SUMMARY
OBJECTIVE:
The aim of this study was to evaluate the correlation between P-wave indexes, echocardiographic parameters, and CHA2DS2-VASc score in patients without atrial fibrillation and valvular disease.
METHODS:
This retrospective cross-sectional study included patients of a tertiary hospital with no history of atrial fibrillation, atrial flutter, or valve disease and collected data from June 2021 to May 2022. The exclusion criteria were as follows: unavailable medical records, pacemaker carriers, absence of echocardiogram report, or uninterpretable ECG. Clinical, electrocardiographic [i.e., P-wave duration, amplitude, dispersion, variability, maximum, minimum, and P-wave voltage in lead I, Morris index, PR interval, P/PR ratio, and P-wave peak time], and echocardiographic data [i.e., left atrium and left ventricle size, left ventricle ejection fraction, left ventricle mass, and left ventricle indexed mass] from 272 patients were analyzed.
RESULTS:
PR interval (RHO=0.13, p=0.032), left atrium (RHO=0.301, p<0.001) and left ventricle diameter (RHO=0.197, p=0.001), left ventricle mass (RHO=0.261, p<0.001), and left ventricle indexed mass (RHO=0.340, p<0.001) were positively associated with CHA2DS2-VASc score, whereas P-wave amplitude (RHO=-0.141, p=0.02), P-wave voltage in lead I (RHO=-0.191, p=0.002), and left ventricle ejection fraction (RHO=-0.344, p<0.001) were negatively associated with the same score. The presence of the Morris index was associated with high CHA2DS2-VASc (p=0.022).
CONCLUSION:
Prolonged PR interval, Morris index, increased left atrium diameter, left ventricle diameter, left ventricle mass, and left ventricle indexed mass values as well as lower P-wave amplitude, P-wave voltage in lead I, and left ventricle ejection fraction values were correlated with higher CHA2DS2-VASc scores.
Keywords: Heart function tests, Electrocardiography, Echocardiography, Risk factors
INTRODUCTION
The CHA2DS2-VASc score is used to assess the risk of stroke in patients with atrial fibrillation (AF) 1 , 2 . However, recent studies have shown validation of this score as a predictor of cardiovascular outcomes (including the development of AF), thromboembolic events, and death, even in the absence of AF 3 - 7 .
Electrocardiographic parameters such as P-wave duration (PWD), variability and dispersion, interatrial block, maximum P (Pmax), and P-wave voltage in lead I (PVL1) have been studied as risk stratifiers for AF 8 - 11 . Echocardiographic parameters, including left atrial (LA) and left ventricular (LV) size, LV ejection fraction (LVEF), and LV mass, have also been associated with the risk of developing AF as well as all-cause mortality, myocardial infarction, and stroke or transient ischemic attack (TIA) 12 - 14 .
Despite the data presented, there are no enough data on the correlation between these parameters and the CHA2DS2-VASc score in the population without AF.
The aim of this study was to evaluate the correlation between P-wave indexes [i.e., Morris index, mean duration, standard deviation (SD) and variability of P-wave, Pmax, minimum P (Pmin), P-wave dispersion, PVL1, PR interval (PRi), P/PR ratio (PPRi), and P-wave peak time] and echocardiographic findings (i.e., LA and LV size, LVEF, LV mass, and LV indexed mass) and CHA2DS2-VASc score in patients without AF and without valvular disease.
METHODS
The research project that resulted in this article was sent to Plataforma Brasil, received the number CAAE 46451521.2.0000.5462, and was approved on June 01, 2021 by the Research Ethics Committee of Dante Pazzanese Cardiology Institute. All patients included in the study signed an informed consent form.
This was a retrospective cross-sectional study that included patients with no history of AF, atrial flutter, or valve disease, who were followed up at Dante Pazzanese Cardiology Institute and underwent electrocardiogram (ECG) and echocardiogram at the same institution. Patients with unavailable medical records, pacemaker carriers, absence of echocardiogram report, or with uninterpretable ECG were excluded from the study. Overall, 321 patients were included in the study period and data collection was performed in the same period (06/01/2021 to 05/01/2022).
The insufficient data on the correlation of ECG parameters and CHA2DS2-VASc score made it impossible to calculate the sample size before carrying out this study, which, in turn, may serve as a basis for sample calculations for other future studies with similar objectives. Therefore, the sample size of this study was defined by convenience.
Calculation of the CHA2DS2-VASc score
The CHA2DS2-VASc score was calculated based on the data available on medical records. Information about heart failure (HF), hypertension (HTN), diabetes mellitus (DM), vascular disease, history of stroke or TIA, gender, and age at the time of ECG were obtained. A high CHA2DS2-VASc score was considered if ≥2 for males and ≥3 for females.
ECG analysis
All ECGs were analyzed by an investigator to determine the P-wave indexes using the CardioCalipers® program. A second investigator performed the same measurements on 20% of the sample in order to assess the interobserver agreement. Both investigators were unaware of the patients’ clinical data.
PWD was measured in all 12 leads. The highest value was chosen to determine Pmax and the lowest for Pmin. P-wave dispersion was calculated by the difference between Pmax and Pmin. The mean PWD and SD were also calculated. P-wave variability was obtained by dividing the SD by the mean PWD.
The PRi was measured in lead II. The PPRi ratio was calculated by dividing the PWD by the PRi.
P-wave peak time was measured from the beginning to the peak of the P-wave in lead II. P-wave voltage (PVL1) was measured in lead I, while P-wave amplitude was measured in lead II.
The presence of the Morris index was considered when the product of the amplitude (mm) and time (ms) of a terminal negative P-wave in V1 was>40.
Echocardiographic analysis
The following echocardiographic variables were collected: LA dimension, LV diastolic diameter, LVEF, LV mass, and LV indexed mass.
Statistical analysis
Continuous variables were presented by measures of central tendency (mean and median) and dispersion (variation and SD), and categorical variables were presented by frequency distribution (number of cases and relative percentage).
Categorical variables (high or low CHA2DS2-VASc score) were compared in relation to numerical variables (P-wave and echocardiographic measurements) with Student’s t-test. Shapiro-Wilk’s tests were used to test the normality of the data. If data normality was not verified, the Mann-Whitney U-test was adopted.
The chi-square test was used to verify the association between the categories. To verify the correlation between numerical variables, Spearman’s rank correlation coefficient (RHO) was used. The kappa coefficient was applied to measure inter-rater reliability.
RESULTS
A total of 49 patients were excluded due to unavailable medical records (n=40) or the absence of available echocardiogram reports (n=9).
The mean age of the 272 individuals included in the final analysis was 62.4 (12.6) years, 56.6% (n=154) were females, 82% (n=223) of patients had HTN, 72.4% (n=197) had dyslipidemia, 35.3% (n=96) had atherosclerotic disease, 34.2% (n=93) had DM, and 21% (n=57) had HF. The mean CHA2DS2-VASc score was 3. The majority of patients [68% (n=185)] were on beta-blockers, and 18% (n=49) were on antiarrhythmics. Beta-blockers were indicated due to coronary disease, HF, and refractory HTN. Antiarrhythmics were indicated for the treatment of ventricular and supraventricular arrhythmias, excluding AF and atrial flutter (Table 1).
Table 1. Demographic characteristics, echocardiographic parameters, P-wave indexes, and CHA2DS2-VASc score.
| Variable | Category/ Measurements |
Frequency (%)/ Measurements |
|---|---|---|
| Age | Mean (SD) | 62.4 (12.6) |
| Age range | 18–64 | 140 (51.5) |
| 65–74 | 89 (32.7) | |
| ≥75 | 43 (15.8) | |
| Gender | Male | 118 (43.4) |
| Female | 154 (56.6) | |
| BMI (kg/m2) | Mean (SD) | 28.4 (5.5) |
| HF | 57 (21.0) | |
| HTN | 223 (82.0) | |
| DM | 93 (34.2) | |
| Stroke/TIA | 16 (5.9) | |
| Atherosclerotic disease | 96 (35.3) | |
| Dyslipidemia | 197 (72.4) | |
| Hypothyroidism | 43 (15.8) | |
| Smoking | Smoker | 15 (5.5) |
| Former smoker | 69 (25.4) | |
| Never smoker | 188 (69.1) | |
| Beta-blocker | 185 (68.0) | |
| Antiarrhythmic | 49 (18.0) | |
| LA (mm) | Mean (SD) | 40.1 (5.1) |
| LVEF (%) | Median (variation) | 62.0 (22–79) |
| LV (mm) | Median (variation) | 50 (36–88) |
| LV mass (g) | Median (variation) | 198 (36–464) |
| LV indexed mass (g/m2) | Median (variation) | 113.1 (34–243) |
| Average PWD (ms) | Mean (SD) | 110.3 (14.2) |
| P SD (ms) | Mean (SD) | 14.4 (4.1) |
| P variability | Median (variation) | 0.13 (0.03–0.24) |
| Maximum P (ms) | Mean (SD) | 131.9 (15.2) |
| Minimum P (ms) | Mean (SD) | 85.5 (16.1) |
| P dispersion (ms) | Median (variation) | 44.0 (16–108) |
| PVL1 (mm) | Median (variation) | 0.8 (0.3–2.2) |
| P amplitude (mm) | Median (variation) | 1.1 (0.2–2.6) |
| PPRi | Median (variation) | 0.69 (0.34–1.24) |
| P-wave peak time (ms) | Median (variation) | 60 (28–100) |
| PRi (ms) | Median (variation) | 172 (88–276) |
| Morris index | 42 (15.4) | |
| CHA2DS2-VASc | Median (variation) | 3.0 (0–7) |
| CHA2DS2-VASc | 0 | 5 (1.8) |
| 1 | 31 (11.4) | |
| 2 | 67 (24.6) | |
| 3 | 68 (25.0) | |
| 4 | 59 (21.7) | |
| 5 | 31 (11.4) | |
| 6 | 10 (3.7) | |
| 7 | 1 (0.4) | |
| High CHA2DS2-VASc | 193 (71.0) |
BMI: body mass index; DM: diabetes mellitus; HF: heart failure; LA: left atrium; LV: left ventricle; LVEF: left ventricular ejection fraction; PPRi: P/PR ratio; PRi: PR interval; PVL1: P-wave voltage in lead I; PWD: P-wave duration; HTN: hypertension; SD: standard deviation; TIA: transient ischemic attack.
The mean LA and LV diameters were 40.1 (5.1) and 51.6 (6.9) mm, respectively. The mean LVEF was 57.9 (11)%. The mean LV mass and LV indexed mass were 209.5 (63.3) g and 117.2 (31.6) g/m2, respectively. For P-wave indexes, the mean PWD was 110.3 (14.2) ms, PVL1 was 0.79 (0.27) mm, P amplitude was 1.1 (0.39) mm, and the PRi was 174.4 (39.9) ms. The presence of the Morris index was observed in 15.4% of patients (Table 1).
The ECG analysis showed a slight correlation between the CHA2DS2-VASc score and PRi (RHO=0.13, p=0.032), P-wave amplitude (RHO=-0.141, p=0.02), and PVL1 (RHO=-0.191, p=0.002), when analyzed as continuous variables. The correlation was positive for PRi and negative for P-wave amplitude and PVL1. The other variables showed no correlation with the CHA2DS2-VASc score (Table 2).
Table 2. Correlation between P-wave indexes, echocardiographic parameters, and CHA2DS2-VASc score.
| Variable | Variation | Median | Mean (SD) | RHO | p-Value |
|---|---|---|---|---|---|
| Mean PWD (ms) | 63–153.1 | 110.3 | 110.3 (14.2) | 0.084 | 0.167 |
| P dispersion (ms) | 16–108 | 44 | 46.4 (13.5) | 0.026 | 0.669 |
| P amplitude (mm) | 0.2–2.6 | 1.1 | 1.1 (0.4) | (-0.141) | 0.020 |
| PRi (ms) | 88–276 | 172 | 174.4 (29.9) | 0.130 | 0.032 |
| PPRi | 0.3–1.2 | 0.7 | 0.7 (0.1) | (-0.078) | 0.200 |
| P-wave peak time (ms) | 28–100 | 60 | 59.0 (13.2) | (-0.027) | 0.656 |
| P SD (ms) | 4.3–29.3 | 14.2 | 14.4 (4.1) | 0.053 | 0.379 |
| P Variability | 0.03–0.24 | 0.13 | 0.13 (0.04) | 0.027 | 0.662 |
| PVL1 (mm) | 0.3–2.2 | 0.8 | 0.8 (0.3) | (-0.191) | 0.002 |
| LA (mm) | 25–57 | 40 | 40.1 (5.1) | 0.301 | <0.001 |
| LVEF (%) | 22–79 | 62 | 57.9 (11.0) | (-0.344) | <0.001 |
| LV (mm) | 36–88 | 50 | 51.6 (6.9) | 0.197 | 0.001 |
| LV mass (g) | 36–464 | 198 | 209.5 (63.3) | 0.261 | <0.001 |
| LV indexed mass (g/m2) | 34–243 | 113.1 | 117.2 (31.6) | 0.340 | <0.001 |
LA: left atrium; LV: left ventricle; LVEF: left ventricular ejection fraction; PPRi: P/PR ratio; PRi: PR interval; PVL1: p-wave voltage in lead I; PWD: P-wave duration; RHO: Spearman’s rank correlation coefficient; SD: standard deviation. Statistically significant values are indicated in bold.
All echocardiographic parameters analyzed were significantly correlated with the CHA2DS2-VASc score. The LA diameter (RHO=0.301, p<0.001), LV diameter (RHO=0.197, p=0.001), LV mass (RHO=0.261, p<0.001), and LV indexed mass (RHO=0.340, p<0.001) were positively correlated with the CHA2DS2-VASc score, whereas LVEF (RHO=-0.344, p<0.001) had a negative correlation (Table 2).
The CHA2DS2-VASc score was categorized into high (≥2 for males and ≥3 for females) and low (<2 for males and<3 for females). There was a statistically significant comparison between high CHA2DS2-VASc score and PRi (median of 176 ms in high CHA2DS2-VASc versus 164 ms in low CHA2DS2-VASc). A similar finding was observed with a high CHA2DS2-VASc score and all studied echocardiographic variables. The presence of the Morris index was also associated with high CHA2DS2-VASc. Morris index was observed in 18.6% of the individuals with high CHA2DS2-VASc (Table 3).
Table 3. P-wave indexes, echocardiographic parameters, and high or low CHA2DS2-VASc score.
| Variable | Category/Measurements | CHA2DS2-VASc | p-Value | |
|---|---|---|---|---|
| Low | High | |||
| PPRi | Mean (SD) | 0.7 (0.1) | 0.7 (0.1) | 0.153* |
| Mean PWD (ms) | Mean (SD) | 109.3 (13.3) | 110.7 (14.6) | 0.468* |
| P SD (ms) | Mean (SD) | 13.9 (4.1) | 14.6 (4.2) | 0.224* |
| P variability | Median (variation) | 0.13 (0.03–0.24) | 0.13 (0.05–0.24) | 0.292** |
| P-wave peak time (ms) | Median (variation) | 60 (28–88) | 60 (28–100) | 0.946** |
| P dispersion (ms) | Median (variation) | 44 (16–92) | 48 (16–108) | 0.339** |
| PVL1 (mm) | Median (variation) | 0.8 (0.4–1.5) | 0.7 (0.3–2.2) | 0.220** |
| P amplitude (mm) | Median (variation) | 1.1 (0.6–2.3) | 1.1 (0.2–2.6) | 0.183** |
| PRi (ms) | Median (variation) | 164 (128–256) | 176 (88–276) | 0.020 ** |
| Morris index | 6 (7.6) | 36 (18.6) | 0.022 *** | |
| LA (mm) | Mean (SD) | 36.7 (4.5) | 41.5 (4.7) | <0.001 * |
| LVEF (%) | Median (variation) | 64 (32–75) | 60 (22–79) | <0.001 ** |
| LV (mm) | Median (variation) | 49 (36–61) | 51 (38–88) | <0.001 ** |
| LV mass (g) | Median (variation) | 172 (53.8–341) | 213 (36–464) | <0.001 ** |
| LV indexed mass (g/m2) | Median (variation) | 99 (34–179.6) | 118.7 (56.6–243) | <0.001 ** |
*p-value obtained by Student’s t-test.
**p-value obtained by the Mann-Whitney U test.
***p-value obtained by the chi-square test. LA: left atrium; LV: left ventricle; LVEF: left ventricular ejection fraction; PPRi: P/PR ratio; PRi: PR interval; PVL1: P-wave voltage in lead I; PWD: P-wave duration; SD: standard deviation. Statistically significant values are indicated in bold.
Interobserver variation analysis revealed CCC of 0.915 for PVL1 and 0.937 for P-wave amplitude and kappa coefficient of 1.0 for the presence of Morris index, 0.7047 for P-wave peak time, 0.9483 for PRi, and 0.9196 for PWD, indicating substantial to almost perfect agreement for all the examined variables.
DISCUSSION
In this study, we found a correlation between P-wave indexes, echocardiographic parameters, and the CHA2DS2-VASc score.
P-wave indexes and CHA2DS2-VASc score
The analysis of P-wave indexes should be stimulated by the wide availability and reproducibility of ECG in clinical practice, as it is a low-cost test.
The positive and significant correlation between PRi and the CHA2DS2-VASc score reflects that patients with cardiovascular comorbidities tend to have a higher occurrence of first-degree atrioventricular block. PRi prolongation alone is associated with an increased risk of AF, pacemaker implantation, and all-cause mortality 15 .
PVL1, when reduced, is associated with recent-onset AF in the population with coronary artery disease 10 . This finding may be related to the propagation of the electrical stimulus of the heart. By means of electrophysiological mapping, it was demonstrated that the electrical impulse of interatrial conduction is more displaced in the area of the Bachmann bundle in individuals with low PVL1 16 . The negative correlation between PVL1 and CHA2DS2-VASc score in individuals without AF reinforces that this P-wave index should be valued in clinical practice.
P-wave amplitude in lead II was also negatively correlated with the CHA2DS2-VASc score. The P-wave amplitude, when reduced, is associated with greater rates of early AF recurrence after electrical cardioversion 17 .
Echocardiographic parameters and CHA2DS2-VASc score
In individuals with AF, echocardiographic abnormalities are commonly found such as changes in LA diameter, LA strain, left atrial appendage emptying velocity, presence of spontaneous contrast, and thrombus. Atrial abnormalities are also associated with thromboembolic risk and mortality 18 .
CHADS2 and CHA2DS2-VASc scores are associated with echocardiographic risk factors for thromboembolism, such as decreased left atrial appendage emptying velocity, presence of spontaneous contrast, and thrombus 19 . Left atrial stasis, the presence of thrombi, and complex aortic plaque were associated with an increased risk of stroke, regardless of CHADS2 and CHA2DS2-VASc scores in patients with AF 20 . The addition of echocardiographic risk parameters can complement the clinical assessment to estimate stroke risk in patients with AF 19 .
Ventricular abnormalities also predict thromboembolic risk in patients with AF, such as increased LV mass, LV hypertrophy, and left ventricular dysfunction 19 , 21 .
Even in the absence of AF, increased LV mass, abnormal LV geometry, and reduced LVEF are independent risk factors for death and cardiovascular diseases such as myocardial infarction and stroke 13 , 14 , 22 - 24 .
In this study, a significant correlation between all echocardiographic parameters and the CHA2DS2-VASc score was demonstrated, being positive for LA diameter, LV, LV mass, and LV indexed mass and negative for LVEF.
ECG and echocardiographic parameters in clinical practice
The results of this study highlight the importance of the association of clinical, electrocardiographic, and echocardiographic variables in the stratification of systemic thromboembolism in patients with sinus rhythm.
High-cost and less-available devices, such as implantable monitoring devices, have been gaining ground to identify individuals with silent AF as the identification can prevent stroke with early institution of anticoagulation. However, there is still no well-defined consensus on which patients such devices should be recommended considering health system costs 25 .
There is still not enough evidence to establish anticoagulation as a preventive treatment for stroke in the absence of AF; however, the applicability of clinical, ECG, and echocardiographic parameters may be confirmed in the future with the development of randomized clinical trials.
Limitations
The unicentric, observational, and cross-sectional nature is the main limitation of this study. The sample size was not calculated before the start of the study because of insufficient data on the correlation of ECG parameters and CHA2DS2-VASc score. Moreover, information about AF and valve disease was based on medical records. Therefore, silent AF patients may be included in the study.
CONCLUSIONS
Prolonged PRi, Morris index, increased LA diameter, LV diameter, LV mass, and LV indexed mass values as well as lower P-wave amplitude, PVL1, and LVEF values were correlated with higher CHA2DS2-VASc scores.
Footnotes
Funding: none.
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