Abstract
Left ventricular diastolic dysfunction (LVDD) is commonly seen in hypertensive patients, and it is associated with increased morbidity and mortality. Hence, the detection of LVDD with a simple, inexpensive, and easy‐to‐obtain method can contribute to improving patient prognosis. Therefore, we aimed to evaluate whether there was any association between the electrocardiographic P wave peak time (PWPT) and invasively measured left ventricular end‐diastolic pressure (LVEDP) in hypertensive patients who had undergone coronary angiography following preliminary diagnosis of coronary artery disease. A total of 78 patients were included in this cross‐sectional study. The PWPT was defined as the time from the beginning of the P wave to its peak, and it was calculated from the leads DII and VI. In all patients, LVEDP was measured in steady state. The PWPT in lead DII was significantly longer in patients with high LVEDP; however, there was no significant difference between groups in terms of PWPT in the lead VI. In multivariable analysis, PWPT in lead DII was found to be independent predictor of increased LVEDP (OR: 1.257, 95% CI: 1.094‐1.445; P = 0.001). In receiver operating characteristic curve analysis, the optimal cut‐off value of PWPT in the lead DII for prediction of elevated LVEDP was 64.8 ms, with a sensitivity of 68.7% and a specificity of 91.3% (area under curve: 0.882, 95% CI: 0.789‐0.944, P < 0.001). In conclusion, this study result suggested that prolonged PWPT in the lead DII may be an independent predictor of increased LVEDP among hypertensive patients.
Keywords: hypertension, left ventricular diastolic dysfunction, left ventricular end‐diastolic pressure, P wave peak time
1. INTRODUCTION
Left ventricular diastolic dysfunction (LVDD), which results from an abnormal left ventricle myocardial relaxation and elasticity, is a condition characterized by an increase in the diastolic filling of the left ventricle. This abnormal filling of the left ventricle may lead to adverse cardiovascular outcomes, such as heart failure (HF) or arrhythmia.1 HF with preserved ejection fraction (HFpEF) accounts for approximately half cases of HF, and hypertension, which is a modifiable risk factor, is the most common comorbidity in HFpEF patients. Also, it is involved both in the pathogenesis and the prognosis of the disease. Hypertension causes an increase in the diastolic pressure, resulting in expansion and fibrosis in the left atrium. This deterioration in the structure and function of the left atrium may trigger arrhythmia.2, 3 In clinical practice, although the Doppler echocardiography is the most commonly used tool to determine LVDD, the gold standard method of assessing left ventricular filling pressure is the measurement of left ventricular end‐diastolic pressure (LVEDP) during cardiac catheterization.4 However, the invasive nature of this method limits its routine use. For this reason, attempts to detect LVDD with noninvasive, easily accessible methods will undoubtedly contribute to improving the prognosis of patients.
Electrocardiography (ECG) is the main diagnostic tool in the diagnosis and management of cardiovascular diseases, especially in ischemic and arrhythmic conditions. However, ECG has a limited role in determining volume/pressure overload of the cardiac chambers. Although no specific ECG findings demonstrate the presence of diastolic dysfunction, there is evidence that certain ECG findings, such as electrocardiographic left ventricular hypertrophy (LVH) voltage criteria, P wave duration (PWD), P wave dispersion (PWDISP), and P wave terminal force (PWTF) in the lead VI, are associated with LVDD.5, 6, 7
P wave peak time (PWPT), a recently introduced ECG parameter, has been shown to be associated with imperfect reperfusion in patients with acute coronary syndrome.8 The investigators speculated that imperfect reperfusion might lead to an increase in the LVEDP, causing elevation of left atrial pressure, which manifests itself on the ECG as prolongation of PWPT. However, their study did not investigate diastolic dysfunction parameters, and the association between PWPT and LVEDP has not yet been empirically determined in hypertensive patients. Hence, in the present study, we aimed to investigate whether there is any association between PWPT and invasively measured LVEDP in hypertensive patients who had undergone coronary angiography following preliminary diagnosis of coronary artery disease.
2. METHODS
2.1. Study population
Patients with a diagnosis of hypertension who had undergone coronary angiography between January 2015 and June 2017 following preliminary diagnosis of coronary artery disease were screened. The following patients were excluded from the study; patients with a SYNTAX score greater than 0, had a history of coronary artery disease, more than mild valvular heart disease, pulmonary hypertension, left ventricular systolic dysfunction, cardiomyopathy, tachyarrhythmia and/or bradyarrhythmia, chronic kidney disease, electrolyte imbalance, or thyroid dysfunction. A total of 78 patients were found to be eligible for analysis. The demographic data of these patients, their medications, and laboratory parameters were obtained from the hospital's electronic database. The study protocol was reviewed and approved by the ethics committee of our institution in accordance with the principles of the Declaration of Helsinki.
2.2. Echocardiographic examination and coronary angiography
Echocardiographic examinations of the patients included in the study were performed with a Vivid S6 Pro ultrasound system (GE Vingmed Ultrasound AS N‐3190, Horten, Norway) using the standard imaging techniques recommended by the American Society of Echocardiography (ASE) just before the procedure.9 Left atrial volume and left ventricular mass measurements were carried out using the biplane disk summation and truncated ellipsoid techniques, respectively. Relative wall thickness (RWT) was calculated with “2 × posterior wall thickness/LV end diastolic internal diameter” formula to categorization of LVH as either concentric (RWT > 0.42) or eccentric (RWT ≤ 0.42) and the identification of concentric remodeling in case of normal LV mass with increased RWT.9 Standard 2‐dimensional echocardiography, color flow Doppler, continuous‐ and pulsed‐wave Doppler, and tissue Doppler measurements of the mitral annulus were obtained from all patients.
According to ASE's left ventricular diastolic function guideline, presence of at least three of the following criteria is accepted as diastolic dysfunction: Average E/E’ >14, Septal E’ velocity <7 cm/s or Lateral E’ velocity <10 cm/s, TR velocity >2.8 m/s, and LA volume index >34 mL/m2. Diastolic functions of patients with two of the aforementioned parameters were considered indeterminate, and those with one or none of the criteria were considered as normal diastolic function.10 Coronary angiography was performed via the femoral artery using the standard catheters. In order to measure LVEDP, a 6‐F pigtail catheter was inserted into the left ventricle. Baseline left ventricular peak pressure and LVEDP were measured at rest in a steady state. The LVEDP was measured during expiration at end‐diastole which was defined electrocardiographically by the onset of the next cycle’s QRS wave from left ventricular pressure tracing recorded with a 50 mm Hg scale.
2.3. Electrocardiographic analysis
The standard 12‐lead ECG was recorded for each patient with a paper speed of 25 mm/s, amplitude of 10 mm/mV, and filter range of 0.15‐100 Hz just before the procedure. All ECG strips were scanned, transferred to the computer, and analyzed using ImageJ digital image processing software (available at imagej.nih.gov/ij/). All measurements were performed by two experienced cardiologists, taking account of the opinion of a third cardiologist in case of disagreement. Sokolow‐Lyon and Cornell voltage criteria were used to evaluate LVH. The maximum P wave duration (PWDmax) and the minimum P wave duration (PWDmin) were measured in each lead, and the algebraic difference between the two was accepted as the PWDISP.11 The PWPT was defined as the time from the beginning of the P wave to its peak and was calculated from the leads DII and VI (Figure 1).8 The PWTF was calculated by multiplying the amplitude and time of the terminal negative component of the P wave in the lead VI.12
Figure 1.
Measurement of the P wave peak time in the lead DII
2.4. Statistical analyses
SPSS statistical software version 17.0 (SPSS Inc, Chicago, IL) was used to analyze the data. The Kolmogorov‐Smirnov test was used to analyze the normality of continuous variables. The continuous variables with normal distribution are presented as mean ± standard deviation, and those without normal distribution are presented as a median (interquartile range). Categorical variables are presented as numbers and percentages (%). Student's t test or the Mann‐Whitney U test were used to compare continuous variables between two independent groups. Categorical data were compared using a chi‐squared test or Fisher's exact test. Statistical significance was defined as a P value <0.05. Correlations between continuous variables were assessed using the Pearson correlation coefficient for variables with normal distribution and Spearman's rank correlation coefficient for variables without normal distribution. Multivariate logistic regression analyses were performed to identify the independent predictors of increased LVEDP using the variables that showed marginal association in univariate analysis. Receiver operating characteristic (ROC) curve analysis was used to calculate the PWPT value that predicted increased LVEDP with the best specificity and sensitivity.
3. RESULTS
The study population was divided into two groups according to LVEDP values (measured by means of cardiac catheterization). The patients with LVEDP < 16 mm Hg formed a low LVEDP group (n = 46) and those with LVEDP ≥ 16 mm Hg formed a high LVEDP group (n = 32). Baseline demographic characteristics and laboratory parameters of study patients are listed in Table 1. There were no statistically significant differences between the groups in terms of age, sex, diabetes mellitus, or medications including acetylsalicylic acid, statins, and diuretics (P > 0.05 in each case). Systolic and diastolic blood pressure values were significantly higher in patients with a high LVEDP in addition to use of antihypertensive drugs, including calcium channel blockers, angiotensinogen‐converting enzyme inhibitors, and beta‐blockers (P < 0.05 in each case). The laboratory findings were similar between the groups, with the exception of urea, which was found to be higher in patients with a high LVEDP.
Table 1.
The baseline characteristics and laboratory results of all patients and patients stratified according to LVEDP
| All patients (n:78) | Normal LVEDP group (n:46) | Increased LVEDP group (n:32) | P value | |
|---|---|---|---|---|
| Age, years | 54 ± 6 | 54 ± 7 | 54 ± 5 | 0.134 |
| Female gender, n (%) | 50 (64.1) | 28 (60.9) | 22 (68.8) | 0.475 |
| Body surface area, kg/m2 | 1.87 ± 0.16 | 1.83 ± 0.15 | 1.93 ± 0.16 | 0.214 |
| Body mass index, kg/m2 | 28 (26‐32) | 28 (25‐32) | 30 (27‐33) | 0.016 |
| Diabetes mellitus, n (%) | 8 (10.3) | 4 (8.7) | 4 (12.5) | 0.71 |
| Smoking, n (%) | 22 (28.2) | 15 (32.6) | 7 (21.9) | 0.300 |
| Acetylsalicylic acid, n (%) | 8 (10.3) | 6 (13.0) | 2 (6.3) | 0.331 |
| Statin, n (%) | 4 (5.1) | 2 (4.3) | 2 (6.3) | 0.708 |
| ACE/ARB, n (%) | 34 (43.6) | 14 (30.4) | 20 (62.5) | 0.005 |
| Beta‐blockers, n (%) | 20 (25.6) | 8 (17.4) | 12 (37.5) | 0.045 |
| Calcium channel blockers, n (%) | 20 (25.6) | 8 (17.4) | 12 (37.5) | 0.045 |
| Thiazide, n (%) | 19 (24.4) | 9 (19.6) | 10 (31.3) | 0.237 |
| Systolic blood pressure, mm Hg | 135 ± 14 | 131 ± 14 | 139 ± 14 | <0.001 |
| Diastolic blood pressure, mm Hg | 79 ± 13 | 75 ± 11 | 86 ± 13 | <0.001 |
| Hemoglobin, gr/dL | 13.9 ± 1.3 | 13.6 ± 1.3 | 14.3 ± 1.2 | 0.355 |
| White blood cell count, cells/µL | 6.5 (5.4‐8.0) | 6.4 (5.2‐6.9) | 6.9 (5.7‐9.4) | 0.56 |
| Platelet count, cells/µL | 224 ± 62 | 220 ± 67 | 230 ± 52 | 0.744 |
| Glucose, mg/dL | 95 ± 22 | 93 ± 24 | 96 ± 21 | 0.479 |
| Urea, mg/dL | 34 ± 10 | 33 ± 11 | 36 ± 8 | 0.018 |
| Creatinine, mg/dL | 0.78 ± 0.17 | 0.78 ± 0.19 | 0.79 ± 0.15 | 0.76 |
| Sodium, mmol/L | 139 ± 3 | 139 ± 3 | 140 ± 3 | 0.539 |
| Potassium, mmol/L | 4.3 ± 0.3 | 4.3 ± 0.3 | 4.3 ± 0.3 | 0.148 |
| Calcium, mg/dL | 9.6 ± 0.4 | 9.4 ± 0.3 | 9.7 ± 0.3 | 0.754 |
| Alanine transaminase, mU/mL | 21 ± 9 | 22 ± 8 | 20 ± 9 | 0.131 |
| Total cholesterol, mg/dL | 183 (162‐223) | 175 (157‐191) | 209 (173‐238) | 0.268 |
| Uric acid, mg/dL | 4.6 ± 1.0 | 4.6 ± 1.0 | 4.7 ± 1.1 | 0.122 |
| C reactive protein, mg/dL | 0.26 (0.19‐0.42) | 0.28 (0.22‐0.42) | 0.21 (0.10‐0.42) | 0.471 |
ACE/ARB, angiotensinogen‐converting enzyme, angiotensinogen receptor blocker, respectively; LVEDP, left ventricular end‐diastolic pressure.
Systolic and diastolic aortic pressures and left ventricular peak pressure (measured by invasive means) were found to be higher in patients with a high LVEDP (P < 0.05 for each; Table 2). In terms of echocardiography findings, left ventricular mass index, tissue Doppler velocities, E/E′ ratio, and tricuspid regurgitation jet velocity were similar between the groups (P > 0.05 for each). Even though there was no difference between the groups in terms of LV concentric remodeling, there were six patients with concentric LVH and all of them had an increased LVEDP. Left atrial volume index was higher and E/A ratio was lower in patients with a high LVEDP (P < 0.05 for each). While 91.3% (n: 42) of the patients with normal LVEDP had normal diastolic function, this ratio decreased to 68.8% (n: 22) in the increased LVEDP group (P = 0.011). The frequency of indeterminate LVDD was not different between the groups, but; the definite LVDD was more frequent in the group with increased LVEDP (P = 0.017). The number of patients who met the electrocardiographic voltage criteria for LVH was small. Although there was no significant difference between the two groups according to the Sokolow‐Lyon voltage criteria, four patients in a high LVEDP group met the Cornell voltage criteria, and none of the patients in a low LVEDP group met this criterion (12.5% vs 0.0%, P = 0.025). We noted that the PWDmax and PWDISP were prolonged in a high LVEDP group. The patients with a high LVEDP had a higher frequency of PWTF in the lead V1 > 40 than those with a normal LVEDP. Although we observed that PWPT in the lead DII was significantly longer in patients with a high LVEDP, there was no significant difference between the groups in terms of PWPT in the lead VI. The PWPT in the lead DII (79 ± 15 vs 55 ± 15; P < 0.001) and PWPT in the lead VI (71 ± 17 vs 50 ± 15; P = 0.001) were longer in patients with impaired diastolic function (indeterminate and definite; n: 14) compared with patients with normal diastolic function (n: 64). PWPT in the lead DII (92 ± 14 vs 68 ± 13; P = 0.001) and PWPT in the lead VI (83 ± 17 vs 52 ± 15; P < 0.001) were also longer in patients with LV concentric hypertrophy compared to those without hypertrophy and concentric remodeling (n: 6) in the increased LVEDP group. Table 3 provides the correlation analysis of the electrocardiographic parameters including PWDISP, PWPT in the leads DII and VI with LVEDP, left atrial volume index, and E/E′ ratio. LVEDP was positively correlated with PWDISP and PWPT in the lead DII, but not with PWPT in the lead VI. PWDISP and PWPT in the leads DII and VI were positively correlated with the left atrial volume index.
Table 2.
Angiographic, echocardiographic, and electrocardiographic findings of all patients and patients stratified according to LVEDP
| All patients, n:78 | Normal LVEDP group, n:46 | Increased LVEDP group, n:32 | P value | |
|---|---|---|---|---|
| Aortic systolic pressure, mm Hg | 151 ± 25 | 142 ± 20 | 164 ± 26 | <0.001 |
| Aortic diastolic pressure, mm Hg | 82 ± 14 | 75 ± 9 | 91 ± 14 | <0.001 |
| LVEDP, mm Hg | 15 ± 7 | 10 ± 4 | 21 ± 6 | <0.001 |
| LV peak systolic pressure, mm Hg | 162 ± 30 | 147 ± 20 | 184 ± 29 | <0.001 |
| LV ejection fraction, % | 67 ± 4 | 67 ± 5 | 67 ± 3 | 0.87 |
| LV mass index, g/m2 | 71 ± 20 | 68 ± 15 | 75 ± 25 | 0.272 |
| LVH pattern, n (%) | ||||
| Concentric remodeling | 7 (9.0) | 5 (10.9) | 2 (6.3) | 0.694 |
| Concentric hypertrophy | 6 (7.7) | 0 (0.0) | 6 (18.8) | 0.004 |
| LAVI, mL/m2 | 29 ± 9 | 26 ± 8 | 32 ± 8 | <0.001 |
| Peak E‐wave velocity, m/s | 0.67 ± 0.22 | 0.69 ± 0.17 | 0.64 ± 0.28 | 0.127 |
| Peak A‐wave velocity, m/s | 0.73 ± 0.17 | 0.70 ± 0.18 | 0.76 ± 0.17 | 0.464 |
| E/A ratio | 0.97 ± 0.39 | 1.06 ± 0.42 | 0.83 ± 0.28 | 0.003 |
| Septal E', m/s | 0.09 ± 0.03 | 0.09 ± 0.03 | 0.09 ± 0.03 | 0.87 |
| Lateral E', m/s | 0.13 ± 0.05 | 0.13 ± 0.04 | 0.12 ± 0.05 | 0.159 |
| E/E' ratio | 6.86 ± 2.92 | 6.74 ± 2.39 | 7.04 ± 3.58 | 0.815 |
| TR systolic jet velocity, m/s | 2.50 ± 0.42 | 2.50 ± 0.43 | 2.49 ± 0.42 | 0.655 |
| Echocardiographic DD, n (%) | ||||
| Normal diastolic function | 64 (82.1) | 42 (91.3) | 22 (68.8) | 0.011 |
| Definite | 7 (9.0) | 1 (2.2) | 6 (18.8) | 0.017 |
| Indeterminate | 7 (9.0) | 3 (6.5) | 4 (12.5) | 0.436 |
| Heart rate, bpm | 72 ± 11 | 73 ± 10 | 71 ± 12 | 0.569 |
| QRS duration, ms | 93 ± 15 | 93 ± 18 | 94 ± 11 | 0.119 |
| Left axis deviation, n (%) | 10 (12.8) | 4 (8.7) | 6 (18.8) | 0.191 |
| Sokolow‐Lyon voltage criteria, n (%) | 6 (7.7) | 4 (8.7) | 2 (6.3) | 0.69 |
| Cornell voltage criteria, n (%) | 4 (5.1) | 0 (0.0) | 4 (12.5) | 0.025 |
| PWDmax, ms | 104 ± 17 | 99 ± 13 | 112 ± 20 | 0.004 |
| PWDISP, ms | 26 ± 13 | 21 ± 11 | 33 ± 13 | 0.001 |
| PWDmin, ms | 78 ± 11 | 78 ± 9 | 79 ± 14 | 0.684 |
| P‐wave morphology in the lead VI | ||||
| Negative, n (%) | 8 (10.3) | 2 (4.3) | 6 (18.8) | 0.084 |
| Positive, n (%) | 26 (33.3) | 18 (39.1) | 8 (25.0) | |
| Biphasic, n (%) | 44 (56.4) | 26 (56.5) | 18 (56.3) | |
| PWTF in the lead VI > 40, n (%) | 14 (26.9) | 3 (10.7) | 11 (45.8) | 0.004 |
| PWPT in the lead DII, ms | 59 ± 18 | 50 ± 12 | 73 ± 16 | <0.001 |
| PWPT in the lead VI, ms | 56 ± 18 | 52 ± 15 | 60 ± 21 | 0.125 |
DD, diastolic dysfunction; LAVI, left atrial volume index; LVEDP, left ventricular end‐diastolic pressure; LVH, left ventricular hypertrophy; PWDmax, the maximum P wave duration; PWDmin, the minimum P wave duration; PWPT, P wave peak time; PWTF, P wave terminal force; TR, tricuspid regurgitation.
Table 3.
Correlation analysis of the electrographic parameters
| Age | BSA | LAVI | E/A ratio | E/E' ratio | LVEDP | |
|---|---|---|---|---|---|---|
| PWDISP | ||||||
| r value | 0.182 | 0.149 | 0.512 | −0.327 | 0.224 | 0.497 |
| P value | 0.111 | 0.194 | 0.000 | 0.003 | 0.049 | 0.000 |
| PWPT in the lead DII | ||||||
| r value | 0.048 | 0.368 | 0.656 | −0.405 | 0.103 | 0.715 |
| P value | 0.678 | 0.001 | 0.000 | 0.000 | 0.368 | 0.000 |
| PWPT in the lead VI | ||||||
| r value | 0.018 | 0.061 | 0.478 | −0.109 | 0.262 | 0.197 |
| P value | 0.896 | 0.666 | 0.000 | 0.444 | 0.061 | 0.162 |
BSA, body surface area; LAVI, left atrial volume index; LVEDP, left ventricle end‐diastolic pressure; PWDISP, P wave dispersion; PWPT, P wave peak time.
To identify the independent predictors of increased LVEDP, multivariable logistic regression analyses were performed using clinical and electrocardiographic variables that showed marginal association with increased LVEDP in the univariable analyses including body mass index, systolic blood pressure, Cornell voltage criteria, PWDISP, and PWPT in the leads DII and VI (Table 4). PWDISP (odds ratio [OR]: 0.867, 95% CI: 0.737‐0.995; P = 0.043) and PWPT in the lead DII (OR: 1.257, 95% CI: 1.094‐1.445; P = 0.001) were found to be independent predictors of increased LVEDP. ROC curve analysis revealed that the optimal cut‐off value of PWPT in the lead DII for prediction of increased LVEDP was 64.8 ms, with a sensitivity of 68.7% and a specificity of 91.3% (area under curve [AUC]: 0.882, 95% CI: 0.789‐0.944, P < 0.001; Figure 2). PWPT in the lead DII ≥ 1.5 mm and PWPT in the lead DII ≥ 2 mm predicted increased LVEDP with sensitivities of 75.0% and 31.3% and specificities of 78.3% and 100.0%, respectively. A comparison of ROC curves revealed that PWPT in the lead DII surpassed PWDISP in prediction of increased LVEDP (AUC: 0.882, 95% CI: 0.789‐0.944 vs AUC: 0.724, 95% CI: 0.611‐0.819; P = 0.0002).
Table 4.
Univariable and multivariable logistic regression analysis for the prediction of elevated LVEDP
| Univariable analysis | Multivariable analysis | |||
|---|---|---|---|---|
| P value | OR (95% CI) | P value | OR (95% CI) | |
| Systolic blood pressure | 0.017 | 1.045 (1.008 −1.083) | – | – |
| Body mass index | 0.030 | 1.118 (1.011 −1.237) | – | – |
| Cornell voltage criteria | 0.025 | 0.378 (0.283 −0.507) | – | – |
| PWDISP | <0.001 | 1.088 (1.038 −1.139) | 0.043 | 0.856 (0.737‐0.995) |
| PWPT in the lead VI | 0.004 | 3.070 (1.097‐8.59) | – | – |
| PWPT in the lead DII | <0.001 | 1.132 (1.073 −1.194) | 0.001 | 1.257 (1.094‐1.445) |
LVEDP, left ventricle end‐diastolic pressure; PWDISP, P wave dispersion; PWPT, P wave peak time.
All clinically relevant parameters were included in the model.
Figure 2.
Receiver operating characteristic curve analysis was performed to determine the optimal cut‐off value of the P wave peak time in the lead DII for prediction of elevated the left ventricular end‐diastolic pressure
4. DISCUSSION
Our study showed that prolonged PWPT measured in the lead DII and PWDISP were independent predictors for increased LVEDP in hypertensive patients.
Although the LVEDP measured by invasive means is the gold standard method for diagnosis of diastolic dysfunction, the frequency of diastolic dysfunction in hypertensive patients is unknown because of the invasive nature of the procedure. In the present study, we found that LVEDP was higher than 16 mm Hg in 32 patients out of 78 (41%). Although hypertension is the most important risk factor for elevated LVEDP, coronary artery disease, age, obesity, and diabetes mellitus may also be caused.12 In the present study, patients with a diagnosis of coronary artery disease were not recruited, and sex, age, and diabetes mellitus were not found to be statistically different between the groups. Although body mass index was significantly higher in the patients with high LVEDP, it was not an independent predictor of LVEDP in multivariable analysis. We observed that blood pressure values measured using invasive and noninvasive methods were higher in the elevated LVEDP group. This may indicate that LVEDP was higher among these patients even when the amount of medication had been increased.
In hypertensive patients, left ventricular workload is increased, resulting in LVH, impaired left ventricular relaxation, left atrial enlargement, and increased risk of arrhythmia (especially atrial fibrillation) and HF.13 Previous studies have shown a relationship between the severity of LVH and LV geometry with diastolic dysfunction.5, 14, 15 In the present study, although left ventricular mass index was higher in the increased LVEDP group, there was no statistically significant difference between the two groups. This may be due to hemodynamic changes in the left ventricle and atrium that occur before the development of the LVH that is considered to be the end‐organ damage. Also, in our study, the incidence of concentric LVH was more frequent in the increased LVEDP group which was consistent with a previous study conducted by Li et al15, but there was no significant difference in terms of LV concentric remodeling.
Left ventricular diastolic dysfunction is characterized by deterioration in the left ventricular diastolic filling, including the impairment of myocardial relaxation and dispensability as a consequence of LVH and myocardial fibrosis.1, 4 This deterioration leads to pathologic changes in the mitral flows and tissue Doppler velocities, which may be detectable by using echocardiography. In the early stages of diastolic dysfunction, the left ventricle relaxation is impaired, the E/A ratio decreases, and the deceleration time is prolonged. In the subsequent stages, where the left ventricle compliance is impaired and the filling pressure increases, the E/A and E/E′ ratios increase, and tissue Doppler velocities decrease.16 In our study, E/A ratios were lower in the increased LVEDP group, and there was no difference in terms of E′ velocity or E/E′ ratio between the groups. In hypertensive patients, the left atrium dimensions are usually increased because of the increase of the left ventricular filling pressures, which are associated with adverse cardiovascular events, atrial fibrillation, and diastolic dysfunction.17, 18, 19, 20 In line with these previous findings, we noted a positive correlation between the LVEDP and the left atrial volume index. A recent 2016 ASE guideline facilitated the diagnosis and grading of diastolic dysfunction in patients with normal ejection fraction. In our study, normal diastolic function was infrequent in patients with elevated LVEDP, while the incidence of definite diastolic dysfunction was elevated.10
Electrocardiography is a simple and easily accessible tool, which is used in routine evaluation of all hypertensive patients. Although the prevalence of electrocardiographic LVH findings increases with the severity of hypertension, the absence of LVH cannot be excluded on the basis of ECG findings alone, owing to low sensitivity.21 It has been shown that the Cornell voltage criteria predict diastolic dysfunction with a high specificity (90%) but only 20%‐40% sensitivity.14, 22, 23 A recent review showed that LVH diagnosed electrocardiographically was a powerless predictor of echocardiographic diagnosis of LVH, with a sensitivity of 10.5%‐21% and a specificity of 89%‐99%.24 In the present study, electrocardiographic LVH criteria were not found to be independent predictors of the increased LVEDP. This may be because of the relatively low number of patients who met the LVH criteria on the basis of ECG findings.
An increase in the terminal force of the P wave in the lead VI, known as PWTF, is an another electrocardiographic reflection of the left atrial anomaly. In previous studies, this ECG finding was found to be associated with diastolic dysfunction in hypertensive patients.7 In the present study, PWTF was associated with increased LVEDP in univariable analysis, but it was not an independent predictor of elevated LVEDP in multivariable analysis. PWPT is a fairly new parameter in the literature, and PWPT in the lead DII has been shown to be associated with impaired reperfusion in acute coronary syndrome patients.8 The major limitations of the abovementioned study were the absence of left atrial volumes, echocardiographic diastolic parameters, and invasive LVEDP measurement; therefore, the authors claimed that the relationship with increased left atrial pressure was due to imperfect reperfusion.
In the present study, the relationship between prolonged PWPT in the lead DII with an elevated LVEDP and left atrial volume index was investigated in details. In our correlation analysis, we found that prolonged PWPT in the lead VI was associated with elevated left atrial volume index, but we did not find any correlation with elevated LVEDP. ROC curve analysis revealed that the PWPT in the lead DII was superior to PWDISP in prediction of increased LVEDP. This relationship between the PWPT in the lead DII and LVEDP might be explained by the following mechanisms. It is well‐known that an increase in pressure in the left atrium can cause delayed inter‐ and intra‐atrial conduction time, as long‐term left atrial high pressure leads to remodeling, resulting in dilatation and fibrosis of the left atrium.25, 26 Each of these pathological processes might prolong inter‐ and intra‐atrial conduction time. Although the duration of interatrial conduction could not be documented in this study, the left atrial volume was clearly higher in the increased LVEDP group, and the PWPT in the leads DII and VI was shown to be positively correlated with the left atrial volume index. In the present study, we also observed that LV geometry was significantly associated with increased LVEDP and prolonged PWPT in the leads DII and VI. This result is not surprising because LVH, especially concentric hypertrophy, may be associated with more severe diastolic dysfunction, increased LVEDP, and more severe left atrial remodeling.
4.1. Limitations
The present study has some limitations that should be noted. First, the design was cross‐sectional; thus, the lack of prognostic data is a major limitation. Second, we may have underestimated the number of cases of diastolic dysfunction, because no measurements performed during exercise were available. Third, the number of patients included in this study was limited; hence, large, multicenter studies are necessary to confirm our findings.
5. CONCLUSION
We found that the PWPT in the lead DII was associated with an elevated left atrial volume index and LVEDP that might directly demonstrate LVDD in hypertensive patients. Prolonged PWPT in the lead DII may be an independent predictor of increased LVEDP among such patients. This easily obtainable parameter may be valuable in helping clinicians to detect LVDD.
CONFLICT OF INTEREST
None declared.
ACKNOWLEDGMENT
None declared.
Burak C, Çağdaş M, Rencüzoğulları I, et al. Association of P wave peak time with left ventricular end‐diastolic pressure in patients with hypertension. J Clin Hypertens. 2019;21:608–615. 10.1111/jch.13530
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