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Enzymatische Marker der Reperfusion bei akutem Myokardinfarkt

Cardiac markers for non-invasive prediction of coronary reperfusion in myocardial infarction — Including data from the I.S.A.M. study

mit Daten aus der I.S.A.M.-Studie

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Zusammenfassung

Beim akuten Myokardinfarkt kommt es durch Verschluß eines Koronargefäßes zur Minderdurchblutung des Myokards mit Zellnekrose. Durch rasche und effektive Thrombolyse (definiert als Wiedereröffnung des Infarktgefäßes mit normalem Fluß [TIMI-Grad 3]) können die Infarktgröße begrenzt und die Mortalität deutlich gesenkt werden. Dieses wird in Abhängigkeit vom verwendeten Thrombolytikum jedoch nur in 50 bis 80% der Patienten erreicht.

Verschiedene Herzmarker zeigen bei Reperfusion eine unterschiedliche Kinetik mit einem steilen Anstieg bis zu einem hohen Gipfel und einer schnelleren Normalisierung, so daß das Ergebnis der Lysetherapie nichtinvasiv abgeschätzt werden kann.

Myoglobin wird beim Infarkt frühzeitig freigesetzt (bereits zwei Studden nach dem Schmerzereignis Sensitivität von über 60%) und erreicht seinen Gipfel nach vier bis acht Stunden. Der steile Enzymanstieg bei Reperfusion (innerhalb der ersten zwei Stunden >-150 ng/ml/Stunde bzw. ein Verhältnis von Myoglobin 90 Minuten nach Lyse zu Myoglobin zu Lysebeginn > 4) mit einem Erreichen des Myoglobinmaximums innerhalb von fünf Stunden legt mit hoher Wahrscheinlichkeit (und höherem negativen prädiktiven Wert als bei allen anderen Markern) einen Lyseerfolg nahe. Dies belegen unter anderem die I.S.A.M.-Studie und Studien mit angiographisch nachgewiesenem TIMI-Grad-3-Fluß nach Thrombolyse. Für eine Reintervention (erneute Thrombolyse oder Rescue-PTCA) bleibt dann immer noch Zeit.

Troponin und Kreatinkinase (CK) steigen beim Myokardinfarkt frühestens nach drei bis vier Stunden an, so daß beide Marker bei frühem Lysebeginn noch negativ sein können. Dennoch erlauben Anstiegssteilheit oder ein früheres Erreichen des Enzymmaximums (bei der CK/CK-MB-Aktivität innerhalb von neun Stunden) den Rückschluß auf eine Reperfusion, wobei die Differenzierung zwischen TIMI-Grad-2-und-3-Fluß im klinischen Alltag schwierig ist.

Abstract

Despite advances in therapy acute myocardial infarction is associated with a mortality rate of up to 30%. Early and complete reperfusion of the infarct related artery (-defined as TIMI flow 3 at 90 minutes following therapy) as obtained with thrombolytic therapy in 50 to 80% of patients improves survival and enhances ventricular function. Failure to achieve recanalization should prompt further intervention (second attempt of thrombolysis or rescue-PTCA). Various cardiac markers known from diagnosing acute myocardial infarction or risk stratification in unstable angina pectoris have been assessed in their ability to predict successful reperfusion/failure of therapy. Following reperfusion creatin-kinase (CK) and its isoform CK-MB, troponin and myoglobin show an early and rapid rise to a high maximum value with rapid normalization. For creatinkinase time to peak values of less than 9 hours or rates of increase of > 50 U/h (>-10 U/h for CK-MB activity) within the first 2.5 hours following thrombolysis have been suggested as useful indicators of successful reperfusion. The same applies for a troponin (T)slope >0.5 ng/ml/h within the first hour (Table 5).

The major limitation in applying either creatinkinase, troponin or even lactatdehydrogenase (LDH) is their comparatively late release (4 to 6 hours) following myocardial infarction. In that respect myoglobin (though not specific for cardiac injury) seems ideal for guidance of intervention after failed thrombolysis.

The I.S.A.M. study included 1,741 patients with acute myocardial infarction of less than 6 hours duration being given either streptokinase or placebo. Serial blood samples for measurement of cardiac enzymes were drawn within the first 50 hours. In the streptokinase group the time to peak concentration of CK-MB activity was significantly lower (mean 10.9 hours vs 16.1 hours following initiation of treatment) as was the area under the CK-MB curve indicating reduction of infarct size (Table 2).

A substudy investigating the myoglobin release in 120 patients having received streptokinase or placebo demonstrated higher maximum values in the streptokinase group (mean 3008 vs 2097 ng/ml), a shorter time to peak interval following treatment (3.4 vs 6.5 hours) and a reduction in infarct size as suggested by a smaller area under the myoglobin curve (17,377 vs 23,240 ng/ml × h) (Table 3).

For LDH/α-HBDH the reduction in time to peak intervals was less impressive (Table 4). In angiographic studies with TIMI flow 3 at 90 minutes in the infarct related artery in 22 patients (Figure 5) the maximum myoglobin value was reached in less than 4,2 hours (mean value plus SEM) following treatment (9,5 hours for CK-MB activity). Therefore, myoglobin seems to be the preferred marker in reperfusion assessment.

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Authors and Affiliations

  1. Medizinische Klinik I, Klinikum Lippe-Detmold, Detmold, Deutschland

    Sabine Walter

  2. Abteilung für Kardiologie, Kerckhoff-Klinik, Bad Nauheim

    Joerg Carlsson

  3. Medizinische Klinik II, Klinikum Lippe-Detmold, Röntgenstraße 18, D-32756, Detmold

    Eckhardt Sorges & Ulrich Tebbe

  4. Universitätsklinikum Benjamin Franklin, Berlin

    Rolf Schröder

  5. Medizinische Klinik II, Klinikum Kassel, Kassel, Deutschland

    Karl-Ludwig Neuhaus

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Walter, S., Carlsson, J., Schröder, R. et al. Enzymatische Marker der Reperfusion bei akutem Myokardinfarkt. Herz 24, 430–439 (1999). https://doi.org/10.1007/BF03044429

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