Peak Creatine Kinase Values Research Articles

Immune Checkpoint Inhibitor-Related Myositis Overlapping With Myocarditis: An Institutional Case Series and a Systematic Review of Literature.

Background: Immune checkpoint inhibitor (ICI)-related myositis with myocarditis is a rare but potentially fatal immune-related adverse event. However, its clinical features, response to immunosuppressive treatment, and prognosis remain poorly understood. Here, we describe the clinical course of patients with ICI-related myositis overlapping with myocarditis treated at our institution and a systematic review focusing on the response to immunosuppressive therapy. Methods: We identified patients who developed ICI-induced myositis with myocarditis and were treated at our hospital using a retrospective chart review of electronic medical records. For the systematic review, studies reporting ICI-induced myositis with myocarditis were identified using the Cochrane Library and PubMed databases. Results: Of the 625 patients treated with ICIs, four developed myositis with concurrent myocarditis. All the patients received immunosuppressive therapy. We assessed the activity of myocarditis and myositis based on temporal changes in troponin and creatine kinase (CK) levels. In all patients, peak troponin values appeared later than the peak CK values (median, 17 days). The median time from the start of ICI therapy to the peak of troponin and CK levels was 42.5 and 28 days, respectively. In all patients, CK levels decreased rapidly and steadily after the initiation of immunosuppressants. However, troponin levels were unstable and increased. In all patients, CK levels normalized within one month (range, 12–27 days), but troponin levels took several months to normalize (range, 84–161 days). Fourteen cases of ICI-related myositis with myocarditis were included in the systematic review. Of the 14 cases, 12 (86%) had their CK level decreased after the initial steroid treatment, but the troponin level increased and was higher than that before the start of treatment. In addition, the peak troponin values appeared later than the peak CK values (a median of 6.5 days). Eight (89%) of 9 long-term follow-up patients had troponin levels above the normal range even after CK normalization. Conclusion: In most cases of ICI-related myositis with myocarditis, troponin levels increased after the initial steroid treatment despite decreased CK levels, and exceeded pre-steroid levels. In addition, troponin remained elevated for several months after CK normalized.

Incidence and influence of hyperCKemia in Legionella infection

IntroductionA number of case and case series descriptions established an association between Legionella infection and hyperCKemia, but the frequency and severity of hyperCKemia in Legionella infection remain unknown. This study aims to investigate the incidence, extent, and consequences of hyperCKemia in a large group of patients with Legionella infection. MethodsThis retrospective study included patients with confirmed Legionella infection during a ten-year period who received creatine kinase (CK) testing. Comparisons were performed between groups of Legionella patients with and without hyperCKemia. ResultsA total of 267 patients were included. HyperCKemia was present in 144 (53.9%) patients. The mean peak CK value was 9598 IU/L (range: 226 to 462,000 IU/L) while peak CK exceeded 1000 IU/L in 82 (56.9%) patients and 5000 IU/L in 33 (22.9%). When compared to patients without hyperCKemia, patients with hyperCKemia had higher incidences of neurologic symptoms (p = 0.036), acute renal failure (p = 0.028), dialysis requirement (p = 0.009), and need for ICU care (p = 0.016). HyperCKemia resolved in most Legionella patients by 7 days from CK peaking. DiscussionLegionella infection requiring hospitalization appears to be associated with increased incidence of hyperCKemia and rhabdomyolysis. Greater awareness of the high incidence and the possible severity of hyperCKemia is needed when treating patients with Legionella infection.

Anti-Cortactin Autoantibodies Are Associated With Key Clinical Features in Adult Myositis But Are Rarely Present in Juvenile Myositis.

To define the prevalence and clinical phenotype of anti-cortactin autoantibodies in adult and juvenile myositis. In this longitudinal cohort study, anti-cortactin autoantibody titers were assessed by enzyme-linked immunosorbent assay in 670 adult myositis patients and 343 juvenile myositis patients as well as in 202 adult healthy controls and 90 juvenile healthy controls. The prevalence of anti-cortactin autoantibodies was compared among groups. Clinical features of patients with and those without anti-cortactin autoantibodies were also compared. Anti-cortactin autoantibodies were more common in adult dermatomyositis (DM) patients (15%; P=0.005), particularly those with coexisting anti-Mi-2 autoantibodies (24%; P=0.03) or anti-NXP-2 autoantibodies (23%; P=0.04). In adult myositis, anti-cortactin was associated with DM skin involvement (62% of patients with anti-cortactin versus 38% of patients without anti-cortactin; P=0.03), dysphagia (36% versus 17%; P=0.02) and coexisting anti-Ro 52 autoantibodies (47% versus 26%; P=0.001) or anti-NT5c1a autoantibodies (59% versus 33%; P=0.001). Moreover, the titers of anti-cortactin antibodies were higher in patients with interstitial lung disease (0.15 versus 0.12 arbitrary units; P=0.03). The prevalence of anti-cortactin autoantibodies was not different in juvenile myositis patients (2%) or in any juvenile myositis subgroup compared to juvenile healthy controls (4%). Nonetheless, juvenile myositis patients with these autoantibodies had a higher prevalence of "mechanic's hands" (25% versus 7%; P=0.03), a higher number of hospitalizations (2.9 versus 1.3; P=0.04), and lower peak creatine kinase values (368 versus 818 IU/liter; P=0.02) than those without anti-cortactin. The prevalence of anti-cortactin autoantibodies is increased in adult DM patients with coexisting anti-Mi-2 or anti-NXP-2 autoantibodies. In adults, anti-cortactin autoantibodies are associated with dysphagia and interstitial lung disease.

Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study

BackgroundProurokinase is a single-chain plasminogen activator presenting with fewer hemorrhagic complications and reduced reocclusion rate compared with the conventional fibrinolytic agents in patients with coronary artery disease. However, prourokinase intracoronary injection during PCI for treating patients with ST-segment elevation myocardial infarction (STEMI) is rarely investigated. Therefore, this study aimed to evaluate the efficacy and safety of intracoronary prourokinase during the percutaneous coronary intervention (PCI) in treating STEMI patients.MethodsFifty STEMI patients who underwent primary PCI were consecutively enrolled and randomly assigned to intracoronary prourokinase group (N = 25) or control group (N = 25). During the primary PCI procedure, patients in the intracoronary prourokinase group received 10 ml prourokinase injection, while patients in control group received 10 ml saline injection as control. The primary endpoints were coronary physiological indexes, the secondary endpoints were angiographic assessments, myocardial infarct size/reperfusion assessment, cardiac function evaluations, major adverse coronary events (MACEs) and hemorrhagic complications. All patients were followed up for 3 months.ResultsPost PCI, the index of microcirculatory resistance (IMR) was decreased in intracoronary prourokinase group than that in control group (34.56 ± 7.48 vs. 49.00 ± 8.98, P < 0.001), while no difference of coronary flow reserve (CFR) (2.01 ± 0.32 vs. 1.88 ± 0.23, P = 0.267) or fractional flow reserve (FFR) (0.89 ± 0.05 vs. 0.87 ± 0.04, P = 0.121) was found between the two groups. The thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) (P = 0.024), peak values of creatine kinase (CK) (P = 0.028), CK isoenzyme-MB (CK-MB) (P = 0.016), cardiac troponin I (cTnI) (P = 0.032) and complete ST-segment resolution (STR) (P = 0.005) were better in intracoronary prourokinase group compared with control group. At 3-months post PCI, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were higher, while left ventricular end-diastolic diameter (LVEDd) was lower in intracoronary prourokinase group compared with control group (all P < 0.05). There was no difference in hemorrhagic complication or total MACE between the two groups.ConclusionIntracoronary prourokinase during PCI is more efficient and equally tolerant compared with PCI alone in treating STEMI patients.Trial registrationChinese Clinical Trial Registry ChiCTR1800016207. Prospectively registered.

Routinely Available Biomarkers as Long-Term Predictors of Developing Systolic Dysfunction in Completely Revascularized Patients with Acute ST Elevation Myocardial Infarction

SUMMARYThe aim of this study was to assess the efficacy of high-sensitivity C-reactive protein (hsCRP), cardiac troponin T (cTnT) and creatine kinase (CK) as long-term predictors of reduced systolic function in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with complete revascularization. This prospective study evaluated consecutive patients with acute STEMI who had normal left ventricular ejection fraction (LVEF ≥50%) at admission with single-vessel disease and underwent complete revascularization. Blood samples were collected from admission to day 7. The primary endpoint was reduction of LVEF <50% after 12 months. The study included 47 patients, median age 59±10 years, 74.5% of them men. Patients who developed systolic dysfunction (LVEF <50%) had significantly higher mean values of cTnT after 24 hours (5.11 vs. 2.82 µg/L, p=0.010) and peak values of CK (3375.5 vs. 1865 U/L, p=0.008). There was no significant relation between hsCRP and development of reduced LVEF (p=0.541). In conclusion, cTnT and CK could serve as long-term predictors of reduced left ventricular systolic function (<50%) in acute STEMI patients with normal systolic function at admission, single-vessel coronary disease and complete revascularization during primary PCI.

Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction.

Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).Methods and Results:A total of 44 patients diagnosed with AMI were included in the current study. All patients underwent emergency percutaneous coronary intervention (PCI). The median of peak creatine kinase (CK) and CKMB values was 1,816 U/L and 159 U/L, respectively. Serum levels of FGF23, calcium, and inorganic phosphate (iP) were measured before PCI, and on days 1, 3, 5, 7 after PCI. Serum FGF23 levels showed a slight, but significant decrease on days 1 and 3 after PCI, and a 1.5- and 2.0-fold increase on days 5 and 7, respectively, after PCI. As compared with propensity score-matched patients without AMI, serum FGF23 was significantly lower among the current cohort of AMI patients. In 22 subjects who underwent a follow-up echocardiographic examination at 6 months after the onset of AMI, the log-transformed relative increase in FGF23 on day 7 significantly and negatively correlated with changes between LVEF on admission and that at 6 months afterward. After a slight decrease on days 1 and 3 after admission, serum FGF23 increased significantly on days 5 and 7. The underlying mechanism and potential clinical importance of these observations require further investigation.

Influence of Protein Supplement on the Process of Rehabilitation in Damage of Muscles Caused by Physical Loads

Resistance exercise is a common mode of training may precipitate temporary exercise-induced muscle damage that manifests as a reduction in neuromuscular function, reduced range of motion, increased muscle soreness, limb swelling and the elevation of intramuscular proteins in blood. The purpose of this study was to study the effect of protein supplements on the process of rehabilitation for muscle injuries caused by physical stress. The study involved 21 clinically healthy men. Participants perform eccentric contractions of the quadriceps femoris muscle. All participants in the studies were randomly assigned to three groups. The first group received the protein supplement before exercise and placebo after the load. The second group received a placebo before the load and a protein drink after. The third group received a placebo both before and after the load. Before the load and 24, 48, 72 hours after the load, the maximum possible reduction (MPR) of the quadriceps muscle was studied, the severity of muscle soreness (MS), the content of creatine kinase (CK) in the serum. The dynamics of changes in the studied indicators was unidirectional in all groups. The index of the maximum possible reduction reached a minimum value 24 hours after exercise and gradually returned to the initial values in 72 hours. Between the first group and the control group no significant differences were found in any of the stages of restitution. At the same time, there was a significant difference in recovery in the participants of the second group and the control group at 48 hours after the load (94 ± 3.81 and 84 ± 3.12, P <0.05), which indicates a faster recovery of contractile ability of the muscles in the studied persons of second group. Just as in the study of MPR dynamics, there were no significant differences between the indices of participants in the first and control groups. In the case of participants in the third group, significant differences in indices are determined in the intervals 48 and 72 hours after the load. The peak values of CK recorded 48 hours after the load. Significant differences were found between second group and control (1448 ± 208 and 864 ± 113, P <0.05). Consequently the intake of protein supplements immediately after physical exertion reduces the duration of the subjective sensation of muscle soreness and promotes the fastest regeneration of damaged muscle fibers.

The contemporary value of peak creatine kinase-MB after ST-segment elevation myocardial infarction above other clinical and angiographic characteristics in predicting infarct size, left ventricular ejection fraction, and mortality.

Complex multimarker approaches to predict outcome after ST-elevation myocardial infarction (STEMI) have only considered a single baseline sample, while neglecting easily obtainable peak creatine kinase and creatine kinase-MB (CK-MB) values during hospitalization. We studied 476 patients undergoing primary percutaneous coronary intervention for STEMI and cardiac magnetic resonance imaging (CMRI) at 4-6 months after STEMI. We determined the association with cardiac biomarkers (peak CK-MB, peak troponin T, N-terminal pro-brain natriuretic peptide), clinical and angiographic characteristics with infarct size, and LVEF, followed by association with mortality in 1120 STEMI patients. Peak CK-MB was the strongest predictor for infarct size (P<0.001, R 2 =0.60) and LVEF (P<0.001, R 2 =0.40). The additional value of clinical and angiographic characteristics was limited. The optimal peak CK-MB cutpoints, for differentiation among small (<10% of the left ventricle), moderate (≥10%-<30%), and large infarct size (≥30%), were 210 U/L and 380 U/L, respectively. These cutpoints were associated with 90-day mortality; the hazard ratio for moderate infarct was 2.99 (95% confidence interval [CI]: 1.51-5.93, P=0.002) and for large infarct 6.53 (95% CI: 3.63-11.76, P<0.001). Classical peak CK-MB measured during hospitalization for STEMI was superior to other clinical and angiographic characteristics in predicting CMRI-defined infarct size and LVEF, and should be included and validated in future multimarker studies. Peak CK-MB cutpoints differentiated among infarct size categories and were associated with increased 90-day mortality risk.

MPS 04-07 SHORT AND MID-TERM OUTCOMES OF ACUTE MYOCARDIAL INFARCTION WITH ELEVATED SYSTOLIC BLOOD PRESSURE ON ADMISSION

Objective: Although lower admission systolic blood pressure (SBP) has been established as a poor prognostic factor in patients with acute myocardial infarction (AMI), the impact of preserved admission SBP on short and mid-term outcomes has not been fully evaluated. Design and Method: From January 2013 to March 2015, 1281 consecutive patients with AMI were registered in Mie ACS Registry, a prospective, multicenter registry in Japan. We evaluated 1122 patients (mean age 68 ± 13 years, male 78%) except for 159 patients with admission SBP < 100 mmHg. Patients were divided into three groups according to admission SBP: 100–139 mmHg (normal admission SBP; NBP group, n = 612), 140–179 mmHg (moderately elevated admission SBP; MBP group, n = 419) and ≥180 mmHg (excessively elevated admission SBP; EBP group, n = 91). The clinical characteristics, 30-day and 1-yaer outcomes (follow-up rate 94.7%) were compared among the three groups. Results: The rate of primary percutaneous coronary intervention and the number of diseased coronary vessels were not significantly different among the three groups. The Killip classification and the peak creatine kinase values were lowest in the MBP group. Heart failure, arrhythmia, shock and multi-organ failure during hospitalization were most often in the NBP group, but myocardial rupture was no significant difference in the three groups. The 30-day cumulative mortality was trend to be high in the NBP group (6.5%, 3.3% and 4.4% for NBP, MBP and EBP group, respectively, Log-Rank P = 0.069), and 1-year cumulative mortality after hospital discharge was significantly high in NBP group (5.5%, 1.6% and 2.4% for NBP, MBP and EBP group, respectively, Log-Rank P = 0.007) than other two groups (Figure). Conclusions: Admission SBP of less than 140 mmHg can be a risk of hemodynamic instability during hospitalization and an indicator of poor outcomes after hospital discharge in patients with AMI and preserved admission SBP.

STEMI notification by EMS predicts shorter door-to-balloon time and smaller infarct size

BackgroundEmergency medical services (EMS) transportation is associated with shorter door-to-balloon (DTB) time in patients with ST-segment elevation myocardial infarction (STEMI). In addition to EMS transportation, prehospital notification of STEMI by EMS to receiving hospital might be able to further shorten DTB time. We evaluated the impact of STEMI notification on DTB time as well as infarct size. MethodsWe performed a retrospective analysis of consecutive patients with anterior wall STEMI who underwent emergent coronary angiography. We excluded patients who presented with cardiac arrest and those who were transferred from non–percutaneous coronary intervention–capable hospitals. Mode of transportation were categorized into the 3 groups: (1) EMS transport with STEMI notification, (2) EMS transport without STEMI notification, and (3) self-transport. Baseline characteristics, laboratory data, left ventricular ejection fraction (LVEF), and DTB time were compared among the 3 groups. ResultsA total of 148 patients were included in the final analysis. Of the 148 patients, 56 patients arrived by EMS transport with STEMI notification, 56 patients arrived by EMS transport without STEMI notification, and 36 patients arrived by self-transport. Patients who arrived by EMS transport with STEMI notification had the shortest DTB time among the 3 groups. Patients who arrived by EMS transport with STEMI notification had smaller infarct size, as indicated by lower peak creatine kinase value and higher LVEF, compared with those who arrived by EMS transport without STEMI notification. ConclusionEmergency medical services transport with STEMI notification was associated with shorter DTB time and smaller infarct size in patients with anterior wall STEMI.

Absence of ST-segment elevation in lead V1 predicts worse long-term outcomes in patients with first anterior ST-segment elevation myocardial infarction

BackgroundThe prognostic value of ST-segment elevation in lead V1 (STE in V1) in anterior ST-segment elevation myocardial infarction (STEMI) has not been elucidated. MethodsWe performed a retrospective analysis of 190 consecutive first anterior STEMI patients. STE in V1 ≥0.1mV was recorded. Major adverse cardiac events (MACE) were defined as a composite of all-cause death, recurrent myocardial infarction, or target vessel revascularization. ResultsAmong 190 patients, 42 patients did not have STE in V1. The patient without STE in V1 had a higher peak creatine kinase value and a higher incidence of 1-year MACE (36% vs. 13%, p<0.001), driven by a higher mortality (24% vs. 5%, p<0.001). The absence of STE in V1 was an independent predictor for 1-year MACE (odds ratio 3.16; 95% confidence interval 1.28–7.83; p=0.01). ConclusionThe absence of STE in V1 was an independent predictor for worse long-term outcomes in patients with first anterior STEMI.

Commentary "Recent advances in circadian rhythms in cardiovascular system".

We read the recent publication by Chen and Yang with interest (Chen and Yang, 2015). In this review of excellent quality, the authors detail our current understanding of the links between circadian rhythms and cardiovascular system. Nevertheless, several important aspects of many recent key-findings have been overlooked in the Section “Circadian Rhythms and Myocardial Infarction.” In fact, the authors focus on the well-documented higher rate of myocardial infarction occurring in the morning and on the circadian variation of cardiac functions related to the heart remodeling. From our point of view, they fail to discuss various recent important publications based on robust data supporting a link between circadian rhythms and myocardial infarction size and death from myocardial infarction. Indeed, different clinical studies recently reported circadian variations of ischemic burden in patients with acute ST-elevation myocardial infarction (STEMI). In Reiter et al. (2012) and our team (Fournier et al., 2012) observed higher peak creatine kinase (CK) activity (as a proxy for myocardial infarction size) in patients with symptoms onset occurring between 00:00 and 05:59. Accordingly, these data indicate a shift between hour of maximal occurrence (in the second part of the morning) and time of maximal severity. In 2013, differences in terms of vulnerability of the cardiomyocyte to ischemia were studied in 1021 patients undergoing elective percuaneous coronary intervention (PCI) between 2007 and 2011 (Fournier et al., 2014). Patients were divided into two groups according to the starting time of the PCI: the morning group (n = 651) between 07:00 and 11:59, and the afternoon group (n = 370) between 12:00 and 18:59. The rate of periprocedural myocardial infarction was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p < 0.001). This difference remained statistically significant after propensity score matching (21% vs. 29%, p = 0.03). Finally, in 2014 and 2015, two important studies by Mahmoud et al. (2014) and by our team (Fournier et al., 2015) confirmed the initial results based on STEMI patients. From a multicenter registry of 6799 consecutive STEMI patients undergoing primary PCI between 2004 and 2010, Mahmoud et al. observed that infarct size exhibited circadian variation with largest infarct size in patients with symptom onset around 3 in the morning (estimated peak CK 1322 U/l; 95% confidence interval (CI): 1217–1436) and smallest infarct size around 11:00 in the morning (estimated peak CK 1071 U/l; 95% CI: 1001–1146; relative reduction 19%; p = 0.001). In our data based on 6223 STEMI patients admitted to 82 acute-care hospitals in Switzerland and treated with PCI within 6 h of symptom onset, only a 24-h harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2017 U/L) was for onset at 11:00. In these studies, the relation between myocardial infarction size and hour at symptom onset was independent of ischemic time (time from symptoms onset to revascularization) or myocardial infarction management. Furthermore, different data suggest that patients with symptom onset occurring by night have higher rate of mortality during their hospitalization or even at follow-up. In our first publication (Fournier et al., 2012) based on 353 consecutive patients with STEMI treated by PCI, 30-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than in any other time group (p < 0.05). In our second study based on the 6223 patients, 23 patients (3.58%) died during their hospitalization and only the 24-h harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. Thus, the evidence of higher vulnerability of the heart to ischemia when a myocardial infarction occurs by night is now robust and based on a large number of studies. These data confirm recent observations based on animal models where cardiomyocyte circadian clock affected cardiac responses to various stressors, including ischemia/reperfusion, by modulating multiple cardioprotective signaling pathways (Durgan and Young, 2010; Durgan et al., 2010). Indeed, in the study of Durgan et al. (2010), myocardial infarctions occurring during the sleep-to-wake transition time were 3.5 times larger than those occurring between the mid activity time but deletion of the clock gene abolished these differences, proving a central role of the circadian molecular machinery.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

BackgroundDifferent studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry.MethodsThis retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods.Results6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00.DiscussionAs a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Impact of the Presence of Chronic Total Occlusion in a Non-Infarct-Related Coronary Artery in Acute Myocardial Infarction Patients.

Chronic total occlusion (CTO) in a non-infarcted-related artery was reported to worsen immediate clinical outcome in acute myocardial infarction (AMI) patients. However, the prognosis of such patients with preserved left ventricular function after successful primary percutaneous coronary intervention (PCI) has not yet been clarified. The aim of the present study was to evaluate whether the presence of CTO contributes to a worse prognosis even in patients with preserved left ventricular function after primary PCI.We retrospectively analyzed 353 consecutive patients with acute myocardial infarction, whose left ventricular ejection fraction (LVEF) was not less than 40% in the echocardiography performed 1 day after primary PCI. We divided the patients into two groups according to the presence (n = 25) or absence (n = 328) of CTO in the non-infarct-related coronary artery, and compared the clinical outcome of patients between the two groups.The LVEF estimated by echocardiography after primary PCI was similar between patients with and without CTO (55.1 ± 8.6% versus 58.0 ± 9.4%; P = 0.07). The peak creatine kinase value was also similar between the two groups (1539 versus 1921 U/L; P = 0.33); however, CTO patients were significantly more likely to undergo intra-aortic balloon pumping (56.0% versus 12.5%; P < 0.001) during primary PCI, and 30-day mortality was significantly higher in CTO patients (12.0% versus 0.9%; P < 0.001). By multivariate analysis, cardiogenic shock at arrival was significantly correlated with 30-day mortality.Even though the LVEF of AMI patients with CTO was preserved after successful PCI, a high mortality rate was observed.

Malignant Hyperthermia in Children

Clinical characteristics of malignant hyperthermia (MH) in pediatric patients have not been elucidated. In this study, we used the North American Malignant Hyperthermia Registry to determine differences in clinical characteristics of acute MH across pediatric age groups. We hypothesized that there are differences in clinical presentation, clinical course, and outcomes, which correlate with age. A secondary aim was to determine the types of preexisting medical conditions associated with pediatric MH. We performed a retrospective review of the North American Malignant Hyperthermia Registry to identify pediatric subjects (up to and including 18 years) with an MH clinical grading score at or above 35 indicating "very likely" or "almost certain" MH. Preoperative patient characteristics, perianesthetic factors, and outcome data were compared for 3 cohorts based on age: 0 to 24 months, 25 months to 12 years, and 13 to 18 years. We used statistical analysis to determine differences among the groups. We analyzed 264 records: 35 in the youngest age group, 163 in the middle age group, and 66 in the oldest group. There was no indication of any predisposing risk factors for MH based on family history or physical examination. Sinus tachycardia, hypercarbia, and rapid temperature increase were the most common signs of acute MH (observed in 73.1%, 68.6%, and 48.5%, respectively) and were more common in the oldest age cohort. Higher maximum temperatures and higher peak potassium values were seen in the oldest age cohort. Masseter spasm was more common in the middle age cohort. The youngest age cohort was more likely to develop skin mottling and was approximately half as likely to develop muscle rigidity. The youngest age group also demonstrated significantly higher peak lactic acid levels and lower peak creatine kinase values. Treatments were similar across age cohorts. There were 10 MH-associated deaths, 6 in the middle age group and 4 in the oldest age group. Recrudescence of symptoms after initial treatment occurred in 14.4% of subjects, with no difference across age cohorts. Two of these subjects, 1 in the middle age group and 1 in the oldest age group, died after the recrudescence event. There are differences in clinical characteristics of acute MH among different age cohorts in childhood. Older subjects demonstrated higher body temperatures and higher potassium levels, and the youngest subjects had greater levels of metabolic acidosis. Most children in each age group were phenotypically normal before developing MH.

Impact of plasma renin activity on clinical outcomes and left ventricular remodeling in patients with ST-segment elevation myocardial infarction

Aims: This study was designed to investigate the relationships between plasma renin activity (PRA) and clinical and functional outcomes in patients with ST-segment elevation myocardial infarction. Methods: Our study included 445 patients who underwent primary percutaneous coronary intervention (PPCI). C-reactive protein (CRP), brain natriuretic peptide, aldosterone (PAC), and PRA were measured immediately after PPCI, and the patients were equally divided into two groups according to the median PRA values. Left ventriculograms after PCI and at 14 days were used to evaluate left ventricular (LV) function. Main outcome measures were mortality, cardiogenic shock, infarct size estimated by peak creatine kinase (CK) values, neurohormonal activation, and changes in LV function. Results: The high-PRA patients demonstrated significantly larger infarct size and highly complicated shock. CRP and PAC were higher in the high-PRA patients than in the low-PRA patients (CRP, 2.23±3.24 vs. 3.35±4.30 mg/dL, p = 0.002; PAC, 6.02±4.56 vs. 10.03±12.2 ng/dL, p < 0.001). LV remodeling assessed by changes in LV end-diastolic volume index were more prominent in the high-PRA patients (2.5±16.9 mL/m2) than in the low-PRA patients (7.9±15.3 mL/m2, p = 0.005). Multiple stepwise regression analysis adjusted for time to admission, anterior infarct location, PAC, CRP, peak CK, and PRA showed that PRA and peak CK were positive determinants of LV remodeling. View this table: Independent predictorf for delta LVEDVI Conclusions: PRA may be an integrated biomarker of neurohormonal activation and inflammation. Higher PRA was a positive predictor of LV remodeling.

Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction

Previous studies have shown that intracoronary (IC) nitroprusside (NTP) injection is a safe and effective strategy for the treatment of no-reflow (NR) during percutaneous coronary intervention (PCI). The present study tested the hypothesis that, on the basis of thrombus aspiration for the treatment of ST-segment elevation myocardial infarction (STEMI), the selective IC administration of a fixed dose of NTP (100 μg) plus tirofiban is a safe and superior treatment method compared with the IC administration of tirofiban alone for the prevention of NR during primary PCI. A total of 162 consecutive patients with STEMI, who underwent primary PCI within 12 h of onset, were randomly assigned to two groups: Group A, IC administration of a fixed dose of NTP (100 μg) plus tirofiban (10 μg/kg) and group B, IC administration of tirofiban (10 μg/kg) alone (n=80 and n=82, respectively). The drugs were selectively injected into the infarct-related artery (IRA) via a thrombus aspiration catheter advanced into the IRA. The primary end-point was post-procedural corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The proportion of complete (>70%) ST-segment resolution (STR); the TIMI myocardial perfusion grade (TMPG) 2–3 ratio following PCI; the peak value of creatine kinase (CK)-MB; the TIMI flow grade; the incidence of major adverse cardiac events (MACEs) and the left ventricular ejection fraction (LVEF) after 6 months of follow-up were observed as the secondary end-points. There were no significant differences in the baseline clinical and angiographic characteristics between the two groups. Compared with group B, group A had i) a lower CTFC (23±7 versus 29±11, P=0.000); ii) a higher proportion of complete STR (72.5 versus 55.9%, P=0.040); iii) an enhanced TMPG 2–3 ratio (71.3 versus 53.7%, P=0.030) and iv) a lower peak CK-MB value (170±56 versus 210±48 U/l, P=0.010). There were no statistically significant differences in the final TIMI grade-3 flow between the two groups (92.5 versus 91.5% for groups A and B, respectively; P=0.956). The LVEF at 6 months was higher in group A than group B (63±9 versus 53±11%, respectively; P=0.001); however, the incidence of MACEs was not statistically different between the two groups, although there was a trend indicating improvement in group A (log rank χ2=0.953, P=0.489). The selective IC administration of a fixed dose of NTP (100 μg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA is a safe and superior treatment method compared with tirofiban alone in patients with STEMI undergoing primary PCI. This novel therapeutic strategy improves the myocardial level perfusion, in addition to reducing the infarct size. Furthermore, it may improve the postoperative clinical prognosis following PCI.

Prognostic value of reverse left ventricular remodeling after primary angioplasty for STEMI

AimsThus far, the prognostic value of reverse left ventricular (LV) remodeling after ST-elevation acute myocardial infarction (STEMI) has not been fully evaluated. We sought to investigate the incidence, major determinants, and long-term clinical significance of reverse LV remodeling in a large series of STEMI patients successfully treated with primary percutaneous coronary intervention (P-PCI). Methods and resultsSerial complete 2D-echocardiograms were obtained within 24h after P-PCI, and at 1 and 6 months in 512 consecutive reperfused STEMI patients. Reverse remodeling was defined as a reduction >10% in LV end-systolic volume (LVESV) at 6 month follow-up. Reverse LV remodeling occurred in 49% of study population. At follow-up (41.6±23 months), late heart failure (HF) rate was significantly higher among patients without reverse LV remodeling as compared with those with it (32% vs. 11%, P<0.0001). At multivariate analysis, independent predictors of reverse LV remodeling were a small infarct size measured as peak creatine kinase value (P<0.0001), a small functional myocardial damage measured as wall motion score index within the infarct zone (P=0.018) and baseline LVESV (P<0.0001). After adjustment for several clinical, echographic and angiographic variables, Cox analysis identified reverse LV remodeling as the only beneficial independent predictor of long-term heart failure-free survival (HR: 0.44, 95% CI: 0.275–0.722). ConclusionsReverse LV remodeling occurred in half of successfully reperfused STEMI patients. Small structural and functional myocardial damages within the infarct zone are the major determinants of reverse LV remodeling. As expression of effective myocardial salvage by P-PCI, the reverse remodeling is an important predictor of favorable long-term outcome.

Anxiety trait in patients with stress-induced cardiomyopathy: a case–control study

Stress-induced Tako-tsubo cardiomyopathy (TTC) is an acute cardiac syndrome, mimics ST elevation myocardial infarction (STEMI), largely confined to postmenopausal women, frequently precipitated by a stressful event. The pathogenesis of TTC is still unknown. Some authors hypothesized a possible connection between TTC and anxiety disease, but no previous study analyzed the relationship between anxiety trait and TTC. This study sought to assess the potential role of anxiety trait in the development and clinical course of TTC. We included in the present prospective case-control study 50 consecutive patients admitted to our Hospital with a diagnosis of TTC according to the Mayo Clinic criteria. Fifty control patients with anterior STEMI matched for clinical characteristics such as age, gender, and hypertension were selected. During the hospitalization, all patients were asked to complete the Spielberger Trait Anxiety Inventory (STAI) scale for measuring self-reported trait anxiety (Trait-A). Outcome measures at follow-up were death, TTC recurrence, and rehospitalization. The mean value of STAI scale was 46 ± 12 in TTC patients and 45 ± 14 in STEMI patients (p = 0.815). High-anxiety trait (STAI scale value ≥ 40) was documented in 30 (60%) TTC patients and in 26 (52%) STEMI patients (p = 0.387). At multivariate analysis, predictors of TTC were lower peak creatine kinase value (HR 0.999; 95% CI 0.998-0.999; p = 0.018) and an antecedent stressful trigger event (HR 45.487; 95% CI 6.471-319.759; p = 0.001), but anxiety trait was not. There were no differences in outcome measures between TTC patients with or without high-anxiety trait. In TTC patients, high-anxiety trait is a common finding but it is not significantly more frequent than in patients with STEMI. Moreover, a high-anxiety trait seems to be neither associated with a worse clinical outcome nor a predictor of TTC. Our study do not support the routine evaluation of anxiety trait in patients with TTC.

Heart rate on admission is an independent risk factor for poor cardiac function and in-hospital death after acute myocardial infarction

Increased resting heart rate (HR) due to sympathetic hyperactivity is associated with coronary risk factors and increased cardiovascular events. Acute myocardial infarction (AMI) is accompanied by autonomic imbalance, which is characterized by sympathetic activation and parasympathetic inactivation. Although an increased HR in patients with acute coronary syndrome has been reported to be associated with 30-day and 6-month mortality before the coronary intervention era, it is unclear if an increased HR on admission is associated with the prognosis of AMI in the coronary intervention era. We enrolled 200 consecutive patients with AMI within 24 h of symptom onset. All patients underwent coronary angiography. They were divided into quartiles based on resting HR on admission. There was no difference in coronary risk factors and previous medical treatment among the four groups. Anterior AMI was significantly lower in the lowest quartile compared with other quartiles. There was no difference in peak creatine kinase value among the four groups, however left ventricular ejection fraction (LVEF) before discharge evaluated by echocardiography in the highest quartile group was significantly reduced compared to other quartiles. An increased HR was significantly associated with in-hospital death. Patients in the highest quartile of HR were about nine times more likely to have a poor prognosis after AMI compared to those in the lowest quartile. Multiple logistic analysis revealed that HR ≥93 was an independent risk factor for in-hospital death. HR was significantly associated with Killip class and LVEF on admission. These findings indicate that increased HR on admission predicts for poor cardiac function and in-hospital death after AMI.