Elektrokardiografinių kairiojo skilvelio hipertrofijos kriterijų ryšys su jaunų sveikų vyrų širdies kairiojo skilvelio mase

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1 ElectrocardiograPHIC LEFT VENTRICULAR HYPERTROPHY CRITERIA and left ventricular mass in young healthy males Elektrokardiografinių kairiojo skilvelio hipertrofijos kriterijų ryšys su jaunų sveikų vyrų širdies kairiojo skilvelio mase Jolanta J. Vaškelytė 1, Justas Simonavičius 2, Aurimas Mikalauskas 3, Birutė Kaminskaitė 1, Sima Šimkutė 2 1 Lietuvos sveikatos mokslų universiteto Kardiologijos klinika 2 Lietuvos sveikatos mokslų universiteto Medicinos fakultetas 3 Lietuvos sveikatos mokslų universiteto Vidaus ligų klinika 1 Lithuanian University of Health Sciences, Cardiology Department 2 Lithuanian University of Health Sciences, Medical Academy, Medical Faculty 3 Lithuanian University of Health Sciences, Internal Medicine Department ABSTRACT Key words: electrocardiography, left ventricular mass, left ventricular hypertrophy. Objective. This study was designed to assess ECG as a tool to indicate left ventricular mass in young healthy males with sedentary life style. Methods. Standard 12-lead ECGs were obtained from 60 Caucasian male university students aged (mean ± standard deviation) 22.4 ± 1.9. SV1, RV5, RV6, RaVL, SV3, RI, SIII and QRS duration (in ms) were measured to calculate 6 commonly used ECG criteria: Sokolow-Lyon Amplitude, Sokolow-Lyon Product, Cornell Amplitude, Cornell Product, Gubner-Ungerleider Amplitude and RaVL. Echocardiography was performed to calculate left ventricular mass (LVM). LVM was indexed to body surface area. Subjects were divided into subgroups: those with body mass index (BMI) < 25, and the rest with BMI 25. Results. Moderate statistically significant correlation appeared between LVMI and Gubner-Ungerleider Amplitude (r = 0.477, p = 0.019) as well as RaVL (r = 0.355, p = 0.044) in subjects with BMI 25. Sokolow-Lyon Product showed weak statistically significant correlation to LVMI in subjects with BMI < 25 (r = 0.253, p = 0.045). No statistically significant correlation between LVMI and other criteria was noticed. Conclusions. Commonly used ECG defined LVH criteria are associated with subjects BMI and demonstrate weak (for Sokolow-Lyon Product in subjects with BMI < 25) to moderate (for Gubner-Ungerleider Amplitude and RaVL in subjects with BMI 25) correlation with LVMI thus they do little to reflect LVM. Justas Simonavicius Ukmergės g. 6-33, Kaunas j.simonavicius@gmail.com SANTRAUKA Reikšminiai žodžiai: elektrokardiografija, kairiojo skilvelio masė, kairiojo skilvelio hipertrofija. Tyrimo tikslas. Įvertinti elektrokardiografiją kaip tyrimo metodą, kuriuo naudojantis galima spręsti apie jaunų, sveikų, nesportuojančių vyrų kairiojo skilvelio masę. Metodika. 12-kos standartinių derivacijų ramybės elektrokardiograma buvo užrašyta 60-čiai kaukaziečių rasės universiteto studentų, kurių amžius (vidurkis ± standartinis nuokrypis) buvo 22,4 ± 1,9. Siekiant apskaičiuoti 6 dažnai naudojamus elektrokardiografinius kairiojo skilvelio hipertrofijos kriterijus, tiriamųjų elektrokardiogramose buvo įvertinti SV1, RV5, RV6, RaVL, SV3, RI, SIII ir QRS trukmė (milisekundėmis). Panaudojant gautas reikšmes buvo apskaičiuoti Sokolow-Lyon amplitudė, Sokolow-Lyon sandauga, Cornell amplitudė, Cornell sandauga, Gubner-Ungerleider amplitudė ir R dantelis avl. Kairiojo skilvelio masei apskaičiuoti, buvo atlikta echokardioskopija. Kairiojo skilvelio masės indeksas buvo apskaičiuotas padalinant kairiojo skilvelio masę iš tiriamojo kūno paviršiaus ploto. Tiriamoji grupė buvo suskirstyta į pogrupius: tiriamuosius, kurių kūno masės indeksas (KMI) < 25, ir tuos, kurių KMI 25. Rezultatai. Tiriamiesiems, kurių KMI 25 tarp kairiojo skilvelio masės indekso ir Gubner-Ungerleider amplitudės (r = 0,477, p = 0,019) bei RaVL (r = 0,355, p = 0,044) buvo aptiktas vidutinio stiprumo statistiškai patikimas koreliacinis ryšys. Tiriateorija ir praktika T. 20 (Nr. 2), p. doi: /mtp

2 miesiems, kurių KMI buvo < 25, statistiškai patikimas silpnas koreliacinis ryšys buvo stebėtas tarp Sokolow-Lyon sandaugos ir kairiojo skilvelio masės indekso (r = 0,253, p = 0,045). Kitų statistiškai reikšmingų ryšių tarp elektrokardiografinių kairiojo skilvelio hipertrofijos kriterijų ir kairiojo skilvelio masės indekso nebuvo aptikta. Išvados. Elektrokardiografinių kairiojo skilvelio hipertrofijos kriterijų reikšmės priklauso nuo tiriamųjų KMI ir pasižymi silpnu arba vidutinio stiprumo ryšiu su kairiojo skilvelio masės indeksu, todėl jų vertės mažai atspindi jaunų nesportuojančių vyrų kairiojo skilvelio masę. INTRODUCTION Left ventricular hypertrophy (LVH) is a consequence of a variety of physiological and pathological states [1 3]. This morphological change is an independent cardiovascular risk factor and a strong predictor of cardiovascular morbidity and mortality. Electrocardiography (ECG) remains a screening method of choice in many countries due to its low price, wide availability and easy interpretation to suspect cardiac abnormalities including LVH [4]. The increase in left ventricular mass (LVM) is detected by evaluating voltages and QRS duration. However, both parameters depend not only on LVM, but also on many individual aspects like anthropometric data, fat deposition in the upper body layer as well as on individual peculiarities of cardiac conduction system [5, 6]. Therefore, ECG LVH criteria demonstrate low sensitivity. Apart from this, different hypertrophic criteria prevail depending on the underlying pathological condition, sex, race and age [7 10]. Many ECG LVH criteria were analysed in groups of subjects having systemic hypertension, as well as in elite athletes, trained soldiers and their means were measured. It was noticed that different groups of patients demonstrate different sensitivities and specificities of the same ECG criteria [1, 2, 11]. Furthermore, healthy individuals often have false-positive ECG criteria for LVH [1]. This makes it difficult to separate individuals with normal LVM from those with not in young subjects especially in primary care where higher sensitivity and specificity methods like echocardiography (ECHO) are unavailable. It is important to emphasise that early detection of such conditions as hypertrophic cardiomyopathy is crucial, because it is the leading cause of sudden cardiac arrest in males age < 35 years in the USA. Limited information is available about correlation between ECG LVH criteria and LVM in young healthy sedentary male subjects. Researchers have noticed high rates of false-positive ECG LVH criteria in this population, but direct ability of ECG criteria to reflect LVM is not yet well revealed. The present study was designed to check the relationship between LVM obtained by ECHO and 6 common ECG LVH criteria: Sokolow-Lyon Amplitude, Sokolow-Lyon Product, Cornell Amplitude, Cornell Product, Gubner-Ungerleider Amplitude and R wave in lead avl (RaVL) as well as body mass index (BMI) influence on hypertrophic criteria in young healthy sedentary males. METHODS This study complies with the Declaration of Helsinki and had appropriate ethics approval. Study subjects 60 Healthy young sedentary Caucasian male university students (age years) studying biomedical and engineering sciences were enrolled after their written informed consent was obtained. Parameters of subjects were: age 22.4 ± 1.9 years, height ± 7.0 cm, weight 80.0 ± 10.3 kg, BMI 23.6 ± 3.2 kg/m 2 (41 subjects with BMI < 25 and 19 subjects with MBI 25), systolic blood pressure ± 7.2 mmhg, diastolic blood pressure 74.7 ± 4.1 mmhg. The study was carried out between September 2012 and September All subjects with a diagnosed underlying systemic disease or any cardiac pathology, first or higher degree murmur, also those with any regular medication use or having blood pressure higher than 140 mmhg for systolic and 90 mmhg for diastolic were excluded. All subjects were sedentary students and were not doing any regular sports for at least 3 years prior the study. Subjects height and weight were recorded using electronic scales Omron BF-511 and body surface area (BSA) estimated using the Dubois formula: BSA = x height (m) x weight (kg) BMI was calculated using formula BMI = weight (kg) / height (m 2 ). Electrocardiography Electrocardiographic assessment was performed immediately prior to ECHO analysis. A standard resting 12-lead recording was performed during quiet respiration, with subjects in a supine position. All ECGs were recorded using resting ECG system (SCHILLER AT-1) at 25 mm/s and 0.1 mv/mm standardization. All ECG parameters were taken manually by two independent observers. Any disagreement was resolved by adjudication from a third cardiologist. Voltages (in mm) of SV1, RV5, RV6, RaVL, SV3, RI, SIII and QRS duration (in ms) were measured to calculate 6 commonly used ECG criteria: Sokolow-Lyon Amplitude [14], Sokolow-Lyon Product [15], Cornell Amplitude [16], Cornell Product [15] and Gubner-Ungerleider Amplitude [17]. LV hypertrophy was defined as: a Sokolow- Lyon Amplitude of [SV1 + RV5 or RV6 (depending on a higher mean)] 35 mm; a Sokolow-Lyon Product of [(SV1 + RV5) or (RV6) (depending on a higher mean) x QRS duration] 2940 mm ms; a Cornell Amplitude of [RaVL 124 teorija ir praktika T. 20 (Nr. 2)

3 + SV3] 28 mm; a Cornell Product of [(RaVL + SV3) x QRS duration] 2440 mm ms and Gubner-Ungerleider Amplitude of [RI + SIII] 25 mm. Sergio. L. Rodrigues et al [18] proposed that Cornell Amplitude correlation to LVM is dependent only on RaVL and the usage of it alone increases its correlation to LVMI. Regarding this proposal RaVL was analysed as a separate criterion. LV hypertrophy by RaVL was defined as RaVL 11 mm. Echocardiography Standard transthoracic two-dimensionally guided echocardiography was performed with the subjects resting in a left lateral and supine position, by means of an ultrasound device (Philips IE33) using a 1 5 MHz transducer. The sonographer had no knowledge about subject s clinical data. LV measurements were made from two-dimensional guiding in long-axis and short-axis views and in the apical four and two-chamber views. LV end-diastolic diameter (LVEDD) as well as interventricular septum thickness (IVST) and posterior wall thickness (PWT) were measured at end-diastole at or just below the mitral valve tips as recommended by the American Society of Echocardiography [12]. The same cardiologist made three measurements at three separate frozen views and the average for each LV parameter was calculated. The relative wall thickness (RWT) was calculated by dividing the sum of IVST and PWT by LVEDD. The reference cut point value for increased RWT was chosen Subjects exceeding this value were excluded from the study. LV mass (in g) was also calculated using formula: LVM = 0.8 x (1.04 ((LVEDD + PWT + IVS) 3 LVEDD 3 )) g [13]. Left ventricular mass index (LVMI) was obtained by dividing LVM by BSA. Statistical analysis The results were analysed with the use of SPSS (ver. 17.0, SPSS Inc., Chicago, IL, USA). Normality of data was assessed using the Kolmogorov Smironov test. For all variables, standard indices (mean and standard deviation) were calculated and distribution of frequencies of variables was assessed. The relationship between LVMI and Sokolow-Lyon Amplitude, Sokolow-Lyon Product, Cornell Amplitude, Cornell Product, Gubner-Ungerleider Amplitude and RaVL was assessed using Sperman correlation coefficient because distribution of LVMI was not normal. Correlation coefficients between ECG criteria under the investigation and LVMI were calculated in the subgroups separately. All statistical tests were two-sided, and a P-value of 0.05 was considered to be statistically significant. RESULTS 60 subjects were enrolled whose (mean ± standard deviation) age was LVM ± 23.9 g and LVMI 71.4 ± 10.9 g/m 2 (Table I). Prevalence of ECG defined LV hypertrophy was 11.7 %, 30.0 %, 1.7 %, 3.3 %, 0 %, 0 % for Sokolow-Lyon Amplitude, Sokolow-Lyon Product, Cornell Amplitude, Cornell Product, Gubner-Ungerleider Amplitude criteria and RaVL respectively. All subjects had normal LVMI, not exceeding 100 g/m 2. Correlation between Sokolow-Lyon Amplitude, Sokolow-Lyon Product, Cornell Amplitude, Cornell Product, Gubner-Ungerleider Amplitude, RaVL and LVMI was assessed. Correlation analysis was carried out in three groups: all subjects (N = 60), subjects with BMI < 25 (N = 41) and subjects with BMI 25 (N = 19). The analysis of all subjects without stratification revealed that weak correlation exists between LVMI and Sokolow-Lyon Product (r = 0.245, p = 0.03). No other ECG criteria showed statistically significant correlation to LVMI (Table II). Subjects were stratified by BMI (Table III) and correlation links between ECG criteria and LVMI in the subgroups were calculated. When analysing ECG criteria under research among subjects with BM I 25, it was revealed that moderate statistically significant correlation appears between LVMI and Gubner-Ungerleider Amplitude (r = 0.477, p = 0.019) as well as RaVL (r = 0.355, p = 0.044). Sokolow-Lyon Product showed weak statistically significant correlation to LVMI in subjects with BMI < 25 (r = 0.253, Table 1. Demographic characteristics ECG variables and ECHO parameters of subjects Age (years) 22.42±1.87 Height (cm) ±7.05 Weight (kg) 80.02±10.31 BMI (kg/m2) 23.64±3.11 Normal ( ) (%) 41 (68.33) Overweight ( ) (%) 19 (31.67) BSA (m2) 2.03±0.14 SBP (mmhg) ±7.22 DBP (mmhg) 74.70±4.10 HR (beats/min) 70.23±15.96 Sokolow-Lyon Amplitude (mm) 26.79±7.70 Sokolow-Lyon Product (mm) ± Cornell Amplitude (mm) 14.51±4.77 Cornell Product (mm) ± RI+SIII (mm) 6.90±3.52 RaVL (mm) LVM (g) 2.06± ±23.92 LVMI (g/m2) 71.41±10.92 BMI-body mass index (kg/m2); BSA-body surface area (m2), DBP-diastolic blood pressure (mmhg), HR-heart rate (beats/ min.), LVMI-left ventricular mass indexed to body surface area, SPB-systolic blood pressure (mmhg), LVM left ventricular mass, LVMI-left ventricular mass indexed to body surface area. teorija ir praktika T. 20 (Nr. 2) 125

4 p = 0.045). No statistically significant correlation between LVMI and other criteria was noticed (Table IV). DISCUSSION Electrocardiography as a tool to assess LVM is still widely analysed [19, 20]. Our research focuses on healthy individuals and brings findings about differentiation Table 2. Correlation between LVMI and ECG defined left ventricular hypertrophy criteria in all subjects Sperman Criteria Correlation P-value Coefficient Sokolow-Lyon Amplitude (mm) Sokolow-Lyon Product (mm) Cornell Amplitude (mm) Cornell Product (mm) Gubner-Ungerleider Amplitude (mm) RaVL (mm) between normal and pathological means in young healthy sedentary males. It contributes to previous scientific findings and shows that voltage criteria do little to reflect left ventricular mass [1, 21]. On the other hand, we found that false positive meanings of Sokolow-Lyon Product prevail in 30 % of healthy male subjects, however, its ability to reflect LVM is the highest and statistically significant among all criteria under investigation in subjects with normal BMI (< 25). Apart from this, Gubner-Ungerleider Amplitude and RaVL were not detected as false positive while their ability to reflect LVM was highest and statistically significant in patients with increased BMI (> 25). Scientists who analysed subjects with hypertrophic cardiomyopathy and other types of pathological hypertrophy have found that these patients demonstrate highest positive means for Cornell Amplitude and Cornell Product criteria [5, 6, 22, 23] while we found that false-positive meanings for these criteria are 1.7 % and 3.3 % respectively. These findings reveal that positive Cor- Table 3. Demographic characteristics of subjects and comparison of ECG variables and ECHO parameters after stratification by BMI BMI<25 (n=41) BMI>25 (n=19) Age (years) 22.17± ±1.54 Height (cm) ± ±8.63 Weight (kg) 75.41±7.61* 89.95±8.17 BMI (kg/m2) 21.97± ±2.16 BSA (m2) 1.99±0.12* 2.11±0.14 SBP (mmhg) ± ±8.11 DBP (mmhg) 75.66± ±4.01 HR (beats/min) 70.61± ±15.87 Sokolow-Lyon Amplitude (mm) 27.24± ±6.06 Sokolow-Lyon Product (mm) ± ± Cornell Amplitude (mm) 14.69± ±4.20 Cornell Product (mm) ± ± RI+SIII (mm) 6.04±2.87* 8.75±4.11 RaVL (mm) 1.56±1.04* 3.13±2.40 LVMI (g/m2) 71.99± ±11.2 *p<0.05 compared with a group of BMI 25. BMI-body mass index (kg/m2); BSA-body surface area (m2), DBP-diastolic blood pressure (mmhg), HR-heart rate (beats/min.), LVMI-left ventricular mass indexed to body surface area, SPB-systolic blood pressure (mmhg), LVMI-left ventricular mass indexed to body surface area. Table 4. Correlation between LVMI and ECG defined left ventricular hypertrophy criteria according to BMI Subjects with BMI<25 Subjects with BMI 25 Criteria Sperman Correlation P-value Sperman Correlation P-value Coefficient Coefficient Sokolow-Lyon Amplitude (mm) Sokolow-Lyon Product (mm) Cornell Amplitude (mm) Cornell Product (mm) Gubner-Ungerleider Amplitude (mm) RaVL (mm) teorija ir praktika T. 20 (Nr. 2)

5 nell Amplitude or Cornell Product or Gubner-Ungerleider Amplitude or RaVL criteria are alert signs and require further investigation. On the other hand, positive Sokolow-Lyon Amplitude or Sokolow-Lyon Product criteria in young healthy sedentary males are not subjects for deeper analysis. Physiologists analysing voltage criteria must take into consideration that they are influenced by subject s anthropometric parameters (for eg. BMI). Even though the sensitivities of the criteria under analysis are low, they remain a method of choice to rule out LVH in primary care especially in developing countries [2]. This study differs from previously carried out because it tries to find out the relationship between commonly used ECG defined LVH criteria and left ventricular morphology in sedentary subjects with no risk factors for LVH and with normal ECHO defined cardiac morphology and function. The specificities of analysed ECG criteria are rather high; however, low sensitivities make them poor diagnostic tools. There are a number of strengths of this study. Contrary to previous studies, it analysed young sedentary males. It also revealed that voltage without consideration of BMI loses its strength in relationship with LVM. The findings are also useful for physiologists and researchers working in the field of medical physiology. There are, however, some limitations. The sample is relatively small and the subjects are all male. The population is white and does not account for racial differences. CONCLUSION To conclude, the means of commonly used ECG defined LVH criteria depend on subjects BMI and demonstrate weak (Sokolow-Lyon Product in subjects with BMI < 25) to moderate (Gubner-Ungerleider Amplitude and RaVL in subjects with BMI 25) correlation with LVMI thus they do little to reflect LVM. ACKNOWLEDGEMENT This work was partly supported by project Promotion of Student Scientific Activities (VP1-3.1-ŠMM- 01-V ) from the Research Council of Lithuania (Justas Simonavičius). This project is funded by the Republic of Lithuania and European Social Fund under the Human Resources Development Operational Programme s priority 3. CONFLICT OF INTERESTS None declared. REFERENCES 1. Sohaib SM, Payne JR, Shukla R, World M, Pennell DJ, Montgomery HE. Electrocardiographic (ECG) criteria for determining left ventricular mass in young healthy men; data from the LAR- GE Heart study. J Cardiovasc Magn Reson Jan 16; 11: Pewsner D, Jüni P, Egger M, Battaglia M, Sundström J, Bachmann LM. Accuracy of electrocardiography in diagnosis of left ventricular hypertrophy in arterial hypertension: systematic review. BMJ Oct 6; 335(7622): Erice B, Romero C, Andériz M, Gorostiaga E, Izquierdo M, Ibáñez J. 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