Letters to the Editor
287
Left ventricular hypertrophy in asymptomatic individuals without overt heart disease☆,☆☆ Gustavo Ferreira Correia a, Talita Cardoso Gonçalves a, Bruna Affonso Madaloso a,⁎, Rafael Amorim Belo Nunes a, Renata Thiemi Uemura b, Roberta Carolina de Matos Justo b, Nelson Ithiro Tanaka b, Alfredo José Mansur a a b
From Heart Institute (InCor), Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil Center of Applied Statistics, Institute of Mathematics and Statistics, São Paulo, Brazil
a r t i c l e
i n f o
Article history: Received 29 November 2013 Accepted 30 December 2013 Available online 10 January 2014 Keywords: Left ventricular hypertrophy Cardiac hypertrophy Electrocardiography Echocardiography
We have been following up a cohort of 1608 asymptomatic individuals enrolled between 1998 and 2005 without past medical history of cardiovascular disease with normal clinical examination as well as normal 12-lead electrocardiogram, stress testing, echocardiogram and laboratory evaluation, diagnosed as without any evidence of heart disease. The study was approved by the Committee of Ethics of the Hospital; all participants signed an informed consent. Left ventricular mass was occasionally observed in the upper range of the distribution and prompted us to investigate left ventricular mass in the range defined as left ventricular hypertrophy in this specific population. We studied 539 patients whose electrocardiograms and echocardiograms were retrieved for analysis, mean age was 41.7 (standard deviation 11.7) years, 236 (43.8%) men and 303 (56.2%) women. The interpretation of the electrocardiogram followed published guidelines [1]. Amplitude and duration of QRS complexes were measured with a digitizer table. We studied: a) Sokolow Lyon criteria (the sum of the largest R wave of leads V5 or V6 with the S wave of lead V1) [2,3]; b) Cornell criteria (sum of R wave amplitude in lead aVL with the S wave in lead V1) [2]; c) Lewis criteria (sum of positive RS in lead I with the negativity in lead III) [2,4]; and d) the sum of the largest S wave amplitude with the largest R wave in the horizontal plane multiplied by QRS duration [(S + R) × QRS)] [5]. Left ventricular mass was estimated by echocardiograms performed following recommendations of the American Society of Echocardiography [6]. Left ventricular mass was estimated by 0,8 × {1,04 [(LVIDd + PWTd + SWTd) [3] − (LVIDd) [3]]} + 0.6 g, where LVIDd is the left ventricle internal diameter at end diastole, PWTd is the posterior wall thickness at end diastole and SWTd is the septal wall thickness at end diastole [7]. Hypertrophy was defined as values of left ventricular mass on echocardiography indexed by height, body surface area and by
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ The authors state that there are no potential conflicts of interest with any companies, organizations whose products or services may be discussed in this article. ⁎ Corresponding author at: Heart Institute (InCor), Hospital das Clinicas, São Paulo University Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo ZIP Code 05403-900, Brazil. Tel.: + 55 11 2661 5237; fax: +55 11 2661 5247. E-mail address: [email protected] (B.A. Madaloso).
height2.7 equal or greater than two standard deviations above the mean in men and in women [7]. After descriptive statistics that included Pearson correlation, clinical characteristics of the study sample (n = 539) were compared with the whole sample (n = 1608) using Hotelling's T [2] test. The comparison included 19 variables and 167 patients with all 19 variables; results demonstrated that the means of the variables in the study sample (n = 539) were not significantly different from the mean of the variables in whole sample (n = 1608) (p = 0.19). Clinical and electrocardiographic variables that might predict left ventricular hypertrophy were assessed with a logistic model (stepwise–backward method; significance level 0.05). Subsequently multiple linear regression models were fitted to describe the relationship between left ventricular mass and clinical, laboratory and electrocardiographic variables. Pearson correlations of left ventricular mass on echocardiography and the four studied electrocardiographic criteria for left ventricular hypertrophy varied according to left ventricular mass indexation (no indexation, indexation to height, body surface area, and height2.7). The sum of the largest S wave amplitude with the largest R wave in the horizontal plane multiplied by QRS duration [5] demonstrated the highest correlation with left ventricular mass (absolute value, no indexation) (Pearson coefficient 0.248) and with left ventricular mass indexed to body surface area (Pearson coefficient 0.220). Lewis criteria showed the highest correlation with left ventricular mass indexed to height2.7 (Pearson coefficient 0.195) and the Cornell criteria showed the highest correlation with left ventricular mass indexed by height (Pearson coefficient 0.212). Sokolow-Lyon criteria demonstrated highest correlation (Pearson coefficient 0.140) with left ventricular mass (absolute value, no indexation). The difference between the highest and lowest values of duration of QRS complex in the 12 leads of electrocardiogram demonstrated good correlations with QRS duration in leads V2 (Pearson coefficient 0.857) and V3 (Pearson coefficient 0.909). The comparison of frequency of hypertrophy by Cornell criteria and by echocardiographic criteria in the study sample revealed left ventricular hypertrophy in 2.4% (Cornell criteria) and between 1.8% and 3% (left ventricular mass on echocardiography with different indexations) (Table 1). Logistic regression model demonstrated that age (odds ratio 1.09, confidence interval 95% 1.04–1.14; p b 0.001), height (odds ratio 8,34.e− 10, confidence interval 3,16. e− 13 − 2,2. e− 6, p b 0.001), weight (odds ratio 1.11, confidence interval 1.07–1.16; p b 0.001) and the duration of QRS complex in lead V3 (odds ratio 1.03, confidence interval 1.00–1.07, p = 0.027) were independently predictive of left ventricular hypertrophy. The probability of detecting hypertrophy on the basis of the variables selected by logistic regression was 3.7%; the specificity of the modeling was 78.3% and the sensitivity 79.2%. Left ventricular mass was estimated on the basis of clinical and electrocardiographic variables with multiple linear regressions (Table 2); the final multiple linear regressions adjusted model (R [2] 97.6) was: Left ventricular mass = 13.7 × Sex (0 = women; 1 = men) − 0.302 × age + 0.482 × body weight + 0.665 × QRS duration in lead V2 + 0.445 × R wave amplitude in lead I + 4.13 × S wave amplitude
288
Letters to the Editor
Table 1 Frequency of ventricular hypertrophy in the study sample identified by Cornell criteria and by echocardiography indexing to height, body surface area and height 2.7. Criteria
Men (236)
Women (303)
Cornell 3 10 Left ventricular 5 (≥116 g/m) ⁎ 7 (≥104 g/m) ⁎ mass/height (g/m) Left ventricular 5 (≥103.8 g/m [2])⁎ 5 (≥95.8 g/m [2])⁎ mass/body surface area (g/m [2]) Left ventricular 7 (≥48.4 g/m [2,7])⁎ 9 (≥48.5 g/m [2,7])⁎ mass height [2,7] (g/m [2,7])
Table 2 Left ventricular mass estimated by clinical and electrocardiographic variables (multiple linear regressions) (R[2] 97,61).
Total (%) 13 (2.4%) 12 (2.2%) 10 (1.8%)
16 (3%)
⁎ Values of left ventricular mass above the value of 2 standard deviations above the mean.
in lead V2 + 0.0107 × (weight ∗ age) − 0.0380 × (QRS duration in lead V2 ∗ S in lead V2). Adjustment of the model was evaluated and considered appropriate. Homocedasticity, independence and normal distribution of errors were tested and no deviations were found neither from the supposition of homocedasticity nor from normal distribution. In conclusion, values of left ventricular mass that meet electrocardiographic criteria of left ventricular hypertrophy was detected in asymptomatic individuals without any evidence of heart disease in the range of 2.2% (indexation to height) to 3% (indexation to height [2,7]) depending on the criteria used. In addition to age and body weight already recognized as variables associated with left ventricular mass, the duration of QRS in leads V2 and V3 may also contribute to estimation of left ventricular mass. Long term followup and further studies may help to clarify the clinical meaning of these findings. References [1] Kadish AH, Buxton AE, Kennedy HL, et al. American College of Cardiology/American Heart Association/American College of Physicians–American Society of Internal
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.234
Sex Body weight (kg) Age (years) ⁎ QRS duration in lead V2 R (mm) in lead I S in lead V2 Body weight age interaction QRS duration — S amplitude in lead V2 interaction
Intercept
Standard error
p Value
13.668 0.482 − 0.302 0.665 0.445 4.128 0.011 − 0.038
2.169 0.179 0.294 0.131 0.154 0.989 0.004 0.011
b 0.001 0.008 0.305 b 0.001 0.004 b 0.001 0.013 b 0.001
Weight was significant. ⁎ Though not significant age was kept in the model because interaction with body.
[2] [3] [4] [5] [6]
[7]
Medicine Task Force; International Society for Holter and Noninvasive Electrocardiology. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography: a report of the ACC/AHA/ACP-ASIM task force on clinical competence (ACC/AHA Committee to develop a clinical competence statement on electrocardiography and ambulatory electrocardiography) endorsed by the International Society for Holter and noninvasive electrocardiology. Circulation 2001;104:3169–78. Casiglia E, Schiavon L, Tikhonoff V, et al. Electrocardiographic criteria of left ventricular hypertrophy in general population. Eur J Epidemiol 2008;23:261–71. Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J 1949;37:161–86. Tranchesi J. Eletrocardiograma Normal e Patológico. Fundo Editorial Procienx: Noções de vectorcardiografia. São Paulo; 1962. Mazzaro CL, Costa FA, Bombig MT, et al. Ventricular mass and electrocardiographic criteria of hypertrophy: evaluation of new score. Arq Bras Cardiol 2008;90:227–31. Chiller N, Shah P, Crawford M, et al. Society of Echocardiography. Committee on Standards. Recommendations for quantification of the left ventricle by twodimensional echocardiography. J Am Soc Echocardiogr 1989;2:358–67. Lang RM, Bierig M, Devereux RB, et al. Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63.
287
Left ventricular hypertrophy in asymptomatic individuals without overt heart disease☆,☆☆ Gustavo Ferreira Correia a, Talita Cardoso Gonçalves a, Bruna Affonso Madaloso a,⁎, Rafael Amorim Belo Nunes a, Renata Thiemi Uemura b, Roberta Carolina de Matos Justo b, Nelson Ithiro Tanaka b, Alfredo José Mansur a a b
From Heart Institute (InCor), Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil Center of Applied Statistics, Institute of Mathematics and Statistics, São Paulo, Brazil
a r t i c l e
i n f o
Article history: Received 29 November 2013 Accepted 30 December 2013 Available online 10 January 2014 Keywords: Left ventricular hypertrophy Cardiac hypertrophy Electrocardiography Echocardiography
We have been following up a cohort of 1608 asymptomatic individuals enrolled between 1998 and 2005 without past medical history of cardiovascular disease with normal clinical examination as well as normal 12-lead electrocardiogram, stress testing, echocardiogram and laboratory evaluation, diagnosed as without any evidence of heart disease. The study was approved by the Committee of Ethics of the Hospital; all participants signed an informed consent. Left ventricular mass was occasionally observed in the upper range of the distribution and prompted us to investigate left ventricular mass in the range defined as left ventricular hypertrophy in this specific population. We studied 539 patients whose electrocardiograms and echocardiograms were retrieved for analysis, mean age was 41.7 (standard deviation 11.7) years, 236 (43.8%) men and 303 (56.2%) women. The interpretation of the electrocardiogram followed published guidelines [1]. Amplitude and duration of QRS complexes were measured with a digitizer table. We studied: a) Sokolow Lyon criteria (the sum of the largest R wave of leads V5 or V6 with the S wave of lead V1) [2,3]; b) Cornell criteria (sum of R wave amplitude in lead aVL with the S wave in lead V1) [2]; c) Lewis criteria (sum of positive RS in lead I with the negativity in lead III) [2,4]; and d) the sum of the largest S wave amplitude with the largest R wave in the horizontal plane multiplied by QRS duration [(S + R) × QRS)] [5]. Left ventricular mass was estimated by echocardiograms performed following recommendations of the American Society of Echocardiography [6]. Left ventricular mass was estimated by 0,8 × {1,04 [(LVIDd + PWTd + SWTd) [3] − (LVIDd) [3]]} + 0.6 g, where LVIDd is the left ventricle internal diameter at end diastole, PWTd is the posterior wall thickness at end diastole and SWTd is the septal wall thickness at end diastole [7]. Hypertrophy was defined as values of left ventricular mass on echocardiography indexed by height, body surface area and by
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ☆☆ The authors state that there are no potential conflicts of interest with any companies, organizations whose products or services may be discussed in this article. ⁎ Corresponding author at: Heart Institute (InCor), Hospital das Clinicas, São Paulo University Medical School, Av Dr Eneas de Carvalho Aguiar, 44, São Paulo ZIP Code 05403-900, Brazil. Tel.: + 55 11 2661 5237; fax: +55 11 2661 5247. E-mail address: [email protected] (B.A. Madaloso).
height2.7 equal or greater than two standard deviations above the mean in men and in women [7]. After descriptive statistics that included Pearson correlation, clinical characteristics of the study sample (n = 539) were compared with the whole sample (n = 1608) using Hotelling's T [2] test. The comparison included 19 variables and 167 patients with all 19 variables; results demonstrated that the means of the variables in the study sample (n = 539) were not significantly different from the mean of the variables in whole sample (n = 1608) (p = 0.19). Clinical and electrocardiographic variables that might predict left ventricular hypertrophy were assessed with a logistic model (stepwise–backward method; significance level 0.05). Subsequently multiple linear regression models were fitted to describe the relationship between left ventricular mass and clinical, laboratory and electrocardiographic variables. Pearson correlations of left ventricular mass on echocardiography and the four studied electrocardiographic criteria for left ventricular hypertrophy varied according to left ventricular mass indexation (no indexation, indexation to height, body surface area, and height2.7). The sum of the largest S wave amplitude with the largest R wave in the horizontal plane multiplied by QRS duration [5] demonstrated the highest correlation with left ventricular mass (absolute value, no indexation) (Pearson coefficient 0.248) and with left ventricular mass indexed to body surface area (Pearson coefficient 0.220). Lewis criteria showed the highest correlation with left ventricular mass indexed to height2.7 (Pearson coefficient 0.195) and the Cornell criteria showed the highest correlation with left ventricular mass indexed by height (Pearson coefficient 0.212). Sokolow-Lyon criteria demonstrated highest correlation (Pearson coefficient 0.140) with left ventricular mass (absolute value, no indexation). The difference between the highest and lowest values of duration of QRS complex in the 12 leads of electrocardiogram demonstrated good correlations with QRS duration in leads V2 (Pearson coefficient 0.857) and V3 (Pearson coefficient 0.909). The comparison of frequency of hypertrophy by Cornell criteria and by echocardiographic criteria in the study sample revealed left ventricular hypertrophy in 2.4% (Cornell criteria) and between 1.8% and 3% (left ventricular mass on echocardiography with different indexations) (Table 1). Logistic regression model demonstrated that age (odds ratio 1.09, confidence interval 95% 1.04–1.14; p b 0.001), height (odds ratio 8,34.e− 10, confidence interval 3,16. e− 13 − 2,2. e− 6, p b 0.001), weight (odds ratio 1.11, confidence interval 1.07–1.16; p b 0.001) and the duration of QRS complex in lead V3 (odds ratio 1.03, confidence interval 1.00–1.07, p = 0.027) were independently predictive of left ventricular hypertrophy. The probability of detecting hypertrophy on the basis of the variables selected by logistic regression was 3.7%; the specificity of the modeling was 78.3% and the sensitivity 79.2%. Left ventricular mass was estimated on the basis of clinical and electrocardiographic variables with multiple linear regressions (Table 2); the final multiple linear regressions adjusted model (R [2] 97.6) was: Left ventricular mass = 13.7 × Sex (0 = women; 1 = men) − 0.302 × age + 0.482 × body weight + 0.665 × QRS duration in lead V2 + 0.445 × R wave amplitude in lead I + 4.13 × S wave amplitude
288
Letters to the Editor
Table 1 Frequency of ventricular hypertrophy in the study sample identified by Cornell criteria and by echocardiography indexing to height, body surface area and height 2.7. Criteria
Men (236)
Women (303)
Cornell 3 10 Left ventricular 5 (≥116 g/m) ⁎ 7 (≥104 g/m) ⁎ mass/height (g/m) Left ventricular 5 (≥103.8 g/m [2])⁎ 5 (≥95.8 g/m [2])⁎ mass/body surface area (g/m [2]) Left ventricular 7 (≥48.4 g/m [2,7])⁎ 9 (≥48.5 g/m [2,7])⁎ mass height [2,7] (g/m [2,7])
Table 2 Left ventricular mass estimated by clinical and electrocardiographic variables (multiple linear regressions) (R[2] 97,61).
Total (%) 13 (2.4%) 12 (2.2%) 10 (1.8%)
16 (3%)
⁎ Values of left ventricular mass above the value of 2 standard deviations above the mean.
in lead V2 + 0.0107 × (weight ∗ age) − 0.0380 × (QRS duration in lead V2 ∗ S in lead V2). Adjustment of the model was evaluated and considered appropriate. Homocedasticity, independence and normal distribution of errors were tested and no deviations were found neither from the supposition of homocedasticity nor from normal distribution. In conclusion, values of left ventricular mass that meet electrocardiographic criteria of left ventricular hypertrophy was detected in asymptomatic individuals without any evidence of heart disease in the range of 2.2% (indexation to height) to 3% (indexation to height [2,7]) depending on the criteria used. In addition to age and body weight already recognized as variables associated with left ventricular mass, the duration of QRS in leads V2 and V3 may also contribute to estimation of left ventricular mass. Long term followup and further studies may help to clarify the clinical meaning of these findings. References [1] Kadish AH, Buxton AE, Kennedy HL, et al. American College of Cardiology/American Heart Association/American College of Physicians–American Society of Internal
0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.234
Sex Body weight (kg) Age (years) ⁎ QRS duration in lead V2 R (mm) in lead I S in lead V2 Body weight age interaction QRS duration — S amplitude in lead V2 interaction
Intercept
Standard error
p Value
13.668 0.482 − 0.302 0.665 0.445 4.128 0.011 − 0.038
2.169 0.179 0.294 0.131 0.154 0.989 0.004 0.011
b 0.001 0.008 0.305 b 0.001 0.004 b 0.001 0.013 b 0.001
Weight was significant. ⁎ Though not significant age was kept in the model because interaction with body.
[2] [3] [4] [5] [6]
[7]
Medicine Task Force; International Society for Holter and Noninvasive Electrocardiology. ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography: a report of the ACC/AHA/ACP-ASIM task force on clinical competence (ACC/AHA Committee to develop a clinical competence statement on electrocardiography and ambulatory electrocardiography) endorsed by the International Society for Holter and noninvasive electrocardiology. Circulation 2001;104:3169–78. Casiglia E, Schiavon L, Tikhonoff V, et al. Electrocardiographic criteria of left ventricular hypertrophy in general population. Eur J Epidemiol 2008;23:261–71. Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J 1949;37:161–86. Tranchesi J. Eletrocardiograma Normal e Patológico. Fundo Editorial Procienx: Noções de vectorcardiografia. São Paulo; 1962. Mazzaro CL, Costa FA, Bombig MT, et al. Ventricular mass and electrocardiographic criteria of hypertrophy: evaluation of new score. Arq Bras Cardiol 2008;90:227–31. Chiller N, Shah P, Crawford M, et al. Society of Echocardiography. Committee on Standards. Recommendations for quantification of the left ventricle by twodimensional echocardiography. J Am Soc Echocardiogr 1989;2:358–67. Lang RM, Bierig M, Devereux RB, et al. Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63.
