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M Malik

Publications and source records attributed to M Malik.

At least 73 records · Page 4Linked to original sources

Summer-winter differences in 24 h variability of heart rate.

OBJECTIVE: To examine possible seasonal changes in heart rate variability (HRV). BACKGROUND: Greater than normal mortality from cardiovascular disease (CVD) in the winter has been reported for many countries and might be partly explained by considering seasonal changes in CVD risk factors. Depression of HRV is an independent predictor of arrhythmic complications and of cardiac death, and it is also among the variables that may be affected by the season of the year. METHODS: We compared pairs of 24 h HRV data of 120 healthy men who were examined once in the summer and once in the winter. Multivariate analyses were performed for each dependent variable (HRV indexes) in separate statistical models with age, resting heart rate, serum level of cholesterol, cigarette smoking, body mass index, sports habits, alcohol consumption, systolic blood pressure, physical activity at work, years of education, consumption of energy, and season as the independent variables. RESULTS: Although there were no seasonal differences in mean R-R interval, all indexes of HRV were found to be lower in the summer than they were during winter. Differences and 95% confidence intervals were standard deviation (SD) of coupling intervals between normal beats 12 ms, 6-17 ms; SD of 5 min mean R-R intervals 14 ms, 8-20 ms; mean of all 5 min SD of R-R intervals 2.0 ms, 0.6-2.5 ms; proportion of adjacent R-R intervals differing by > 50 ms 1.5%, 0.6-2.5% and root mean square of the difference between successive normal intervals 3.1 ms, 1.5-4 ms. Multivariate analyses showed that HRV in the winter was less than that in the summer even after adjustment for age, serum level of cholesterol, systolic blood pressure, and body mass index. CONCLUSIONS: HRV indexes of healthy men vary physiologically by season, with lowest values obtained in the winter. Since low HRV is linked to pathologic conditions, the significance of seasonal changes for those suffering from CVD and their possible contribution to the greater mortality rates in winter have to be considered.

Cardiovascular Diseases↗

Relation of mean heart rate and heart rate variability in patients with left ventricular dysfunction.

The new finding was that mean heart rate and heart rate variability were more closely coupled in patients with more advanced LV dysfunction. Mean heart rate explained a larger portion of variance in heart rate variability in patients in the lowest LVEF quartile than in those in the highest one. These results support our hypothesis that sympathetic activation in patients with more severe LV dysfunction results in closer correlation between heart rate and heart rate variability. Generally, the correlation between mean heart rate and heart rate variability is weak because heart rate and heart rate variability represent different modalities of cardiovascular regulation. Mean heart rate is normally determined by the interactions of both the sympathetic and parasympathetic nervous systems, whereas modulation of these activities, with different gains, determines the magnitude of heart rate variability. This results in great complexity in control of the heart by the autonomic nervous system. However, heart rate is likely to be more dominantly regulated by the sympathetic nervous system because of vagal withdrawal in patients with more severe LV dysfunction. The effect of sympathetic cardiac modulation has been shown to be more sluggish than that of the parasympathetic nervous system in beat-to-beat regulation of heart rate. This may result in more blunted heart rate variability concomitantly with elevated mean heart rate. Thus, variation in heart rate variability in any given mean heart rate is likely to be lower than in patients with more preserved LV function, and hence with more complex cardiac autonomic regulation with involvement of the parasympathetic nervous system. Indeed, even the slopes of regression lines between mean heart rate and heart rate variability were similar in the first and fourth LVEF quartile; the intercept of the regression line was significantly higher in the fourth quartile than in the first one. This further supports our hypothesis.

Adult↗

Double-blind placebo-controlled trial of digoxin in symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Digoxin is commonly prescribed in symptomatic paroxysmal atrial fibrillation (AF) but has never been evaluated in this condition. METHODS AND RESULTS: From a multicenter registry, 43 representative patients with frequent symptomatic AF episodes were recruited into a randomized, double-blind crossover comparison of digoxin (serum concentration, 1.29+/-0.35 nmol/L) and placebo. The study end point was the occurrence of 2 AF episodes (documented by patient-activated monitors), censored at 61 days. The median time to 2 episodes was 13.5 days on placebo and 18.7 days on digoxin (P<0. 05). The relative risk (95% CI) of 2 episodes (placebo:digoxin) was 2.19 (1.07 to 4.50). A similar effect was seen on the median time to 1 episode: increased from 3.5 to 5.4 days (P<0.05), relative risk 1. 69 (0.88 to 3.24). The mean+/-SD ventricular rates during AF recordings during placebo and digoxin treatment were 138+/-32 and 125+/-35 bpm, respectively (P<0.01). Twenty-four-hour ambulatory ECG recordings did not show significant differences in the frequency or duration of AF or in ventricular rate. CONCLUSIONS: Digoxin reduces the frequency of symptomatic AF episodes. However, the estimated effect is small and may be due to a reduction in the ventricular rate or irregularity rather than an antiarrhythmic action.

Ambulatory Care↗

Regression of acromegalic left ventricular hypertrophy after lanreotide (a slow-release somatostatin analog).

A group of 13 acromegalic patients was treated with lanreotide for 18 months and followed-up echocardiographically; these patients showed significant correlations between the decrease of both growth hormone (GH) and insulin-like growth factor-1 and the decrease of left ventricular mass index. This documents a regression of left ventricular hypertrophy in acromegaly after lanreotide treatment, the degree of which is dependent on the magnitude of the decrease of GH and insulin-like growth factor-1 serum levels.

Acromegaly↗

Effect of moderate physical exercise on noninvasive cardiac autonomic tests in healthy volunteers.

BACKGROUND: In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which is sensitive enough to detect subtle improvement in cardiovascular fitness in cardiac patients. AIM: This study modelled subtle clinical improvement by a moderate physical activity programme in healthy volunteers and investigated whether the improved fitness is detectable by non-invasive tests of cardiac autonomic status. METHODS: Twenty healthy volunteers (ten women, mean age 39.6+/-7.8 years) were divided into two groups of five women and five men in each. One group (the active group) was subjected to a moderate physical training programme for 6 months. The other group (the passive group) served as controls and continued with a predominantly sedentary lifestyle. Twice before commencing the exercise programme and regularly afterwards, subjects were investigated by a series of non-invasive autonomic tests including controlled respiration, active postural change, isometric handgrip, and Valsalva manoeuvre. A continuous three lead semi-orthogonal electrocardiogram and continuous blood pressure monitoring was obtained. Statistical descriptors of heart rate and blood pressure, spectral descriptors of their modulation, and baroreflex index giving the proportion between simultaneous heart rate and blood pressure changes were obtained from each test. RESULTS: Although the exercise programme was not extensive enough to be detected in changes of the baseline heart rate, the minimum RR interval during the Valsalva manoeuvre prolonged significantly with exercise in the active group. The mean arterial diastolic pressure decreased significantly. High frequency components of RR interval modulations decreased in supine controlled respiration and increased in standing controlled respiration and a trend towards an increase of both high frequency and low frequency components of diastolic arterial pressure modulations was noted with exercise. Baroreflex index assessed from Valsalva manoeuvre increased significantly. CONCLUSION: The study suggests that a selected set of non-invasive autonomic tests is sensitive enough to depict moderate improvement in cardiovascular fitness and that a multivariate assessment of cardiovascular fitness based on these tests might be applicable to monitoring chronic cardiac patients subjected to different clinical management modes.

Adult↗

Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction.

BACKGROUND: Identification of high-risk patients after acute myocardial infarction is essential for successful prophylactic therapy. The predictive accuracy of currently used risk predictors is modest even when several factors are combined. Thus, establishment of a new powerful method for risk prediction independent of the available stratifiers is of considerable practical value. METHODS: The study investigated fluctuations of sinus-rhythm cycle length after a single ventricular premature beat recorded in Holter electrocardiograms, and characterised the fluctuations (termed heart-rate turbulence) by two numerical parameters, termed turbulence onset and slope. The method was developed on a population of 100 patients with coronary heart disease and blindly applied to the population of the Multicentre Post-Infarction Program (MPIP; 577 survivors of acute infarction, 75 deaths during a median follow-up of 22 months) and to the placebo population of the European Myocardial Amiodarone Trial (EMIAT; 614 survivors of acute myocardial infarction, 87 deaths during median follow-up of 21 months). Multivariate risk stratification was done with the new parameters and conventional risk factors. FINDINGS: One of the new parameters (turbulence slope) was the most powerful stratifier of follow-up mortality in EMIAT and the second most powerful stratifier in MPIP: MPIP risk ratio 3.5 (95% CI 2.2-5.5, p<0.0001), EMIAT risk ratio 2.7 (1.8-4.2, p<0.0001). In the multivariate analysis, low left-ventricular ejection fraction and turbulence slope were the only independent variables for mortality prediction in MPIP (p<0.001), whereas in EMIAT, five variables were independent mortality predictors: abnormal turbulence onset, abnormal turbulence slope, history of previous infarction, low left-ventricular ejection fraction, and high mean heart rate (p<0.001). In both MPIP and EMIAT, the combination of abnormal onset and slope was the most powerful multivariate risk stratifier: MPIP risk ratio 3.2 (1.7-6.0, p<0.0001), EMIAT risk ratio 3.2 (1.8-5.6, p<0.0001). INTERPRETATION: The absence of the heart rate turbulence after ventricular premature beats is a very potent postinfarction risk stratifier that is independent of other known risk factors and which is stronger than other presently available risk predictors.

Aged↗

Relation of ventricular repolarization to cardiac cycle length in normal subjects, hypertrophic cardiomyopathy, and patients with myocardial infarction.

BACKGROUND: Prolonged QT interval and QT dispersion have been reported to reflect an increased inhomogeneity of ventricular repolarization, which is believed to be responsible for the development of arrhythmic events in patients with long QT syndrome, coronary heart disease, and myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy (HC). HYPOTHESIS: This study was undertaken to determine whether an abnormal QT/RR dynamicity may reflect autonomic imbalance and may contribute to arrhythmogenesis in patients with heart disease. METHODS: The relation between QT, QTpeak (QTp), Tpeak-Tend (TpTe) intervals and cardiac cycle length was assessed in 70 normal subjects, 37 patients with HC, and 48 survivors of myocardial infarction (MI). A set of 10 consecutive electrocardiograms was evaluated automatically in each subject using QT Guard software (Marquette Medical Systems, Milwaukee, Wisc.). RESULTS: In patients with HC, all intervals were significantly prolonged compared with normals (p < 0.001 for QT and QTp; p < 0.04 for TpTc); in survivors of MI, this was true for the maximum QT and QTp intervals (p < 0.05). A strong linear correlation between QT, QTp, and RR intervals was observed in normals and in patients with MI and HC (r = 0.65-0.59, 0.82-0.77, 0.79-0.74, respectively, p < 0.0001). TpTe interval only showed a weak correlation with heart rate in normals (r = 0.24, p < 0.05) and was rate-independent in both patient groups (p = NS). Compared with normals, the slopes of QT/RR and QTp/RR regression lines were significantly steeper in patients with MI and HC (0.0990-0.0883, 0.1597-0.1551, 0.1653-0.1486, respectively). Regression lines were neither parallel nor identical between normals and patients (T > 1.96, Z > 3.07). There was no difference in steepness for TpTeR/RR lines between groups (0.0110, 0.0076, 0.0163, respectively). TpTe/QTp ratio was similar in normals and in patients with MI and HC (0.30 +/- 0.03, 0.31 +/- 0.07, 0.30 +/- 0.04, respectively), in the absence of any correlation between QTp and TpTe intervals, suggesting disproportional prolongation of both components of QT interval. CONCLUSION: Compared with normals, a progressive increase in QT and QTp intervals at slower heart rates in patients with MI and HC may indicate an enhanced variability of the early ventricular repolarization and may be one of the mechanisms of arrhythmogenesis.

Adolescent↗

Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology.

Three new approaches for the analysis of ventricular repolarisation in 12-lead electrocardiograms (ECGs) are presented: the spatial and temporal variations in T-wave morphology and the wavefront direction difference between the ventricular depolarisation and repolarisation waves. The spatial variation characterises the morphology differences between standard leads. The temporal variation measures the change in interlead relationships. A minimum dimensional space, constructed by ECG singular value decomposition, is used. All descriptors are measured using the ECG vector in the constructed space and the singular vectors that define this space. None of the descriptors requires time domain measurements (e.g. the precise detection of the T-wave offset), and so the inaccuracies associated with conventional QT interval related parameters are avoided. The new descriptors are compared with the conventional measurements provided by a commercial system for an automatic evaluation of QT interval and QT dispersion in digitally recorded 12-lead ECGs. The basic comparison uses a set of 1100 normal ECGs. The short-term intrasubject reproducibility of the new descriptors is compared with that of the conventional measurements in a set of 760 ECGs recorded in 76 normal subjects and a set of 630 ECGs recorded in 63 patients with hypertrophic cardiomyopathy (ten serial recordings in each subject of both these sets). The discriminative power of the new and conventional parameters to distinguish normal and abnormal repolarisation patterns is compared using the same set. The results show that the new parameters do not correlate with the conventional QT interval-related descriptors (i.e. they assess different ECG qualities), are generally more reproducible than the conventional parameters, and lead to a more significant separation between normal and abnormal ECGs, both univariately and in multivariate regression models.

Adolescent↗

Automatic measurement of long-term heart rate variability by implanted single-chamber devices.

Heart rate variability (HRV) measurement is an established technology for the assessment of cardiac autonomic status. Recently 24 h HRV has been shown to correlate with disease severity in heart failure. This potentially makes continuous 24 h HRV measurement suitable for monitoring of heart-failure patients. Day-to-day 24 h measurement of HRV is, in principle, feasible when implemented using implanted devices (pacemakers and defibrillators) used in patients who are predominantly in the sinus rhythm. However, a number of such devices used in heart-failure patients are single-chamber devices, in which the distinction between sinus rhythm beats and ectopic beats is problematic. The study investigates whether a reasonably accurate 24 h HRV measurement can be achieved by automatic algorithms, suitable for implementation using implanted devices, without the need for identification of ectopic beats. A set of 5321 nominal 24 h Holter recordings of cardiac patients are used. Each of the recordings contains at least one ectopic beat; approximately 30% of the recordings have more than 1% of ectopic beats. Conventional 24 h measures of HRV, that is the SDNN, HRV index, and SDANN indices, are obtained from each recording after elimination of the ectopic beats and are approximated by HRV measures computed by the same formulas without exclusion of the ectopic beats. The SDANN values are also approximated by the standard deviation of 5 min medians of all RR intervals (SDMRR measure). The errors introduced by including the ectopic beats in the HRV computation were evaluated using the Bland-Altman statistics and by Cohen's kappa statistics investigating the precision of identifying patients with depressed and preserved 24 h HRV. The SDNN measure is very sensitive to the quality of the RR interval sequence and cannot be reasonably used without distinction between sinus rhythm and ectopic beats. The HRV index measure is marginally more acceptable when used without ectopic elimination. The SDANN is rather insensitive, and its replacement by SDMRR values leads to relative errors in the region of 2-5% that are almost independent of the number of ectopic beats included. Even in recordings with a substantial proportion of ectopic beats, a practically acceptable (kappa > 0.9) identification of depressed and preserved SDANN values is possible without ectopic elimination. Thus, continuous monitoring of 24 h HRV is technically feasible within implanted devices, provided the SDANN measure is monitored and either computed from the sequence of all RR intervals or, potentially preferably, replaced by the SDMRR measure.

Defibrillators, Implantable↗

Comparison of different methods for manual P wave duration measurement in 12-lead electrocardiograms.

To determine whether different methods for the manual measurement of P wave duration are mutually consistent, we evaluated the intraobserver and interobserver errors of P wave measurements obtained in three different ways: (1) by cursor on a high resolution computer screen (on screen), (2) by calipers and a magnifying glass (on paper), and (3) by a high resolution digitizing board (on board). The agreement between the methods was assessed in 30 normal subjects and 30 patients with a history of atrial fibrillation. The maximum P wave duration (P maximum), the minimum P wave duration (P minimum), mean P wave duration (P mean), P wave dispersion (P dispersion = P maximum - P minimum), and the standard deviation of the P wave duration in all measured leads (P SD) were calculated from a 12-lead electrocardiogram in each subject. Only P maximum, P mean, and P dispersion were significantly higher in patients than in controls with all three methods. Intraobserver and interobserver relative errors were significantly different among the three methods; the lowest errors were associated with the on-screen measurement. The agreement between the three different methods was acceptable for P maximum, P mean, and P SD and rather poor for P minimum and P dispersion in both groups. The differences of the measurement by different methods did not consistently differ between the two groups. Hence, the on-screen measurements are consistent with other manual methods and provide more stable results. Manual measurement of ECG patterns should be preferably performed with digital ECG recordings displayed on a high resolution computer screen.

Adult↗

"Optimum" formulae for heart rate correction of the QT interval.

The study investigated the performance of several generic QT/RR regression models in a dataset of QT and RR intervals obtained from resting electrocardiograms of 1,100 healthy subjects (913 male, mean age 33+/-12 years). All the investigated models have three degrees of freedom and included the hyperparabolic and hyper-hyperbolic models, algorithmic models, negative exponential models, and models involving inverse tangent, hyperbolic tangent, and inverse hyperbolic sign functions. For each generic model, the combination of parameters leading to the lowest regression residuum was found. The results of the study show that the goodness of the optimum fit is practically independent of the generic form of the regression model and that different datasets lead to different combinations of the numerical values of parameters of the corresponding regression models. The study concludes that the search for a universally applicable QT/RR regression model that would provide the best fit in all circumstances is most likely fruitless. Rather, individual studies such as those investigating drug related QT prolongation might benefit from establishing a best-fit regression that would provide the optimum model for each particular dataset.

Adolescent↗

The impact of the millennium problem on implantable pacemakers and defibrillators.

The unpredictable behavior of computer systems on January 1, 2000, known as the millennium problem or millennium 'bug,' also affects medical establishments and, due to the large use of computers in all kind of applications, cardiological clinics in particular. This review discusses the effect of the millennium computer problem on the implantation procedures and follow-up registries of implantable pacemakers and defibrillators. The review concludes that the transition in the next millennium will not influence the proper functioning of implanted pacemakers and defibrillators. The function of pacemaker/defibrillator programmers seems to be safe and no major difficulties are anticipated. Pacemaker databases and the logistics linked to the implantation and follow-up of patients and their pacemaker may and probably will be affected by the millennium transition. Using the FDA database on biomedical equipment, the actual status of all biomedical devices can be assessed.

Chronology as Topic↗

Comparison of formulae for heart rate correction of QT interval in exercise electrocardiograms.

The study investigated the differences in five different formulae for heart rate correction of the QT interval in serial electrocardiograms recorded in healthy subjects subjected to graded exercise. Twenty-one healthy subjects (aged 37+/-10 years, 15 male) were subjected to graded physical exercise on a braked bicycle ergometer until the heart rate reached 120 beats/min. Digital electrocardiograms (ECG) were recorded on baseline and every 30 seconds during the exercise. In each ECG, heart rate and QT interval were measured automatically (QT Guard package, Marquette Medical Systems, Milwaukee, WI, USA). Bazett, Fridericia, Hodges, Framingham, and nomogram formulae were used to obtain QTc interval values for each ECG. For each formula, the slope of the regression line between RR and QTc values was obtained in each subject. The mean values of the slopes were tested by a one-sample t-test and the comparison of the baseline and peak exercise QTc values was performed using paired t-test. Bazett, Hodges, and nomogram formulae led to significant prolongation of QTc intervals with exercise, while the Framingham formula led to significant shortening of QTc intervals with exercise. The differences obtained with the Fridericia formula were not statistically significant. The study shows that the practical meaning of QT, interval measurements depends on the correction formula used. In studies investigating repolarization changes (e.g., due to a new drug), the use of an ad-hoc selected heart rate correction formula is highly inappropriate because it may bias the results in either direction.

Adult↗

QT dispersion and risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy.

This study examines the relation of QT dispersion (QTd) on a surface electrocardiogram (ECG) to clinical features and established risk factors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HC). One hundred fifty-six consecutive patients with HC (91 men, mean age 41+/-15 years, range 7 to 79) and 72 normal subjects (41 men, mean age 39+/-9 years, range 20 to 60) were studied. Standard 12-lead ECGs were recorded from each subject using a MAC VU electrocardiograph. Patients with nonsinus rhythm, atrioventricular conduction block, QRS duration > 120 ms, age < 15 years, and low amplitude T waves were excluded from the analysis (n=51). Another 22 patients who were receiving amiodarone and/or sotalol therapy were also excluded. QT interval and QTd were measured using automated analysis in the remaining 83 patients (46 men, age 40+/-14 years, range 16 to 76). QT interval (406+/-38 ms), QTc interval (432+/-27 ms), and QTd (43+/-25 ms) were significantly greater in patients with HC than in normal controls (386+/-31 ms, 404+/-16 ms, 26+/-16 ms, respectively) (p <0.0001). QTd was significantly greater in patients with HC with chest pain compared with asymptomatic or mildly symptomatic patients (50+/-28 ms vs 37+/-20 ms, p=0.02). Increased QTd was found in patients with dyspnea New York Heart Association functional classes II/III than in those with dyspnea New York Heart Association functional class I (50+/-27 ms vs 38+/-22 ms, p=0.04). QTd was weakly correlated with maximum left ventricular wall thickness (r=0.228, p=0.038). No significant association was found between QTd and any risk factors for SCD. Thus, patients with HC have increased QTd. The QTd correlates with symptomatic status. Assessment of QTd might provide complementary clinical characterization of patients with HC but its relation to SCD remains uncertain.

Adolescent↗

Circadian variation of the QT interval in patients with sudden cardiac death after myocardial infarction.

To evaluate the potential prognostic value of the circadian variation of QT intervals in predicting sudden cardiac death (SCD) in patients after myocardial infarction (MI), 15 pairs of post-MI patients (15 died suddenly within 1 year after MI [SCD victims] and 15 remained event-free [MI survivors]) were studied (mean age 60 +/- 8 years; 24 men and 6 women). The pairs were matched for age, gender, infarct site, presence of Q wave, left ventricular ejection fraction, thrombolytic and beta-blocker therapy. Fourteen normal subjects served as controls (mean age 55 +/- 9 years; 12 men). A 24-hour Holter electrocardiographic (ECG) recording was obtained from each subject. All recordings were analyzed using a Holter ECG analyser. QT, RR, and heart rate-corrected QT intervals (QTc) were automatically calculated by the analyzer, and hourly and 24-hour mean values of each measurement were derived from each recording. There was a pronounced circadian variation in the QT interval in parallel with the trend in the RR interval in normal subjects and in MI survivors. Circadian variation in both indexes was blunted in SCD victims. The QT interval was significantly longer at night than during the day in normal subjects (388 +/- 28 vs 355 +/- 21 ms, p = 0.001) and in MI survivors (358 +/- 25 vs 346 +/- 15 ms, p = 0.008), but not in SCD victims (357 +/- 32 vs 350 +/- 31 ms, p = 0.6). The 24-hour mean value of the QT interval in SCD victims did not differ significantly from that in normal subjects or MI survivors. The QT interval at night was significantly shorter in SCD victims than in normal subjects (357 +/- 32 vs 388 +/- 28 ms, p = 0.02), but daytime values were similar. The QT interval in SCD victims did not differ significantly from that of MI survivors at any time. The QTc interval exhibited a small circadian variation in normal subjects. This variation was abolished in SCD victims and MI survivors. The 24-hour mean value of QTc was significantly longer in SCD victims than in normal subjects (424 +/- 25 vs 402 +/- 21 ms, p = 0.02), and in MI survivors (424 +/- 25 vs 404 +/- 32 ms, p < 0.05). The QTc interval of SCD victims differed from that of normal subjects during both the day (421 +/- 25 vs 400 +/- 17 ms, p = 0.02) and night (424 +/- 26 vs 403 +/- 23 ms, p = 0.03). Thus, blunted circadian variation in QT intervals, abolished circadian variation in QTc intervals, and prolonged QTc intervals may suggest an increased risk of SCD in patients after MI.

Circadian Rhythm↗

Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.

BACKGROUND: We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. METHODS: 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. Ileocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. FINDINGS: Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age-matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. INTERPRETATION: We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.

Child↗

Exercise-induced changes in the QT interval duration and dispersion in patients with sudden cardiac death after myocardial infarction.

BACKGROUND: Prolongation of the QT interval and increased QT dispersion have been proposed to be associated with arrhythmic risk after myocardial infarction. However, controversy remains regarding the prognostic value of ventricular repolarization abnormalities in the risk stratification of patients surviving acute myocardial infarction. HYPOTHESIS AND OBJECTIVE: The QT interval is sensitive to myocardial ischaemia, and exercise-induced ischaemia may change the QT interval regionally, resulting in increased QT dispersion. This study examined whether there are abnormalities of ventricular repolarization during exercise and whether assessment of the exercise-induced changes in QT interval duration and dispersion would be able to differentiate patients at high risk from those at low risk of sudden cardiac death after myocardial infarction. METHODS: Twenty-six post-myocardial infarction patients (mean age 54.5+/-8.9 years, 22 men) were retrospectively studied. Thirteen patients who died suddenly (SCD patients) during a follow-up of 39+/-6 months were compared to 13 patients who remained event-free, i.e. no ventricular tachyarrhythmias, no reinfarction, no by-pass (MI survivors). The two groups were pair-matched for age, gender, site of infarction, left ventricular ejection fraction and use of beta blocker. A further 13 patients with chest pain, normal coronary arteriograms and negative exercise test results were studied as controls. They were age and gender matched with the post-infarction patients. A 12-lead exercise ECG was recorded from each patient before, during and after exercise. QT and RR interval were measured on the exercise ECGs at each stage and QT dispersion was defined as the difference between the maximum and minimum QT intervals across the 12-lead ECG. RESULTS: There were no significant differences in RR, QT and QTc (Bazett's and Fridericia's correction) intervals, or QT dispersion between any groups before exercise. A significant difference in QT and QT dispersion was found at peak exercise between post-infarction patients and controls (P=0.03 and P=0.0001, respectively), but no difference was observed between SCD patients and MI survivors. The maximum QTc at peak exercise was longer in SCD patients compared with MI survivors (P=0.02) and a maximum QTc>440 ms (Bazett's correction) was common in SCD patients but not in MI survivors or controls (62%, 15%, 15%, P=0.01). The differences in QT, QTc or QT dispersion observed at peak exercise were no longer significant after exercise. CONCLUSIONS: Exercise-induced prolongation of the QTc interval differentiates patients at high risk of sudden cardiac death from those at low risk, whereas exercise-induced changes in QT dispersion failed to identify patients at high risk of sudden cardiac death after myocardial infarction.

Adult↗