Quantitative analysis of signal-averaged P waves in idiopathic paroxysmal atrial fibrillation.

Detailed analysis of the QRS complex can identify patients at risk from ventricular arrhythmias, but similar techniques applied to the atria have been disappointing. This study attempts to quantitate differences in the fine morphology of P waves in a group of 9 patients with paroxysmal atrial fibrillation (AF) versus 15 control subjects. Atrial triggered signal-averaging was combined with a detailed investigation of P-wave duration, high-frequency spatial voltage and spatial velocity. Signal-averaged P-wave duration was significantly increased in patients with paroxysmal AF (135 +/- 8 vs 126 +/- 4 ms, p less than 0.05). The root-mean-square voltage at frequencies greater than 35 Hz in these patients was also significantly greater (16 +/- 3 vs 12 +/- 1 microV, p less than 0.05). Similar observations were made at frequencies greater than 40 Hz (10 +/- 3 vs 7 +/- 1 microV, p less than 0.05). These differences appeared to be confined to the third quarter of the P wave (third quarter root-mean-square voltage at greater than 40 Hz expressed as a ratio of total P-wave root-mean-square voltage, 1.4 +/- 0.1 vs 1.2 +/- 0.1, p = 0.005). Spatial velocity was also increased in the paroxysmal AF group (peak spatial velocity 6.4 +/- 1.8 vs 4.6 +/- 0.5 mV/s, p less than 0.05). These observations support previous intracardiac data that implicate delay and fragmentation of intraatrial conduction in the pathogenesis of paroxysmal AF.

The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol.

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases. The exercise-induced tachycardia was maintained within 12% of pre-dose levels, presumably by withdrawal of vagal tone.5. Cardiac inotropism, as indicated by dPLv/dt max, was not affected by ZD7288 or zatebradine at rest,although the inotropic response to exercise decreased in proportion to the decreases in exercise-induced tachycardia. Propranolol caused a marked dose-dependent decrease in the exercise-induced inotropic response (by 85% at 0.3mg kg-1).6. Whilst the sino-atrial node modulators increased stroke volume at rest, and augmented increases in response to exercise, propranolol did not affect resting stroke volume and decreased the responses to exercise.7. Cardiac output at rest and cardiac output increases during exercise were well maintained in the presence of ZD7288 and zatebradine in contrast to propranolol which induced a significant depression of cardiac output, both at rest and during exercise. Propranolol also caused significant systemic vasoconstriction.8. In conclusion, ZD7288 has haemodynamic actions comparable to those of zatebradine despite their chemical dissimilarity. ZD7288 may be of benefit in the treatment of ischaemic heart disease by reducing heart rate without impairing cardiac function.

Reproducibility of the signal averaged P wave: time and frequency domain analysis.

OBJECTIVE: To assess the reproducibility of time and frequency domain variables derived from the signal averaged P wave. DESIGN: Longitudinal within patient study. SETTING: Regional cardiothoracic centre. PATIENTS: 20 patients (10 with documented paroxysmal atrial fibrillation and 10 normal controls) were studied on three occasions to assess the reproducibility of repeated signal averaged P wave recordings. Digital P wave recordings were made on a further 10 patients on a single occasion and the recordings signal averaged twice in order to assess the reproducibility of the averaging system itself in the absence of biological variation. MAIN OUTCOME MEASURES: P wave duration, spatial velocity, and energies contained in frequency bands from 20, 30, and 60-150 Hz of the P wave spectrum were measured after P wave specific signal averaging. Coefficients of reproducibility were calculated for paired signal averaged P waves derived by signal averaging the same digital recordings on two separate occasions, for recordings performed in the same patients immediately after each other ("back to back") and those performed one week apart. RESULTS: System reproducibility when the same digital P wave recordings were signal averaged on two separate occasions was high (< 11% for all variables). For P wave duration the coefficient of reproducibility was 11.4% for back to back recordings and 13.1% for those one week apart. The reproducibility of spatial velocity and P wave energy was low. Variation in P wave morphology was noted when successive P waves from the same subject were examined. If recordings with the same P wave morphology were analysed the reproducibility of spatial velocity and P wave energy improved but remained significantly poorer than that for P wave duration. CONCLUSIONS: P wave duration is reproducible within subjects in the short and medium term. Frequency domain and spatial velocity analysis are poorly reproducible, due more to spontaneous variation in P wave morphology than to instability of the signal averaging process. This may limit the utility of signal averaged P wave variables other than duration for the prediction of atrial arrhythmia.

Effect of sequential radiofrequency ablation lesions at fast and slow atrioventricular nodal pathway positions in patients with paroxysmal atrial fibrillation.

OBJECTIVE: To examine the hypothesis that the anatomic equivalents of the fast and slow pathways identified in patients with atrioventricular (AV) nodal tachycardia may be universal and represent the principal sites of atrial input into the normal compact AV node. METHODS: 15 patients undergoing complete AV junction ablation for paroxysmal atrial fibrillation were studied. Radiofrequency energy was delivered first in the anterior "fast pathway" position so as to prolong the atrium to bundle of His (AH) interval by over 50% of baseline (protocol 1) and then to the "slow pathway" position using the anatomical technique (protocol 2). RESULTS: Ablation protocol 1 resulted in prolongation of AH interval in all patients. Subsequent lesions at the level of the coronary sinus produced complete heart block in four patients, and in five caused a further increase in AH interval above that produced by protocol 1. Four of these latter patients developed complete block after delivery of RF energy slightly anterior to the level of the coronary sinus os, as did three further patients in whom ablation at the level of the coronary sinus had no effect. In four patients complete heart block could not be achieved by protocol 2. CONCLUSIONS: A discrete anterior "fast" pathway and a posterior "slow" pathway or network of posterior pathways form the principal inputs to the compact AV node in most patients with atrial fibrillation. The absence of dual AV nodal physiology in the majority of these patients may be related to the functional properties of the individual components of this posterior network.

Signal averaged P wave compared with standard electrocardiography or echocardiography for prediction of atrial fibrillation after coronary bypass grafting.

OBJECTIVE: To define the clinical value of the signal averaged P wave (SAPW) and to compare it with the standard electrocardiogram (ECG), echocardiogram, and clinical assessment for the prediction of atrial fibrillation after coronary bypass grafting (CABG). DESIGN: Prospective validation cohort study. SETTING: Regional cardiothoracic centre. PATIENTS: 201 unselected patients undergoing first elective CABG were recruited over six months. Patients requiring concomitant valve surgery were excluded. MAIN OUTCOME MEASURES: Age, sex, cardiothoracic ratio, and cardioactive drugs were noted. P wave specific SAPW recordings, ECG, and M mode echocardiograms from which left atrial diameter was measured were performed within 24 hours of surgery. Filtered P wave duration (SAPWD), spatial velocity, and energy were calculated from the SAPW. From the ECG, lead II P wave duration, P terminal force in lead V1, total P wave duration, and isoelectric interval were measured. Patients had Holter monitoring for 48 hours postoperatively and daily ECGs until discharge. RESULTS: Two patients died (1%) and 10 were unsuitable for analysis (5%). Of the remaining 189, 51 (27%) had atrial fibrillation (AF) lasting > 1 hour at a mean of 2 (0.5 to 7) days after CABG. Of the variables examined, only SAPWD (AF group 148 (SD 12), v 142 (14) ms, P = 0.008) and male sex (AF group 96%, v 78%, P < 0.01) were significantly different. A prospectively defined SAPWD of > 141 ms predicted atrial fibrillation with positive and negative predictive accuracies of 34% and 83%. Logistic regression analysis identified both male sex and SAPWD as significant independent predictors of postoperative atrial fibrillation. CONCLUSIONS: Signal averaged P wave duration was a better predictor of atrial fibrillation after coronary bypass grafting than standard electrocardiographic or echocardiographic criteria. The predictive value of this test is such that it is likely to be useful in the design of prospective trials of prophylactic antiarrhythmic treatment but is of limited use using current techniques in the clinical management of individual patients.

The signal averaged P wave in atrioventricular block--evidence for abnormal atrial conduction?

The incidence of atrial fibrillation in patients with atrioventricular block (AVB) appears increased over that for the unpaced population even if atrioventricular synchrony is maintained by dual chamber pacing. To assess whether atrial fibrillation in these patients might be due to concurrent abnormality in atrial activation we performed signal averaged P wave (SAPW) recordings in 15 patients with dual chamber pacemakers implanted for AVB and compared the results to those from 21 unpaced controls. The median (range) age was 69 (53-89) years for patients and 60 (51-78) years for controls. Eleven patients and 12 controls were male. All patients were pacing in VDD mode at the time of study. SAPW recordings were obtained using our previously reported selective P wave averaging system. We measured P wave duration after high pass filtering at 40 Hz, the rate of change of P wave voltage over time (spatial velocity) and low and high frequency spectral energy after Fourier transformation of the P wave signal. We found increased P wave duration, mean spatial velocity and lower frequency energy in patients with AVB compared to controls [duration, 144 (5) vs. 134 (2) ms, p<0.05; mean spatial velocity, 5.6 (0.4) vs. 4.6 (0.1) mV/s, p<0.05; energy 20-150 Hz, 57.4 (8.2) vs. 36.3 (2.8) muV2.s, p<0.01. All values mean (SEM)]. These results suggest that the increased incidence of atrial fibrillation in patients paced for AVB may be related to intrinsic abnormalities of atrial activation and not solely to the pacing mode. Ensuring sequential atrioventricular pacing in these patients may not completely abolish the increased incidence of atrial fibrillation.

Multiple microemboli after disintegration of clot during thrombolysis for acute myocardial infarction.

Seven of 475 consecutive patients treated with thrombolysis for acute myocardial infarction had severe embolic complications that were believed to be caused by disintegration of pre-existing clot. Three patients had symptoms that persisted for many weeks, and five died. Any potential site of pre-existing blood clot within the vascular system, notably an enlarged left atrium, ventricular aneurysm, or aortic aneurysms, should be regarded as a contraindication to treatment with thrombolytic agents.

Analysis of QRS-T subtraction in unipolar atrial fibrillation electrograms.

This paper presents a QRS-T subtraction approach for atrial fibrillation (AF) intracardiac atrial electrograms (AEG). It also presents a comparison between the proposed method and two alternative ventricular subtraction techniques: average beat subtraction (ABS) using a fixed length window and an approach based on flat interpolation for QRS cancellation. Areas of the atrium close to the mitral valve showed stronger ventricular influence on the AEGs when compared with the remaining atrial regions. Ventricular influence affects the spectral power distribution of the AEG and can also affect the estimation of the dominant frequency unless the whole ventricular activity influence (QRS-T) is removed. The average power after QRS-T subtraction is significantly reduced for frequencies above 10 Hz (mostly associated with QRS complexes), as well as for frequencies between 3 and 5.5 Hz, (mostly related to T waves). The results indicate that the proposed approach removes ventricular influence on the AF AEGs better than the QRS cancellation method. Spectral analysis showed that both the ABS and the proposed method do well and no method should be preferred to the other. In the time domain, the proposed approach is matched to the lengths and timings of onset and offset for individual QRS-T segments while the ABS approach uses an arbitrary length around the QRS for the pattern used for QRS-T removal.

Recurrent pneumothorax following abdominal paracentesis.

A 62 year old man presented with abdominal ascites, without pleural effusion, due to peritoneal mesothelioma. He had chronic obstructive airways disease and a past history of right upper lobectomy for tuberculosis. On two occasions abdominal paracentesis was followed within 72 hours by pneumothorax. This previously unreported complication of abdominal paracentesis may be due to increased diaphragmatic excursion following the procedure and should be considered in patients with preexisting lung disease.

Spectrotemporal and spectral turbulence analysis of the signal-averaged P wave in paroxysmal atrial fibrillation.

Patients with paroxysmal atrial fibrillation (AF) have greater overall P wave magnitude than control subjects, but the temporal localization of the increased energy is unknown. P wave spectral turbulence has not been investigated in such patients, and the optimum methodology for studying P wave signals has not been defined. This study, therefore, applied both spectrotemporal and spectral turbulence analyses to the signal-averaged P waves of patients with paroxysmal AF and to representative control subjects. Group A, 58 persons without cardiopulmonary disease (24 patients with paroxysmal AF, 34 control subjects), and group B, 57 with such disease (31 patients with paroxysmal AF, 26 control subjects), were studied. Spectral analysis was performed on a windowed 64-ms data segment that was advanced through the P wave in 2-ms steps. Spectral turbulence was measured from differentiated 24-ms data segments, by either cross-correlation between adjacent spectra, or differentiation of adjacent spectral coefficients over time (SV, spectral velocity). Patients had greater maximum P wave energy than control subjects, between 80-150 Hz for group A (means, 0.9 vs 0.7 microV2 x s), and 20-150 Hz for group B (means, 22.4 vs 16.3 microV2 x s). Spectral velocity was greater in patients with paroxysmal AF than in control subjects in both groups (group A: Peak SV, 11.6 vs 7.4 microV2 and group B: Peak SV, 12.0 vs 7.6 microV2). Increased energy and SV were reported in the central P wave. Spectrotemporal analysis suggested abnormal atrial activation in the central P wave associated with paroxysmal AF. A localized abnormality in atrial electrophysiology may cause the electrogenesis of the arrhythmia.

Improved recovery of high frequency P wave energy by selective P wave averaging.

Most signal averaging processes used for cardiac signals align successive waveforms using a template matching process. In addition to achieving accurate temporal alignment of the signals, this operation must also ensure that the signal average comprises signals of the same morphology. For P wave signal averaging, systems designed for QRS complex averaging are often used, with the template acquisition window shifted to include the P wave. Theoretically, with this technique, variations in P wave morphology could reduce the high frequency content of the signal. We tested this hypothesis by comparing the performance of a selective P wave averaging system with a conventional system, based on template matching by cross-correlation over a fixed acquisition window, on identical P wave recordings from 15 subjects. The selective system identifies variations in P wave morphology and generates up to five candidate templates for averaging. Subsequently, the most frequently matched template over a 100-beat sample is used for averaging. Only P waves with the same morphology as this template are averaged. Selective averaging mainly increased the measured high frequency P wave energy, without affecting P wave duration after high pass filtering at 40 Hz, (Duration: 157(4)ms selective vs 155(4) nonselective. Energy 80-150 Hz: 1.77(0.28), microV2.s selective vs 1.61(0.3) microV2.s non selective, P < 0.01). These observations confirm that nonselective P wave averaging can reduce apparent P wave energy, especially at high frequency. Before meaningful studies of the value of frequency domain analysis of the P wave can be performed, it is important that signal averaging systems of sufficient fidelity are utilized.

Optimal analysis of the signal averaged P wave in patients with paroxysmal atrial fibrillation.

OBJECTIVE: To define the ability of analysis of the signal averaged P wave to identify patients with paroxysmal atrial fibrillation (AF) and establish whether differences in quantitative variables between patients and controls are due to concurrent cardiopulmonary disease, greater atrial dimension, or to unrelated changes in atrial electrophysiology. DESIGN: An observational parallel group study. SETTING: Cardiac department of a busy district general hospital. PATIENTS: 58 participants without cardiopulmonary disease (24 with paroxysmal AF and 34 controls, group A) and 57 with cardiac or respiratory conditions (31 with paroxysmal AF and 26 controls, group B). Mean (range) age of patients was 54 (25-71) and controls 53 (34-78) for group A and 65 (45-81) and 62 (36-78) respectively for group B. Left atrial size was similar in patients and controls in each group (mean (SEM)) group A: 2.39 (0.1) v 2.19 (0.07) cm; group B: 2.51 (0.10) v 2.71 (0.12) cm). MAIN OUTCOME MEASURES: Analysis of the P wave after P-wave-specific signal averaging. Filtered P wave duration and spatial velocity were calculated. Energies contained in frequency bands from 20, 30, 40, 60, and 80 to 150 Hz after spectral analysis were expressed as absolute values (P20, P30 etc) and ratios of high to low frequency energy (PR20, PR30, etc). RESULTS: Duration and peak spatial velocity were increased in patients with paroxysmal AF (median (interquartile range) duration group A: 144 (137-155) v 136 (129-143) ms, P = 0.007; group B: 155 (144-159) v 142 (136-151) ms, P = 0.002; peak spatial velocity group A: 16.5 (14.1-21.2) v 14.5 (11.7-18.1) mV/s, P = 0.02; group B: 18.9 (14.8-21.8) v 14.3 (12.6-17.6) mV/s, P = 0.01). Energy contained in frequency bands from 20, 30, 40, 60 and 80 to 150 Hz was expressed as absolute values (P20, P30, P40, P60, and P80) and percentage energy ratios. P30, P60, and P80 were significantly greater in patients with AF in group A (for example P60: 3.9 (3.0-5.3) v 3.1 (2.0-4.3) microV2.s, P = 0.02) and P20, P30, and P40 were increased in those with AF in group B (for example P40: 16.7 (9.9-20.8) v 10.8 (8.1-14.8) microV2.s, P = 0.02). A score developed from logistic regression analysis of duration and P60 identified patients with paroxysmal AF with a sensitivity of 81% and specificity of 73%. CONCLUSIONS: Increased P wave duration and magnitude are associated with paroxysmal AF with and without additional cardiopulmonary disease. The discriminant ability of the signal averaged P wave is improved by analysis of duration and a magnitude variable. These results invite prospective assessment of the ability of the signal averaged P wave to predict paroxysmal AF in unselected patients.

Effect of low dose sotalol on the signal averaged P wave in patients with paroxysmal atrial fibrillation.

OBJECTIVE: To investigate the effects of low dose sotalol on the signal averaged surface P wave in patients with paroxysmal atrial fibrillation. DESIGN: A longitudinal within patient crossover study. SETTING: Cardiac departments of a regional cardiothoracic centre and a district general hospital. PATIENTS: Sixteen patients with documented paroxysmal atrial fibrillation. The median (range) age of the patients was 65.5 (36-70) years; 11 were men. MAIN OUTCOME MEASURES: Analysis of the signal averaged P wave recorded from patients not receiving antiarrhythmic medication and after 4-6 weeks' treatment with sotalol. P wave limits were defined automatically by a computer algorithm. Filtered P wave duration and energies contained in frequency bands from 20, 30, 40, 60, and 80 to 150 Hz of the P wave spectrum expressed as absolute values (P20, P30, etc) and as ratios of high to low frequency energy (PR20, PR30, etc) were measured. RESULTS: No difference in P wave duration was observed between the groups studied (mean (SEM) 149 (4) without medication and 152 (3) ms with sotalol). Significant decreases in high frequency P wave energy (for example P60: 4.3 (0.4) v 3.3 (0.3) microV2.s, P = 0.003) and energy ratio (PR60: 5.6 (0.5) v 4.7 (0.6), P = 0.03) were observed during sotalol treatment. These changes were independent of heart rate. CONCLUSIONS: Treatment with low dose sotalol reduces high frequency P wave energy but does not change P wave duration. These results are consistent with the class III effect of the drug and suggest that signal averaging of the surface P wave may be a useful non-invasive measure of drug induced changes in atrial electrophysiology.

Prediction of maintenance of sinus rhythm after cardioversion of atrial fibrillation by analysis of serial signal-averaged P waves.

After cardioversion from atrial fibrillation (AF) many patients develop early recurrence of the arrhythmia. While these patients may be appropriate for immediate prophylaxis against AF recurrence their identification at the time of cardioversion is not possible. Since the signal-averaged P wave (SAPW) is abnormal in individuals with atrial arrhythmia, we assessed its utility for predicting early AF recurrence after cardioversion. Seventy-five cardioversions in 31 patients were evaluated. The mean age was 59 (range 28-79) years; 26 were male. Fifty-eight cardioversions were internal using low energy biphasic DC shocks delivered via electrodes placed in the right atrial appendage and coronary sinus. P wave specific signal averaging was performed at 3 and 24 hours after each cardioversion to estimate filtered P wave duration and energy from 20, 40, and 60 to 150 Hz. Follow-up was by regular clinic visits and transtelephonic ECG monitoring. Early recurrence of AF (prospectively defined as sinus rhythm duration < 1 week) occurred after 30 cardioversions. No differences were found in any P wave variable measured at 3 hours between these cardioversions and those that resulted in a longer duration of sinus rhythm. Paired 3- and 24-hour signal-averaged data were available in 47 cardioversions. There were significant falls in P wave energy from 3 to 24 hours after 31 cardioversions that resulted in sinus rhythm for > 1 week, (P40: 3 hours 11.2 [+/- 1.5] micro V2.s, 24 hours 8.6 [+/- 1.2] micro V2.s, P < 0.001), but not following the 16 after which AF returned within 1 week (P40: 3 hours 9.0 [+/- 1.2] micro V2.s, 24 hours 8.5 [+/- 1.2 micro V2.s, P = NS). A fall in P40 of > 25% had a positive predictive accuracy for maintenance of sinus rhythm of 87%; negative predictive accuracy was only 37%. Similar falls in P wave energy occurred after cardioversions that resulted in longer term (> 4 weeks) sinus rhythm, but not in those that did not. However, the predictive accuracy of a fall in P40 was less (positive predictive accuracy 38%, negative predictive accuracy 62%). Patients with relapsing permanent AF who remain in sinus rhythm for at least 1 week after cardioversion show a fall in P wave energy within the first 24 hours. However, in these patients the technique does not predict recurrent AF within 1 week nor sinus rhythm > 4 weeks. These observations suggest persistent disordered atrial activation as a mechanism for early recurrence of AF after cardioversion.

Left ventricular dysfunction resulting from frequent unifocal ventricular ectopics with resolution following radiofrequency ablation.

A case is presented, in which asymptomatic but persistent right ventricular outflow tract (RVOT) ectopics resulted in left ventricular (LV) dilatation and systolic dysfunction. The patient underwent extensive investigation with no other cause for the cardiomyopathy being found. Successful ablation of the RVOT ectopic focus resulted in normalization of LV size and function. This case suggests that frequent ventricular ectopy should be considered as a potentially remediable cause of LV dysfunction.

Reduction in hospital time to thrombolytic therapy by audit of policy guidelines.

Despite the importance of early thrombolysis in the treatment of acute myocardial infarction, unacceptable delays in drug administration still occur in hospital. From March 1989 we decided to monitor our performance, and thereby to reduce avoidable in-hospital delay to a minimum. Potential candidates for thrombolytic therapy were identified by paramedic ambulancemen whenever this was feasible. Rapid check-lists were used for inclusion and exclusion criteria in the Accident and Emergency Department. A target of 15 min was set for time to treatment, and reasons for any gross deviation (greater than 30 min) were explored in each instance. As a result of these strategies, we achieved a median time from admission to initiation of thrombolysis in 50 consecutive patients of 17 min. The 39 patients treated with injections of APSAC as opposed to infusions of streptokinase had a median in-hospital delay to treatment of only 13 min.

The pituitary-adrenal response to CRF-41 is unaltered by intravenous somatostatin in normal subjects.

We have previously reported that the hypothalamo-pituitary-adrenal response to insulin-induced hypoglycaemia is normal while the cortisol release to pituitary stimulation by corticotrophin releasing factor (CRF-41) is reduced in obesity. Impaired growth hormone (GH) secretion is also found in obesity which may result from altered central levels of somatostatin (SMS). We have investigated, by giving a simultaneous infusion of SMS to six volunteer normal weight men during a CRF test, whether it is possible for SMS to modify pituitary-adrenal function. Each subject received intravenous CRF-41 (0.5 micrograms/kg) on two occasions during an infusion of isotonic saline or SMS (4 micrograms/min) in a randomized double-blind study. Plasma GH, cortisol, ACTH and SMS were measured. Three subjects demonstrated GH peaks during saline infusion but no peaks were seen in any subject during SMS infusion. No significant difference was found between peak cortisol responses during saline or SMS infusion (SMS cortisol 443 +/- 61 nmol/l, saline cortisol 485 +/- 52 nmol/l); neither was there any difference in the ACTH responses. We conclude that SMS does not alter the pituitary response to CRF in normal weight men and is thus less likely to be responsible for the altered pituitary-adrenal function seen in obesity. Further studies of alternative mechanisms are required to explain the cause of this abnormality.

The Midlands Trial of Empirical Amiodarone versus Electrophysiology-guided Interventions and Implantable Cardioverter-defibrillators (MAVERIC): a multi-centre prospective randomised clinical trial on the secondary prevention of sudden cardiac death.

AIMS: MAVERIC was a randomised clinical trial designed to test the possibility of prospectively identifying patients who would benefit most from the implantable cardioverter-defibrillator (ICD) by electrophysiology (EP) study in the context of secondary prevention of sudden cardiac death (SCD) through comparing EP-guided interventions (anti-arrhythmic drugs, coronary revascularization, and ICD) against empirical amiodarone therapy. METHODS: Two hundred and fourteen survivors of sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or SCD were randomized to either treatment strategy, pre-stratified for haemodynamic status at index event, and followed up for a median of 5 years. RESULTS: Of the 106 amiodarone arm patients, 89 (84%) received the drug and 5 (5%) received an ICD after crossing over. Of the 108 EP arm patients, 31 (29%) received an ICD, 46 (43%) received anti-arrhythmic drugs only (mainly amiodarone or sotalol) and 18 (17%) received coronary revascularization but no ICD. No significant differences in survival or arrhythmia recurrence existed between the two treatment arms after 6 years. However, ICD recipients had a lower mortality than non-ICD recipients, regardless of allocated treatment (hazard ratio=0.54, p=0.0391). CONCLUSIONS: Prospective selection of patients to receive the ICD by EP study did not improve survival compared with empirical amiodarone therapy among survivors of VT, VF or SCD, whereas ICD implantation improved survival regardless of allocated treatment. On this basis, routine EP study has no role in the management of such patients, who should be offered empirical ICD therapy according to the results of other secondary prevention ICD trials.