J.C.P. Crick

Anisoylated plasminogen streptokinase activator complex in acute myocardial infarction: A placebo-controlled arteriographic coronary recanalization study

Anisoylated plasminogen streptokinase activator complex (APSAC) is a new thrombolytic agent that is of interest because of its ease of administration as an intravenous bolus injection. This report describes the first double-blind, placebo-controlled evaluation of intravenous APSAC for coronary recanalization in acute myocardial infarction. Unequivocal documentation of recanalization was provided by coronary arteriography before and after the drug intervention. Forty patients with acute myocardial infarction underwent coronary arteriography 3.1 +/- 1.2 hours after the onset of symptoms. This demonstrated occlusion of the infarct-related coronary artery in 29 patients who were then randomized to treatment with intravenous APSAC, 30 mg (n = 16), and placebo (n = 13) 3.3 +/- 1.3 hours after the onset of symptoms. Repeat arteriography 90 minutes later demonstrated recanalization of the infarct-related coronary artery in nine patients who had received APSAC compared with only one patient who had received placebo (56 versus 8%, p less than 0.05). The 95% confidence limits for this 48% difference between the groups are 20 to 76%. Arteriography at 3 days showed persistent patency of all recanalized coronary arteries except one (APSAC group) and also showed late recanalization in another four patients, three of whom had received APSAC. In the patients who had a patent infarct-related coronary artery at the initial arteriographic study, patency was maintained throughout the study period regardless of whether the patient was randomized to APSAC (n = 4) or placebo (n = 7). Complications related to APSAC therapy were excessive bruising at the catheterization site in seven patients and minor sensitivity reactions in three.(ABSTRACT TRUNCATED AT 250 WORDS)

Early percutaneous transluminal coronary angioplasty in the management of unstable angina

This report describes the results of percutaneous transluminal coronary angioplasty in 56 patients with unstable angina. In each case diagnostic coronary angiography had demonstrated a critical proximal stenosis in a major vessel. The stenosis was successfully dilated without complication in 70% of cases. Angiographic success was reflected by the abolition of symptoms and a nonischaemic predischarge stress test in 82 and 72% of cases, respectively. Importantly, at six months follow-up 69% of these patients remained symptom free though repeat angioplasty had been necessary in 21% of cases. The in-hospital incidence of myocardial infarction and death was 7.1 and 5.4%, respectively, but during the six month follow-up period only one additional complicating event occurred. Results were particularly favourable in patients with single vessel disease, 83% of whom had successful procedures. There was one uncomplicated myocardial infarct in this subgroup but no deaths. These data indicate that percutaneous transluminal coronary angioplasty may be undertaken with relative safety in patients with unstable angina and leads to a substantial improvement in symptoms that is sustained during early follow up. The benefits of this therapeutic approach may be particularly marked in patients with single vessel disease.

Successful Long‐Term Ventricular Pacing Via the Coronary Sinus After the Fontan Operation

A man with double inlet left ventricle and severe subpulmonary stenosis underwent a Fontan operation at the age of 29 years. Eight years later he developed atrial flutter with complete heart block. To avoid a further thoracotomy, a unipolar carbon tipped electrode was placed into the posterior cardiac vein via the coronary sinus. More than 8 years after implantation of the original lead, and after two generator changes, telemetric thresholds remain between 1.8–2.1 volts. Percutaneous transvenous ventricular pacing via the coronary sinus can produce an excellent long‐term result and should be the initial approach of choice after a Fontan‐type operation.

Intravenous amiodarone in the acute termination of supraventricular arrhythmias

This study was performed to ascertain whether intravenous amiodarone would revert supraventricular tachycardias to sinus rhythm, and if so, whether this effect depended upon the underlying mechanism of the arrhythmia. Fourteen patients were studied. Seven had Wolff-Parkinson-White (WPW) syndrome, 1 had dual atrioventricular nodal pathways and 1 an ectopic atrial tachycardia. Five patients had atrial fibrillation without accessory pathways. An atrial electrode was inserted to initiate tachycardias and record the electrogram. If tachycardias were stable for more than 5 min, amiodarone (5 mg/kg) diluted with dextrose saline was infused intravenously over 5 min. Two electrocardiographic leads and the right atrial electrogram were monitored. In 7 patients with atrial fibrillation (2 with accessory pathways), 6 did not revert to sinus rhythm, 1 reverted only after 1 hr. In 5 cases without accessory pathways the ventricular rate fell 5-10 min after commencing amiodarone. Four of the 5 patients with WPW syndrome and re-entrant tachycardias returned to sinus rhythm within 6 min of commencing the infusion (atrioventricular and ventriculoatrial times increased by 0-38% and 0-14% respectively). (Tachycardias terminated in the anterograde limb.) Three patients underwent intermittent right atrial stimulation for 1 hr. No tachycardias could be initiated for 30 min post amiodarone. The ectopic atrial tachycardia and that due to dual atrioventricular nodal pathways terminated within 7 and 2 min, respectively, of commencing intravenous amiodarone. Thus the use of intravenous amiodarone would be appropriate in the acute management of sustained supraventricular tachycardias.

Evolution of atrial signals from a single Lead VDD pacemaker

The atrial sensing capabilities of a new single pass lead VDD pacing system (Pacesetter AddVent) were assessed in a prospective multicenter study of 101 implants during the period July 1994 through March 1996. The pacing lead (Pacesetter AV Plus) has a unique quadripolar 4‐in‐line connector and uses a pair of ring electrodes with an interelectrode spacing of 12 mm for atrial sensing. The mean age of the patients (51 men) was 73 years (range 19–91). Seventy‐five patients had complete heart block; the others had 2:1 AV block. Wide variations were found in signal amplitude: mean P wave amplitude, measured over four cycles in the supine position, was 2.4 ± 1.9 mV at implant, dropping to 1.9 ± 1.7 mV predischarge, and remaining constant at follow‐up but with a narrower range. Holter monitoring was undertaken in 24 patients, with a total of 550 monitored hours. Mean AV synchrony was 98.2%± 4.6% (excluding premature ventricular contractions), with 20 patients (83%) showing > 99% AV synchrony, with atrial sensing at 0.1 mV where needed. No oversensing was observed in any patient. There was a low incidence of atrial fibrillation (2%) and sinus bradycardia (0%). The findings show that the range of atrial signals, although wide initially, converges over the first year and remains adequate for reliable AV synchronous pacing.

Antitachycardia pacing: a comparison of burst overdrive, self-searching and adaptive table scanning programs.

Eight patients with the Siemens Elema “Tachylog” genera for implanted for management of paroxysmal reentrant tachycardia were studied to assess the safety and efficiency of three antitachycardia programs. The programs investigated were burst overdrive, self‐searching, and adaptive table scanning. There were five males and three females aged 19–62 years. Seven had Wolff‐Parkinson‐White syndrome, and one had dual atrioventricular nodal pathways. Four had right atrial electrodes and four had right ventricular electrodes. Patients were studied lying, standing, and exercising in all three modes, and the appropriate long‐term programs were chosen. The generator remained in a program for 1 month, if was interrogated and the memory was read, and then it was reprogrammed to a different antitachycardia mode. Burst overdrive was unsuitable for long‐term use in four patients, producing atrial fibrillation in one and ventricular arrhythmias in three. In this group, self‐searching and adaptive table scanning were safe and equally effective (mean number of attempts/tachycardia 6.97 and 6.3, respectively). In the four patients in whom all three programs could be used, burst overdrive proved to be most efficient, the mean number of attempts/tachycardia were 2.4 (cf 9.6 and 9.0 for self‐searching and adaptive table scanning). Thus, burst overdrive was only suitable for long‐term use in 50% of our patients, but when safe it was more efficient than the other two programs, especially in those with narrow termination windows on exercise.

Low energies and Helifix electrodes in the successful ablation of atrioventricular conduction.

High energies delivered via standard pacing catheter electrodes produce permanent atrioventricular conduction block and generate high pressures. We investigated the use of lower energies and an active fixation electrode. Ten patients with refractory supraventricular tachycardias (six with paroxysmal atrial fibrillation, three with dual AV nodal pathways, and one with a concealed accessory atrioventricular pathway) were treated. A 6F Vitatron Helifix electrode was positioned to give the maximum His bundle deflection. Four shocks of only 50 joules each were delivered at 1‐minute intervals. Long‐term follow‐up showed that seven patients (70%) had persistent complete heart block and two had atrial fibrillation with slower ventricular rates. Nine patients (90%) were symptom‐free without antiarrhythmic therapy. Permanent pacemakers were implanted in eight patients. There were no complications resulting from the procedure. Transvenous ablation of atrioventricular conduction can be safely achieved using a Vitatron Helifix eleclrode and much lower energy values than have been previously employed.

Clinical Evaluation of a Single-Pass Implantable Electrode for All Modes of Pacing. The “Crown of Thorns” Lead

Physiological pacing was instituted in 37 patients (33 men and 6 women), mean age 67 years (range 33–77 years), using a variety of multiprogram‐mable generators attached to a permanent single‐pass dual chamber electrode. Eleven patients were paced in VAT mode (Cordis 208A or Siemens‐Elema 625 generator), two patients in DVI mode (Inter‐medics Cyberlith IV generator) and four patients in DDD mode (Siemens‐Elema 664/P33 or Telec‐tronics Autima unit). Mean intracardiac P wave amplitude was 2.0 mV ± 0.78/SD, range 0.7–3.6 mV, and mean atrial and ventricular pacing thresholds were 1.0 V and 0.5 V, respectively. Fourteen patients had completely successful A‐V pacing during a follow‐up period of 4‐33 months (mean 7 ± 2.7 months). Two failures were associated with malposition of the atrial crown and occurred exclusively with the Cordis 208A generator. In both patients generator replacement using a more sensitive unit (Siemens‐Elema 625) resulted in successful VAT pacing for most of the time, Complete failure of A‐V pacing occurred in only one patient who died from coronary artery disease after four months of follow‐up. Thus, all of the remaining 36 patients achieved long‐term (6 months) satisfactory physiological pacing using this new lead. We conclude that the “Crown of Thorns” electrode is a successful single‐pass unipolar lead and can be used with all types of dual chamber generator for all modes of pacing.

Successful Treatment of Ventricular Tachycardia by Physiological Pacing

The case is presented of a young patient with atrioventricular (AV) block but no evidence of other disease; in this patient exercise or stress‐related syncope continued after implantation of a ventricular inhibited (VVI) pacemaker. Investigation revealed exercise‐induced limited rapid multiform ventricular tachycardia (VT) which was associated with faintness or syncope. Temporary atrial triggered ventricular inhibited ventricular (VDD) pacing resulted in enhanced exercise tolerance with no significant arrhythmia. A permanent full function dual chamber [DDD] pacemaker was implanted and prevented the VT. There have been no further exercise‐related symptoms during two years 0f follow up.

An interim report of a double-blind placebo-controlled recanalisation study of anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

SummaryThis is an interim report of the initial 36 patients entered into the first double-blind, placebo-controlled invasive arteriographic study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) for coronary recanalisation in acute myocardial infarction. Coronary arteriography was performed before and 90 minutes after a single intravenous bolus injection of APSAC or placebo given over 2 to 5 minutes.Pretreatment coronary arteriography was performed in 36 patients at a mean time of 189 ± 75 minutes after the onset of symptoms. 28 patients had occluded infarct-related coronary arteries and were randomised to receive APSAC 30U (n = 15) or placebo (n = 13) by intravenous injection 195 ± 72 minutes after the onset of symptoms. Coronary arteriography 90 minutes after treatment demonstrated recanalisation of the infarct-related coronary artery in 8 APSAC-treated patients compared with only 1 placebo-treated patient (p < 0.02). Repeat coronary arteriography 3 days after treatment showed reocclusion in 1 of the 8 APSAC-treated patients and persistent perfusion in the single patient who reperfused on placebo.All patients with patent vessels at pretreatment coronary arteriography (3 APSAC, 5 placebo) remained patent throughout the study period. There were no haemorrhagic complications related to APSAC therapy. These data confirm that APSAC is a safe, effective thrombolytic agent which, when administered by the intravenous route, resulted in a 53% recanalisation rate.