MYBPC3 hypertrophic cardiomyopathy can be detected by using advanced ECG in children and young adults. Eva I Fernlund MD 1 , Petru Liuba MD PhD 1 , Jonas Carlson , PhD 2, Pyotr G. Platonov MD PhD 2 , Todd T Schlegel MD PhD 3 1 – Childrens Heart Center , Skåne University Hospital, Lund, Sweden ; 2 – Department of Cardiology, Skåne University Hospital, Lund, Sweden; 3– NASA Johnson Space Center, Houston, Texas, USA Results Conclusion Background Conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting, advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG score could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3-HCM with greater specificity. In children and young adults, a 2- parameter 12-lead A-ECG score is significantly more sensitive than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM when performing at a similar level of specificity as the pooled conventional ECG criteria in both non-athlete healthy controls and in endurance-trained athletes. Further prospective studies are warranted to assess whether A-ECG scoring may improve ECG-based screening for pre- symptomatic and early onset HCM. Five-minute 12-lead ECGs were obtained from 10 young patients (median age 17 years, range 1 month-30 years) with MYBPC3 mutation and abnormal echocardiogram (>2.5 SD hypertrophy of the septum or posterior wall), and from 173 healthy children and young adults (median age 15,5, range 1 month-30 years) with unremarkable echocardiograms. The 173 healthy controls included 23 young endurance-trained athletes. ECGs were analyzed by using pooled, age-specific conventional ECG criteria and also A-ECG scoring techniques that consider both advanced and conventional ECG parameters. Methods Figure 1 The Cardiax Device . Compared with commonly used, age-specific pooled criteria from the strictly conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 advanced ECG parameters (spatial QRS-T angle and the change in the three-dimensional QRS azimuth angle during the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 40% to 100% (P<0.05) while maintaining the same level of specificity as the pooled criteria in both the entire set of 173 controls (97%) and in the subset of 23 healthy, young endurance- trained athletes (96%). Correspondance to: eva.fernlund@gmail.com DRAPER ET AL. years. Data recording and analysis were facili- tated by tape equipment and a digital com- puter. Materials and Methods Records were taken from 510 "normal' male subjects who had been admitted to the Veterans Administration Hospitals, Washington, D.C., or West Roxbury, Massachusetts, for reasons other than cardiovascular disease. Selection of cases was based on a complete history, physical ex- amination, and routine laboratory data. The majority had also chest x-rays and 12-lead elec- trocardiograms. Subjects with heart rates outside the range of 60 to 100 per minute or with elec- trocardiographic evidence of ventricular conduc- tion defects were excluded. The age and race dis- tribution is shown in figure 1. Frank's lead system 15 was used, with elec- trodes placed in the fourth intercostal space as recommended for patients in the supine posi- tion.20 The three orthogonal leads were recorded simultaneously on frequency modulated magnet- ic tape. Subsequently, they were digitized at a sampling rate of 1,000 per second for each lead. An IBM 7094 digital computer was used for further data processing and analysis. Details of the computational procedures have been re- ported previously.21-23 Measurements from scalar leads X, Y, and Z included amplitudes and durations of P, Q, R, S, and T waves. The beginning of the T wave was omitted because of the gradual transition from the ST segment to the T wave. Further- FRONTAL SAGITTAL QRS Figure 3 ST-T Schematic representation of time normalization of the QRS and ST-T complex. The total duration of these two electrocardiographic components, derived from three simultaneously recorded orthogonal leads, is divided into eight equal time segments regardless of their absolute duration. When the three scalar com- ponents of the orthogonal leads are combined, a spatial vector is obtained for each eighth of QRS and ST-T. This time normalization leads to better comparability of instantaneous vectors through elimination of inter- individual variability in wave duration. more, amplitude ratios were determined for Q/R, R/S, and R/T. For the P wave the TP segment was used as baseline. For all QRS measurements the PR segment served as base- line at the level of the first deflection of the QRS complex.24 Durations of waves were determined in the following manner. At first a search was made for the first deflection in any one of the t-hree simultaneously recorded leads. This point indicat- ed the beginning of the wave or complex. The last deflection in any one of the leads was used 854 Schematic representation of normal time intervals in QRS-T complex. Simultaneously recorded orthogonal leads is divided into eight equal time segments. When the three scalar components of the ortogonal leads are combines a spatial vector is obtained for each eight of the QRS and ST-T. Pictures from Draper 1964 DRAPER years. Data recording and analysis were facili- tated by tape equipment and a digital com- puter. Materials and Methods Records were taken from 510 "normal' male subjects who had been admitted to the Veterans Administration Hospitals, Washington, D.C., or West Roxbury, Massachusetts, for reasons other than cardiovascular disease. Selection of cases was based on a complete history, physical ex- amination, and routine laboratory data. The majority had also chest x-rays and 12-lead elec- trocardiograms. Subjects with heart rates outside the range of 60 to 100 per minute or with elec- trocardiographic evidence of ventricular conduc- tion defects were excluded. The age and race dis- tribution is shown in figure 1. Frank's lead system 15 was used, with elec- trodes placed in the fourth intercostal space as recommended for patients in the supine posi- tion.20 The three orthogonal leads were recorded simultaneously on frequency modulated magnet- ic tape. Subsequently, they were digitized at a sampling rate of 1,000 per second for each lead. An IBM 7094 digital computer was used for further data processing and analysis. Details of the computational procedures have been re- ported previously.21-23 Measurements from scalar leads X, Y, and Z included amplitudes and durations of P, Q, R, S, and T waves. The beginning of the T wave was omitted because of the gradual transition from the ST segment to the T wave. Further- FRONTAL SAGITTAL SUPERIOR SUPERIOR 2700 270` 180° 0° z8 ° 0° RIGHT LEFT ANTERIOR. POSTERIOR 90 90 INFERIOR INFERIOR HORIZONTAL 8 AZIMUTH ELEVATION INFERIOR Figure 2 Reference frame used for the angular measurements of planar and spatial vectors. Azimuth and elevation figures indicate spatial angles in a Cartesian reference system. QRS Figure 3 ST-T Schematic representation of time normalizati QRS and ST-T complex. The total duration two electrocardiographic components, deri three simultaneously recorded orthogonal divided into eight equal time segments rega their absolute duration. When the three sca ponents of the orthogonal leads are combined, vector is obtained for each eighth of QRS a This time normalization leads to better comp of instantaneous vectors through elimination individual variability in wave duration. more, amplitude ratios were determi Q/R, R/S, and R/T. For the P wave segment was used as baseline. For measurements the PR segment served line at the level of the first deflection QRS complex.24 Durations of waves were determined following manner. At first a search wa for the first deflection in any one of t simultaneously recorded leads. This point ed the beginning of the wave or compl last deflection in any one of the leads w as end-point. By this method measu differ somewhat from those derived fro leads.25 Maximal vectors for P, QRS, and T w termined in space and in the three c used plane projections, frontal, left sagit horizontal. Since amplitude measureme pend upon projection planes, these maxi tors are not necessarily identical in all pla reference frame for angular measurem shown in figure 2. Amplitude and direction of instantane tors were determined at fixed time int 0.01 second during QRS and 0.02 seco vals during the ST segment. Five such were taken after the QRS onset up to 0 ond. A similar series of five was determ the terminal part of QRS beginning at and progressing in retrograde fashion. Such absolute time measurements m either to a gap or an overlap in the mi Circulation, Volume XXX, Dece 854