Eike Hoberg

Silent myocardial ischemia as a potential link between lack of premonitoring symptoms and increased risk of cardiac arrest during physical stress

The risk of cardiac arrest is increased during strenuous physical exercise in patients with stable coronary artery disease (CAD). Because premonitoring symptoms are rarely observed, silent myocardial ischemia may represent the pathophysiological basis for the induction of malignant ventricular arrhythmias. Holter monitoring was, therefore, performed in 40 consecutive patients entering a randomized intervention trial on progression of CAD. In 20 of 21 participants (95%) in the intervention program greater than or equal to 1 episode of silent myocardial ischemia was observed during the initial training session. The mean duration of silent myocardial ischemia per patient was 25 +/- 13 min/hr of training session. During normal daily activity only 5 patients (24%) experienced greater than or equal to 1 episode of silent myocardial ischemia (p less than 0.001) yielding a mean duration of 0.6 +/- 1.3 minutes of silent myocardial ischemia/hr of ordinary activity per patient (p less than 0.001 vs training session). During a control period of 24 hours without exercise training the incidence (33%) and mean duration of silent myocardial ischemia (0.8 +/- 2.1 min/hr/patient) were similar to those during normal daily activity on the day of the training session. During the training session the occurrence of frequent or repetitive ventricular arrhythmias was related to 10 silent myocardial ischemia episodes detected in 5 patients. During normal daily activity in 1 patient only was the onset of malignant ventricular arrhythmias associated with silent myocardial ischemia (p less than 0.05). Conditions and results of the Holter studies in the control group patients were comparable to those of the patients in the intervention group on the day without physical exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating cardiac myosin light chains in patients with angina at rest: Identification of a high risk subgroup

To detect myocardial cell damage, serum samples of 42 consecutive patients with angina at rest were screened for cardiac myosin light chains, which were detected in 22 patients (52%). In 17 of these patients there was a persistent release of myosin light chains lasting until the 4th hospital day, whereas in 7 patients myosin light chains were only detectable during the initial 24 h after admission. The presence of myosin light chains correlated with signs of ischemia in the electrocardiogram (ECG) (p less than 0.05) and with the extent of coronary artery narrowing (p less than 0.05). Cardiac myosin light chains were elevated in serum only if there was a greater than or equal to 75% diameter narrowing in at least one major vessel. In all five patients who developed transmural myocardial infarction during the course of their hospital stay, myosin light chains were detectable greater than or equal to 28 h before the diagnosis of myocardial infarction could be established by ECG criteria and conventional serum enzymes. Thus the detection of circulating cardiac myosin light chains enables one to identify a subgroup of patients with angina at rest having more severe coronary artery disease with a worse outcome.

Holter monitoring before, during and after percutaneous transluminal coronary angioplasty for evaluation of high-resolution trend recordings of leads CM5 and CC5 for ST-segment analysis

Frequency-modulated Holter monitoring of leads CM5 and CC5 was performed before, during and after percutaneous transluminal coronary angioplasty (PTCA) in 16 patients with stenosis of the left anterior descending coronary artery, in 5 patients with stenosis of the left circumflex coronary artery, and in 5 patients with stenosis of the right coronary artery. All patients presented with 1-vessel coronary artery disease and stable or unstable angina pectoris. ST-segment analysis was based on high-resolution trend recordings. During balloon inflations all patients had significant (at least 0.1 mV) ST-segment changes in lead CM5. In lead CC5, associated ST-segment deviations were found in 22 of 26 patients. During 29.2 +/- 13.6 hours before PTCA, 90 spontaneous episodes with significant ST-segment deviations were detected in 10 patients. Of these episodes, 17% were characterized by ST-segment deviations in lead CC5 only, 57% by ST-segment deviations in lead CM5 only, and 27% by simultaneous ST-segment deviations in both leads. Asymptomatic episodes occurred twice as frequently as symptomatic episodes (66 vs 34%). Symptomatic episodes were more often characterized by ST-segment deviations of at least 0.15 mV (48 vs 9%, p less than 0.001) and by ST-segment deviations observed in both leads simultaneously (48 vs 15%, p less than 0.001). During 34.8 +/- 10.6 hours after successful PTCA, 5 spontaneous asymptomatic episodes with significant ST-segment deviations were detected in 2 patients.

Prevention of restenosis after PTCA: role of calcium antagonists.

Summary: The recurrence of coronary obstruction after initially successful percutaneous transluminal coronary angioplasty (PTCA) represents a major problem of this interventional procedure at present. In the pathogenesis of restenosis the growth factor-dependent proliferation and migration of medial smooth muscle cells into the intima of the vessel wall may play a very important role. In experimental studies this process could be inhibited by calcium antagonists. However. the first two placebo-controlled clinical trials showed disappointing results: the restenosis rate was not decreased by the treatment with 10 mg of nifedipine four times daily or by the treatment with 90 mg of diltiazem three times daily. The influence of high-dose verapamil treatment [Isoptin RR (240 mg) twice daily] on the recurrence of coronary stenosis has been investigated by a recently completed double-blind. placebo-controlled trial. the verapamil angioplasty study (VAS). The VAS included 196 consecutive patients with at least one risk factor for restenosis after successful PTCA for stable angina pectoris (n = 75) or unstable angina pectoris/non-Q-wave infarction (n = 97). Eight-eight percent of the patients underwent follow-up angiography at 4.3 ± 2.3 months. The publication of detailed data of the VAS including restenosis rates in both clinical subgrups is being prepared.

Instabile Angina pectoris

Jede Angina pectoris, die in ihrer Symptomatik — sei es in der Intensitat, in der Anfallshaufigkeit oder in beidem — zunimmt, wird im Gegensatz zur stabilen Form als „instabile Angina“ bezeichnet.

Diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease in patients with variable threshold angina pectoris

Patients with chronic stable angina pectoris may present with either fixed or variable threshold symptoms. To evaluate the diagnostic value of ambulatory Holter monitoring for the detection of coronary artery disease (CAD) in patients with variable threshold angina, 216 consecutive candidates for coronary angiography were investigated prospectively. For comparison, a group of 55 consecutive patients with fixed threshold angina was studied under the same conditions. Patients with prior myocardial infarction or angiographically documented CAD were excluded. Within 4 months of Holter monitoring, the advised coronary angiography was performed in 77% of the patients with variable threshold angina and in 89% of the patients with fixed threshold angina (p less than 0.05). The prevalence of CAD was markedly lower in patients with variable threshold angina compared to patients with fixed threshold angina (54 vs 90%, p less than 0.001). CAD patients of both subgroups, however, did not differ significantly with respect to the number of obstructed vessels, the Gensini coronary score, the number with impaired left ventricular function (ejection fraction less than 50%) or the duration of ischemic episodes during Holter monitoring. Diagnostic accuracy of Holter monitoring did not differ between variable and fixed threshold angina groups (67 vs 78%). In 91% of the patients results obtained by Holter monitoring could be compared to the results of a bicycle stress test. In patients with fixed threshold angina the diagnostic accuracy was similar for both tests (80 vs 80%). In patients with variable threshold angina, the diagnostic accuracy of Holter monitoring exceeded that of the exercise stress test (68 vs 55%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Mügliche Bedeutung der ST-Segmentanalyse im Langzeit-EKG für die kardiologische Routinediagnostik

Ob eine Methode, die sich fur bestimmte wissenschaftliche Fragestellungen bewahrt hat, Eingang in die klinische Routine findet, hangt wesentlich von 2 Faktoren ab: erstens vom Personal- und Zeitaufwand, der fur die Durchfuhrung und Auswertung der Untersuchung erforderlich ist, und zweitens vom Ausmas der Zusatzinformation, die die Methode im Vergleich zu herkommlichen Techniken bietet.

Passagere Myokardischämien und ventrikuläre Arrhythmien

Experimentelle Befunde belegen, das durch passagere Myokardischamien bedrohliche ventrikulare Arhythmien (VA) induziert werden konnen (Janse 1987; Pogwizd u. Corr 1987). Auch bei einzelnen Patienten konnte ein Zusammenhang zwischen ischamietypischen ST-Streckenveranderungen und dem Auftreten maligner VA nachgewiesen werden (Bleifer et al. 1974; Gradman et al. 1977; Savage etal. 1983; v. Arnim et al. 1985; Hohnloser et al. 1988). Die Haufigkeit und damit die klinische Relevanz eines solchen Zusammenhangs ist bisher nicht an definierten Patientenkollektiven untersucht worden. Daher wurden die Langzeit-EKG-Aufzeichnungen der 271 ambulanten Patienten mit stabiler Angina pectoris (genaue Definition des Kollektivs s. unter 3.1) und zusatzlich die Aufzeichnungen von 26 stationaren Patienten mit instabiler Angina pectoris einer Rhythmusanalyse unterzogen.

Passagere Myokardischämien und Angina pectoris

Erste Berichte uber asymptomatisch verlaufende Episoden mit ischamietypischen ST-Streckensenkungen im Langzeit-EKG gehen auf das Jahr 1974 zuruck (Stern et al. 1974). Die klinische Relevanz dieser Beobachtung blieb zunachst offen. Erst als durch EKG-unabhangige Methoden gezeigt werden konnte, das solche „stummen“ Episoden bei Patienten mit nachgewiesener KHK durch Myokardischamien bedingt sind (Chierchia et al. 1983; Deanfield et al. 1984; Levy et al. 1986), wuchs das Interesse an dem zugrundeliegenden pathophysiologischen Mechanismus. Nach Untersuchungen von Droste u. Roskamm (1983) konnten unterschiedliche Schmerzschwellen zu interindividuellen Unterschieden der Schmerzperzeption beitragen. Ob sich zusatzlich die Ausdehnung oder Intensitat der Myokardischamie auf das Auftreten pectanginoser Beschwerden auswirken, wird kontrovers diskutiert (Cocco et al. 1982; Cecchi et al. 1983; Chierchia et al. 1983; Deanfield et al. 1983; Droste u. Roskamm 1983; Stern etal. 1986; Hoberg et al. 1987). Bei Patienten mit sowohl symptomatischen als auch stummen Ischamien last sich der Einflus der Ischamieausdehnung auf die Schmerzwahrnehmung untersuchen. Als Langzeit-EKG-Parameter fur das Ausmas einer Myokardischamie konnen die Amplitude der maximalen ST-Streckenabweichung wahrend einer Episode und das simultane Auftreten signifikanter ST-Streckenabweichungen in beiden registrierten Ableitungen gewertet werden. Daher sollten die Aufzeichnungen von KHK-Patienten mit stabiler Angina pectoris und sowohl symptomatischen als auch asymptomatischen Ischamieepisoden auf diese Parameter hin analysiert werden. Als Kollektiv sollten die Patienten mit stabiler Angina pectoris dienen, die zur Beurteilung der diagnostischen Bedeutung des Langzeit-EKG untersucht wurden (s. Kap. 3).

Validierung einer trendgestützten ST-Segmentanalyse im Langzeit-EKG

Eine ausschlieslich visuelle Analyse aller Herzaktionen von 24-Stunden-Langzeit-EKG-Aufzeichnungen ist zeitraubend und an spezielle Erfahrungen des Auswerters gebunden. Die Darstellung relativer ST-Streckenabweichungen als Trend ermoglicht es, die visuelle EKG-Analyse auf die relevanten Phasen der Aufzeichnung zu konzentrieren. Voraussetzung ist eine quantitative Ubereinstimmung der im Trend wiedergegebenen ST-Streckenabweichungen mit den ST-Streckenabweichungen im Original-EKG. QRS-Komplexe mit gegenuber dem Grundrhythmus veranderter Morphologie mussen fur die Berechnung der Trenddaten zuverlassig eliminiert werden. Daneben wird die Qualitat einer Trenddarstellung dadurch bestimmt, wieviele Einzelinformationen zu einem Punkt zusammengefast werden. Eine Mittelung uber zu viele Einzelwerte nivelliert bestehende Differenzen; der Verzicht auf eine Mittelung — also die Darstellung aller Einzelpunkte — beeintrachtigt die Ubersichtlichkeit. In beiden Fallen ist mit einem Sensitivitatsverlust fur den Nachweis von relativen Anderungen zu rechnen. Daher sollte der Einflus der Mittelungstechnik auf die Sensitivitat einer trendgestutzten ST-Segmentanalyse fur den Ischamienachweis im Langzeit-EKG gepruft werden.