Lothar Volbracht

Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction.

Background—Stenting-related myocardial injury has been recognized as a frequent and prognostically important event, the extent of which depends on microcirculatory impairment in association with platelet aggregation, inflammation, and increased oxidative stress. Recent studies underscored the non–lipid-lowering effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with antithrombotic, antiinflammatory, and antioxidative aspects. Thus, we tested the hypothesis that preprocedural statin therapy is associated with a reduction in the extent of stenting-related myocardial injury. Methods and Results—We stratified 296 consecutive patients who were undergoing stenting of a de novo stenosis according to the preprocedural status of statin therapy (229 statin-treated and 67 control patients). Incidence of periprocedural myocardial injury was assessed by analysis of creatine kinase (CK; upper limit of normal [ULN] 70 IU/L for women, 80 IU/L for men) and cardiac troponin T (cTnT; bedside test; threshold 0.1 ng/mL) before and 6, 12, and 24 hours after the intervention. Relative to control patients, the incidence of CK elevation >3× ULN was more than 90% lower in statin-treated patients (0.4% versus 6.0%, P =0.01). Statin therapy was the only factor independently associated with a lower risk of CK elevation >3× ULN (OR: 0.08, 95% CI: 0.01 to 0.75;P =0.03). The overall incidences of CK and cardiac troponin T elevation were slightly lower in statin-treated than in control patients (14.4% versus 20.9%, P =0.3, and 17.9% versus 22.4%, P =0.5, respectively). Conclusions—Preprocedural statin therapy is associated with a reduction in the incidence of larger-sized, stenting-related myocardial infarctions. Prospective, randomized trials are warranted to further assess this cardioprotective effect of statins in coronary intervention.

Abnormal Coronary Flow Velocity Reserve After Coronary Intervention Is Associated With Cardiac Marker Elevation

Background—Residual reduction of relative coronary flow velocity reserve (rCVR) after successful coronary intervention has been related to microvascular impairment. However, the incidence of cardiac enzyme elevation as a surrogate marker of an underlying embolic myocardial injury in these cases has not been studied. Methods and Results—A series of 55 consecutive patients with successful coronary stenting, periprocedural intracoronary Doppler analysis, and determination of creatine kinase (CK; upper limit of normal [ULN] for women 70 IU/L, for men 80 IU/L) and cardiac troponin T (cTnT; bedside test, threshold 0.1 ng/mL) before and 6, 12, and 24 hours after intervention were studied. Postprocedural rCVR was the only intracoronary Doppler parameter that independently correlated with cTnT (r =−0.498, P <0.001) and CK outcome (r =−0.406, P =0.002). Receiver operating characteristic analysis identified a postprocedural rCVR of 0.78 as the best discriminating value, with a sensitivity of 83.3% and 69.2% and a specificity of 79.1% and 76.2% for detection of cTnT and CK elevation, respectively. Stratified according to this cutoff value, the incidence of cTnT elevation was 52.6% in patients with (n=19) and 5.6% in patients without (n=36) a postprocedural rCVR <0.78 (P <0.001), associated with a CK elevation >1 times the ULN in 36.8% and 5.6% (P =0.005) of patients, respectively. Conclusions—Cardiac marker elevation can frequently be found after coronary procedures that are associated with a persistent reduction of rCVR, indicating procedural embolization of atherothrombotic debris with microvascular impairment and myocardial injury as a potential underlying mechanism.

Analysis of intrathecal interleukin-6 as a potential predictive factor for vasospasm in subarachnoid hemorrhage

OBJECTIVEInflammatory response seems to be one of the relevant pathophysiological aspects for developing vasospasm in subarachnoid hemorrhage. The probable diagnostic value of intrathecal proinflammatory markers is still unclear and is assessed in this study. METHODSWe analyzed daily clinical data and laboratory tests of the cerebrospinal fluid (CSF) of 64 patients with mostly poor-grade subarachnoid hemorrhage during a period of 14 days. Special attention was given to the relationship between the development of vasospasm and the time course of the intrathecal interleukin (IL)-6 concentrations in CSF (IL-6CSF). The potential power of IL-6CSF for predicting vasospasm was studied. RESULTSVasospasm developed in 28.1% of the patients, with a mean onset of 6.4 days after bleeding, and was detected by conventional methods. Patients with vasospasm demonstrated statistically significant higher median values of IL-6CSF on Days 4 and 5 (P < 0.05). Most importantly, the increase of IL-6CSF preceded the conventional signs of vasospasm. A cut-off value of IL-6CSF of at least 2000 pg/ml on Day 4 yielded an 11.72-fold higher relative risk (95% confidence interval, 2.93–46.60) of developing vasospasm, predicting vasospasm with a sensitivity of 88.9% and a specificity of 78.3%. We found a statistically significant correlation between IL-6CSF and delayed cerebral ischemia for Day 7 (P = 0.03). However, there was no correlation with IL-6CSF on any other day and outcome. CONCLUSIONIL-6CSF seems to be a reliable early marker for predicting vasospasm after subarachnoid hemorrhage on Days 4 and 5 before clinical onset.

Prognostic implication of cardiac troponin T increase following stent implantation

Objective: To identify the incidence and clinical significance of myocardial injury following elective stent implantation. Design: Prospective clinical study with 278 consecutive patients undergoing stenting of de novo coronary or saphenous vein graft lesions. Incidence of periprocedural myocardial injury was assessed by analysis of 12 lead ECG, creatine kinase (CK; upper limit of normal (ULN) 70 IU/l for women, 80 IU/l for men), and cardiac troponin T (cTnT; point of care test; threshold 0.1 ng/ml) before and 6, 12, and 24 hours after the intervention. Major adverse cardiac events (MACE: acute myocardial infarction, bypass surgery, and cardiac death) were recorded during clinical follow up (mean (SD) 7.8 (5.3) months). Results: Following elective stenting, the rate of a positive cTnT status was 17.3%, the rate of CK increase of 1–3× ULN 14.7%, the rate of CK increase of > 3× ULN 1.4%, and the rate of Q wave myocardial infarction 0.4%. Cardiac mortality during follow up was higher in patients with postprocedurally increased CK (7.1% v 1.3%, p = 0.01, log rank) and cTnT (9.1% v 0.9%, p < 0.001, log rank). In addition, postprocedurally increased cTnT was associated with a higher overall incidence of MACE (13.1% v 4.0%, p < 0.01, log rank) and was identified as an independent factor for MACE during follow up (hazard ratio 3.27, 95% confidence interval 1.14 to 9.41, p = 0.028). Conclusions: Following elective stent implantation, a positive cTnT status identified patients at risk of a worse long term outcome. Treatment strategies have to be developed that lead to prognostic improvement by reducing periprocedural myocardial injury.

Biochemische Marker bei ischämischen und nicht ischämischen Myokardschädigungen

ZusammenfassungHintergrund: Biochemische Marker sind seit fast 50 Jahren integrativer Bestandteil der nicht invasiven kardialen Diagnostik und haben mit den kardialen Troponinen angesichts ihres prognostischen Potentials bei akutem Koronarsyndrom eine Renaissance erfahren. Diagnostik: Nach den Empfehlungen der National Acadamy of Clinical Biochemistry und der International Federatuion of Clinical Chemistry stellen das kardiale Troponin T und das kardiale Troponin I den neuen Goldstandard in der biochemischen kardialen Ischämiediagnostik dar. Charakteristikum dieser neuen Marker ist zum einen das verbesserte diagnostische Potential, das sich in der Wahl zweier Grenzwerte zur Differenzierung einer minimalen Myokardschädigung vom definitiven akuten Myokardinfarkt widerspiegelt. Zum anderen erlauben die neuen kardiospezifischen Marker eine Risikostratifizierung in dem klinisch bedeutsamen Szenario des akuten Koronarsyndroms (zwei- bis dreifach erhöhte Mortalitätsrate für Patienten mit ST-Strecken-Hebung oder Ruhe-Angina pectoris und kardialer Troponinerhöhung zum Zeitpunkt der Aufnahme). Eine weitere Indikation für die Bestimmung karidaler Marker liegt in der Beurteilung des Therapieerfolgs invasiver und nicht invasiver Reperfusionsstrategien und in der nicht invasiven Diagnostik von nicht ischämischen Myokardschädigungen (Myokarditis, Herzkontusion und Chemotherapie). Schlussfolgerung: Biochemische kardiale Marker sind zur Diagnostik ischämischer und nicht ischämischer Myokardschädigungen einsetzbar. Die kardialen Troponine scheinen sich dabei als Goldstandard für das neue Millennium zu etablieren.AbstractBackground: Biochemical markers have been an integrative part of non-invasive diagnostic strategies in cardiology for nearly 50 years, experiencing a renascence by the recently acknowledged prognostic potential of cardiac troponins in acute coronary syndromes. Diagnosis: According to the guidelines of the National Academy of Clinical Biochemistry and the International Federation of Clinical Chemistry cardiac troponin T and cardiac troponin I should be considered as the new “gold markers” of ischemic myocardial injury. One characteristic feature of these new markers is the improved diagnostic potential, reflected by the choice of two cut-off values to distinguish minor myocardial injury from acute myocardial infarction. In addition, cardiac troponins allow risk stratification in the clinical setting of acute coronary syndromes: approximately threefold higher mortaligy rate for patients with rest angina or ST segment elevation and cardiac troponin elevation on admission. Other indications for cardiac marker analysis are monitoring of therapeutic success in case of invasive and non-invasive reperfusion strategies and non-invasive diagnosis of non-ischemic myocardial injury (myocarditis, cardiac contusion and chemotherapy). Conclusion: Biochemical cardiac markers are a useful tool in the diagnosis of both ischemic and non-ischemic myocardial injury. Among these, cardiac troponins seem to become the gold markers for the new millennium.

Acute changes of coagulation and fibrinolysis parameters after experimental thromboembolic stroke and thrombolytic therapy.

Thrombolysis is the only effective pharmaceutical therapy in acute ischemic stroke in humans but has a high risk of intracerebral hemorrhage. We aimed to establish an animal model to study changes of coagulation and fibrinolytic parameters during thromboembolic ischemic stroke and thrombolysis with recombinant tissue plasminogen activator (rt-PA). We used a thromboembolic stroke model in the rat. Animals were treated with rt-PA thrombolysis (n=10) and compared with untreated (n=10), sham operated (n=10) and control animals (n=20). Coagulation parameters (APTT, PT, TT, fibrinogen, AT III, TAT) and fibrinolytic parameters (t-PA antigen concentration, t-PA activity, PAI-1 concentration, PAI activity, plasminogen, antiplasmin) were measured at two time points (2.5 and 5h after stroke induction) with a battery of commercially available test kits. We observed an (1) initiation of coagulation and inhibition of fibrinolysis by the operation procedure itself, (2) simultaneous activation of fibrinolysis and its inhibitors after stroke induction and (3) potent initiation of fibrinolysis and consumption of fibrinolysis inhibitors after rt-PA therapy of stroke. We established a model system to monitor coagulation and fibrinolysis during thrombolytic therapy of stroke in the rat. This model may be used to study the influence of these parameters on hemorrhagic stroke transformation and outcome in experimental stroke in future.