Preservation of autonomic function following successful reperfusion with streptokinase within 12 hours of the onset of acute myocardial infarction.

Successful reperfusion following thrombolysis results in increased heart rate variability in the first 24 hours after administration. Preservation of autonomic function may contribute to improved prognosis when coronary artery patency is restored with intravenous thrombolysis.

Failure of plasma atrial natriuretic peptide levels to increase during exercise in patients with chronic atrial fibrillation.

It is generally accepted that plasma atrial natriuretic peptide release occurs secondary to atrial stretch. The influence of coordinated atrial contraction (AC) upon this process is not fully appreciated. The aim of the study was to determine the importance of coordinated AC upon peripheral atrial natriuretic peptide levels (alpha-hANP) during exercise. Peripheral alpha-hANP levels were measured at rest and during exercise in 12 patients with complete heart block (CHB) and permanent rate responsive pacemakers. Seven patients had coordinated AC and five had chronic atrial fibrillation (AF). Each patient performed three treadmill exercise tests. Maximal inspired oxygen volume (VO2 max) was determined during test 1. Tests 2 and 3 were performed to 70% VO2 max, the pacemaker being programmed to either VVI or VVIR mode. Plasma alpha-hANP was measured using a two-site immunoradiometric assay. At rest there was a small but significant difference between the two patient groups: AF 60.2 pg/mL versus AC97.6 pg/mL; P = 0.03. During exercise in the AC patients, there was a significant increase in alpha-hANP levels, in VVIR mode, to 238.4 pg/mL, and in VVI mode, to 207.9 pg/mL, P = 0.002 and 0.003, respectively. In those patients with chronic AF, there was no significant rise or fall in alpha-hANP levels in either pacing mode, VVIR 65.2 pg/mL, VVI 46.6 pg/mL. Previous workers have suggested that alpha-hANP release by nonfunctioning atria is normal. We have shown that the presence of coordinated AC is required for the release of alpha-hANP during exercise in patients with CHB, and that this appears to be independent of ventricular rate.

Octreotide treatment increases exercise capacity in patients with acromegaly.

This prospective study was conducted to determine the effect of Octreotide treatment on cardiovascular function in patients with active acromegaly. Ten acromegalic patients who failed to suppress growth hormone (GH) to < 5 mU/l during a 2 h oral glucose tolerance test were treated with 100 micrograms of Octreotide subcutaneously three times daily for 2 months, followed by 200 micrograms three times daily if the mean GH level was > 5 mU/l, for a total of 1 year. All patients had GH and insulin-like growth factor I (IGF-I) estimation, ejection fraction determined by Echocardiogram and multigated image acquisition scan, electrocardiogram (ECG), exercise ECG, 24-h ECG and chest x-ray. At 6 and 12 months, both GH and IGF-I were reduced but ECG, heart size and ejection fraction were unchanged. The patients improved symptomatically and had significant reduction in resting heart rate and increase in weight. Exercise time (mean +/- SD) increased from 637 +/- 137s at baseline to 787 +/- 101s at 1 year (p < 0.01) and work done increased from 9 +/- 3.3 to 11.9 +/- 2.7 metabolic equivalents (p < 0.001). We conclude that the decrease in GH and IGF-I following Octreotide treatment of acromegaly is accompanied by decreased heart rate and increased exercise capacity despite an unchanged ejection fraction.

Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.

OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.

Successful treatment by balloon venoplasty and stent insertion of obstruction of the superior vena cava by an endocardial pacemaker lead.

A 63 year old man with symptomatic obstruction of the superior vena cava associated with an indwelling pacemaker was successfully treated with balloon venoplasty and stent insertion. He was symptom free with normal pacemaker function nine months later.

The response of implanted dual chamber pacemakers to 50 Hz extraneous electrical interference.

Twenty-two patients with dual chamber pacemakers with interchangeable lead configuration were exposed to 50 Hz electromagnetic interference. Current, at corporeal levels from 0-600 microA, was applied between electrodes on shoulders and feet using a bedside injection unit. Pacemaker behavior was monitored with telemetered event markers and intracardiac electrograms. In bipolar mode, noise reversion mode was induced in all except two Medtronic units at high (> 170 microA) levels of corporeal current. In the Intermedics, Siemens Pacesetter, and Telectronics models, onset of noise reversion mode was preceded by a window of inappropriate function, characterized by rate acceleration due to atrial malsensing, or pacemaker inhibition due to ventricular malsensing. In unipolar mode, pacemaker malfunction occurred at much lower current levels. Inappropriate behavior preceded the onset of protective noise reversion mode. During current injection, all pacemakers could be interrogated and reprogrammed, and intracardiac telemetry was reliably obtained except in two Medtronic units at high current levels. No pacemaker was reset by the electrical interference, and no cross-talk was seen. Use of bipolar mode confers a high degree of protection from extraneous electrical interference, but in unipolar mode pacemakers may be inhibited by small amounts of corporeal current, potentially encountered in every day life. The current injection unit allows safe, controllable, and quantifiable investigation of the effects of the electric field induced by a current on implanted pacemakers. Telemetry of annotated intracardiac signals during electromagnetic interference clarifies observations of pacemaker acceleration and inhibition.

Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation.

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.

Comparison of unipolar and bipolar ventricular paced evoked responses.

OBJECTIVES: To study the differences between endocardial bipolar and unipolar ventricular paced evoked responses and surface electrocardiograms. PATIENTS: 10 patients with conduction system disease awaiting insertion of a permanent pacemaker were studied with temporary ventricular pacing from the right ventricular apex. MAIN OUTCOME MEASURE: Comparison of the durations of the QRS complexes and QTa and QTe intervals of the endocardial bipolar paced evoked response and the surface electrocardiogram with those of the reference unipolar paced evoked response. RESULTS: By comparison with the unipolar reference, the mean durations of the QRS complexes of the bipolar signal and the surface electrocardiogram were 41.8% and 132.1% respectively. The mean QTa interval was 85.9% and 112.2% respectively and the mean QTe interval was 86.9% and 109.5% respectively. All these differences were significant. The amplitudes of the unipolar QRS complexes and T waves were significantly larger than those recorded in the bipolar configuration. CONCLUSIONS: Differences between the unipolar and bipolar ventricular paced evoked responses are significant. The time course of the unipolar signal is closer to that of the surface electrocardiogram. This indicates that the unipolar paced evoked response does not reflect local electrophysiological events, as has been suggested previously.

Amiodarone-induced torsades de pointes: the possible facilitatory role of digoxin.

Poorly controlled supraventricular arrhythmias in a hypokalaemic 74 year old woman were treated with oral amiodarone. This caused torsades de pointes, and was preceded by marked prolongation of the QT interval. The induction of torsades de pointes by amiodarone is thought to be an idiosyncratic reaction to amiodarone itself which is facilitated by electrolytic abnormalities. The present case, however, indicates the possibility of a pro-arrhythmic effect secondary to an interaction between amiodarone and digoxin.

One-year follow-up of automatic adaptation of the rate response algorithm of the QT sensing, rate adaptive pacemaker.

Optimal functioning of a rate adaptive pacemaker depends upon reliable sensing of the sensor and appropriate programming of the rate of response algorithm. QT sensing pacemakers use data derived from the endocardial electrogram in the programming of the rate response algorithm. In the latest versions of these pacemakers, programming of the rate response algorithm may be performed using either a semiautomatic Fast Learn (FL) procedure or by using the newly developed, fully Automatic Slope Adaptation (ASA) mechanism. We report our experience in a prospective study of 17 patients in the first year postimplantation. ASA was characterized by significant changes only in the values of the slope settings at the lower rate limit (3.7 msec/msec at time 0 to 5.77 msec/msec at 2 weeks, P less than 0.001) during the first 2 weeks after its enablement. Further adaptation between weeks 2 to 4 was observed (5.77 msec/msec to 6.4 msec/msec, P = 0.2) but this was not significant. The slope settings derived using the FL procedure were also checked at 2 and 4 weeks and were reproducible. They were closest in value to the values attained by the automated mechanism at 4 weeks. This suggests that the final value of the slope setting at the lower rate limit using ASA is reached between weeks 2 to 4. Both methods of slope determination result in satisfactory and similar rate response profiles but the time to achieve slope stability will necessarily be slower with ASA.

A randomized double-blind, cross-over study of the linear and nonlinear algorithms for the QT sensing rate adaptive pacemaker.

We have compared the pacing rate responses during cardiopulmonary exercise testing in 11 patients (mean 59 years, six female) with implanted QT sensing rate adaptive pacemakers who were randomly programmed to 1-month periods in the linear and nonlinear algorithms using a double-blind, cross-over design. Exercise testing was performed at the end of each month block and symptoms were scored with the MacMaster questionnaire. With exercise, the time to a 10 beats/min increment in rate was significantly less with the nonlinear compared to the linear algorithm (126 sec vs 255 sec, P = 0.02) but there were no significant differences in exercise duration, the peak pacing rate, the peak VO2, the VO2 at the anaerobic threshold or the mean correlation coefficients of the pacing rate VO2 relationship. Rate oscillation occurred in seven patients in the linear algorithm and in two patients in the nonlinear setting. Initial deceleration of the pacing rate at the onset of exercise occurred in seven patients in the linear algorithm and in four patients in the nonlinear setting. The nonlinear algorithm is associated with a faster response time during exercise and fewer instances of rate instability. However, it has not overcome the problem of a dip in the pacing rate at the beginning of exercise. The major difference in the function of the two algorithms is faster initial acceleration with the nonlinear algorithm. This is explained by the significantly higher values of the slope setting at the lower rate limit for the nonlinear versus the linear algorithm (6.3 ms/ms vs 5.1 ms/ms).

Improved rate responsive algorithm in QT driven pacemakers--evaluation of initial response to exercise.

The QT pacemaker is a rate modulated pacemaker that uses the evoked QT interval as an indicator to determine its optimal pacing rate. Despite the generally favorable clinical results with this form of pacing, some flaws in the system have been reported, such as the frequently observed rather slow initial response of the pacing rate to physical exercise, and the phenomenon of oscillation of the heart rate. These problems can be attributed to the rate adaptive algorithm used in the current QT pacemaker. Recently, in a reexamination of the relationship between evoked QT interval and pacing rate, a curvilinear relationship between these parameters has been demonstrated. As a result, a new algorithm has been developed for the next generation of the QT pacemaker. Before this new algorithm was implemented in new implantable devices, it was evaluated in a multicenter clinical investigation, with emphasis on the initial response of the pacing rate to exercise. This study was carried out by means of special software in the programmer of the QT pacemaker. By employing real-time bidirectional telemetry, it was possible to submit the study population, consisting of 37 patients with implanted QT pacemakers of the current generation, to identical exercise tests. Comparing these exercise tests, it appears that a considerable gain in speed of response to exercise can be achieved by using the same sensor with a faster reacting, nonlinear rate adaptive algorithm.

Can central neuropeptides be implicated in carotid sinus reflex hypersensitivity?

Carotid sinus reflex hypersensitivity involves profound and intermittent changes in heart rate and blood pressure associated with symptoms of dizziness and syncope. This involves a reflex arc in which the main defect is believed to lie within the central nervous system. The discovery of classical and peptidergic neurotransmitters within the same neurone, and the presence of these peptides within the central nervous system raises the possibility that carotid sinus reflex hypersensitivity may be related to an abnormality of peptide distribution or function.

Improved pattern of rate responsiveness with dynamic slope setting for the QT sensing pacemaker.

We have recently described the electrophysiological basis of a new algorithm for the QT (TX) sensing rate responsive pacemaker. By using the new software program running on the standard programmer it has been possible to simulate the new algorithm in ten patients with complete heart block (seven patients had implanted TX units and three were paced with an external TX pacemaker) during routine exercise testing. In this way a single-blind, intra-patient comparison of the pattern of pacing rate change using both the existing and new algorithms was possible. In nine out of the ten cases the time taken to increase the pacing rate from 70 to 80 bpm was reduced significantly when the new algorithm was used (P = 0.037). Additionally, the correlation between the atrial and ventricular rates in those patients with normal sinus node function (seven patients) was determined. In all cases we have observed a significantly improved correlation between the atrial and ventricular paced rates during exercise with the new algorithm (P less than 0.001).

Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.

Nonlinear relationship between pacing and evoked QT intervals.

The paced evoked response is an established biosensor which has been used in the design of a rate responsive pacemaker. The unit is capable of sensing the interval between the delivery of a pacing stimulus and the downslope of the evoked T wave. With fixed rate pacing this interval has been shown to shorten with exercise and the main cause of this effect is thought to be mediated by the increase in the plasma catecholamines which are released on exertion. The detection of a reduction in the stimulus-T interval results in an increase in pacing rate. The rate of change of pacing rate is referred to as the slope setting and this must be determined for each individual patient so that optimal rate responsive pacing can be effected. The algorithm underlying the slope setting is the pacing rate-evoked QT interval relationship. This relationship was implemented as a linear function, but this study, which was conducted to reevaluate it, has demonstrated nonlinearity between the pacing and evoked QT intervals. The degree of QT shortening is least at low heart rates. This finding has resulted in the development of a new algorithm for the pacemaker in the form of a new program for the pacing system. This should result in a more physiological rate of change of heart rate with exercise and less chance of sudden changes in rate. These postulates are the subject of current clinical trials.

Incidence of spasm at the site of previous successful transluminal coronary angioplasty: effect of ergometrine maleate in consecutive patients.

The incidence of coronary artery spasm at the site of previous successful angioplasty and its importance in leading to subsequent restenosis or recurrence of symptoms are unknown. Fourteen consecutive patients with single vessel coronary artery disease who had undergone successful percutaneous transluminal angioplasty were studied. All patients were given ergometrine maleate (ergonovine maleate) intravenously during repeat cardiac catheterisation six weeks to three months after angioplasty. Five patients demonstrated excessive luminal reduction (spasm) at the site of previous angioplasty that led to luminal stenoses ranging from 50% to 79%. Two of these patients developed chest pain and ST segment changes during ergometrine maleate provocation and they also showed maximal vasoconstriction. The remaining nine patients did not develop important luminal change at the site of angioplasty after ergometrine maleate. Ergometrine maleate administration resulted in less than or equal to 20% reduction in lumen diameter of adjacent apparently normal sections of the coronary arteries in all but two patients. At the site of previous angioplasty in the five patients with spasm, however, the lumen was constricted by a mean (SD) of 51 (12)%, whereas in the nine patients not demonstrating spasm mean reduction was 12 (7)%. Thus hypersensitivity to ergometrine maleate at the site of previous successful angioplasty was demonstrated in over a third of consecutive patients with single vessel coronary artery disease. The importance of this finding to long term results of coronary angioplasty needs to be investigated further.