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BACKGROUND: The clinical utility of serum periostin as a type 2 biomarker in asthma is limited by lack of reference range values derived from a population without respiratory disease. OBJECTIVE: To derive age- and sex-related reference intervals for serum periostin from an adult population without asthma or COPD. METHODS: Serum periostin levels were measured in 480 individuals, comprising 60 female and 60 male adults in each of the 18- to 30-year, 31- to 45-year, 46- to 60-year and 61- to 75-year age groups. Key exclusion criteria included a doctor's diagnosis of asthma, chronic bronchitis or COPD, and a history of wheezing or use of respiratory inhalers in the last 12 months. The distribution of periostin and logarithm-transformed periostin levels was derived, and 90% confidence intervals for an individual prediction were calculated. RESULTS: The distribution of serum periostin was right skewed with a mean (SD) periostin of 51.2 (11.9) ng/mL, median (IQR) 50.1 (43.1 to 56.9) ng/mL and range 28.1 to 136.4 ng/mL. There was no association between logarithm periostin and age or sex, although levels were low in current smokers. The 90% confidence limits for periostin were 35.0 and 71.1 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Serum periostin levels in adults without asthma or COPD are similar to those in adults with asthma. Serum periostin measurements do not need to be adjusted to take account of a patient's age or sex, although levels are lower in current smokers. Reference values for serum periostin levels in adults without asthma or COPD are provided.

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OBJECTIVES: To compare the clinical- and cost-effectiveness of minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery (LAD). DESIGN: Multi-centre randomised trial without blinding. The computer-generated sequence of randomised assignments was stratified by centre, allocated participants in blocks and was concealed using a centralised telephone facility. SETTING: Four tertiary cardiothoracic surgery centres in England. PARTICIPANTS: Patients with ischaemic heart disease with at least 50% proximal stenosis of the LAD, suitable for either PTCA or MIDCAB, and with no significant disease in another vessel. INTERVENTIONS: Patients randomised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure. Patients randomised to MIDCAB had general anaesthetic. The chest was opened through an 8-10-cm left anterior thoracotomy. The ribs were retracted and the left internal thoracic artery (LITA) harvested. The pericardium was opened in the line of the LAD to confirm the feasibility of operation. The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD. All operators were experienced in carrying out MIDCAB. MAIN OUTCOME MEASURES: The primary outcome measure was survival free from cardiac-related events. Relevant events were death, myocardial infarction, repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up. Secondary outcome measures were complications, functional outcome, disease-specific and generic quality of life, health and social services resource use and their costs. RESULTS: A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001. Of the 1091 patients with proximal stenosis of the LAD, 127 were eligible and consented to take part; 100 were randomised and the remaining 27 consented to follow-up. All randomised participants were included in an intention-to-treat analysis of survival free from cardiac-related events, which found a non-significant benefit from MIDCAB. Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2% for MIDCAB and PTCA, respectively. There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life. The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA, respectively. The costs of resources used during 1 year of follow-up were 1033 British pounds and 843 British pounds, respectively. CONCLUSIONS: The study found no evidence that MIDCAB was more effective than PTCA. The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA. Given these findings, it is unlikely that MIDCAB represents a cost-effective use of resources in the reference population. Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB. At the same time, cardiologists are treating more patients with multi-vessel disease by PTCA. Future primary research should focus on this comparison. Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review.

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OBJECTIVE: To compare symptoms and exercise tolerance during dual chamber universal (DDD) and ventricular rate response (VVIR) pacing in elderly (> or = 75) patients. DESIGN: Randomised, double blind, crossover study. SETTING: Regional cardiac department. PATIENTS: Twenty elderly patients (mean age 80.5 (1) years) with high grade atrioventricular block and sinus rhythm. Patients with pre-existing risk factors for the pacemaker syndrome and chronotropic incompetence were excluded. INTERVENTION: After four weeks of VVI pacing following pacemaker implantation, patients underwent consecutive two week periods of VVIR and DDD pacing. MAIN OUTCOME MEASURES: Patient preference, symptom scores, "daily activity exercises," and perceived level of exercise (Borg score). RESULTS: Eleven patients preferred DDD mode to either VVI or VVIR mode. Mean (SE) total symptom scores during VVI, VVIR, and DDD pacing were 5.9 (1.1), 6.1 (1.0), and 3.5 (0.9) respectively (P < 0.01). The corresponding mean (SE) pacemaker syndrome symptom scores were 4.8 (0.7), 5.2 (0.8), and 2.9 (0.8) (P < 0.05). Symptom scores during VVI and VVIR pacing were not significantly different. Exercise performance and Borg scores were significantly worse during VVI pacing compared with VVIR or DDD pacing but did not significantly differ between VVIR and DDD modes. CONCLUSIONS: In active elderly patients with complete heart block both DDD and VVIR pacing are associated with improved exercise performance compared with fixed rate VVI pacing. The convenience and reduced cost of VVIR systems, however, may be offset by a higher incidence of the pacemaker syndrome. In elderly patients with complete heart block VVIR pacing results in suboptimal symptomatic benefit and should not be used instead of DDD pacing.

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High gain, signal-averaged ECGs using conventional surface lead technique and a transesophageal lead technique were performed in 45 idiopathic paroxysmal atrial fibrillation patients and in 33 normal controls. Both techniques showed increased P wave duration in patients compared with the controls (P < 0.001), but higher P wave amplitudes were obtained using the transesophageal technique compared with surface leads (patients: 169.8 +/- 81.7 microV vs 15.8 +/- 7.3 microV; P < 0.0005; controls: 163.5 +/- 22.1 microV vs 18.5 +/- 5.2 microV; P < 0.0005). The signal-averaged transesophageal lead, but not the surface recordings, identified the presence of atrial late potentials evidenced by lower root mean square voltages in the terminal portion of the P wave: in last 10 seconds, 4.4 +/- 1.3 microV versus 8.5 +/- 3.0 microV; P < 0.001; in last 20 seconds, 7.0 +/- 2.3 microV versus 16.0 +/- 7.9 microV; P < 0.001; in last 30 seconds, 12.5 +/- 5.3 microV versus 23.8 +/- 12.8 microV; P < 0.001, in patients with respect to controls. The criterion P wave duration > or = 110 msec had 85% sensitivity, 100% specificity, and 100% positive predictive value in identifying the patients; the combined criteria P wave duration > or = 110 msec and root mean square for the last 10 msec < or = 6.5 showed 80% sensitivity, 100% specificity, and 100% predictive value. The signal-averaged transesophageal lead produces a higher amplitude signal, which reveals fractionation of atrial activation in atrial fibrillation and allows identification of individuals predisposed to this arrhythmia.

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We studied 16 patients aged 77-88 years to determine whether elderly patients gain significant benefit from dual-chamber (DDD) compared with single-chamber ventricular demand (VVI) pacing. The study was designed as a double-blind randomized two-period crossover study--each pacing mode was maintained for 7 days. End points included: (i) overall symptoms scores; (ii) exercise tests related to daily activities; and (iii) perceived level of difficulty (Borg score). The mean symptom score in DDD mode was 7.07 (6.38) vs. 12.27 (7.29) in VVI mode (p < 0.006). Dizziness, breathlessness and fatigue were the most noticed symptoms during VVI pacing. One patient dropped out from follow-up and three patients requested early reprogramming, all from VVI mode. Overall, no patient preferred VVI mode, 11 preferred DDD mode and four expressed no preference. There were significant improvements in all objective test performances in DDD mode. Mean (SD) total Borg scores in DDD mode and VVI mode were 36.57 (5.85) and 41.93 (6.49), respectively (p < 0.002). Ventricular demand pacing in elderly patients with complete heart block is associated with higher symptom scores, reduced exercise ability and greater perceived exercise difficulty compared with dual-chamber pacing.

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OBJECTIVES: To document the incidence of hypoxic episodes in a series of patients with impaired left ventricular function, and to correlate the occurrence of hypoxia with severity of arrhythmia. PATIENTS: 34 patients with breathlessness and clinical evidence of left ventricular dysfunction. MAIN OUTCOME MEASURES: Simultaneous overnight finger oximetry and electrocardiographic monitoring. RESULTS: High grade arrhythmias (Lown grade > III) occurred in 20/34 (59%) of patients, and frequent dips in oxygen saturation were noticed (mean dip frequency 4.8/h, range 0.1-20.0). 20/34 (59%) of patients had episodic hypoxaemia, including 13/34 (38%) with a classical Cheyne Stokes pattern. There was a correlation between dip frequency and the presence of high grade arrhythmias (those with high grade arrhythmia had mean (SD) 6.7 (5.5) dips/h v 2.2 (3.4) in those without, p < 0.01); there was also a correlation between the presence of arrhythmias and episodic hypoxaemia (episodic hypoxaemia in those with high grade arrhythmias occurred in 17/20 (85%) v 3/14 (21%) of those without arrhythmias, p < 0.002). There was no correlation between the presence of high grade arrhythmias or dip frequency and the extent of left ventricular impairment, which was present in all patients (mean (SD) ejection fraction 26% (13%)). CONCLUSION: Noticeable abnormalities of nocturnal oxygen saturation occur in patients with impaired left ventricular function, and these are associated with high grade arrhythmias. Interventions that limit desaturation may have valuable anti-arrhythmic effects.

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AIMS: To examine the influence of age on the prediction of sudden death after acute myocardial infarction based on heart rate variability (HRv), left ventricular ejection fraction (LVEF), and the frequency of ventricular extrasystoles. BACKGROUND: Autonomic and left ventricular function and the frequency of ventricular extrasystoles change with age but the influence of age on the prediction of sudden death from these variables has not been examined. METHODS: The 477 patients who had been through an early postinfarction risk stratification protocol and followed up for a mean of 790 days were dichotomised at 60 years of age. RESULTS: Sudden deaths occurred with similar frequency in both age groups (12 (4.7%) of the 256 patients aged < 60 years and seven (3.2%) of the 221 older patients). Sudden death, however, accounted for 52% of all deaths in the young group but only 18.4% of all deaths in the older group (p < 0.01). An HRv index of < 20 units combined with an average of more than 10 ventricular extrasystoles an hour on Holter monitoring (VE10) had a sensitivity of 50%, a positive predictive accuracy of 33%, and a risk ratio of 18 in the young group (p < 0.001) but was not significantly predictive in older patients. The situation was similar when the combination of an LVEF < 40% with VE10 was considered. This combination had a sensitivity of 44%, positive predictive accuracy of 36.4%, and a risk ratio of 16.1 in young patients (p < 0.001), but was not significantly predictive in older patients. The combination of VE10 with either LVEF < 40% or HRv < 20 units gave a sensitivity of 75%, positive predictive accuracy of 30%, and a risk ratio of 30 in young patients (p < 0.001), but the relation between this combination and sudden death in older patients was not statistically significant. CONCLUSION: In postinfarction patients aged < 60 sudden death was a more predominant mode of death and was more reliably predicted from a depressed HRv index, an LVEF < 40%, and VE10 than in older postinfarction patients. These findings may have important implications for post-infarction risk stratification and management.

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BACKGROUND: Disturbances of autonomic function are recognised in both the acute and convalescent phases of myocardial infarction. Recent studies have suggested that disordered autonomic function, particularly the loss of protective vagal reflexes, is associated with an increased incidence of arrhythmic deaths. The purpose of this study was to compare the value of differing prognostic indicators with measures of autonomic function and to assess the safety of arterial baroreflex testing early after infarction. METHODS: As part of a prospective trial of risk stratification in post-infarction patients arterial baroreflex sensitivity, heart rate variability, long term electrocardiographic recordings, exercise stress testing, and ejection fraction were recorded between days 7 and 10 in 122 patients with acute myocardial infarction. RESULTS: During a one year follow up period there were 10 arrhythmic events. Baroreflex sensitivity was appreciably reduced in these patients suffering arrhythmic events (1.73 SD (1.49) v 7.83 (4.5) ms/mm hg, 95% confidence interval (CI) 4.8 to 7.3, p = 0.0001). Significant correlations were noted with age (r = -0.68, p less than 0.001) but not left ventricular function. When baroreflex sensitivity was adjusted for the effects of age and ventricular function baroreflex sensitivity was still considerably reduced in the arrhythmic group (2.1 v 7.57 ms/mm Hg, p less than 0.0001). Depressed baroreflex sensitivity carried the highest relative risk for arrhythmic events (23.1, 95% CI 7.7 to 69.2) and was superior to other prognostic variables including left ventricular function (10.4, 95% CI 3.3 to 32.6) and heart rate variability (10.1, 95% CI 5.6 to 18.1). No major complications were noted with baroreflex testing and in particular no patients developed ischaemic or arrhythmic symptoms during the procedure. CONCLUSIONS: Disordered autonomic function as measured by depressed baroreflex sensitivity or reduced heart rate variability was associated with an increase incidence of arrhythmic events in post-infarction patients. Baroreflex testing can be safely performed in the immediate post-infarction period.

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The value of heart rate variability, ambulatory electrocardiographic (ECG) variables and the signal-averaged ECG in the prediction of arrhythmic events (sudden death or life-threatening ventricular arrhythmias) was assessed before hospital discharge in 416 consecutive survivors of acute myocardial infarction. During the follow-up period (range 1 to 1,112 days), there were 24 arrhythmic events and 47 deaths. The initial relation between several prognostic factors and arrhythmic events was explored with use of the Kaplan-Meier product limit estimates of survival function. Impaired heart rate variability less than 20 ms (p less than 0.0000), late potentials (p less than 0.0000), ventricular ectopic beat frequency (p less than 0.0000), repetitive ventricular forms (p less than 0.0000), left ventricular ejection fraction less than 40% (p less than 0.02) and Killip class (p less than 0.02) were identified as significant univariate predictors of arrhythmic events. When these variables were analyzed by using a stepwise Cox regression model, only impaired heart rate variability, followed by late potentials and repetitive ventricular forms remained independent predictors of arrhythmic events. The combination of impaired heart rate variability and late potentials had a sensitivity of 58%, a positive predictive accuracy of 33% and a relative risk of 18.5 for arrhythmic events and was superior to other combinations including those incorporating left ventricular function, exercise ECG, ventricular ectopic beat frequency and repetitive ventricular forms. These results suggest that a simple method of assessment based on heart rate variability and the signal-averaged ECG can select a small subgroup of survivors of myocardial infarction at high risk of future life-threatening arrhythmias and sudden death.

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A total of 32 (3.6%) patients of 880 undergoing coronary angioplasty during a nine year period at one hospital had extensive dissection (defined as a dissection extending beyond the limits of the dilated angioplasty balloon) in the coronary artery in which the angioplasty procedure was performed. Two (6.25%) of the 32 patients (both of whom were undergoing angioplasty because of unstable angina that was refractory to medical treatment) died as a consequence of the coronary artery dissection. Twelve (38%) needed immediate coronary artery bypass surgery and 11 (34%) had a myocardial infarction, which in four was minor in extent. During follow up, 20 of the 32 patients were successfully managed by medical treatment; only two needed further angioplasty procedures. There were no late deaths. Extensive coronary artery dissection is a serious complication of coronary angioplasty, with a high early mortality and a high incidence of infarction and requirement for bypass surgery. None the less, patients with extensive dissection who are free from the manifestations of acute ischaemia at the end of the procedure can be managed conservatively and have a good immediate and medium term outlook. Attempts should be made to stabilise extensive dissection during coronary angioplasty so that surgical intervention can be delayed or avoided altogether if possible.

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BACKGROUND: Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death. METHODS AND RESULTS: To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266). CONCLUSIONS: This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.

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The relation between heart rate variability, measured from standard 24 hour electrocardiogram recordings in patients convalescent after a myocardial infarction, and the occurrence of sudden death and spontaneous, symptomatic, sustained ventricular tachycardia were assessed in a consecutive series of 177 patients admitted with acute myocardial infarction and surviving to 7 days. In addition to the analysis of heart rate variability, the occurrence of non-sustained arrhythmias on 24 hour electrocardiographic monitoring, and the results of clinical assessment, signal averaged electrocardiography and ejection fraction were analysed and were related to outcome. During a median of 16 months of follow up (range 10-30 months) there were 17 end point events (11 (6.2%) sudden deaths) and six (3.4%) episodes of sustained ventricular tachycardia. An index of the width of the frequency distribution curve for the duration of individual RR intervals was used to measure heart rate variability. This mean (SD) index was significantly smaller in those with end point events (16.8 (8.0)) than in those without events (29.0 (11.2)). The relative risk of the occurrence of an end point event in those with a heart rate variability index less than 25 was 7.0. Multivariate analysis showed that of all the variables examined a reduced heart rate variability index was the single most powerful predictor of end point events. Measurement of heart rate variability by this simple, automated, operator-independent method provided useful information on the arrhythmic propensity in patients convalescent after myocardial infarction.

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A major goal in the management of patients with hypertrophic cardiomyopathy is the prediction of sudden death. To evaluate the high gain signal-averaged electrocardiogram (ECG) in this setting, 64 patients with hypertrophic cardiomyopathy and 50 age- and gender-matched control subjects were studied. An abnormal signal-averaged ECG was more common in patients than in control subjects: 13 (20%) of 64 patients with hypertrophic cardiomyopathy had abnormalities compared with 2 (4%) of the 50 control subjects (p less than 0.001). There was a significant association between the presence of nonsustained ventricular tachycardia on 48 h ECG Holter monitoring and the presence of an abnormal signal-averaged ECG: 8 (47%) of the 17 patients with nonsustained ventricular tachycardia and 6 (86%) of 7 patients with more than three episodes of nonsustained ventricular tachycardia per 24 h had signal-averaged ECG abnormalities. There was no association between an abnormal signal-averaged ECG and a family history of premature sudden cardiac death, a history of syncope, symptomatic status, maximal left ventricular wall thickness, the presence of systolic anterior motion of the mitral valve or maximal rate of oxygen uptake on exercise. However, of four patients with a history of cardiac arrest, three had an abnormal signal-averaged ECG. Sensitivity was 50%; specificity was 93% and positive predictive accuracy was 77% for the signal-averaged ECG in detecting patients with electrical instability (defined as a history of cardiac arrest or the presence of nonsustained ventricular tachycardia, or both).(ABSTRACT TRUNCATED AT 250 WORDS)

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Automatic analysis of heart rate variability from Holter recordings may be invalidated by beat recognition errors and recording artefact, necessitating filtering and editing of the computer-recognized RR interval sequence. Two new methods for heart rate variability analysis have been developed, based on an estimation of the width of the main peak of the frequency distribution curve of the computer-recognized normal-to-normal beat sequence. These methods are independent of a low level of recognition error and artefact, thus removing the need for operator-dependent, time-consuming editing. The value of the new methods (heart variability indices 1 and 2) in identifying patients with serious events (death and symptomatic, sustained documented ventricular tachycardia) during a 6-month follow-up after acute myocardial infarction was assessed in a case-control study comparing 20 patients who had experienced such events (Group I) with 20 patients who, following admission with acute myocardial infarction, had remained free of complications for greater than 6 months after discharge (Group II). Group II was selected to match Group I with regard to age, sex, infarct site, ejection fraction, and beta-blocker treatment. Analysis of the unfiltered computer-recognized normal-to-normal interval sequence showed that heart rate variability indices 1 and 2 were significantly lower (P less than 0.005, P less than 0.002) in those who had experienced events compared with those free from complications. Two other methods of expressing heart rate variability, including the standard deviation method, in combination with four different data-filtering techniques, gave less significant distinction between those with and without events during follow-up. It is concluded that using the methods described, reduced heart rate variability in patients at risk from death or sustained ventricular tachycardia after acute myocardial infarction can be detected automatically from unfiltered Holter tape recordings even in the presence of a low level of beat recognition error and recording artefact.

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