QT intervals and QT dispersion determined from a 12-lead 24-hour Holter recording in patients with coronary artery disease and patients with heart failure.

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.

Circadian variation in QT dispersion determined from a 12-lead Holter recording: a methodological study of an age- and sex-stratified group of healthy subjects.

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.

Increased ventricular ectopic activity in relation to C-reactive protein, and NT-pro-brain natriuretic peptide in subjects with no apparent heart disease.

BACKGROUND: Subjects with frequent ventricular premature complexes (VPC) and no apparent heart disease make a heterogenic group with regard to prognosis. Some biomarkers have recently proved useful in risk stratification in different heart diseases. We examined prognostic impact of NT-Pro-brain natriuretic peptide (NT-Pro BNP), and C-reactive protein (CRP) in relation to frequent VPC in subjects with no apparent heart disease. METHODS: Six hundred seventy-eight healthy subjects between 55 and 75 years of age with no history of cardiovascular disease were included in the study. All were tested with fasting laboratory testing and 48-hour ambulatory ECG monitoring. Frequent VPC was defined as VPC > or =30/hour. RESULTS: In 56 subjects (8%) with frequent VPC the prognosis was much poorer compared to those without frequent VPC (Hazard ratio and 95% CI: 2.3;1.2-4.4, P = 0.01), after adjustment for conventional risk factors. In subjects with frequent VPC increased levels of CRP (above 2.5 microg/mL) was the only factor among the tested biomarkers, which was associated with a poor prognosis. Taking subjects without frequent VPC as reference, the hazard ratio and 95% CI for subjects with frequent VPC and increased CRP was 3.6;1.8-7.1, P = 0.0004, and for those with frequent VPC and normal CRP 0.8;0.2-3.5, P = 0.83, after correction for conventional risk factors. CONCLUSIONS: Among middle-aged and elderly subjects with no apparent heart disease and frequent VPCs, a CRP value > or =2.5 microg/mL is associated with a significantly higher risk of death and acute myocardial infarction. These subjects deserve primary prevention measures and further work up for structural heart disease.

Ventricular arrhythmias and risk of death and acute myocardial infarction in apparently healthy subjects of age >or=55 years.

Increased ventricular ectopic activity and even more complex arrhythmias are not uncommon in subjects without apparent heart disease. However, their prognostic significance has been controversial and not updated in recent years. The prevalence and prognostic significance of different ventricular arrhythmias were studied in a cohort of middle-aged and elderly subjects without apparent heart disease. Six hundred seventy-eight men and women aged 55 to 75 years without a history of heart disease or stroke were included. Baseline examinations included physical examinations, fasting laboratory testing, and 48-hour ambulatory electrocardiographic monitoring. All patients were followed for up to 5 years. Combined events were defined as all-cause mortality or acute myocardial infarction. A cardiovascular event was defined as cardiovascular death or acute myocardial infarction. In total, 84% had 0 to 10 ventricular premature complexes (VPCs)/hour, 8% had 11 to 30 VPCs/hour, and 8% had >30 VPCs/hour; 10.8% had >or=1 run of >or=3 VPCs. Frequent VPCs (>or=30/hour) was a significant predictor of combined (hazard ratio 2.47, 95% confidence interval 1.29 to 4.68, p = 0.006) and cardiovascular (hazard ratio 2.85, 95% confidence interval 1.16 to 7.0, p = 0.023) event rates, after adjustment for conventional risk factors. Runs of >or=4 VPCs/day or >or=2 doublets/day were also associated with a poor prognosis, but only in the presence of frequent VPCs. The detection of a single VPC on standard electrocardiography was a significant predictor of frequent VPCs and an independent predictor of events (hazard ratio 2.6, 95% confidence interval 1.02 to 6.66, p = 0.045). In conclusion, apparently healthy, middle-aged and elderly subjects with frequent VPCs (>or=30/hour) have a poor prognosis. According to current guidelines, strict risk-factor modification and primary prevention are justified in these high-risk subjects.

Autonomic dysfunction and impaired cerebral autoregulation in cirrhosis.

Cerebral blood flow autoregulation is lost in patients with severe liver cirrhosis. The cause of this is unknown. We determined whether autonomic dysfunction was related to impaired cerebral autoregulation in patients with cirrhosis. Fourteen patients with liver cirrhosis and 11 healthy volunteers were recruited. Autonomic function was assessed in response to deep breathing, head-up tilt and during 24-h Holter monitoring. Cerebral autoregulation was assessed by determining the change in mean cerebral blood flow velocity (MCAVm, transcranial Doppler) during an increase in blood pressure induced by norepinephrine infusion (NE). The severity of liver disease was assessed using the Child-Pugh scale (class A, mild; class B, moderate; class C, severe liver dysfunction).NE increased blood pressure similarly in the controls (27 (24-32) mmHg) and patients with the most severe liver cirrhosis (Child-Pugh C, 31 (26-44) mmHg, p=0.405 Mann-Whitney). However, the increase in MCAVm was greater in cirrhosis patients compared to the controls (Child-Pugh C, 26 (24-39) %; controls, 3 (-1.3 to 3) %; respectively, p=0.016, Mann-Whitney). HRV during deep breathing was reduced in the cirrhosis patients (Child-Pugh C, 6.0+/-2.0 bpm) compared to the controls (21.7+/-2.2 bpm, p=0.001, Tukey' test). Systolic blood pressure fell during head-up tilt only in patients with severe cirrhosis. Our results imply that cerebral autoregulation was impaired in the most severe cases of liver cirrhosis, and that those with impaired cerebral autoregulation also had severe parasympathetic and sympathetic autonomic dysfunction. Furthermore, the degree of liver dysfunction was associated with increasing severity of autonomic dysfunction. Although this association is not necessarily causal, we postulate that the loss of sympathetic innervation to the cerebral resistance vessels may contribute to the impairment of cerebral autoregulation in patients with end-stage liver disease.

ECG changes during endoscopic retrograde cholangio-pancreatography and coronary artery disease.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevalence and prognostic significance of daily-life silent myocardial ischaemia in middle-aged and elderly subjects with no apparent heart disease.

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.

Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease.

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.

Lack of circadian variation in the activity of the autonomic nervous system after major abdominal operations.

OBJECTIVE: Most sudden postoperative deaths occur during the night and we conjectured that this was associated with circadian variations in the autonomic nervous tone, reflected in heart rate variability. DESIGN: Prospective clinical study. SETTINGS: University hospital, Denmark. SUBJECTS: 44 patients who had had major abdominal operations. INTERVENTIONS: Patients were monitored with 24-hour Holter ECG on the second postoperative day-evening-night. We calculated heart rate variability from the standard deviation of all normal R-R intervals (excluding ectopics-NN intervals) around the mean NN interval for the period of measurement (SDNN), the root mean square of the standard deviation of the differences between NN intervals (RMSSD), the percentage of NN intervals differing by more than 50 msec from adjacent NN intervals (pNN50) and the coefficient of component variance (meanNN/SDNN). MAIN OUTCOME MEASURES: Heart rate and heart rate variability. RESULTS: Circadian variation calculated from the SDNN (p = 0.43) the pNN50 (p = 0.11), the RMSSD (p = 0.47), and mean NN:SDNN ratio (p = 0.13) was absent postoperatively. Circadian variation in the heart rate was present but was set on a higher level compared with reference values. CONCLUSION: After major abdominal operations there was a lack of circadian variation in the autonomic nervous tone.

Decreased myocardial perfusion reserve in diabetic autonomic neuropathy.

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 (K(i)) 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). K(i) 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.

Factors that affect the variability in heart rate during endoscopic retrograde cholangiopancreatography.

OBJECTIVE: To find out if drugs, position, and endoscopic manipulation during endoscopic retrograde cholangiopancreatography (ERCP) influence the changes in the variability of heart rate. DESIGN: Single-blind randomised trial. SUBJECTS: 10 volunteers given butyscopolamine, glucagon, or saline intravenously on three different study days, and 10 patients who had ERCP without butylscopolamine or glucagon. MAIN OUTCOME MEASURES: Holter tape analysis for ischaemia and changes in the variability of heart rate. RESULTS: 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. CONCLUSIONS: 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.