Bernd Waldecker

Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective, randomized study

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixty-two consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 +/- 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission. A sustained ventricular arrhythmia was induced in 10 (48%) of the 21 patients randomized to streptokinase therapy and in all 15 (100%) control patients (p less than 0.001). Sustained monomorphic ventricular tachycardia was induced in 6 (29%) and 10 (67%) patients, respectively (p less than 0.05). To terminate an induced arrhythmia, direct current countershock was required in 33% of patients in the streptokinase group and 73% of patients in the control group (p less than 0.02). Seventeen of the 21 patients treated with streptokinase and no control patient had evidence of early reperfusion 200 +/- 70 minutes after the onset of pain. In comparison with patients without early reperfusion, patients in the reperfused group had a lower maximal serum creatine kinase value (p less than 0.01), a shorter time to peak creatine kinase value (p less than 0.001) and a higher angiographic left ventricular ejection fraction (62 versus 45%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blockade of Ca2+-Activated K+ Channels Inhibits Proliferation of Human Endothelial Cells Induced by Basic Fibroblast Growth Factor

Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 ± 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25–100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25–100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (–41%) and 100 nmol/l (–50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.

Dysrhythmias after direct-current cardioversion

The success rate of direct-current (DC) countershocks and postshock arrhythmias are of concern for the design of automatic devices. Results of 112 DC shocks for induced ventricular tachycardia/fibrillation (VT/VF) (n = 99) or atrial fibrillation (AF) were analyzed. Clinical and arrhythmia characteristics were related to the success rate of DC shocks as well as postshock arrhythmias. Sixty-one patients were men and 14 were women; mean age was 52 +/- 15 years. Coronary artery disease was present in 56 patients and cardiomyopathy in 4. The other patients had no apparent structural heart disease. The success rate of transchest DC shocks for VT and VF were identical. The first DC shock interrupted 80% of VT and VF episodes. All episodes were terminated by 4 or fewer DC shocks. A single DC shock changed morphologic pattern or rate of 4 episodes of VT. Asystole after VT/VF (1,900 +/- 960 ms) was longer than after atrial fibrillation (1,150 +/- 470 ms, p less than 0.01). VT/VF recurred (within 3 minutes) after 26 of 99 initially successful DC shocks, requiring repeat shocks in 2 cases. Sinus bradycardia (n = 18) or high degree atrioventricular block (n = 11) necessitated rate support pacing in 10 patients. Antiarrhythmic drugs did not prevent postshock tachycardias, but facilitated the development of bradycardias. In conclusion, reliable and continuous analysis of cardiac rhythm after discharge is mandatory to enable automatic devices to correct unsuccessful discharges or recurring VT/VF. In addition, demand pacing capability is desirable to prevent severe bradycardia after DC shocks in patients receiving antiarrhythmic drugs.

Implantable Cardioverter Defibrillator: Possible Hazards of Electromagnetic Interference

We report on three patients with an automatic, implantable Cardioverter defibrillator (AICD, CPI) in whom the device had been deactivated due to electromagnetic interference. In all cases, the source of the electromagnetic disturbances could be identified.

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.

Value of programmed electrical stimulation using a standardized ventricular stimulation protocol in hypertrophic cardiomyopathy

Abstract To establish the value of programmed electrical stimulation in patients with hypertrophic cardiomyopathy (HC), patients with HC with or without documented ventricular arrhythmias were studied by a standardized stimulation protocol.

Programmed electrical stimulation in healed myocardial infarction using a standardized ventricular stimulation protocol

The diagnostic accuracy of programmed electrical stimulation was prospectively assessed in 111 patients with myocardial infarction (MI) with or without a history of spontaneous ventricular arrhythmias. In 29 patients neither ventricular tachycardia (VT) nor episodes of 10 premature ventricular depolarizations per hour was documented. Fifty patients had documented nonsustained VT and 32 had sustained monomorphic VT. One and 2 extrastimuli (twice diastolic threshold, 2 ms in duration) were given during sinus rhythm and ventricular pacing at 100, 120 and 140 beats/min in the right ventricular apex (part I). When this protocol failed to induce a sustained monomorphic VT, a third extrastimulus was introduced (part II). Repetitive ventricular responses were induced in all patients, and in 15 (14%) polymorphic ventricular arrhythmias requiring DC shock were induced. Incidence of initiation of sustained monomorphic VT and polymorphic ventricular arrhythmias requiring DC shock was related to the clinical arrhythmia and the stimulation protocol. In patients with documented sustained monomorphic VT, a third extrastimulus only increased the incidence of sustained monomorphic VT (68% to 94%), whereas in patients with documented nonsustained VT and without VT the incidence of both polymorphic and monomorphic arrhythmias increased by 7 to 12%. Sustained monomorphic VTs induced in patients without such a history were faster (p less than 0.01), depended on site of MI (p less than 0.05) and were more often preceded by nonsustained polymorphic VT (p less than 0.01) than in patients with documented sustained monomorphic VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of modes of electrical termination of ventricular tachycardia for the selection of implantable antitachycardia devices

Different implantable systems for electrical treatment of ventricular arrhythmias are available. Information about mode of termination of ventricular tachycardia (VT) helps to select the most appropriate electrical treatment for drug-resistant VT. During 158 electrophysiologic studies, the mode of termination of 215 episodes of VT was analyzed in 2 groups of patients. Group 1 consisted of 54 patients with documented monomorphic VT and group 2 of 46 patients with other documented or suspected ventricular arrhythmias. Eighty-two patients had coronary heart disease, 8 had other structural heart disease and 10 had idiopathic VT. Termination of VT was attempted using extrastimuli and overdrive pacing; direct-current (DC) shocks were given in case of syncopal VT. During 33 of 96 studies (34%) in group 1, DC shock was required to interrupt VT, compared with 45 of 62 studies (73%) in group 2 (p less than 0.001). This difference was a result of less frequent induction of immediately syncopal VT in group 1 (14 of 129 VTs, vs 40 of 86 in group 2, p less than 0.001). Non-syncopal VT could reliably and safely be terminated by pacing in 61%, irrespective of the clinical arrhythmia. Pacing-induced acceleration of VT occurred in 6% (single extrastimuli) to 36% (over-drive pacing) (mean 26%) of attempts. Subsequent DC shock was required in half of these cases. Immediate collapse after induction of VT was not related to the presence of heart disease, but was related to a combination of VT cycle length (shorter than 260 ms) and left ventricular ejection fraction (less than 40%). Antiarrhythmic drugs reduced the need for DC shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of T wave alternation after acute myocardial infarction and correlation with other prognostic parameters: results of a prospective study.

SCHWAB, J.O., et al.: Incidence of T Wave Alternation After Acute Myocardial Infarction and Correlation with Other Prognostic Parameters: Results of a Prospective Study. Tachycardia induced alternation of the T wave (TWA) has been associated with arrhythmia morbidity in mixed patient populations. However, less is known concerning the general incidence of TWA and its usefulness in risk stratification early after acute myocardial infarction (MI). TWA was prospectively and systematically assessed in 140 consecutive patients 15 ± 6 days after acute MI and prior to discharge. Results of TWA measurements were compared to other noninvasive risk markers, LV function, and coronary angiography. Sustained TWA was present at rest or inducible during exercise in 27% of patients. The patient‐specific heart rate for the onset of TWA was 98 ± 9 beats/min. After multivariate analysis, TWA correlated with age (P = 0.02) and LV function (P = 0.002) and occurred more often in patients after nonanterior MI (P = 0.03). Acute results of Holter monitoring, late potentials by signal‐averaged ECG, and heart rate variability were unrelated to the TWA status. During follow‐up (451 ± 210 days) two major arrhythmic events occurred. The incidence of TWA early after MI is about 25%. TWA is related to age and LV function but not to other common arrhythmia markers. Although TWA does not appear to be related to excessive cardiac morbidity, evaluation of the prognostic significance of TWA requires further study.

Cerivastatin Activates Endothelial Calcium–Activated Potassium Channels and Thereby Modulates Endothelial Nitric Oxide Production and Cell Proliferation

Statins are known to counteract the process of arteriosclerosis by exerting direct pleiotropic effects on vascular endothelium. The aim of this study was to investigate a possible effect of cerivastatin on endothelial Ca(2+)-activated K+ channels (BK(Ca)) and to assess their contribution to cerivastatin-mediated changes of endothelial nitric oxide (NO) production and proliferation. Membrane potential was measured using bis-1,3-dibutylbarbituric acid-trimethine oxonol-fluorescence imaging. Patch-clamp recordings of BK(Ca) were performed on cultured human umbilical vein endothelial cells. NO production was measured using 4,5-diaminofluorescein-fluorescence imaging and a [(3)H]cGMP RIA. Proliferation was analyzed by means of cell counts and [(3)H]thymidine incorporation (TI). Cerivastatin (0.001 to 0.05 micromol/L) caused a significant membrane hyperpolarization (n = 30; P < 0.05). This effect was abolished using the BK(Ca) inhibitor iberiotoxin (IBX; 100 nmol/L). The addition of mevalonate (500 micromol/L) blocked the BK(Ca) activation induced by cerivastatin (n = 19; P < 0.05). Endothelial cGMP level was increased by acetylcholine (ACh; 1 micromol/L). The combination of ACh and cerivastatin additionally increased cGMP levels, with a maximum at 0.03 micromol/L cerivastatin (84%; n = 10, P < 0.01). ACh-induced increase of cGMP-level was significantly reduced by IBX (n = 10, P < 0.01) as it was with all combined administrations of ACh and cerivastatin. 4,5-Diaminofluorescein-fluorescence measurements revealed a significant increase of NO levels by cerivastatin, which was abolished by IBX (n = 30; P < 0.05). Cell counts and TI demonstrated significant inhibition of human umbilical vein endothelial cell proliferation with a maximum at 0.03 micro mol/L (cell count, -32.2%; TI, -70%; n = 12; P < 0.01). These data show that cerivastatin activates endothelial BK(Ca), which plays an important role in the signaling of cerivastatin-mediated endothelial NO production and proliferation.