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Six patients with Wolff-Parkinson-White (WPW) syndrome were given long-term treatment with amiodarone. Symptomatic relief was obtained in all. Tolerance to the drug was good. Reversible corneal changes appeared after some weeks' treatment in five patients. No thyroid side-effects were noticed. Prior to treatment, dual atrioventricular (AV) conduction was demonstrated on His bundle electrograms in all six patients. Recordings were made at varied heart rates, using atrial and ventricular pacing. Reciprocating tachycardia was readily provoked by properly timed extra stimuli in all patients. When amiodarone treatment had become clinically effective, a second comparative study was made in four patients after 26--85 days' treatment. Amiodarone reduced heart rate and second degree AV block appeared at a lower atrial pacing rate. It increased the refractory periods of right atrium, AV node, and the accessory pathway in proportion to the duration of treatment. Induction of tachycardia was effectively prevented by the drug. It appears that amiodarone in chronic treatment has a predictable and unique depressant action on cardiac conduction, supporting the opinion that this compound, despite side-effects, has an important role to play in the treatment of refractory arrhythmias in patients with the WPW syndrome.

The usefulness and feasibility of recording atrial wall motion by M-mode echocardiography guided by two-dimensional examination was evaluated in three groups of consecutive patients: 7 with undefined tachyarrhythmias, 25 in sinus rhythm, and 20 with atrial flutter or fibrillation. Atrial systole was recorded in the left and right atrium in 58 and 98% of the patients, respectively (p less than 0.05). Six of the patients with undefined tachyarrhythmias exhibited electrocardiographic atrioventricular dissociation revealed by preceding echocardiography in all. The precise timing of left and right atrial systole could be recorded in patients in sinus rhythm; right atrial contraction preceded left atrial systole by 42 +/- 31 msec (mean +/- SD). Among patients with atrial flutter or fibrillation, one case of dissimilar atrial rhythms was revealed by echocardiography. Thus, recording of atrial wall motion is feasible in the majority of patients and provides information which is otherwise available only by esophagus ECG or by invasive means.

Cardiac syncopes appeared in four heavily trained male patients without a history of cerebral or heart disease. Three were young athletes participating in competitive sport, one had trained intensively for years after poliomyelitis complicated by paraplegia. On admission all patients had sinus bradycardia; one had second degree atrioventricular (AV) block at rest, and one had transient sinoatrial (SA) block. His bundle studies demonstrated prolonged recovery time of the SA node (SAN) in two, prolonged atrio-His interval in three, and appearance of second degree AV block at abnormally low pacing rates in two. Refractory periods of the AV node (AVN), determined in three, tended to reach the upper limit of the normal range. The dysfunction of SAN and AVN was temporarily abolished in all patients by 1 mg of atropine i.v., and disappeared during exercise test, which was done by the three young athletes. The patient with paraplegia and one of the young athletes, who had second degree AV block at rest, were given atropine, 0.5 mg six times a day, and all three active sportsmen reduced training activity considerably. After 6--12 months all patients were re-examined. None had cerebral symptoms or other complaints. They were in regular sinus rhythm and in excellent physical condition.

Background: QT dispersion is considered to reflect inhomogeneity of myocardial repolarization. Method: The circadian variation of QT interval dispersion was examined in 95 healthy subjects using 24‐hour Holter monitoring. Three different methods of lead selection were applied: all 12 leads (QTdisp 12), only precordial leads (QTdisp 6), and the pair of leads selected at 3 a.m. in which the longest and shortest QT intervals were found in each individual subject (QTdisp 2). Results: A preliminary methodological study including measurements from every minute in 10 subjects revealed no significant circadian variation using mean values of QTdisp 12, QTdisp 6, or QTdisp 2 obtained every hour, every 2, or every 4 hours, except in QTdisp 6, which demonstrated a significant circadian variation (P < 0.01) in 1‐hour measurements. Analysis of all 95 subjects using measurements obtained every 4 hours revealed a significant circadian variation in QTdisp 12 and QTdisp 6 (P < 0.0001), whereas no circadian variation was seen in QTdisp 2. A subdivision into 10‐year age groups revealed that subjects at age >50 years had a significant circadian variation in QTdisp 12 and QTdisp 6, but not in QTdisp 2. Only in males a significant circadian variation was seen in QTdisp 12 (P < 0.0001), whereas QTdisp 6 demonstrated a circadian variation both in females (P < 0.001) and in males (P < 0.0001). Conclusions: Selection of leads is of crucial importance for repetitive measurements of QT dispersion. Circadian variation was detected in subjects over 50 years of age, when all 12 or only the 6 precordial leads were taken into account.

Objective - To assess the risk of atrial fibrillation (AF) recurrence requiring hospitalisation or its transition to long-lasting AF in patients with earlier or present AF from the clinical characteristics, the duration of AF-disease, and the signal-averaged P wave duration (SAPWD). Design -We studied 111 consecutive patients (40 women; median age 65 years, range 30-85 years) with earlier or present AF. The SAPWD was measured on inclusion; the follow-up median follow-up time was 184 days (range 171-437). Endpoints were hospitalisation due to recurrent AF or transition to AF lasting longer than two days. Results -During follow-up 5 patients died, 33 patients were hospitalised with AF, and 9 patients developed long-lasting AF. Multiple logistic regression analysis showed three risk factors of interest: history of hypertension, OR=3.67 (95% CI 1.61 to 8.37), duration of AF disease longer than two years, OR=3.22 (95% CI 1.31 to 7.86), and non-significantly prolonged SAPWD above 140 ms, OR=1.87 (95% CI 0.60 to 5.82). The probability of relapse in patients without risk factors was 9%, with one risk factor 16-27%, with two risk factors 37-54%, and with three risk factors 74% (p=0.0005). Conclusions -Hypertension and long history of AF disease were associated with an increased risk of AF-relapse.

Myocardial ischaemia has been described during endoscopic retrograde cholangio-pancreatography (ERCP), but the pathogenesis remains unclear. The aim of the present study was to evaluate whether coronary artery disease was present in patients with ST-segment changes during ERCP.Forty patients were monitored with a Holter tape recorder during ERCP. Patients with ST-segment deviation during ERCP subsequently underwent a standard exercise ECG test.Twelve patients developed signs of myocardial ischaemia during ERCP (30%) and 9 had concomitant tachycardia. None had a cardiac history or cardiorespiratory symptoms. Ten of the 12 patients did an exercise test and one patient developed silent ischaemia. Subsequent coronary angiography showed no evidence of coronary artery disease.No signs of existing coronary artery disease were found in patients developing ST deviation during ERCP when evaluated with a 12-lead exercise ECG test. Further studies should evaluate other mechanisms responsible for myocardial ischaemia during ERCP.

Aim Elevation of inflammation markers, high heart rate, and reduced heart-rate variability are all strong markers of mortality in a broad spectrum of patients. The association between these markers has not been clarified thoroughly. We investigated the associations between markers of inflammation, heart rate, and heart-rate variability. Methods and results Six hundred and forty-three healthy men and women between 55 and 75 years of age and with no prior history of cardiovascular disease or stroke were included in the study. The baseline study included a physical examination, fasting laboratory tests, and 24-h ambulatory ECG monitoring. We selected the time-domain components of heart-rate variability for further analyses. C-reactive protein concentration and white blood cell count were selected as markers of inflammation. After identifying parameters related to measures of heart-rate variability, we used regression analyses to evaluate independent associations. Heart-rate variability, as measured by the standard deviation of the time between normal-to-normal complexes or the standard deviation of the average of normal-to-normal intervals for each 5-min period, was negatively associated with smoking, C-reactive protein, white blood cell count, blood sugar and triglyceride concentration, female gender, and diabetes. In contrast, physical activity was strongly associated with higher heart-rate variability. In multivariate regression analyses, increased heart-rate and reduced heart-rate variability were significantly and independently related to white blood cell count or C-reactive protein concentration. Conclusion Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in healthy middle-aged and elderly subjects. The increased mortality that has been reported in these settings may thus have a common aetiology. An autonomic imbalance in favour of the sympathetic system may interact with inflammatory processes to play a more important role in the process of atherosclerosis than previously thought.

Heart rate variability (HRV) has been demonstrated to be a risk factor after acute myocardial infarction (AMI). In the present study serial measurement of SDNN (standard deviation of the mean of qualified NN-interval) in short intervals was used to assess HRV changes after AMI, and determine the role of these as independent risk factors compared to clinical, arrhythmic, ischemic and anamnestic variables. Measurements from a normal healthy middle-aged male population were used as reference (n = 63).SDNN from a five-minute period during day and night-time, respectively, was examined in 103 patients 1 week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction.Day SDNN did not change during one-and-a-half years after AMI, and was significantly reduced compared with healthy males. Night SDNN, low after 1 week, with recovery 1 month after AMI, was significantly reduced compared with healthy males early, but not late after AMI. Thus, the study indicated during day-time a continuous abnormal sympathetic preponderance in the course of 16 months after AMI, and during night-time a gradual recovery of parasympathetic preponderance beginning early after AMI.One week after AMI day-time SDNN of30 ms, and night-time SDNN of18 ms, ageor =60 years, and myocardial ischemia (Holter monitoring) were independent predictors of 9 years' mortality. One and 12-16 months after AMI reduced day and night-time SDNN had no prognostic implication.

Arterial hypertension is accompanied by increased morbidity and mortality and constitutes a substantial part of medical care. Antihypertensive intervention reduces the cardiovascular morbidity and mortality. The aims of the study were to evaluate the relationship between cardiovascular risk factors and the blood pressure (BP), and to evaluate the percentage of patients who had achieved a BP level as recommended by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). BP was evaluated in relation to age, body mass index, duration of hypertension, cholesterol and triglyceride level, smoking status, information of regular exercise, a family history of ischemic heart disease (IHD) and drug treatment, in 220 men treated for arterial hypertension. In the univariate analyses we found a higher systolic blood pressure (SBP) with older age, higher SBP in smoking patients and lower SBP in patients with regular exercise. In a multivariate model age (p = 0.0004), smoking status (p = 0.01) and regular exercise (p= 0.06) were independently associated with SBP. There was a lower diastolic blood pressure (DBP) with older age, and age was independently associated with DBP. Office SBP was above 140 mmHg in 83% and above 160 mmHg in 44% of patients. During ambulatory blood pressure monitoring (AMBP), SBP was above 135 mmHg in 40% and above 155 mmHg in 15% of patients. In addition to male sex and hypertension there was a high percentage of other cardiovascular risk factors--43% was smoking, 21% had a family history of IHD, 77% had a se-cholesterol above 5.5 mmol/l and 48% had a se-triglyceride above 1.6 mmol/l. In a consecutive group of asymptomatic male treated hypertensive patients SBP is independently associated with age and smoking status, and DBP with age. A high percentage of the patients do not have a well controlled BP, and a high percentage have additional risk factors such as smoking, hypercholesterolaemia, hypertriglyceridaemia and a family history of IHD. This means that there is room for much improvement in the control of hypertension.

Background Although ST-segment deviation has been evaluated and used during many years both on continuous electrocardiographic Holter monitoring and during exercise stress testing, considerable controversy still remains concerning the prevalence and diagnostic significance of fortuitously discovered ST-segment deviation in asymptomatic healthy persons. Methods and Results The occurrence of ST-segment deviation was studied in a population of 63 clinically healthy male subjects 51 to 75 years of age, with the use of 24-hour Holter monitoring and exercise stress testing. The subjects were recruited from the Copenhagen City Heart Study and were without cardiovascular risk factors, chronic diseases, or medication and without cardiovascular events during 5 to 12 years before and 3 to 5 years after admission. The specificity, that is, the probability of displaying a negative test result in healthy subjects without disease, was 1.0 when using as criterion for significant ST-segment deviation a horizontal or descending ST-segment depression of >0.20 mV or ST-segment elevation ≥0.15 mV during Holter monitoring, and acceptable, for example, 0.95, when using as criterion a horizontal or descending ST-segment depression of ≥0.15 mV during Holter monitoring or at the exercise test, respectively. Furthermore, the specificity was 0.95 when a horizontal or downsloping ST-segment depression of 0.1 mV was displayed in both the Holter and exercise electrocardiographic recording system. Conclusions Thus in asymptomatic persons, the usual criterion for significant ST-segment depression of 0.1 mV can be applied when occurring in both electrocardiographic recording systems. However, if one test alone is used, the criterion of significant ST-segment depression should be 0.15 mV. Absence of ST-segment deviation during Holter monitoring and exercise stress testing, indicated with a specificity of 1.0 or 0.95 according to choice of criterion, implies that the person is in a healthy state. (Am Heart J 1999;137:1070-4.)

Objective: To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day. Design: Randomised controlled trial. Setting: Copenhagen, Denmark. Subjects: 42 alcoholic patients without liver disease admitted for elective colorectal surgery. Interventions: Withdrawal from alcohol consumption for 1month before operation (disulfiram controlled) compared with continuous drinking. Main outcome measures: Postoperative complications requiring treatment within the first month after surgery. Perioperative immunosuppression measured by delayed type hypersensitivity; myocardial ischaemia and arrhythmias measured by Holter tape recording; episodes of hypoxaemia measured by pulse oximetry. Response to stress during the operation were assessed by heart rate, blood pressure, serum concentration of cortisol, and plasma concentrations of glucose, interleukin 6, and catecholamines. Results: The intervention group developed significantly fewer postoperative complications than the continuous drinkers (31% v 74%, P=0.02). Delayed type hypersensitivity responses were better in the intervention group before (37 mm2v 12 mm2, P=0.04), but not after surgery (3 mm2v 3 mm2). Development of postoperative myocardial ischaemia (23% v 85%) and arrhythmias (33% v 86%) on the second postoperative day as well as nightly hypoxaemic episodes (4 v 18 on the second postoperative night) occurred significantly less often in the intervention group. Surgical stress responses were lower in the intervention group (P≤0.05). Conclusions: One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers. The mechanism is probably reduced preclinical organ dysfunction and reduction of the exaggerated response to surgical stress.

Background: Ventricular ectopy early after an acute myocardial infarction (AMI) has previously been demonstrated to predict mortality. Less information is available about the prognostic implications of ventricular ectopy occurring late after an AMI, and no information is available about the prognostic implication of the development of ventricular ectopy during the first year after an AMI. Hypothesis: The purpose of the present prospectively conducted trial, a part of the Danish Verapamil Infarction Trial II (DAVIT II), was to evaluate the prognostic implication of (1) ventricular premature complexes (VPCs) recorded by 24-h Holter monitoring 1 week, 1 month, and 16 months after an AMI; and (2) development of > 10 VPCs/h or of any complex ventricular ectopy, that is, pairs, more than two types of VPCs, ventricular tachycardia, or > 10 VPCs/h during follow-up after an AMI. Methods: Patients were monitored 1 week (n = 250), 1 month (n = 210), and 16 months (n = 201) after AMI. Results: Multivariate analyses based on history, clinical findings, and ventricular ectopy showed the following results: After 1 week, > 10 VPCs/h (p = 0.0006) and heart failure (p 10 VPCs/h (p = 0.003) and resting heart rate (p 10 VPCs/h from 1 week to 1 month (p = 0.003) and 16 months (p = 0.03), and from 1 to 16 months (p = 0.007) after AMI, as well as by the development of any complex ventricular ectopy from 1 week to 1 month (p = 0.02) and 16 months (p = 0.01), and from 1 to 16 months (p = 0.04) after AMI. Conclusion: The present study demonstrated that 1 week and 1 month after an AMI the quantity of VPCs, that is, >10 VPCs/h, predicted mortality, whereas 16 months after an AMI the quality of VPCs, that is, ventricular tachycardia, predicted mortality.

Objective: Criteria for detection of late potentials have not yet been standardized, but the criteria recommended by ESC/AHA/ACC are widely used. In this investigation, the prevalence of late potentials is studied in an age stratified healthy population with likelihood of coronary artery disease < 5%. Relation between signal-averaged variables and clinical variables was studied. Methods: Signal-averaged ECGs were recorded using Butterworth filters at 40 and 250 Hz. The following three time-domain parameters were evaluated: QRS duration (duration of the amplified, filtered QRS complex); LPD (duration of the late potentials, i.e., duration from the point of time when the magnitude of the main complex becomes lower than 40 μV); and RMS40 (root mean square of the activity within the last 40 ms of the amplified, filtered QRS complex). Results: QRS duration was significantly longer in men than in women, and was correlated to the mass of the left ventricle (LVM). The combination LPD and RMS40 gave the highest prevalence of late potentials. The prevalence of late potentials was 25%. Conclusion: Standard criteria should be used with great caution, and normal limits should be established in each laboratory to a preselected noise level. QRSD should be included within the definition of reference limits and should be gender matched. Even though there is correlation between LVM and the QRSD, the upper normal limit of QRSD based on LVM matching is unchanged.

One hundred and ninety consecutive patients discharged with congestive heart failure were examined with clinical evaluation, blood chemistry, 24 h Holter monitoring, exercise test and radionuclide angiography. Median left ventricular ejection fraction was 0.30, 46% were in New York Heart Association class II and 44% in III. Total mortality after 1 year was 21%, after 2 years 32%. Of 60 deaths, 33% were sudden and 49% due to pump failure. Multivariate analyses identified totally different risk factors for sudden death: ventricular tachycardia, s-sodiumor = 137 mmol/l, s-magnesiumor = 0.80 mmol/l, s-creatinine121 mumol/l, and maximal change in heart rate during exerciseor = 35 min-1, and for death from progressive pump failure: New York Heart Association class III + IV, delta heart rate over 24 hor = 50 min-1, low ejection fraction, high resting p-noradrenaline, s-urea7.6 mmol/l, s-potassium3.5 mmol/l, and maximal exercise durationor = 4 min. In conclusion, this study demonstrated different risk factors for sudden death and for death from progressive pump failure.

To evaluate the efficacy of anipamil, a phenylalkylamine calcium antagonist, in treatment of stable angina pectoris, we performed a randomized, double blind placebo-controlled, cross-over study. Inclusion criteria were (a) stable angina pectoris for at least 2 months, (b) an exercise test with > or = 0.1-mV horizontal or downsloping ST-segment depression limited by angina, and (c) at least 10 attacks of angina pectoris in a single-blind 3-week run-in period. Nineteen patients were randomized to enter the study. In 3-week periods, they received either anipamil 80 mg once daily (o.d.), anipamil 160 mg o.d., or placebo. At the end of each period, an exercise test was performed. The number of angina pectoris attacks was significantly reduced during treatment with anipamil 80 mg (p < 0.05) and anipamil 160 mg (p < 0.001) as compared with placebo. Glycerol nitrate consumption was significantly reduced during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.001) as compared with placebo. During exercise testing, the load (W) at start of angina was significantly increased during treatment with anipamil 80 mg (p < 0.01) and 160 mg (p < 0.05) as compared with placebo. Heart rate (HR) at 0.1 mV ST-segment depression was increased during treatment with anipamil 80 mg (p < 0.001). Few adverse events were reported.

The present study was a prospectively planned subset of the postinfarction, double blind, randomized, multicenter, placebo controlled trial of verapamil, DAVIT II. Patients had 24 hours of Holter monitoring before randomization, i.e., second week after infarction (placebo, n=122; verapamil, n=128), after 1 month (placebo, n=108; verapamil, n=94) and after 16 months (placebo, n=75; verapamil, n = 63) of treatment. The purpose was to evaluate the effect of verapamil on the prevalence and changes over time of arrhythmias and heart rate. In patients monitored twice, a significant increase of average ventricular premature complexes (VPC) per hour from before to 1 month (p=0.0007) and 16 months (p=0.02) after was demonstrated in the placebo group, and from before to 1 months (p=0.01) after in the verapamil group. Average VPC/hr did not change from 1 to 16 months of treatment. A significant increment of >10 VPC/hr was found after 1 (p=0.03) and 16 months (p=0.05) compared to prerandomization in the placebo, but not in the verapamil group. A significant increase of supraventricular arrhythmias after 1 month compared with prerandomization was found in the placebo group (p=0.003) but not in the verapamil group. The prevalence of VPC and supraventricular tachycardia was significantly lower in the verapamil compared with the placebo group after 1 month of treatment. At 16 months no significant difference was found between the two groups. The 24 hour mean heart rate was significantly lower, 3 beats/min, in the verapamil compared with placebo after 1 and 16 months of treatment. Thus a significant increase of ventricular and supraventricular arrhythmias during the first postinfarction month, without change the following year, was seen in the placebo group. Verapamil significantly lowered heart rate, prevented supraventricular tachycardia, and reduced VPC early after an AMI. This rather limited effect of verapamil on postinfarction arrhythmias cannot explain the beneficial effect of verapamil on mortality and major events in patients without heart failure.

The purpose of this study was to examine the 24-hour antiischemic efficacy of once-a-day anipamil compared to placebo in the treatment of patients with stable angina. The study was designed as a double-blind, placebo-controlled crossover study with an initial 3 week single-blind placebo period. The patients received anipamil 80 mg once daily, anipamil 160 mg once daily, and placebo in a randomized order. At the end of each treatment period the patients underwent 24-hour ambulatory ECG recording. Nineteen patients were included, all with typical stable angina pectoris for at least 2 months, exercise test withor = 0.10 mV horizontal or down-sloping ST-segment depression and limited by angina pectoris, and at least 10 attacks of angina pectoris in the initial single-blind placebo period. During the placebo period, a total duration of transient myocardial ischemiaor = 0.10 mV during the 24-hour ambulatory ECG monitoring period was 2263 minutes, 75% of which were asymptomatic. Anipamil 80 mg and 160 mg significantly reduced the duration of episodes to 712 minutes (p0.001), with 87% asymptomatic, and to 913 minutes (p0.001), with 92% asymptomatic, respectively. In conclusion, anipamil given once a day is an effective 24-hour antiischemic drug in the treatment of transient myocardial ischemia.

To determine the best sites for ambulatory monitoring leads to detect myocardial ischaemia.50 consecutive patients recovering from myocardial infarction. Six patients were excluded because of unsatisfactory recordings or baseline electrocardiographic abnormalities that influenced the diagnostic accuracy of ST segment depression. In 38 patients important ST segment changes were seen before the study recordings.Reproducibility of detecting the electrocardiographic ST segment changes with 12 bipolar leads alone or in combination.The highest reproducibility rate was found in infarcts involving both the anterior and inferior left ventricular walls (80%). The reproducibility decreased as the extent of ventricular wall involvement decreased and was lowest in inferior infarcts (31%) (p0.001). For large infarcts the detection rate was almost equal for the 12 study leads, whereas disparity between leads increased as the infarct size decreased. The highest overall reproducibility was found in a transthoracic lead (V2, V9R) (76%). This lead was significantly better (p = 0.03) than lead CM5 (50%). When the transthoracic lead was combined with an inferior lead, the reproducibility increased (82%) and was significantly better than the combination of CM5 and an inferior lead (58%) (p = 0.02).Extensive ischaemic electrocardiographic changes are better detected than smaller ones and anterior infarcts better than inferior. A transthoracic lead (V2, V9R) was significantly better than CM5 both alone and when CM5 and the transthoracic lead were combined with an inferior lead.

Background: QT dispersion is considered an index of spatial inhomogeneity of repolarization duration and increased dispersion of ventricular repolarization is supposed to increase the risk of ventricular arrhythmia. Circadian variation in QT dispersion was investigated. Methods: Three different modes of lead selection was used: all 12‐leads (QTdisp 12), only precordial leads (QTdisp 6), and one pair of preselected leads (QTdisp 2) in a 24‐hour Holter recording every fourth hour each comprising 10 consecutive measurements in 54 healthy subjects, 29 patients with coronary artery disease (CAD), and 29 patients with heart failure (HF). Results: A significant circadian variation was observed in healthy subjects when modes QTdisp 12 and QTdisp 6 were used (Mean ± SD 35.58 ± 16.48 ms; P < 0.0001; and 28.82 ± 16.02 ms; P < 0.0001, respectively), and in patients with CAD (Mean ± SD 37.86 ± 17.87 ms; P < 0.01; and 28.72 ± 17.06 ms; P < 0.0001, respectively), whereas no circadian variation was observed in QTdisp 2. No circadian variation was observed in patients with HF irrespectively of lead selection. Patients with CAD without myocardial infarction (MI) had a circadian variation in QTdisp 12 (Mean ± SD 33.13 ± 14.86 ms; P < 0.05), whereas no circadian variation was observed in patients with MI (Mean ± SD 40.35 ± 18.80 ms; P = NS). Conclusions: Circadian variation of QT dispersion was detected in healthy subjects and in patients with uncomplicated CAD, but not in those who had suffered a previous MI and in patients with HF. The number of leads among which selection of the longest and shortest QT intervals took place was critical for the disclosure of circadian variation of QT dispersion.

To find out if drugs, position, and endoscopic manipulation during endoscopic retrograde cholangiopancreatography (ERCP) influence the changes in the variability of heart rate.Single-blind randomised trial.10 volunteers given butyscopolamine, glucagon, or saline intravenously on three different study days, and 10 patients who had ERCP without butylscopolamine or glucagon.Holter tape analysis for ischaemia and changes in the variability of heart rate.5 volunteers developed tachycardia after butylscopolamine, while 2 developed tachycardia after glucagon. During ERCP 9 patients developed tachycardia, and 2 developed myocardial ischaemia. Vagal tone decreased in the volunteers after butylscopolamine, but no changes were seen after glucagon or placebo, or in patients during ERCP.Butylscopolamine reduced vagal tone in volunteers. Patients who were having ERCP without butylscopolamine had a stable vagal tone. The previously observed reduced vagal tone during ERCP may therefore be primarily the result of giving butylscopolamine.

The pathophysiological mechanisms responsible for increased cardiovascular mortality in diabetic autonomic neuropathy are unknown. To investigate the effect of autonomic neuropathy on myocardial function, we performed dynamic contrast-enhanced magnetic resonance perfusion imaging during baseline conditions and after Dipyridamole-induced vasodilatation in nine type 1 diabetic patients with autonomic neuropathy (AN+), defined by cardiovascular tests, as well as in 10 type 1 diabetic patients without autonomic neuropathy (AN−) and 10 healthy control subjects. Baseline myocardial perfusion index (Ki) was similar in the three groups (AN+ 88.6 ± 8.7 ml · 100 g−1 · min−1, AN− 82.6 ± 7.2, control subjects 93.7 ± 9.0) (means ± SE). Ki during Dipyridamole vasodilatation was significantly lower in the patients with autonomic neuropathy (P < 0.001) than in the other groups (AN+ 131.1 ± 13.0 ml · 100 g−1 · min−1, AN− 177.3 ± 8.6, control subjects 197.2 ± 8.9). Mean blood pressure was unchanged during Dipyridamole infusion in AN− and control subjects, whereas a significant blood pressure decrease was found in AN+ (15.6 ± 2.6 mmHg, P < 0.025). There was a significant correlation between blood pressure response to Dipyridamole and myocardial perfusion reserve index. We conclude that type 1 diabetic patients with autonomic neuropathy have a decreased myocardial perfusion reserve capacity when challenged with a vasodilatator, a finding that may in part be the pathophysiological substrate for the increase in mortality in these patients. The underlying mechanism may be defective myocardial sympathetic vasodilatation, a lack of ability to maintain blood pressure during vasodilatation, or both.

Background and Study Aims: Previous studies have shown that up to 50% of healthy patients may develop ST-segment changes during upper gastrointestinal endoscopy. The aim of the study was to evaluate myocardial blood flow in patients during endoscopic retrograde cholangiopancreatography (ERCP). Patients and Methods: 11 patients scheduled for ERCP were monitored with a Holter tape recorder and underwent myocardial perfusion scintigraphies, to evaluate myocardial perfusion at rest and during ERCP. Results: Ten patients completed the study. Eight patients had no sign of myocardial ischemia with either of the two methods, while two patients developed signs of ischemia during ERCP with both the Holter tape recording and on myocardial scintigraphy (P = 0.02). Conclusions: Patients undergoing ERCP may develop true myocardial ischemia with reduced myocardial blood flow. Although this is a small-scale study, these findings strongly support the use of alternative methods for diagnostic evaluation of the pancreatic duct and biliary tree.

OBJECTIVE Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus cyclic norethisterone acetate (NETA) or placebo in two 12-week periods separated by a 3-month washout Clinic blood pressure was measured sitting by the same observer with a mercury manometer at four visits in each period. Twenty-four hour ambulatory blood pressure was measured at baseline and in the ninth weeks of treatment in both periods. RESULTS Clinic systolic and diastolic BP were reduced after 10 days of oestradiol (-5.1 and -3.2 mmHg respectively, P < or = 0.05). After 9 weeks of cyclic HRT, prior to progestogen addition, clinic BP returned to baseline. During addition of NETA, diastolic blood pressure was again reduced (-3.6 mmHg, P= 0.037). Mean 24 h ambulatory systolic and diastolic blood pressures were significantly lower than clinic measurements (-15.7 and -5.9 mmHg, P < 0.001) but were unaffected by HRT. CONCLUSIONS Clinic blood pressure is reduced during a cyclic HRT regimen but the reduction varies with the HRT regimen, which might explain the diversity in previous BP findings during HRT. Norethisterone acetate might possess additive blood pressure-lowering effects in postmenopausal women.

Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk of developing cardiorespiratory complications, but the mechanism is still unknown. Treatment with metoprolol 2 h before the endoscopy has been shown to decrease the incidence of myocardial ischaemia during ERCP. The present study evaluated whether the endoscopic stress would decrease vagal tone and whether metoprolol given before the procedure could prevent this defence-like reaction.Thirty-eight patients were randomized to receive either placebo or 100 mg metoprolol 2 h before ERCP. During ERCP the patients were monitored with a Holter tape recorder. Holter tapes from 31 patients (16 receiving metoprolol) were available to analyse the ratio of the standard deviations of the RR intervals (SDRR) to the mean RR intervals (measure of vagal tone) during ERCP.A decreased vagal tone during the ERCP was found, but we observed no difference between the metoprolol and the placebo group. For both groups the lowest vagal tone occurred at maximum heart rate during endoscopy. The SDRR/meanRR ratio returned towards base line for the subsequent 60 min after endoscopy.The existence of a defence-like reaction ('vagal withdrawal') during ERCP has been shown. Metoprolol given 2 h before the procedure did not affect the occurrence of this phenomenon. The interaction of other periendoscopic factors is still unclear and should be studied further.

Hypothesis: Gasless laparoscopy produces smaller cardiopulmonary and systemic changes than carbon dioxide (CO 2 ) laparoscopy during colonic surgery. Design: Prospective randomized trial. Setting: Department of Surgery in a university hospital. Patients: Twenty-two patients scheduled for laparoscopic colonic resection; 5 patients were excluded because of conversion to open surgery (N = 17). Interventions: Patients were randomized to either gasless (n = 9) or conventional CO 2 (n = 8) surgery. Main Outcome Measures: Intraoperative assessment of hemodynamic factors and pulmonary function, and postoperative assessment of pain, pulmonary function, convalescence, and various injury factors were done several times until 30 days after surgery. Surgical complications were noted. Results: Descending aorta blood flow after 30 minutes (P =.03) and heart rate after 150 minutes were higher in the CO 2 group (P = .009). Central venous pressure, Paco 2 . inspiration pressure, and end tidal CO 2 level were significantly higher in the CO 2 group (P = .05, .03, .04, and .01, respectively). Patients in the CO 2 group had less pain during mobilization and coughing (P = .008 and .006, respectively), and were significantly more fatigued (P = .04). No other important differences were observed in intraoperative hemodynamic factors, postoperative convalescence, immunocompetence, or pulmonary function. Conclusion: No clinically important differences in cardiovascular and systemic response were observed between patients undergoing CO 2 or gasless laparoscopy for colonic disease.

Upper gastrointestinal endoscopy is often accompanied by tachycardia, which may lead to myocardial ischaemia. The pathogenesis for tachycardia is unknown, but the classic endocrine stress response may be of importance.Seventeen patients (median age, 60 years) undergoing diagnostic gastroscopy without sedation or supplemental oxygen therapy were monitored by means of electrocardiogram, blood pressure, and pulse oximetry from 20 min before to 2 h after the procedure. Blood concentrations of glucose, cortisol, epinephrine, and norepinephrine were measured before, during, and after the endoscopy. Anxiety level was rated before the examination.Endoscopy was followed by a significant increase in norepinephrine and cortisol levels concomitant with a significant peak in heart rate (76 to 90 min(-1)) and mean arterial blood pressure (97 to 111 mmHg). Epinephrine was significantly reduced after the endoscopic procedure. We found no changes in glucose level or in arterial oxygen saturation. None of the patients developed signs of myocardial ischaemia during the procedure. There was no correlation between preendoscopy anxiety and the different stress variables (P0.3).The endoscopic procedure induces a classic endocrine metabolic stress response, probably causing the observed tachycardia.

Myocardial ischaemia (defined as ST-segment deviation on electrocardiogram (ECG)) may occur during colonoscopy, but the pathogenic mechanisms are unknown. We have evaluated the occurrence of arterial hypoxaemia, tachycardia, and myocardial ischaemia during routine colonoscopy.Eighteen patients underwent colonoscopy under conscious sedation and without supplementary oxygen. Arterial oxygen saturation was measured by continuous pulse oximetry, and ECG was monitored continuously with a Holter tape recorder during the procedure.Arterial oxygen desaturation and tachycardia were common during colonoscopy and occurred in 45% and 35% of patients, respectively. Two patients developed signs of myocardial ischaemia during the colonoscopy: one case of ST depression (1.7 mV) and one case of ST elevation (4.3 mV). In both patients the ST deviation disappeared when the colonoscope was retracted. Myocardial ischaemia occurred in both patients simultaneously with tachycardia, and in one of these arterial hypoxaemia was also present.Myocardial ischaemia occurs during routine colonoscopy, but with a lower incidence than previously reported during upper endoscopy. Myocardial ischaemia during colonoscopy may be associated with tachycardia and/or hypoxaemia. Further studies should clarify the relative role of tachycardia, hypoxaemia, and viscerocardiac reflexes in the pathogenesis of myocardial ischaemia during colonoscopy.

Objective: To evaluate the effect of metoprolol, a s adrenergic blocking drug, on the occurrence of myocardial ischaemia during endoscopic cholangiopancreatography. Design: Double blind, randomised, controlled trial. Setting: University Hospital. Subjects: 38 (two groups of 19) patients scheduled for endoscopic cholangiopancreatography. Interventions: Metoprolol 100 mg or placebo as premedication two hours before endoscopy. Main outcome measures: Heart rate, arterial oxygen saturation by continuous pulse oximetry, ST segment changes during endoscopic cholangiopancreatography (an ST segment deviation >1 mV was defined as myocardial ischaemia), electrocardiogram monitored continuously with a Holter tape recorder. Results: All patients had increased heart rate during endoscopy compared with rate before endoscopy, but heart rate during endoscopy was significantly lower in the metoprolol group compared with the placebo group (P = 0.0002). Twenty one patients (16 placebo, 5 metoprolol; P = 0.0008) developed tachycardia (heart rate > 100/min) during the procedure, and 11 patients (10 placebo, 1 metoprolol; P = 0.003) developed myocardial ischaemia. One patient in the placebo group had an acute inferolateral myocardial infarction. In the 10 other patients with signs of myocardial ischaemia during endoscopy the ST deviation disappeared when the endoscope was retracted. In all patients myocardial ischaemia was related to increases in heart rate, and 10 of the 11 patients had tachycardia coherent with myocardial ischaemia. Conclusions: Metoprolol prevented myocardial ischaemia during endoscopic cholangiopancreatography, probably through lowering the heart rate. Thus, tachycardia seems to be a key pathogenic factor in the development of myocardial ischaemia during endoscopy. Key messages Metoprolol prevented myocardial ischaemia during endoscopy Myocardial ischaemia was related to tachycardia more than to concomitant hypoxaemia Tachycardia seems to be a key pathogenic factor in the development of myocardial ischaemia during endoscopy

Verapamil is effective as antianginal medication but contraindicated in patients with congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure but have limited effect on patients with angina pectoris. No studies have been published on the combined treatment with verapamil and ACE inhibitors in patients with stable angina pectoris and left ventricular dysfunction. We performed an open study in 14 patients with angina pectoris and ejection fraction < 40%. The patients received verapamil 180 mg and trandolapril 2 mg twice daily for 3 months. We found a significant increase in ejection fraction from 28 +/- 6 to 35 +/- 11 (p < 0.03), wall motion index from 1.0 +/- 0.3 to 1.2 +/- 0.3 (p < 0.03), exercise duration from 6.9 +/- 2.5 to 7.7 +/- 2.9 minutes (p < 0.01), and ratio of exercise to rest rate-pressure product from 2.2 +/- 0.4 to 2.5 +/- 0.6 (p < 0.02). Use of nitroglycerin and number of angina pectoris attacks were both significantly reduced after 3 months of treatment. These findings support the hypothesis that the combination of verapamil and trandolapril is useful in patients with attenuated left ventricular function and angina pectoris.

Once-daily administration of 10 mg amlodipine has been compared with two daily doses of 40 mg sustained-release isosorbiddinitrate (ISDN) in 59 patients with stable angina, using a randomized, double-blind, double-placebo, crossover study design. Nine patients dropped out due to side effects (3 during amlodipine and 6 during ISDN therapy), and one patient was excluded for technical reasons. A maximal symptom limited supine bicycle tolerance test and a 48 h ambulatory ECG monitoring were performed at the end of each 5 week period of therapy. During exercise, exercise time, time to onset of angina, and time to onset of ischaemia, i.e., 1 mm ST segment depression were measured. During ambulatory monitoring, number of anginal episodes and duration per hour of ST deviation were assessed. Amlodipine significantly prolonged time to angina (320 ± 155 vs 304 ± 126 sec; p l 0.05) and time to ischaemia (292 ± 153 vs 232 ± 126 sec; p l 0.001). when compared with ISDN, while exercise time was similar for both treatments. Furthermore, amlodipine reduced anginal episodes (1.2 ± 1.6 vs 2.4 ± 3.0 attacks/48 h; p l 0.001), whereas, no difference was found between amlodipine and ISDN in duration of ST deviation during ambulatory monitoring. In conclusions, addressing the long-term treatment of patients with stable angina pectoris, once-daily dosing of amlodipine appears to be more effective than ISDN, as determined by its anti-anginal and anti-ischaemic effects during exercise tolerance testing and ambulatory ECG monitoring.

The purpose of this prospectively conducted study was to determine the prevalence of transient myocardial ischemia, evaluated from 24 h continuous ECG monitoring and exercise test, 6 months after inclusion in the Anglo Scandinavian Study of Early Thrombolysis (the ASSET trial, a randomised, placebo controlled study of alteplase for survival in patients with suspected acute myocardial infarction (AMI)), and to relate these findings to development of cardiac events. Of the 58 consecutively studied patients ischemic responses were found in 13 (45%) of 29 patients initially treated with placebo, and in 21 (72%) of 29 alteplase treated patients (P = 0.03). After another 6 months, i.e. 12 months after the acute event, two patients were dead, two had non-fatal reinfarctions and three had coronary artery by-pass surgery in the group with ischemic response; no events were recorded in patients without ischemia (P0.05). Alteplase treated patients more often had late myocardial ischemia, and cardiac events were found in patients with ischemia. Since the ASSET trial has demonstrated significantly higher short- and long-term survival rate in the alteplase treated group, it was indicated (1) that alteplase treated patients were better positioned for sustaining subsequent ischemia and thus cardiac events due to preservation of viable myocardial tissue, and (2) that late ischemia in the setting of initial alteplase treatment may convey other information than ischemia occurring in placebo treated patients.

Aims We aimed to determine the prevalence and prognostic significance of daily-life silent myocardial ischaemia (SMI) in healthy middle-aged and elderly subjects with no previous heart disease. Methods and results Six hundred and seventy-eight healthy men and women between 55 and 75 years of age and with no history of cardiovascular disease or stroke were included. Baseline examinations included physical examination, fasting laboratory testing, and 48 h ambulatory electrocardiogram monitoring. An episode of ischaemia was defined by a down-sloped or horizontal ST depression of at least 1 mm at a duration of at least 1 min. Seventy-seven subjects (11.4%) had SMI. All participants were followed for up to 5 years. In 77 subjects with SMI, 16 (20.7%) had an event (death or myocardial infarction). In 601 subjects without SMI, 50 (8.3%) had an event. The hazard ratios for SMI in relation to cardiac and combined events after correction for conventional risk factors were 3.1 [(1.24-7.97), P=0.016] and 1.97 [(1.06-3.69), P=0.033], respectively. Conclusion SMI as detected by Holter monitoring was detected in 11.4% of these subjects and was associated with more than three-fold increase in the cardiac event rate after correction for risk factors, implying that this test could be used to identify high-risk individuals among these subjects.

Four young healthy men (17–25 years old) experienced life-threatening arrhythmias during physical exertion. All were successfully resuscitated. One died later. Electrophysiological studies disclosed a lack of normal conduction delay and abnormal His-Purkinje properties indicating congenital malformation of the atrioventricular (AV) node in one patient and the rare and potentially dangerous combination of an accessory AV pathway and intraatrial conduction delay with liability to dissimilar rhythms and fibrillation in the atria in another. The conduction system functioned normally in the other two. One of the latter two patients had cerebral damage during prolonged resuscitation and experienced repeated epileptic spells until he died unexpectedly. Autopsy revealed scarring of unknown origin in the interventricular septum. The other had stress-induced ventricular ectopy, which gradually diminished and disappeared in a few weeks. The etiology of the latter two is suggested to be ischemia. It is warranted to point out the possible danger of maximal physical strain even in young people.

Holter monitoring of 51 patients on the 4th to 6th day after acute myocardial infarction (AMI) disclosed complex ventricular ectopic beats in 17 (35%), nine of whom (53%) died in the following 26 months. Of the remaining patients with no or only non-complex ectopic beats, five (15%) died. The difference was significant using Gehan's test of censored data (p less than 0.01). Multivariate analysis demonstrated a significant increase of death risk associated with complex ventricular ectopic beats as well as with heart failure (relative risk 3.6 and 5.9, respectively). Age, gender, number of ventricular ectopic beats, cardiac enlargement on X-ray and angina pectoris had no significant effect on mortality. The prevalence of ventricular ectopy was 84% (n = 43) irrespective of age and sex and equal to the finding in the late hospital phase reported by other investigators, and in healthy subjects. Complex ventricular ectopic beats appeared in 35% (n = 17). The prevalence increased significantly with age and was significantly higher in post-infarction patients (38%) than in healthy individuals (8%). The present results indicate that a subgroup containing most of the high-risk patients may be identified early after AMI by detecting complex premature ventricular beats in continuous electrocardiographic recordings.