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Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

J Clin Hypertens (Greenwich). 2010;12:687–692. ©2010 Wiley Periodicals, Inc.

Atrial arrhythmias are common problems in hypertensive patients. Atrial electromechanical delay (AEMD) can be used to evaluate development of atrial arrhythmias. The authors aimed to assess inter- and intra-AEMD in hypertensive patients. The study population consisted of 200 medically treated hypertensive patients and 151 normotensive controls. Inter-AEMD and intra-left AEMD were measured from parameters of Doppler tissue imaging. There were 72 (36%) hypertensive patients with diastolic dysfunction, 128 (64%) patients without diastolic dysfunction, and 151 healthy controls. Inter-AEMD (59 ms [36–104 ms] vs 42 ms [36–68 ms] vs 46 ms [30–82 ms]) was significantly higher in hypertensive patients with diastolic dysfunction compared with patients without diastolic dysfunction and controls. Our data demonstrated that inter-AEMD is longer in hypertensive patients with diastolic dysfunction. It may be suggested that diastolic dysfunction is associated with atrial electromechanical abnormalities, which can be associated with atrial fibrillation in hypertension.

Arterial hypertension is a common cause of cardiovascular damage. The effects of hypertension on the heart are both structural and functional. Assessment of the function of the heart is an important requisite for intervention and risk stratification in hypertensive patients.1

Hypertension is the leading cause of impaired diastolic heart function. Left ventricular (LV) hypertrophy, extracellular and perivascular fibrosis, contractile alterations in myocytes, and myocardial ischemia have been implicated in developing diastolic dysfunction in hypertension.2 Hypertension may also cause instability and heterogeneity in atrial conduction by these hemodynamic and morphologic changes in the left atrium and left ventricle.

Echocardiographic evaluation of electrical events, especially atrial electromechanical delay (AEMD), is novel in cardiac ultrasound practice. With recent developments in tissue Doppler echocardiography it is possible to precisely assess atrial mechanical events from different regions with a high temporal resolution. AEMD can be defined as the time from onset of the electrocardiographic P wave to the onset of atrial contraction determined by pulsed wave tissue Doppler echocardiography.3,4

The aim of this study was to compare AEMDs of pulsed Doppler tissue echocardiography between patients with hypertension and healthy controls.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Patients

We examined 200 consecutive medically treated hypertensive patients and 151 normotensive healthy controls. Control were chosen from healthy patients admitted for checkup to the outpatient clinic and referred to the echocardiography laboratory. Healthy controls were patients with no known overt disease and normal systolic and diastolic blood pressure (BP). All patients underwent transthoracic echocardiography after a complete medical history and laboratory examination. Patients’ height, weight, heart rate, and BP on the day of echocardiography were recorded.

Patients receiving heart rate–decreasing drugs (such as β-blockers and non–dihydropyridine calcium channel blockers) and patients with diabetes mellitus, coronary heart disease, or systolic heart failure (ejection fraction [EF] <40%) were excluded. The study protocol was in accordance with the Declaration of Helsinki and was approved by the local ethics committee. All patients provided informed consent.

BP Measurement

The BP of each patient was measured twice in the left arm by one of the clinicians of the research team following approximately 5 minutes of seated rest. Participants were advised to avoid alcohol, cigarettes, coffee/tea, and exercise for at least 30 minutes before BP measurement. Standardized mercury sphygmomanometers were used, and one of two cuff sizes was chosen on the basis of the circumference of the participant’s arm. The Korotkoff phase I (appearance) and phase V (disappearance) were recorded for systolic BP and diastolic BP, respectively. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) criteria were used for defining hypertension.5

Transthoracic Echocardiography

All echocardiographic examinations were performed with a Vivid 3 cardiac ultrasound scanner (GE Vingmed Ultrasound, Horten, Norway) and 2.5- to 3.5-MHz transducers. All patients were examined in the left lateral and supine position by precordial M-mode, 2-dimensional, Doppler and tissue Doppler echocardiography. One lead electrocardiogram was recorded continuously. The position of the electrocardiogram leads was altered for maximizing the P-wave height. Blinded average interobserver and intraobserver reproducibility of measurement was evaluated, and comparison revealed a Spearman correlation coefficient of 0.92 and 0.94, respectively.

LV end-diastolic and end-systolic diameters, EF (%), and end-systolic left atrial (LA) diameters were measured from M-mode in the parasternal long axis views.

LA Diameter and LA Volume

M-mode LA dimension according to the standards of American Society of Echocardiography (ASE) and 2-dimensional maximal LA volume by the biplane area–length method were determined.6 Specifically, the area of the left atrium was obtained at end-ventricular systole before opening of the mitral valve from the 4- and 2-chamber views without foreshortening and excluding the LA appendage and pulmonary vein confluences. The perpendicular lengths from these views were measured from the middle of the plane of the mitral annulus to the superior aspect of the left atrium. LA volume was calculated by the formula 0.85 × 4-chamber area × 2-chamber area/common length.7 LA volumes were indexed to the body surface area.

LV Hypertrophy.  For each patient, LV mass was determined from the LV linear dimensions on the basis of the formula recommended by the ASE and the European Association of Echocardiography (EAE). LV mass = 0.8×{1.04[(LV internal dimension + posterior wall thickness + septal wall thickness)3– (LV internal dimension)3]} + 0.6 g (all measurements done in end-diastole). LV mass was indexed to body surface area (LV mass index). LV hypertrophy was defined as an LV mass index >95 g/m2 in women and >115 g/m2 in men, as recommended by the ASE and the EAE. Indexing mass to body surface area accounts for variations in body size and hence sex differences. The calculation of relative wall thickness was performed using the formula (2 × posterior wall thickness)/LV internal dimension. Concentric LV hypertrophy was defined as a relative wall thickness ≥0.42, and eccentric LV hypertrophy was defined as a relative wall thickness <0.42.8,9

Doppler Echocardiography

Flow velocity indexes were obtained using pulsed and continuous wave Doppler from apical projections, and measurements were made using the ultrasound equipment software. Mitral diastolic flow was obtained after the pulsed Doppler sample volume was positioned perpendicular to the tips of the mitral valve leaflets. The following indexes were measured from the mitral valve diastolic wave form: peak early (E) and atrial (A) flow velocities (m/s), E/A ratio, and deceleration time (DT) (ms) of the LV diastolic filling.

The Doppler cursor was then moved toward the LV outflow position, and the sample volume was placed approximately 1 cm proximal to the aortic valve so that it would come in contact with the anterior mitral valve leaflet. Isovolumic relaxation time (IVRT) (ms) was measured as the interval between the end of the aortic click artefact and the onset of mitral inflow waveform.

Pulsed Doppler Tissue Echocardiography

Tissue Doppler echocardiography was performed by transducer frequencies of 2.5 to 3.5 MHz, adjusting the spectral pulsed Doppler signal filters until a Nyquist limit of 15 to 20 cm/s, and using the minimal optimal gain. The monitor sweep speed was set at 50 to 100 mm/s to optimize the spectral display of myocardial velocities. In apical 4-chamber view, the pulsed Doppler sample volume was subsequently placed at the level of LV lateral mitral annulus, septal mitral annulus, and right ventricular tricuspid annulus.

Tissue Doppler pattern is characterized by a positive myocardial systolic wave (S) and two negative diastolic waves: early (E’) and atrial (A’). Every effort was made to align the pulsed wave cursor that the Doppler angle of incidence was as close to 0 as possible to the direction of these walls.

Time intervals from the onset of P wave on surface electrocardiography to the beginning of A wave (PA), representing AEMD, were obtained from lateral mitral annulus, septal mitral annulus, and right ventricular (RV) tricuspid annulus and named as lateral PA, septal PA, and RV PA, respectively. The timing of mechanical activation of each reference point, namely lateral mitral, septal mitral, and RV tricuspid annuli, depends on the distances of these points to sinus node, ie, the RV tricuspid annulus is the earliest and lateral mitral annulus is the latest points to be activated by the impulse arising from sinus node. Therefore, it is hypothesized that the difference between any two reference points reflects the mechanical delay between these two points. The difference between septal PA and RV PA was defined as intra-right AEMD (septal PA-RV PA), the difference between lateral PA and septal PA was defined as intra-LA electromechanical delay (lateral PA-septal PA), and the difference between lateral PA and RV PA (lateral PA-RV PA) was defined as inter-AEMD.3

Defining of LV Diastolic Dysfunction

Diastolic dysfunction is defined as mitral septal early diastolic annular velocity (E’) <8 cm/s.9

Statistical Analysis

Data are demonstrated as mean ± standard deviation for normally distributed continuous variables, median (minimum – maximum) for skew-distributed continuous variables, and frequencies for categoric variables. Pearson chi-square test was performed for the comparison of categoric variables. Means of normally distributed continuous variables were compared by analysis of variance. Skew-distributed continuous variables were compared by Mann-Whitney U test. Tukey and Kruskal-Wallis tests were used for post hoc analysis. Correlation was tested with Spearman rank order or Pearson correlation coefficient. Multivariate analysis was performed for determining independent correlates for diastolic function. SPSS for Windows version 10.0 (SPSS Inc, Chicago, IL) was used for the analysis, and 2-sided P value of <.05 was considered significant.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

Baseline characteristics in patients and controls are presented in Table I. There was no difference between groups with hypertension and controls with regard to age. Hypertensive patients were divided into two subgroups: group 1 (hypertensive patients with diastolic dysfunction) and group 2 (hypertensive patients without diastolic dysfunction). There were 72 (36%) hypertensive patients in group 1 and 128 (64%) hypertensive patients in group 2. There were 151 healthy controls. Mean duration of hypertension was 7.1±4.1 years. Among hypertensive patients, 87 were receiving dihydropyridine calcium channel blockers, 60 were receiving angiotensin-converting enzyme (ACE) inhibitors, 28 were receiving angiotensin receptor blockers (ARBs), 22 were receiving an ACE inhibitor or ARB + diuretic combination, and 3 were receiving α-blockers. There was no significant difference in heart rate between the groups and controls (74.6±12.8 beats per minute vs 73.0±10.9 beats per minute vs 75.1±12.1 beats per minute; P=not significant).

Table I.   Baseline Characteristics
 Group 1 (n=72)Group 2 (n=128)Controls (n=151)P ValueaP ValuebP Valuec
  1. Abbreviations: BP, blood pressure; bpm, beats per minute; NS, not significant. P values were obtained from Tukey analysis. aP value between group 1 and 2. bP value between group 2 and controls. cP value between group 1 and controls.

Age, y53.0±8.951.5±8.751.5±7.1NSNSNS
Sex (male/female), No. (%)31/41 (43/57)42/86 (33/67)61/90 (40/60)NSNSNS
Heart rate, bpm74.6 ±12.8  73.0±10.975.1±12.1NSNSNS
 Systolic BP130.2±13.1128.4±10.4121.8±2.4NS<.001<.001
 Diastolic BP 83.2±11.681.8±7.877.0±2.4NS<.001<.001

Fourteen patients with systolic LV dysfunction (LVEF <40%) were excluded from the study. LA diameter (3.8±0.4 vs 3.2±0.3 vs 3.0±0.4) and LA volume (64.7 [21.8–334.9] vs 61.1 [31.1–85.0] vs 56.1 [31.6–92.0]) were significantly higher in hypertensive patients with diastolic dysfunction compared with those without diastolic dysfunction and controls. The diastolic parameters of patients are presented in Table II. Ninety hypertensive patients had LV hypertrophy. All patients with LV hypertrophy had concentric hypertrophy. LV mass index (129.2±23.4 vs 93.0±17.9 vs 69.2±16.2) was significantly higher in hypertensive patients with diastolic dysfunction compared with those without diastolic dysfunction and controls.

Table II.   Comparison of Echocardiographic Parameters of Group 1, Group 2, and Control Group
 Group 1 (n=72)Group 2 (n=128)Controls (n=151)P ValueaP ValuebP Valuec
  1. Abbreviations: AEMD, atrial electromechanical delay; DT, deceleration time; E’, mitral septal early diastolic annular velocity; IVRT, isovolumic relaxation time; LA, left atrial; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; LVMI, left ventricular mass index; LVPWT, left ventricular posterior wall thickness; LVSWT, left ventricular systolic wall thickness; NS, not significant. P values of group 1, group 2, and controls were obtained from Tukey or Kruskal-Wallis Analysis. aP value between group 1 and 2. bP value between group 2 and controls. cP value between group 1 and controls.

LA diameter, cm3.8±0.4 3.2±0.3 3.0±0.4<.001NS<.001
LA volume, mL64.7 (21.8–334.9)61.1 (31.1–85.0)56.1 (31.6–92.0).002<.001<.001
Indexed LA volume, mL/m238.0 (12.8–197.0)35.9 (18.3–50.0)31.2 (17.5–51.1).002<.001<.001
LVEDD, cm5.2±0.5 4.6±0.4 4.5±0.7.011NS<.001
LVESD3.0±0.1 2.9±0.2 2.9±0.3NSNSNS
Ejection fraction, %67.5±3.065.5±3.966.5±2.9<.001NS.032
LVSWT1.2±0.2 1.0±0.1 0.8±0.1<.001<.001<.001
LVPWT1.2±0.2 1.0±0.1 0.9±0.1<.001<.001<.001
LVMI129.2±23.4 93.0±17.9 69.2±16.2<.001<.001<.001
E, m/s0.65±0.06 0.70±0.07 0.81±0.12.001<.001<.001
E/A ratio0.89±0.10 1.24±0.23 1.26±0.21<.001.032<.001
DT, ms254.2±28.6180.7±12.1171.9±22.5<.001.001<.001
IVRT, ms114.6±10.3 85.1±10.6 85.8±13.1<.001NS<.001
E’, cm/s7.1±0.810.3±1.512.1±1.9<.001<.001<.001
E/E’9.4±1.8 6.9±1.1 7.0±1.7<.001NS<.001
Inter-AEMD, ms59 (36–104)42 (36–68)46 (30–82)<.001NS<.001
Intra-left AEMD, ms30 (20–71)28 (14–48)20 (14–50)NS<.001<.001
Intra-right AEMD, ms22.4±9.322.4±9.9 23.9±11.0NSNSNS

Inter-AEMD (59 [36–104] vs 42 [36–68] vs 46 [30–82]) was significantly higher in hypertensive patients with diastolic dysfunction compared with those without diastolic dysfunction and controls (Figure 1). Intra-left AEMD (30 [20–71] vs 28 [14–48] vs 20 [14–50]) was significantly higher in hypertensive patients with diastolic dysfunction and without diastolic dysfunction compared with controls (Figure 2). No statistically significant difference was found in intra-right AEMD between the groups (Table II). Inter-AEMD (59 [36–104] vs 44 [30–82]; P<.001) and intra-left AEMD (29 [20–71] vs 22 [14–50]; P<.001) were significantly higher in patients with LV hypertrophy than those without. There was a positive significant correlation between LV mass index and inter-AEMD (r=0.318, P<.001) and intra-left AEMD (r=0.530, P<.001). There was also a positive significant correlation between intra-AEMD and LA diameter (r=0.448, P<.001). LA volume index was positively correlated with both intra-left AEMD (r=0.474, P<.001) and inter-AEMD (r=0.296, P<.001). There was no correlation between heart rate and age and any diastolic function or AEMD parameters. Multivariate analysis demonstrated that LV mass index and inter-AEMD were independent correlates for diastolic function.

image

Figure 1.  Distributions of inter-atrial electromechanical delay (AEMD) in hypertensive patients with diastolic dysfunction and without diastolic dysfunction and control patients. Group 1 represents: hypertensive patients with diastolic dysfunction and group 2 represents hypertensive patients without diastolic dysfunction (group 1 vs group 2, P<.001; group 1 vs controls, P<.001; group 2 vs controls, P=not significant).

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image

Figure 2.  Distributions of intra-left atrial electromechanical delay in hypertensive patients with diastolic dysfunction and without diastolic dysfunction and control patients. Group 1 represents hypertensive patients with diastolic dysfunction and group 2 represents hypertensive patients without diastolic dysfunction. (group 1 vs group 2, P=not significant; group 1 vs controls, P<.001; group 2 vs controls, P<.001).

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Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

In this study, we used a novel noninvasive technique to show inter- and intra-AEMD by tissue Doppler imaging. Inter-atrial and intra-LA electromechanical delays were found to be significantly increased in hypertensive patients with diastolic dysfunction compared with those without diastolic dysfunction and controls. This is the first study evaluating inter- and intra-AEMD in hypertensive patients.

Intra-LA electromechanical delay and inter-AEMD were examined in several studies. Ozer and colleagues3 evaluated intra-AEMD and inter-AEMD in patients with mitral stenosis and reported that inter-AEMD was longer in mitral stenosis and correlated with P-wave dispersion, which is known as a marker of atrial fibrillation. Deniz and colleagues10 assessed intra-LA electromechanical delay and inter-AEMD in paroxysmal atrial fibrillation and demonstrated an increase in intra-LA electromechanical delay in paroxysmal atrial fibrillation patients.

LV hypertrophy, extracellular and perivascular fibrosis, contractile alterations in myocytes, and myocardial ischemia have been implicated in developing diastolic dysfunction in hypertension. Insults to the myocardium are followed by a series of compensatory changes that have short-term beneficial effects but have long-term deleterious effects. Structural remodeling and other factors, including myocardial ischemia, LV hypertrophy, increased heart rate, and abnormal calcium flux, can impair diastolic function in hypertension.2 In our study we found no effect of age and heart rate on diastolic function.

There may be several mechanisms involved in increasing AEMDs in hypertensive patients with diastolic dysfunction. LV hypertrophy may be an important factor. The presence of LV hypertrophy is an indicator of increased myocardial demand for oxygen and hence decreases coronary reserve.11 When coronary blood flow is fixed or reduced, there is a supply-demand mismatch, resulting in increased risk for ischemia. In such a scenario, a decrease in blood flow can be catastrophic to the already increased demand of the myocardial cells. Patients with LV hypertrophy are at increased risk for ischemia, probably causing elongation of AEMDs. We found a positive correlation between LV mass index and inter-atrial and intra-LA electromechanical delays in our study.

Another possible mechanism for increasing AEMDs in hypertensive patients with diastolic dysfunction is LA enlargement. In hypertension, LA size enlargement has been shown, following the development of LV hypertrophy, as a consequence of chronic LV overload.12 LA enlargement is often associated with impaired LV systolic and diastolic function.13 LA size is an important risk factor for developing atrial fibrillation.14 Enlargement of the left atrium can effect atrial conduction time in hypertensive patients.15 This affected conduction time may be related to increased AEMDs.

Conclusions

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References

This study demonstrated elongation in intra-LA and inter-AEMDs in hypertensive patients with diastolic dysfunction. These elongations may be associated with increasing risk of atrial fibrillation. Further prospective studies are needed to evaluate whether intra-LA and inter-AEMDs are risk factors for hypertensive patients with atrial fibrillation.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Conclusions
  7. References