 level is a major independent inflammatory predictor of 30-day MACE. Evaluation of circulating IL-18 might improve the prediction of unfavorable clinical outcomes following AMI.