Establishment of normal limits of the electrocardiogram in healthy Nigerians using automated methods

Automated analysis of the electrocardiogram (ECG) has been of increasing importance over the past five decades. Establishment of the normal limits of the ECG in any population is the first step before computer application in ECG interpretation in that population. Normal limits of the ECG have been established for different racial groups in the Western world using automated methods and subsequently followed up with the design of appropriate computerbased diagnostic software for ECG analysis. Unfortunately, this has not been the case for the indigenous black African nations even though this group represents a quarter of the world population. Earlier studies, using manual ECG analysis in Africans and indeed, more recent comparative studies between White and African Americans on the one hand and British and Chinese populations on the other have convincingly demonstrated racial variation in the ECG. The present study is therefore aimed at deriving normal limits of the ECG from a large population of healthy individuals living in Nigeria. This ultimately will serve as a template for the evolution of appropriate computer software applicable to ECG interpretations in black Africans. In the same vein, by using automated methodsmethods, normal limits of the ECG have been shown to be age and sex-dependent in different racial groups. All previous work on the ECG recorded in Nigeria and indeed, the West African sub region, has mostly quoted a single normal range of ECG variables for all ages. This is probably because robust computer application was never used to analyse the ECGs. For the first time in the indigenous black Africans, the present study aimed to establish age and sex-specific normal limits of the ECG in this population. The thesis initially reviews the number of ECGs that are recorded worldwide annually as a way of underscoring the clinical significance of setting out to establish the age and sex-dependent normal limits for Africans. Thereafter, a chronological review of the history and evolution of the ECG is presented, bringing into perspective, how, at each stage of evolution, the need and genuine desire to make things better had propelled creativity and invention. The history starts with the first recording of the human ECG in 1887, through the early 1900s when buckets of electrolytes served as ECG electrodes and ends at the modern day recording of the 12-Lead resting ECG using portable and sophisticated machines equipped with microprocessor chips for ECG interpretation. Subsequently, other modern applications of the ECG such as the signal averaged ECG, Holter ECG, exercise ECG and vectorcardiography are briefly reviewed before a discussion on the current status of the ECG and its challenges in today’s world which is propelled largely by technology. The historical evolution of computer applications in the field of ECG interpretation is also thoroughly reviewed since the present work is the first comprehensive application of automated ECG analysis undertaken in an apparently healthy Nigerian population and indeed, in any indigenous black African population. Different automated ECG analysis programs from different centres and applied to different racial populations are also presented and in the process, highlight the fact that there has been none adapted for black Africans, in spite of the well established racial dissimilarity in the ECG. The Common Standards for Quantitative Electrocardiography (CSE) project is also discussed to underscore how computer application has come a long way in the analysis and diagnostic interpretation of the ECG. The University of Glasgow ECG Analysis program (Uni-G) is also extensively discussed as this is the program which has been deployed in the analysis of the ECGs in this study. Since the program has already been designed to receive race as an input, the opportunity exists, after this study, to extend the program for the African population, using the new set of normal limits established in this study. The normal electrocardiogram is also reviewed from basic physiology to computer analysis in order to set the appropriate frame-work for the scope of the work done in the study. The normal ECG in different racial groups is also discussed before focusing on the history of ECG recording among Nigerians dating back to the early 1960s. In the present study, 12 lead ECGs were recorded using a Cardiac Science Atria 6100 electrocardiograph in and around Ilorin, Nigeria. A detailed description of the study site is provided in the Thesis. Apparently healthy volunteers were recruited from the University of Ilorin and from surrounding villages. Each was medically examined by the author and a detailed medical history obtained. A total of 1500 participants were initially recruited into the study of whom 239 were excluded from the final analysis due to technical inadequacies in ECG recording or the presence of an unexpected ECG abnormality such as a conduction defect. ECGs recorded in Nigeria were transferred locally to a PC and sent on a CD to the Central Core ECG Laboratory in Glasgow Royal Infirmary for further analysis, using the Uni-G ECG Analysis program. The ECG variable measurements output from the program were subjected to statistical analysis using SAS v9.1 in the Robertson Centre for Biostatistics. Plots and summary statistics were used to assess the relationship with age and sex. Regression techniques were used to assess formal relationships. Normal ranges were established by splitting the data into age and sex subgroups and by calculating the 96th percentile range within each subgroup. This was done for each and every one of the ECG variables which totalled well over 600. The normal limits of the electrocardiogram in Nigerians are presented and the results compared with existing databases for British and Chinese populations derived in the same laboratory where the analysis was done using the same ECG computer analysis program. The results presented confirm, beyond reasonable doubt, that there indeed are striking racial differences in the normal ECG. The study included 782 males and 479 females, all apparently healthy, with a relatively even spread of ages between 20 and 87 years. The normal limits of the R amplitude in lead V5 ranged between 0.64 to 3.45mV and 0.83 to 3.80 mV in males and females respectively. For S amplitude in lead V2, the normal limits ranged between -3.91 to -0.33mV and -3.1 to -3.8mV in males and females respectively. Voltages were generally higher in males than females except in lead I. The younger age group tended to exhibit higher amplitudes for the R wave but not for the S wave which tended to increase with advancing age, particularly in females. The Cornell product {(RaVL+SV3)xQRSd} was higher in all male age groups compared to corresponding female groups. It decreased with increasing age in males but the reverse was true in females. This is at variance with the trend in the British and Chinese populations with which this data was compared. The Nigerian population, in this study, generated higher voltages than either the British or Chinese populations. The 96th percentile range for the heart rate was 55 to 112 beats per minute in females and 53 to 105 beats per minute in males. Ninety percent of the entire study population had a heart rate between 60 and 100 beats per minute. Heart rate was higher in females than males in all age groups and increased with age. The mean heart rate was 81+14 beats per minute in females and 75+13 beats per minute in males (p<0.0001). A similar trend was observed in the British and Chinese populations. Nigerians, however, had the highest mean heart rates for the different age groups among the three populations. Mean QRS duration in males was 87.8+9.4ms and 83.4+7.7ms in females (p< 0.0001). Variation of QRS duration across age groups was not statistically significant. The QRS duration from this study was lower than the values from either the Chinese or British population with a mean difference in males for example of 5.84ms when the Nigerian is compared with the British population. The Chinese population had the longest QRS duration. The upper limit of normal QRS duration was 112ms in males and 100ms in females among Nigerians. The values were 114ms in males and 102ms in females for the British population. The difference of 12ms in the upper limits of normal QRS duration between males and females irrespective of race is, however, of the utmost importance as criteria for conduction defects have hitherto not taken cognizance of this well known observation. The upper limit of normal QTc (Hodges) increased with age while the mean QTc was 393+16ms in males and 407+17ms in females (p<0. 0001). QTc (Hodges) was largely stable across heart rate groups ranging from 70-100 beats per minute, just as was observed in other racial groups. The 96th percentile range for the PR Interval was 110 to 216ms in males and 108 to 224ms in females. There was no statistically significant gender difference or age association observed in the PR Interval. Normal limits of the P and QRS axes followed a similar trend for age and gender in all the three populations but the axes from the Nigerian population were generally more left-ward. There was a clear trend for STj amplitude to be lower in older individuals and to be higher in males compared to females. This was particularly true for V2 and V3. STj amplitude is clearly higher in this population than in either the British or Chinese population, thereby calling for racial adjustment to the diagnostic criteria for STEMI of the European Society of Cardiology. T wave inversion in lead V1 was seen in 67% and 19% of females and males respectively with females in the age group 20-29 years exhibiting greatest depth of T inversion. T wave inversion in V2 was more prevalent in females and was not present in any male over 30 years of age. This was also the case for V3. Application of a standard criterion such as the Sokolow and Lyon index SV1+RV5 >3.5Mv to the Nigerian data set revealed that 30% of the apparently healthy population had left ventricular hypertrophy (LVH). This is the first large study of automated ECG recording in healthy Blacks living in West Africa. There were striking racial variations in amplitudes and morphologies of ECG waveforms, even though many of the age and sex-related changes were similar to those seen in Caucasians. There were also some unexpected findings which require further study. The opportunity now exists to develop the first ECG diagnostic computer program that will be tailored to the indigenous African population