Abstract
Background
Aortic valve stenosis (AS) generates a chronic pressure overload that induces left ventricular hypertrophy (LVH). The aim of this study was to assess the prevalence of the electrocardiographic criteria for LVH in patients with clinically significant AS and to evaluate the relationship between the ECG criteria for LVH and echocardiographic parameters.
Methods
The clinical data of 95 patients with moderate to severe AS were retrospectively analyzed. Eight ECG criteria for LVH were used and compared to the results of transthoracic echocardiography (TTE).
Results
In 59% of patients, at least one of the ECG criteria for LVH was found. These patients had a greater LVMI (142.1 ± 35.6 vs. 124.1 ± 22.5 g/m2, p = 0.01) and peak aortic jet velocity (4.2 ± 0.8 vs. 3.8 ± 0.9 m/s, p = 0.01) along with smaller aortic valve area (0.72 ± 0.28 vs. 0.86 ± 0.22 cm2, p = 0.02) compared to patients with a negative ECG for LVH. The ECG parameters had a low sensitivity (6%–36.9%) with a specificity of up to 100%. The Cornell Voltage criteria had the best sensitivity with a specificity of 63.6% and the highest correlation with the LVMI (r = 0.38, p < 0.001). All of the ECG parameters correlated positively with the peak aortic jet velocity as well as with the mean aortic gradient.
Conclusion
The electrocardiographic criteria for LVH in patients with moderate or severe AS have a poor sensitivity in identifying LVH confirmed by TTE. The values of the selected ECG criteria for LVH correlate weakly with both the TTE indices of LVH and the markers of AS severity.
Keywords: aortic valve stenosis, electrocardiography, left ventricular hypertrophy
1. INTRODUCTION
Aortic stenosis (AS) is the most prevalent valvular disease in highly developed countries, and it especially occurs among elderly patients. The aging of the population and rising global life expectancy have led to an increase in the frequency of AS (Coffey, Cairns, & Iung, 2016; Osnabrugge et al., 2013). Aortic valve obstruction generates a chronic pressure overload that induces left ventricular hypertrophy (LVH), which may be present even in the asymptomatic stage of the disease. Emerging data suggest that an abnormal electrocardiogram (ECG), along with a cardiac murmur on auscultation, is one of the most common incidental findings that leads to a diagnosis of AS—and that this may be the first sign in as many as one‐quarter of patients without symptoms (Chiang et al., 2016); therefore, the accuracy of ECG analysis should be satisfactory for all physicians, not only cardiologists. There are many electrocardiographic parameters of LVH, but, unfortunately, their accuracy in patients with AS has not been well described yet.
Thus, the primary aim of this study was to assess the prevalence of several electrocardiographic criteria for LVH in patients with clinically significant AS. Secondly, the relationship between the indices of LVH and hemodynamic markers of AS severity obtained by transthoracic echocardiography (TTE) and values of the electrocardiographic hypertrophy criteria were evaluated.
2. MATERIAL AND METHODS
This is a retrospective, single‐center study. One hundred and sixty‐two consecutive adult patients hospitalized in the I Department of Cardiology of the Medical University of Silesia in 2015 and 2016 who had a basic diagnosis of clinically significant (moderate or severe) aortic stenosis were screened. All of the clinical, electrocardiographic, and echocardiographic (transthoracic procedure) data were analyzed. The exclusion criteria were mild AS (because of small sample—11 patients), a QRS duration of more than 120 ms, complete and incomplete bundle branch blocks, nonspecific intraventricular conduction disturbances, paced rhythms, electrolyte imbalance, treatment with digoxin, and a previous aortic valve replacement. The pathophysiological models of AS, including the different types of fibrosis and local amyloidosis as well as the hemodynamical types of AS, were not analyzed separately.
2.1. Electrocardiography and echocardiography
The standard 12‐lead ECGs at rest were recorded using Mortara ELI 250c (paper speed 25 mm/s, 10 mm/mV). Two‐dimensional and Doppler TTE were performed using Epiq 7G (Philips, Andover, MA, USA). Each of ECGs was double‐checked, first by younger doctor (5‐year experience), then by noninvasive cardiologist with 20–30 years of clinical experience, and his decision was taken into consideration as final. In few cases of border results, ECGs recordings were consulted with another cardiologist. Moreover, in most cases there were more than one ECG available, so there was possibility to assess QRS amplitude in consecutive ECGs if there was any doubt. To evaluate LVH features in ECG, we used eight well‐known and often used criteria:
the Sokolow‐Lyon index: the sum of the S wave in V1 and the R wave in V5 or V6 > 3.5 mV (Sokolow & Lyon, 1949)
the sum of the S wave in the V2 and the R wave in V5 or V6 > 4.5 mV (Romhilt et al., 1969)
the amplitude of the R wave in V5 or V6 > 2.6 mV (Sokolow & Lyon, 1949)
a comparison of the amplitude of the R wave in V5 and V6; R V6 > R V5 (Holt & Spodick, 1962)
the sum of the largest amplitude of the R wave and the largest amplitude of the S wave in precordial leads >4.5 mV (McPhie, 1958)
the Cornell Voltage: the sum of the R wave in aVL and the S wave in V3 > 2.0 mV for women and >2.8 mV for men (Casale, Devereux, Alonso, Campo, & Kligfield, 1987)
the amplitude of the R wave in aVL > 1.1 mV (Sokolow & Lyon, 1949)
the Gubner‐Ungerleider voltage: the sum of the R wave in I and the S wave in the III lead > 2.5 mV (Gubner & Ungerleider, 1943)
An ECG was classified as positive for LVH if at least one of the LVH criteria was found. All of the echocardiographic examinations were performed by experienced cardiologists. Each performs over 1,000 TTE per year. The measurements of the intraventricular septum diameter (IVSd), left ventricular internal diameter (LVIDd), and posterior wall thickness diameter (PWTd) were used to calculate the left ventricular mass (LVM) according to the formula: 0.8 × 1.4 × [(IVSd + LVIDd + PWTd)3 – LVIDd3] + 0.6g (Lang et al., 2015). The presence of LVH in the TTE was determined using the left ventricular mass index (LVMI), which is defined as LVM/ body surface area (g/m2). The upper normal range for the LVMI was 95 g/m2 in women and 115 g/m2 in men. Higher values indicate LVH. The peak aortic jet velocity and the aortic mean gradient were measured using continuous‐wave Doppler and the multiple acoustic windows approach. The continuity equation was used to calculate the aortic valve area (AVA) (Baumgartner, Falk et al., 2017; Baumgartner, Hung et al., 2017). The severity of the aortic stenosis was assessed according to ESC guidelines on the management of valvular heart (Baumgartner, Falk et al., 2017; Baumgartner, Hung et al., 2017).
2.2. Statistical analysis
Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of electrocardiographic LVH criteria were calculated based on results of TTE. Sensitivity was computed using formula: number of true positives/(number of true positives + number of false negatives). Specificity: number of true negatives/(number of true negatives + number of false positives). PPV: number of true positives/(number of true positives + number of false positives). NPV: number of true negatives/(number of true negatives + number of false negatives).
The continuous variables are presented as the mean ± standard deviation and the categorical variables as the number or percentage of subjects. Differences between any unpaired normally distributed samples were assessed using the Student's t test, while the non‐normal data were compared using the Mann–Whitney U test. The normality of distribution was verified with the Shapiro–Wilk test. The categorical variables were compared using the chi‐square test. The Spearman's rank correlation coefficient was used for testing the strength of the correlation between two variables. A multiple regression model was built to determine the influence of the hemodynamic parameters and body mass index (BMI) on the ECG curve. A p value of < 0.05 was considered to be statistically significant. All statistical analyses were conducted using Statistica version 12 (TIBCO Software Inc., Palo Alto, California, United States).
3. RESULTS
3.1. Demographic and clinical data
A total of 95 patients (women/men: 47/48, age 72.2 ± 11.5 years) met the inclusion criteria. Severe AS was present in 73 (76.8%) of the subjects (Table 1). The presence of LVH was confirmed in 84 (88.4%) cases using echocardiography. The mean LVMI was 134.9 ± 32.2 g/m2. At least one positive criterion for ECG LVH was found in 56 patients. Those patients were characterized by a higher prevalence of severe AS (85.7% vs. 64.1%, p = 0.01), a greater LVM (265.2 ± 73.1 g vs. 232.9 ± 58.4 g, p = 0.03), LVMI (142.1 ± 35.6 g vs. 124.1 ± 22.5 g, p = 0.01), and peak aortic jet velocity (4.2 ± 0.8 m/s vs. 3.8 ± 0.9 m/s, p = 0.01). They also had smaller aortic valve area (0.72 ± 0.28 cm2 vs. 0.86 ± 0.22 cm2, p = 0.02).
Table 1.
Clinical characteristics and echocardiographic assessment of the study population
| All patients (n = 95) | Positive ECG for LVH (n = 56) | Negative ECG for LVH (n = 39) | p Value | |
|---|---|---|---|---|
| Demographic and clinical data | ||||
| Age (years) | 72.2 ± 11.5 | 71.5 ± 11.9 | 73.3 ± 11.0 | NS |
| Sex (men/women) | 48/47 | 25/31 | 23/16 | NS |
| BMI | 28.8 ± 4.7 | 28.6 ± 4.3 | 29.0 ± 5.3 | NS |
| Arterial hypertension | 70 (73.7%) | 37 (66.1%) | 33 (84.6%) | 0.02 |
| History of CAD | 47 (49.5%) | 28 (50%) | 19 (48.7%) | NS |
| Previous MI | 14 (14.7%) | 10 (17.9%) | 4 (10.3%) | NS |
| Diabetes mellitus | 26 (27.4%) | 14 (25%) | 12 (30.8%) | NS |
| Echocardiography | ||||
| LA diameter (mm) | 41.0 ± 5.3 | 41.7 ± 5.6 | 40.1 ± 4.8 | NS |
| IVSd (mm) | 15.2 ± 3.1 | 15.5 ± 3.5 | 14.9 ± 2.6 | NS |
| PWTd (mm) | 11.4 ± 1.8 | 11.7 ± 2.1 | 11.1 ± 1.3 | NS |
| LVESD (mm) | 30.5 ± 8.2 | 31.1 ± 8.9 | 29.6 ± 7.1 | NS |
| LVEDD (mm) | 47.4 ± 6.9 | 48.1 ± 7.0 | 46.4 ± 6.7 | NS |
| LVEF (%) | 54.7 ± 10.4 | 52.9 ± 11.8 | 57.1 ± 7.6 | NS |
| AVA (cm2) | 0.78 ± 0.26 | 0.72 ± 0.28 | 0.86 ± 0.22 | 0.02 |
| Peak aortic jet velocity (m/s) | 4.1 ± 0.89 | 4.2 ± 0.8 | 3.8 ± 0.9 | 0.01 |
| Aortic mean gradient (mmHg) | 42.1 ± 19.8 | 45.1 ± 20.8 | 37.7 ± 17.8 | 0.06 |
| LVM (g) | 252.1 ± 69.1 | 265.2 ± 73.1 | 232.9 ± 58.4 | 0.03 |
| LVMI (g/m2) | 134.9 ± 32.2 | 142.1 ± 35.6 | 124.1 ± 22.5 | 0.01 |
| RWT (cm) | 0.50 ± 0.12 | 0.50 ± 0.14 | 0.49 ± 0.09 | NS |
| LVH in TTE | 84 (88.4%) | 50 (89.3%) | 34 (87.2%) | NS |
| Severe AS | 73 (76.8%) | 48 (85.7%) | 25 (64.1%) | 0.01 |
AVA: aortic valve area; AS: aortic stenosis; BMI: body mass index; CAD: coronary artery disease; IVSd: intraventricular septum diameter; LA: left atrium; LVEDD: left ventricular end‐diastolic diameter; LVEF: left ventricular ejection fraction; LVESD: left ventricular end‐systolic diameter; LVH: left ventricular hypertrophy; LVM: left ventricular mass; LVMI: left ventricular mass index; MI: myocardial infarction; NS: not significant; PWTd: posterior wall thickness diameter; RWT: relative wall thickness; TTE: transthoracic echocardiography.
3.2. Sensitivity and specificity of the ECG criteria for LVH
The most frequent positive criteria were the Cornell Voltage criteria (35 patients, 36.8%) and the Sokolow‐Lyon index (26 patients, 27.4%). The ECG parameters had a low sensitivity, which ranged from 6% to 36.9% (Table 2). The Cornell Voltage criteria had the best sensitivity with the lowest specificity of 63.6%. The sensitivity of those criteria was more than twofold higher in women than in men (50.0% vs. 23.8%, p = 0.01). The sensitivity of the other criteria was similar in men and women (p > 0.05). From zero to seven of the ECG criteria were met in a single ECG.
Table 2.
Diagnostic test characteristics of the eight ECG criteria for LVH compared to echocardiographic‐based LVH
| ECG criteria | Positive results (n) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | |
|---|---|---|---|---|---|---|
| Amplitude of R in aVL | All | 15 | 16.7 | 90.9 | 93.3 | 12.5 |
| Men | 6 | 14.3 | 100 | 100 | 14.3 | |
| Women | 9 | 19.1 | 80 | 88.9 | 10.5 | |
| Gubner‐Ungerleider voltage | All | 10 | 11.9 | 100 | 100 | 12.9 |
| Men | 5 | 11.9 | 100 | 100 | 14 | |
| Women | 5 | 11.9 | 100 | 100 | 11.9 | |
| Sokolow‐Lyon index | All | 26 | 28.6 | 81.8 | 92.3 | 13 |
| Men | 15 | 31 | 66.7 | 86.7 | 12.1 | |
| Women | 11 | 26.2 | 100 | 100 | 13.9 | |
| Sum of S in V2 and R in V5 or V6 | All | 6 | 6 | 90.9 | 83.3 | 11.4 |
| Men | 4 | 7.3 | 83.3 | 75 | 11.9 | |
| Women | 2 | 4.8 | 100 | 100 | 11.1 | |
| Amplitude of R in V5 or V6 | All | 10 | 10.7 | 90.9 | 90 | 11.8 |
| Men | 6 | 11.9 | 83.3 | 83.3 | 11.9 | |
| Women | 4 | 9.5 | 100 | 100 | 11.6 | |
| R in V6 > R in V5 | All | 25 | 27.4 | 81.8 | 92 | 12.9 |
| Men | 9 | 19.1 | 80 | 88.9 | 12.8 | |
| Women | 16 | 35.7 | 83.3 | 93.8 | 12.9 | |
| Sum of the largest R and largest S in precordial leads | All | 12 | 14.3 | 100 | 100 | 13.3 |
| Men | 8 | 19.1 | 100 | 100 | 15 | |
| Women | 4 | 9.5 | 100 | 100 | 11.6 | |
| Cornell Voltagea | All | 35 | 36.9 | 63.6 | 88.6 | 11.7 |
| Men | 12 | 23.8 | 66.7 | 83.3 | 11.1 | |
| Women | 23 | 50 | 60 | 91.3 | 12.5 | |
NPV: negative predictive value; PPV: positive predictive value.
Significant difference in sensitivity between men and women (p < 0.05).
3.3. Relationship of the ECG criteria with the selected clinical and echocardiographic parameters
Although significant relationships were found between the majority of the ECG criteria and LVMI, the strength of those correlations was weak (Table 3). The highest correlation with the LVMI was for the Cornell Voltage (r = 0.38, p < 0.001). Interestingly, there was a positive correlation between all of the ECG parameters and the peak aortic jet velocity as well as the mean aortic gradient. For the Sokolow‐Lyon index, the sum of the S wave in V2 and the R wave in V5 or V6 and the sum of the largest R wave and the largest S wave in the precordial lead corresponded moderately to those parameters. Multiple regression analysis using the peak aortic jet velocity, LVMI, and BMI was performed in order to determine their influence on the QRS complex amplitude and the values of the ECG criteria (Table 4). The adjusted coefficient of determination (R2) was low for all ECG criteria (0.09–0.28). Peak aortic jet velocity and BMI had an influence only on values of the ECG criteria based on precordial leads, while Cornell Voltage and limb lead criteria were independent of those variables.
Table 3.
Correlation between the value of the selected ECG criteria for LVH and the echocardiographic parameters
| LVM | LVMI | Aortic valve area | Peak aortic jet velocity | Mean aortic gradient | ||
|---|---|---|---|---|---|---|
| Amplitude of R in aVL | r | 0.24 | 0.24 | −0.05 | 0.22 | 0.21 |
| p | 0.02 | 0.03 | NS | 0.04 | 0.045 | |
| Gubner‐Ungerleider voltage | r | 0.17 | 0.18 | −0.10 | 0.21 | 0.24 |
| p | NS | NS | NS | 0.04 | 0.02 | |
| Sokolow‐Lyon index | r | 0.14 | 0.27 | −0.26 | 0.49 | 0.46 |
| p | NS | 0.01 | 0.01 | <0.001 | <0.001 | |
| Sum of S in V2 and R in V5 or V6 | r | 0.18 | 0.34 | −0.25 | 0.42 | 0.37 |
| p | NS | 0.002 | 0.02 | <0.001 | <0.001 | |
| Amplitude of R in V5 or V6 | r | 0.02 | 0.14 | −0.10 | 0.34 | 0.32 |
| p | NS | NS | NS | <0.001 | <0.001 | |
| Sum of the largest R and largest S in the precordial leads | r | 0.27 | 0.35 | −0.21 | 0.41 | 0.40 |
| p | 0.008 | 0.001 | 0.049 | <0.001 | <0.001 | |
| Cornell Voltage | r | 0.37 | 0.38 | −0.20 | 0.24 | 0.25 |
| p | <0.001 | <0.001 | NS | 0.02 | 0.02 |
LVM: left ventricular mass; LVMI: left ventricular mass index; NS: not significant.
Table 4.
Multiple regression analysis for the values of the selected ECG criteria for LVH
| Standardized coefficient (β) | p Value | Adjusted R 2 | |
|---|---|---|---|
| Amplitude of R in aVL | |||
| BMI | 0.09 | NS | 0.11 |
| Peak aortic jet velocity | −0.01 | NS | |
| LVMI | 0.36 | 0.002 | |
| Gubner‐Ungerleider voltage | |||
| BMI | 0.004 | NS | 0.09 |
| Peak aortic jet velocity | 0.005 | NS | |
| LVMI | 0.34 | 0.004 | |
| Sokolow‐Lyon index | |||
| BMI | −0.27 | 0.007 | 0.26 |
| Peak aortic jet velocity | 0.36 | 0.001 | |
| LVMI | 0.17 | NS | |
| Sum of S in V2 and R in V5 or V6 | |||
| BMI | −0.26 | 0.009 | 0.28 |
| Peak aortic jet velocity | 0.35 | 0.001 | |
| LVMI | 0.24 | 0.02 | |
| Amplitude of R in V5 or V6 | |||
| BMI | −0.35 | <0.001 | 0.24 |
| Peak aortic jet velocity | 0.33 | 0.002 | |
| LVMI | 0.05 | NS | |
| Sum of the largest R and largest S in the precordial leads | |||
| BMI | −0.21 | 0.03 | 0.28 |
| Peak aortic jet velocity | 0.35 | 0.001 | |
| LVMI | 0.26 | 0.01 | |
| Cornell voltage | |||
| BMI | −0.04 | NS | 0.19 |
| Peak aortic jet velocity | 0.13 | NS | |
| LVMI | 0.41 | <0.001 | |
BMI: body mass index; LVMI: left ventricular mass index; NS: not significant.
4. DISCUSSION
In this study, we analyzed the accuracy of the selected ECG criteria for LVH and their relationship with the echocardiographic parameters in patients with clinically significant aortic stenosis. These ECG criteria have previously been extensively investigated in many different populations, including patients with arterial hypertension or hypertrophic cardiomyopathy. The results of those studies showed an unsatisfactory low sensitivity of the ECG parameters for detecting LVH (Greve et al., 2012; Narayanan et al., 2014; Pewsner et al., 2007; Sundström et al., 2001). In our study, LVH was confirmed in 84 patients using echocardiography, but at least one criterion of LVH was found in ECG in only 56 patients, which means that the low sensitivity of the LVH criteria (6%–36.9%) and high specificity (up to 100%) were similar to other studies on different group of patients. Interestingly, a significant difference in the sensitivity of Cornell Voltage was found between men and women. One of the possible explanations for the higher sensitivity of this criterion in the female subgroup may be the different thresholds for men and women. The second issue that was of interest to us was the relationship between the ECG and echocardiographic parameters—LVH indices and markers of AS severity. It was proved and documented that the presence of the electrocardiographic LVH features is an independent risk factor of cardiovascular death in general population (Narayanan et al., 2014; Sundström et al., 2001). Therefore, the analysis of the ECG recordings and clear knowledge on sensitivity and specificity of LVH criteria seems to be very important. In the present study, values of those criteria correlated rather weakly with echocardiographic parameters, so we assumed that discussion about the predictive value of the presence of these criteria in patients with AS is difficult and does not lead to concrete conclusions. However, some interesting findings should be noticed. The values of limb lead criteria were influenced by LVMI, but not by the peak aortic jet velocity. Surprisingly, ECG criteria based on precordial leads were related more to hemodynamic parameters than mass of the left ventricle. Moreover, there were significant correlations between the values of the ECG criteria and LVMI, but when BMI and the peak aortic jet velocity were added to the regression model, the relationships between the LVMI and the Sokolow‐Lyon index were not found. In our opinion, further examinations to explain all these relationships are absolutely needed.
The body mass index has frequently been reported to be a disturbing factor in an ECG analysis (Abergel, Tase, Menard, & Chatellier, 1996; Nan, Jin‐Xiu, Pei‐Xuan, & Xue‐Rui, 2017; Rider et al., 2016). The amplitude of the QRS complex is lower in obese individuals due to the considerably greater distance between the heart and electrodes. Furthermore, obesity leads to changes in the geometry of the chest, which may cause a problem with the correct placement of the precordial electrodes. In the present study, BMI also had an influence on the value of the ECG criteria that were based on the precordial leads, which was expected.
Sjöberg et al. analyzed the electrocardiographic LVH criteria in patients who were qualified for a transcatheter aortic valve replacement (Sjöberg et al., 2015). Like in our study, the most common positive criterion was the Cornell Voltage. No correlation was observed between the values of the ECG criteria and LVM, but in contrast to our study, the mass of left ventricle was not indexed to the body surface area. The relationship between the Sokolow‐Lyon index and the peak aortic jet velocity was also observed by Greve at al. (Greve et al., 2011). Similarly, the Cornell Voltage criterion corresponded better with the LVMI.
Buchner et al. found a stronger correlation between the values of the ECG criteria and the LVMI (Buchner et al., 2009). In contrast to our study, measurements of the left ventricular parameters were performed using cardiovascular magnetic resonance, which is more accurate than echocardiography. Moreover, the study population consisted of patients with both aortic stenosis and regurgitation, which might have affected the results—they reported a higher sensitivity of the ECG‐derived LVH criteria (from 34% of the Gubner‐Ungerleider voltage to 57% of the Sokolow‐Lyon index) compared to ours.
4.1. Study limitations
This is a retrospective, single‐center study. The echocardiographic examinations were performed by experienced but several cardiologists. The study was focused on the presence of LVH in an echocardiographic examination but not in any specific pathogenetic or hemodynamic type. The number of patients without LVH in TTE was small. This study was not designed to evaluate the effect of the ECG criteria on the further prognosis and clinical outcome. Nevertheless, in our opinion, this study and results may be interesting for next studies assessing the relationships between the ECG criteria and the echocardiographic parameters of LVH, as well as the possible influence of the ECG criteria on the prognosis in this population.
5. CONCLUSIONS
The electrocardiographic criteria for LVH have a rather poor sensitivity in patients with clinically significant aortic valve stenosis with LVH, which was confirmed using echocardiography. The values of the selected ECG criteria for LVH correlate weakly with both the TTE indices of LVH and the markers of AS severity.
CONFLICT OF INTEREST
None.
Bula K, Ćmiel A, Sejud M, et al. Electrocardiographic criteria for left ventricular hypertrophy in aortic valve stenosis: Correlation with echocardiographic parameters. Ann Noninvasive Electrocardiol. 2019;24:e12645 10.1111/anec.12645
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