Blood Pressure, 2014; 23: 349–355
ORIGINAL ARTICLE
The assessment of relationship between left ventricular geometry and microvolt T-wave alternans in sustained hypertension
OZGUR SURGIT1, MEHMET ERTURK1, ALI BUTURAK2, OZGUR AKGUL1, HAMDI PUSUROGLU1, HUSEYIN ALTUG CAKMAK1, SERKAN YAZAN1, MEHMET GUL1, EMRE AKKAYA1 & ABDURRAHMAN EKSIK1 1Mehmet
Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Istanbul, Turkey, and 2Acıbadem University, School of Medicine, Department of Cardiology, Istanbul, Turkey Abstract Objective. Left ventricular (LV) hypertrophy (LVH) predicts increased mortality in part due to an elevated incidence of sudden cardiac death in hypertension. The aim of the present study was to investigate the relation of microvolt T-wave alternans (MTWA) with different LV geometric patterns in patient with sustained hypertension. Methods. This study consisted of 311 consecutive patients with sustained hypertension who were divided into four groups according to LV geometrical patterns. 90 patients were in the normal geometry group (NGG) [mean age 49.6 ⫾ 7.8 years; 60 males (66.7%)], 99 patients were in the concentric remodeling group (CRG) [mean age 50.9 ⫾ 6.6 years; 50 males (50.6%)], 63 patients were in the concentric hypertrophy group (CHG) [mean age 51.6 ⫾ 7.3 years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group (EHG) [mean age 51.6 ⫾ 9.0 years; 30 males (51.7%)]. Physical examination, laboratory work-up, office blood pressure measurement, transthoracic echocardiography and MTWA measurements were performed on all participants. Results. MTWA positivity was significantly higher in EHG and CHG as compared to CRG and NGG (p ⬍ 0.001). Left ventricle mass index (LVMI), LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum diameter (IVSd), posterior wall diameter (PWd) and office systolic blood pressure (SBP) were found to be significantly positively correlated with MTWA (all p-values ⬍ 0.05). Conclusion. We demonstrated that increased LVMI is associated with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically significant LV geometric patterns including both concentric and eccentric hypertrophy are related with a raised MTWA positivity, which may lead to particular predilection to life-threatening ventricular arrhythmias and sudden cardiac death in sustained hypertension. Key Words: Concentric hypertrophy, eccentric hypertrophy, left ventricular geometry, microvolt t-wave alternans, sustained hypertension
Introduction Alteration of the left ventricular (LV) structure and morphology as a consequence of arterial hypertension is a well-known phenomenon. Recent studies have proved that LV hypertrophy (LVH) is a strong and independent predictor of major adverse cardiovascular events including sudden cardiac death (1–3). A longstanding elevation in blood pressure (BP) results in ventricular remodeling, which may lead to ventricular dysfunction. The LV may undergo various different geometrical adaptation mechanisms which is defined as follows: normal LV geometry, concentric remodeling, eccentric hypertrophy and
concentric hypertrophy (4). Different pathophysiological mechanisms leading to electrical instability of the myocardium, which results in malignant ventricular arrhythmias and sudden cardiac death, were demonstrated in patients with LVH (5). Microvolt T-wave alternans (MTWA) is defined as the beat-to-beat changes in shape, amplitude or timing of the ST segments and the T-waves. The predictive value of exercise-induced MTWA in predicting sudden cardiac death and life-threatening ventricular arrhythmia in different patient groups has been reported in several studies. These studies had consisted of patient groups, who had a high risk of
Correspondence: Ozgur Surgit, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Kucukcekmece, 34303 Istanbul, Turkey. Tel: ⫹ 90 212 692 20 00. Fax: ⫹ 90 212 471 94 94. E-mail: [email protected] (Received 20 January 2014 ; accepted 14 April 2014 ) ISSN 0803-7051 print/ISSN 1651-1999 online © 2014 Scandinavian Foundation for Cardiovascular Research DOI: 10.3109/08037051.2014.923252
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malignant ventricular arrhythmias such as impaired LV function (6) and ischemic cardiomyopathy (7). Sustained hypertension along with severe LVH may also increase the risk of ventricular arrhythmias (8). The relationship between different LV geometric patterns and MTWA has not yet been established in the literature. Therefore, the aim of the present study was to investigate the relation of MTWA with different LV geometrical patterns in patients with sustained hypertension.
Materials and methods Study population In this cross-sectional study, a total of 311 consecutive sustained hypertensive patients, who admitted to outpatient clinic for routine control and underwent transthoracic echocardiographic examination (TTE) to investigate target organ damage, were included. The patients were divided into four groups based on their LV geometric patterns. Of the 311 patients with sustained hypertension, 90 patients were in the normal geometry group (NGG) [mean age 49.6 ⫾ 7.8 years; 60 males (66.7%)], 99 patients were in the concentric remodeling group (CRG) [mean age 50.9 ⫾ 6.6 years; 50 males (50.6%)], 63 patients were in the concentric hypertrophy group (CHG) [mean age 51.6 ⫾ 7.3 years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group (EHG) [mean age 51.6 ⫾ 9.0 years; 30 males (51.7%)]. Physical examination, laboratory work-up, office blood pressure measurement, TTE and MTWA measurements were performed on all participants. Patients who had a history or clinical evidence of coronary artery disease, congestive heart failure, renal or hepatic dysfunction, moderate to severe valvular heart disease, hyperthyroidism, hypothyroidism, chronic obstructive pulmonary disease, atrioventricular conduction abnormality or left bundle branch block, as well as patients with a history of drugs or chemical use including marijuana, antiarrhythmic drugs, digitalis, beta-blockers and nondihydropyridine calcium-channel blockers, were excluded from the study. Written informed consent was obtained from all the participants and the study was approved by the local ethics committee and institutional review board. The study was consistent with the Declaration of Helsinki. Blood pressure measurement Blood pressure was measured in an office after 5 min of rest using a mercury sphygmomanometer and recorded to the nearest 2 mmHg. Diastolic blood pressure was determined according to the fifth Korotkoff phase. Three blood pressure measurements were performed in each participant: two at the screening and one before the instrumental
examination (electrocardiography (ECG), TTE). An examinee was classified as hypertensive if mean values of two blood pressure measurements at the screening and/or the third measurement before instrumental examination exceeded 140/90 mmHg. Patients on antihypertensive medication were also considered hypertensives. Blood sampling Blood samples were drawn from the antecubital vein by careful vein puncture, using a 21-gauge sterile syringe without stasis at 08:00–10:00 h after a fasting period of 12 h. Fasting glucose, creatinine and lipid profiles were determined by standard methods. Transthoracic echocardiography examination The measurements used in the present study were obtained from two-dimensionally guided M-mode echocardiograms according to the recommendations of the American Society of Echocardiography and the European Association of Echocardiography guidelines (9). All of the TTE examinations were performed using GE Vivid S6 Vingmed System 5 (Norway, Horten) equipped with 2.5–4-MHz transducers. The LV mass (LVM) was calculated using the regression equation described by Devereux (10). LV mass index (LVMI) was calculated as LVM divided by body surface area. LVH was defined as LVMI ⱖ 115 g/m2 (men), LVMI ⱖ 95 g/m2 (females) according to American Society of Echocardiography guidelines (9). Relative wall thickness (RWT) was calculated by dividing the two-fold dimension of end diastolic posterior wall (PW) thickness to LV end diastolic diameter (LVEDD) [RWT ⫽ (2 ⫻ PW)/LVEDD] (11). When RWT exceeded 0.42, the LV geometric pattern was considered concentric. The patients were thus classified as having one of four geometric patterns: normal geometric pattern (normal LVMI, normal RWT), concentric remodeling (normal LVMI, increased RWT), eccentric LVH (increased LVMI, normal RWT) and concentric LVH (increased LVMI, increased RWT) (4). Exercise test protocol Before beginning the exercise test, all patients reclined in a supine position for 10 min and their resting ECG was digitally recorded. The upright exercise test was performed on a treadmill. The Mason–Likar modification of the standard 12-lead system was used. We used a modified Bruce protocol to increase the workload every 3 min. Continuous ECGs were digitally recorded at 500 Hz using the CardioSoft version 4.14 exercise system (GE Healthcare) and they were completely analyzed automatically using the GE Healthcare-released version of the modified
LV geometry and microvolt T-wave alternans in sustained hypertension moving average (MMA) method (12). During the exercise test, heart rate was recorded continuously via ECG, and systolic and diastolic arterial pressure was measured with a brachial cuff every 2 min. Measurement of MTWA The algorithm used in the identification and quantification of MTWA is based on time-domain MMA analysis. An update is calculated for every incoming beat, which results in continuous moving averages of odd and even beats. In addition, algorithms have been incorporated to reduce the influence of noise and artifacts, such as those caused by running and respiration. The MTWA values were calculated continuously during the entire exercise test, from rest to recovery, using all standard leads (I, II, III, aVR, aVF, aVL and V1–V6). Maximum MTWA values at heart rates ⬍ 125 beats/min were recorded, and MTWA values at higher heart rates were excluded. The analyses were performed using 1/8 incremental update factors. Patient characteristics were compared, and MTWA results ⬍ 65 μV were accepted as negative and MTWA results ⱖ 65 μV were positive (13). Statistics Statistical analyses were performed using the SPSS software version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov–Smirnov/Shapiro– Wilk test) to determine whether a distribution was
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normal. Descriptive analyses were presented using means and standard deviations. The categorical variables were expressed as numbers and percentages. Numerical variables, which did not exhibit normal distribution, were compared using the Kruskal– Wallis test. The Mann–Whitney U test was performed to test the significance of pairwise differences by using Bonferroni correction to adjust for multiple comparisons. Numerical variables exhibiting normal distribution were compared using the one-way analysis of variance (ANOVA) test. Tukey’s test was performed to test the significance of pairwise differences by using Bonferroni correction to adjust for multiple comparisons. Categorical data were compared with the chi-square test. Spearman’s correlation coefficients were used to assess the relationship between continuous variables. A multivariate linear regression analysis was used to assess the relationship between several confounders and MTWA value. A p-value ⬍ 0.05 was considered statistically significant.
Results Baseline demographic, clinical and laboratory characteristics of patients based on their LV geometrical patterns were presented in Table I. There was no difference among the groups in terms of age, male gender, body mass index (BMI), smoking habit, diabetes mellitus (DM), medications, office SBP and DBP, and laboratory parameters (all p-values ⬎ 0.05). However, MTWA positivity was found to be significantly different among the groups (p ⬍ 0.001). In subgroup analysis, MTWA positivity was found to be significantly higher when the CHG was compared
Table I. Baseline demographic, clinical and laboratory characteristics of patients based on their left ventricular geometrical patterns.
Age (year) Sex, male (%) Body mass index (kg/m2) Creatinine (mg/dl) Smokers (%) Diabetes mellitus (%) Hematocrit (%) Glucose (mg/dl) Total cholesterol (mg/dl) HDL (mg/dl) LDL (mg/dl) TG (mg/dl) ARB⫹ ACE (%) CCB (%) Diuretics (%) Other antihypertensive drugs (%) Office Systolic BP (mmHg) Office Diastolic BP (mmHg) MTWA (positivity %)
Normal geometry group (n ⫽ 90)
Concentric remodeling group (n ⫽ 99)
Concentric hypertrophy group (n ⫽ 63)
Eccentric hypertrophy group (n ⫽ 58)
p-value
49.6 ⫾ 7.8 66.7 28.7 ⫾ 4.6 0.81 ⫾ 0.18 34.1 18.9 42.8 ⫾ 4.4 100.7 ⫾ 28.8 200.6 ⫾ 41.2 45 ⫾ 12.2 128.8 ⫾ 36.1 148.4 ⫾ 119 35.6 20 20.1 6.7 147.6 ⫾ 9.4 91 ⫾ 9.1 12.6
50.9 ⫾ 6.6 56.6 29.4 ⫾ 3.4 0.83 ⫾ 0.21 23.5 24.2 42.1 ⫾ 4.8 101.4 ⫾ 35.3 215.3 ⫾ 45.4 47 ⫾ 12.5 138.9 ⫾ 37.8 158.4 ⫾ 81.8 41.4 25.3 33.4 10.1 147.3 ⫾ 8.3 92 ⫾ 9.8 16.2
51.6 ⫾ 7.3 50.7 29.4 ⫾ 3.1 0.77 ⫾ 0.15 23.8 26.4 41.9 ⫾ 4.1 111.6 ⫾ 38.3 194 ⫾ 38.1 45.1 ⫾ 15.7 127.7 ⫾ 45.5 159.9 ⫾ 97.5 47.6 39.7 38.4 12.7 151.1 ⫾ 12.5 92 ⫾ 16 39.7
51.6 ⫾ 9.0 51.7 28.8 ⫾ 4.2 0.80 ⫾ 0.23 25.4 25 41.9 ⫾ 4.3 104.2 ⫾ 24.2 196.2 ⫾ 58.2 44.2 ⫾ 16.5 125.4 ⫾ 35.9 149.7 ⫾ 74.8 44.1 28.8 32.2 13.6 149.3 ⫾ 8.9 90 ⫾ 10.3 37.3
0.445 0.148 0.543 0.303 0.376 0.706 0.484 0.148 0.550 0.692 0.148 0.858 0.486 0.056 0.054 0.234 0.075 0.594 ⬍ 0.001
ACE, angiotensin converting enzyme blockers; ARB, angiotensin receptor blockers; BP, blood pressure; CCB, calcium channel blockers; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MTWA, microvolt T-wave alternance; TG, triglyceride.
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with the NGG (p ⬍ 0.001), the EHG was compared with the NGG (p ⬍ 0.001), the EHG was compared with the CRG (p ⫽ 0.003) and the CHG compared with the CRG (p ⫽ 0.001). On the other hand, MTWA positivity did not reach statistical significance between the NGG and CRG (p ⫽ 0.440), and the CHG and EHG (p ⫽ 0.786). The comparisons of the echocardiographic parameters of patients according to their LV geometrical patterns were reported in Table II. The LV ejection fraction (LVEF) was similar among the groups. LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum diameter (IVSd), PWd, RWT and LVMI values were statistically significant among the groups (all p-values ⬍ 0.05). When the comparison of echocardiographic parameters between different LV geometrical patterns was investigated with subgroup analysis, all groups were found to be significantly different between each other in terms of LVEDD (p ⬍ 0.001). LVESD was also significantly different among the groups (p ⬍ 0.001), except between the NGG and CHG (p ⫽ 0.374). Moreover, all group comparisons demonstrated significant differences between each other (for all p ⬍ 0.001) in terms of IVSd, except between the CRG and NGG (p ⫽ 0.063) and the EHG and CRG (p ⫽ 0.042). For PWd, all groups showed significant differences between each other, except between the CRG and EHG (p ⫽ 0.015). Also, LVMI was found to be significantly different among all groups (for all p-values ⬍ 0.001), except between the NGG and CRG (p ⫽ 0.379) and the CHG and EHG (p ⫽ 0.947). In addition, all groups demonstrated significant differences between each other in terms of RWT (for all, p ⬍ 0.001), except between the EHG and NGG (p ⫽ 0.222). When the relation of MTWA with clinical and echocardiographic parameters of patients was investigated, LVMI, LVEDD, LVESD IVSd, PWd and office SBP were found to be significantly positively correlated with MTWA. However, there was no correlation between age, office DBP, RWT and MTWA in patients with sustained hypertension (Table III).
Table III. The correlation between microvolt T-wave alternans and echocardiographic and clinical parameters of patients. Spearman’s correlation analysis
LVMI IVSd PWd LVEDD LVESD Age Office SBP Office DBP RWT
r
p
0.349 0.236 0.211 0.148 0.180 0.660 0.202 0.109 0.048
⬍ 0.001 ⬍ 0.001 ⬍ 0.001 0.009 0.001 0.244 ⬍ 0.001 0.056 0.396
DBP, diastolic blood pressure; IVSd, interventricular septum diameter; LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; LVMI, left ventricular mass index; PWd, posterior wall diameter; RWT, relative wall thickness; SBP, systolic blood pressure.
Multivariate linear regression analysis showed a significant relation between LVMI and MTWA (R2 ⫽ 0.157, β ⫽ 0.348, p ⬍ 0.001). However, no association was found between RWT, gender, age, office systolic blood pressure, office diastolic blood pressure and MTWA. When this analysis was done among different LV geometrical pattern subgroups, only LVMI was found to be related with MTWA for the NGG (R2 ⫽ 0.348, β ⫽ 0.582, p ⬍ 0.001) and CHG (R2 ⫽ 0.218, β ⫽ 0.446, p ⫽ 0.001). Furthermore, LVMI and office systolic and diastolic BP were found to be associated with MTWA in the EHG (R2 ⫽ 0.357, β ⫽ 0.337, p ⫽ 0.009; β ⫽ 0.408, p ⫽ 0.003, β ⫽ ⫺ 0.303, p ⫽ 0.018, respectively). However, none of the parameters was found to be related with MTWA in the CRG (p ⬎ 0.05).
Discussion The present study demonstrated that there was a significant positive relation between LVMI and MTWA in all LV geometrical patterns in sustained hypertensives. This finding supports the important effect of LVH, defined as LVMI, on MTWA in patients with sustained hypertension. Moreover, both
Table II. The comparisons of the echocardiographic parameters of patients according to their left ventricular geometrical pattern.
Ejection fraction (%) Left ventricle mass index (g/m2) LVEDD (mm) LVESD (mm) IVSd (mm) PWd (mm) RWT
Normal geometry group (n ⫽ 90)
Concentric remodeling group (n ⫽ 99)
Concentric hypertrophy group (n ⫽ 63)
Eccentric hypertrophy group (n ⫽ 58)
p-value
65.8 ⫾ 5.7 92.7 ⫾ 8.5 50.3 ⫾ 3.4 31.1 ⫾ 3.6 10.6 ⫾ 1.3 9.2 ⫾ 0.8 0.37 ⫾ 0.04
64.5 ⫾ 3.9 89.1 ⫾ 11.9 45.4 ⫾ 3.0 28.1 ⫾ 3.4 11.3 ⫾ 1.2 10.6 ⫾ 0.7 0.47 ⫾ 0.04
63.8 ⫾ 3.6 123.1 ⫾ 19.9 48 ⫾ 4.2 30.1 ⫾ 4.3 13.5 ⫾ 2.0 12.1 ⫾ 1.35 0.51 ⫾ 0.07
64 ⫾ 3.6 121.5 ⫾ 21.2 53.3 ⫾ 3.3 33.4 ⫾ 3.7 11.7 ⫾ 2.2 10.1 ⫾ 0.91 0.38 ⫾ 0.03
0.068 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001
IVSd, interventricular septum diameter; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; PWd, posterior wall diameter; RWT, relative wall thickness.
LV geometry and microvolt T-wave alternans in sustained hypertension the eccentric and concentric LVH were found to be associated with raised MTWA levels in subgroup analyses. In chronic arterial hypertension, pressure and volume changes as well as structural alterations in myocardium often lead to an increase in LVM (4). An increase in LVM is defined as LVH. Independent of other risk factors, patients with increased LVM have remarkable risk of future cardiovascular morbidity and mortality (14). In different studies, it was reported that concentric hypertrophy was associated with the elevated risk of future cardiovascular events (2) with the evidence of increased progression to LV dilatation and ultimately heart failure in hypertensives (15,16). Increased LVM in concentric hypertrophy results in impaired coronary hemodynamics exerted by decreased coronary blood flow and flow reserve associated with increased coronary vascular resistance (17). Impaired coronary hemodynamics involve coronary arteriolar compression by the hypertrophied and stiffer LV produced by ventricular fibrosis, the increased arteriolar wall thickening and arteriolar wall-to-lumen diameter (18), insufficient sizing of coronary vessels (19), increased blood viscosity in hypertension (20) and the increased LV chamber diameters designating not only myocytic hypertrophy but also collagen deposition (21). For the reasons mentioned above, patients with arterial hypertension and LVH can experience numerous areas of supply–demand mismatch and this could lead to myocardial ischemia (22). MTWA is a well-established risk factor related to long-term susceptibility to ventricular tachyarrhythmia and sudden cardiac death (23). Positive MTWA has also been reported in acute coronary syndrome with chest pain and ST-T changes and ischemic and non-ischemic cardiomyopathy in human and animal models (24,25). Various studies in animals during coronary artery occlusion and in humans during angioplasty have demonstrated that myocardial ischemia can increase MTWA magnitude (26). In these experimental studies, in which heart rate was kept constant, it was found that myocardial ischemia provokes increases in MTWA magnitude in parallel with increased susceptibility to ischemia-induced ventricular fibrillation (27). This increase in MTWA was accompanied by parallel changes in T-wave complexity and heterogeneity (28). Myocardial ischemia may be responsible for positive MTWA in hypertensive patients with concentric hypertrophy. Myocardial structural changes also occur during genesis of LVH. Two important biological alterations, fibrosis and changes in membrane protein composition, have been observed in LVH (29). Ventricular fibrosis is a substantially well documented entity in LVH. In patients with arterial hypertension and LVH, an increase in collagen volume fraction has been revealed (30). There are also small clinical study
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in the literature concerning occurrence of ventricular arrhythmias in LVH settings (31). However, no attempt has been made to study the role of cardiac hypertrophy and fibrosis in the onset of arrhythmias. Re-entry may be one of the possible mechanisms for arrhythmias. Re-entry involves a conduction block in the normal conductive pathway together with slowed conduction; thus, the conduction time in the re-entry circuit exceeds the refractory period of the conducting tissue. Fibrosis can generate alternative pathway and conduction block, or can lead to slow conduction. In LVH, arrhythmias that originated from triggered activity or abnormal automaticity was also observed (32). In addition, LVH generates the lengthening of the action potential that causes the ventricular repolarization abnormalities on the ECG (33). Increased MTWA positivity, which predicts future ventricular arrhythmias, can be explained by increased fibrosis in patients with concentric hypertrophy. In our study, eccentric hypertrophy revealed an increase in MTWA positivity like concentric hypertrophy. In eccentric hypertrophy, in which an increase in LVM can occur, wall thickness remains normal, while the LV cavity dilates through myocyte elongation. Eccentric hypertrophy is usually observed in states of volume overload, such as mitral regurgitation, and aortic regurgitation. Moreover, it may represent the early manifestation of a cardiomyopathic process without an intervening phase of concentric hypertrophy in hypertensive settings. This alternative pathway for the development of heart failure in hypertension was supported by some previous studies. They have demonstrated the eccentric hypertrophy to be associated with more severe systolic dysfunction as compared with concentric hypertrophy (34,35). Moreover, it was reported that longitudinal systolic function was significantly impaired in both concentric and eccentric hypertrophy as compared with normal LV geometry. Also, in the same study, it was designated that patients with eccentric hypertrophy had worse longitudinal systolic function and lower EF compared with concentric hypertrophy (36). Because eccentric hypertrophy may be the precursor of heart failure, this may lead to an elevated MTWA in this patient population (36). Also, there are small studies reporting that eccentric hypertrophy is associated with higher risk of ventricular arrhythmia as compared with concentric hypertrophy (37). Study limitations This is a single-center study with a relatively small sample size, both of which limit the power of our research findings. In addition, our study provides no information regarding long-term outcomes. We also excluded patients with clinically overt cardiovascular disease (such as coronary artery disease, cerebrovascular disease and renal failure), and therefore our
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results cannot be extrapolated to all hypertensive subjects. Conclusion We demonstrated that increased LVMI is associated with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically significant LV geometric patterns including both concentric and eccentric hypertrophy, which play a pivotal role in the pathophysiology of myocardial ischemia, heart failure and fatal arrhythmias, are related with a raised MTWA positivity, which may lead to particular predilection to life-threatening ventricular arrhythmias and sudden cardiac death in sustained hypertension.
10.
11.
12.
13.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was not financially supported. The authors have no relevant conflicts of interest to disclose.
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33. Hart G. Cellular electrophysiology in cardiac hypertrophy and failure. Cardiovasc Res. 1994;28:933–946. 34. Devereux RB, Bella JN, Palmieri V, Oberman A, Kitzman DW, Hopkins PN, et al. Left ventricular systolic dysfunction in a biracial sample of hypertensive adults: The Hypertension Genetic Epidemiology Network (HyperGEN) Study. Hypertension. 2001;38:417–423. 35. Wachtell K, Rokkedal J, Bella JN, Aalto T, Dahlof B, Smith G, et al. Effect of electrocardiographic left ventricular hypertrophy on left ventricular systolic function in systemic hypertension (The LIFE Study). Losartan Intervention For Endpoint. Am J Cardiol. 2001;87:54–60. 36. Chahal NS, Lim TK, Jain P, Chambers JC, Kooner JS, Senior R. New insights into the relationship of left ventricular geometry and left ventricular mass with cardiac function: A population study of hypertensive subjects. Eur Heart J. 2010;31:588–594. 37. Franchi F, Michelucci A, Padeletti L, Monopoli A, Fabbri G, Cersosimo RM, et al. Arrhythmogenicity in left ventricular hypertrophy in mild to moderate arterial hypertension. G Ital Cardiol. 1992;22:905–918.
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ORIGINAL ARTICLE
The assessment of relationship between left ventricular geometry and microvolt T-wave alternans in sustained hypertension
OZGUR SURGIT1, MEHMET ERTURK1, ALI BUTURAK2, OZGUR AKGUL1, HAMDI PUSUROGLU1, HUSEYIN ALTUG CAKMAK1, SERKAN YAZAN1, MEHMET GUL1, EMRE AKKAYA1 & ABDURRAHMAN EKSIK1 1Mehmet
Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Istanbul, Turkey, and 2Acıbadem University, School of Medicine, Department of Cardiology, Istanbul, Turkey Abstract Objective. Left ventricular (LV) hypertrophy (LVH) predicts increased mortality in part due to an elevated incidence of sudden cardiac death in hypertension. The aim of the present study was to investigate the relation of microvolt T-wave alternans (MTWA) with different LV geometric patterns in patient with sustained hypertension. Methods. This study consisted of 311 consecutive patients with sustained hypertension who were divided into four groups according to LV geometrical patterns. 90 patients were in the normal geometry group (NGG) [mean age 49.6 ⫾ 7.8 years; 60 males (66.7%)], 99 patients were in the concentric remodeling group (CRG) [mean age 50.9 ⫾ 6.6 years; 50 males (50.6%)], 63 patients were in the concentric hypertrophy group (CHG) [mean age 51.6 ⫾ 7.3 years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group (EHG) [mean age 51.6 ⫾ 9.0 years; 30 males (51.7%)]. Physical examination, laboratory work-up, office blood pressure measurement, transthoracic echocardiography and MTWA measurements were performed on all participants. Results. MTWA positivity was significantly higher in EHG and CHG as compared to CRG and NGG (p ⬍ 0.001). Left ventricle mass index (LVMI), LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum diameter (IVSd), posterior wall diameter (PWd) and office systolic blood pressure (SBP) were found to be significantly positively correlated with MTWA (all p-values ⬍ 0.05). Conclusion. We demonstrated that increased LVMI is associated with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically significant LV geometric patterns including both concentric and eccentric hypertrophy are related with a raised MTWA positivity, which may lead to particular predilection to life-threatening ventricular arrhythmias and sudden cardiac death in sustained hypertension. Key Words: Concentric hypertrophy, eccentric hypertrophy, left ventricular geometry, microvolt t-wave alternans, sustained hypertension
Introduction Alteration of the left ventricular (LV) structure and morphology as a consequence of arterial hypertension is a well-known phenomenon. Recent studies have proved that LV hypertrophy (LVH) is a strong and independent predictor of major adverse cardiovascular events including sudden cardiac death (1–3). A longstanding elevation in blood pressure (BP) results in ventricular remodeling, which may lead to ventricular dysfunction. The LV may undergo various different geometrical adaptation mechanisms which is defined as follows: normal LV geometry, concentric remodeling, eccentric hypertrophy and
concentric hypertrophy (4). Different pathophysiological mechanisms leading to electrical instability of the myocardium, which results in malignant ventricular arrhythmias and sudden cardiac death, were demonstrated in patients with LVH (5). Microvolt T-wave alternans (MTWA) is defined as the beat-to-beat changes in shape, amplitude or timing of the ST segments and the T-waves. The predictive value of exercise-induced MTWA in predicting sudden cardiac death and life-threatening ventricular arrhythmia in different patient groups has been reported in several studies. These studies had consisted of patient groups, who had a high risk of
Correspondence: Ozgur Surgit, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Department of Cardiology, Kucukcekmece, 34303 Istanbul, Turkey. Tel: ⫹ 90 212 692 20 00. Fax: ⫹ 90 212 471 94 94. E-mail: [email protected] (Received 20 January 2014 ; accepted 14 April 2014 ) ISSN 0803-7051 print/ISSN 1651-1999 online © 2014 Scandinavian Foundation for Cardiovascular Research DOI: 10.3109/08037051.2014.923252
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malignant ventricular arrhythmias such as impaired LV function (6) and ischemic cardiomyopathy (7). Sustained hypertension along with severe LVH may also increase the risk of ventricular arrhythmias (8). The relationship between different LV geometric patterns and MTWA has not yet been established in the literature. Therefore, the aim of the present study was to investigate the relation of MTWA with different LV geometrical patterns in patients with sustained hypertension.
Materials and methods Study population In this cross-sectional study, a total of 311 consecutive sustained hypertensive patients, who admitted to outpatient clinic for routine control and underwent transthoracic echocardiographic examination (TTE) to investigate target organ damage, were included. The patients were divided into four groups based on their LV geometric patterns. Of the 311 patients with sustained hypertension, 90 patients were in the normal geometry group (NGG) [mean age 49.6 ⫾ 7.8 years; 60 males (66.7%)], 99 patients were in the concentric remodeling group (CRG) [mean age 50.9 ⫾ 6.6 years; 50 males (50.6%)], 63 patients were in the concentric hypertrophy group (CHG) [mean age 51.6 ⫾ 7.3 years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group (EHG) [mean age 51.6 ⫾ 9.0 years; 30 males (51.7%)]. Physical examination, laboratory work-up, office blood pressure measurement, TTE and MTWA measurements were performed on all participants. Patients who had a history or clinical evidence of coronary artery disease, congestive heart failure, renal or hepatic dysfunction, moderate to severe valvular heart disease, hyperthyroidism, hypothyroidism, chronic obstructive pulmonary disease, atrioventricular conduction abnormality or left bundle branch block, as well as patients with a history of drugs or chemical use including marijuana, antiarrhythmic drugs, digitalis, beta-blockers and nondihydropyridine calcium-channel blockers, were excluded from the study. Written informed consent was obtained from all the participants and the study was approved by the local ethics committee and institutional review board. The study was consistent with the Declaration of Helsinki. Blood pressure measurement Blood pressure was measured in an office after 5 min of rest using a mercury sphygmomanometer and recorded to the nearest 2 mmHg. Diastolic blood pressure was determined according to the fifth Korotkoff phase. Three blood pressure measurements were performed in each participant: two at the screening and one before the instrumental
examination (electrocardiography (ECG), TTE). An examinee was classified as hypertensive if mean values of two blood pressure measurements at the screening and/or the third measurement before instrumental examination exceeded 140/90 mmHg. Patients on antihypertensive medication were also considered hypertensives. Blood sampling Blood samples were drawn from the antecubital vein by careful vein puncture, using a 21-gauge sterile syringe without stasis at 08:00–10:00 h after a fasting period of 12 h. Fasting glucose, creatinine and lipid profiles were determined by standard methods. Transthoracic echocardiography examination The measurements used in the present study were obtained from two-dimensionally guided M-mode echocardiograms according to the recommendations of the American Society of Echocardiography and the European Association of Echocardiography guidelines (9). All of the TTE examinations were performed using GE Vivid S6 Vingmed System 5 (Norway, Horten) equipped with 2.5–4-MHz transducers. The LV mass (LVM) was calculated using the regression equation described by Devereux (10). LV mass index (LVMI) was calculated as LVM divided by body surface area. LVH was defined as LVMI ⱖ 115 g/m2 (men), LVMI ⱖ 95 g/m2 (females) according to American Society of Echocardiography guidelines (9). Relative wall thickness (RWT) was calculated by dividing the two-fold dimension of end diastolic posterior wall (PW) thickness to LV end diastolic diameter (LVEDD) [RWT ⫽ (2 ⫻ PW)/LVEDD] (11). When RWT exceeded 0.42, the LV geometric pattern was considered concentric. The patients were thus classified as having one of four geometric patterns: normal geometric pattern (normal LVMI, normal RWT), concentric remodeling (normal LVMI, increased RWT), eccentric LVH (increased LVMI, normal RWT) and concentric LVH (increased LVMI, increased RWT) (4). Exercise test protocol Before beginning the exercise test, all patients reclined in a supine position for 10 min and their resting ECG was digitally recorded. The upright exercise test was performed on a treadmill. The Mason–Likar modification of the standard 12-lead system was used. We used a modified Bruce protocol to increase the workload every 3 min. Continuous ECGs were digitally recorded at 500 Hz using the CardioSoft version 4.14 exercise system (GE Healthcare) and they were completely analyzed automatically using the GE Healthcare-released version of the modified
LV geometry and microvolt T-wave alternans in sustained hypertension moving average (MMA) method (12). During the exercise test, heart rate was recorded continuously via ECG, and systolic and diastolic arterial pressure was measured with a brachial cuff every 2 min. Measurement of MTWA The algorithm used in the identification and quantification of MTWA is based on time-domain MMA analysis. An update is calculated for every incoming beat, which results in continuous moving averages of odd and even beats. In addition, algorithms have been incorporated to reduce the influence of noise and artifacts, such as those caused by running and respiration. The MTWA values were calculated continuously during the entire exercise test, from rest to recovery, using all standard leads (I, II, III, aVR, aVF, aVL and V1–V6). Maximum MTWA values at heart rates ⬍ 125 beats/min were recorded, and MTWA values at higher heart rates were excluded. The analyses were performed using 1/8 incremental update factors. Patient characteristics were compared, and MTWA results ⬍ 65 μV were accepted as negative and MTWA results ⱖ 65 μV were positive (13). Statistics Statistical analyses were performed using the SPSS software version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov–Smirnov/Shapiro– Wilk test) to determine whether a distribution was
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normal. Descriptive analyses were presented using means and standard deviations. The categorical variables were expressed as numbers and percentages. Numerical variables, which did not exhibit normal distribution, were compared using the Kruskal– Wallis test. The Mann–Whitney U test was performed to test the significance of pairwise differences by using Bonferroni correction to adjust for multiple comparisons. Numerical variables exhibiting normal distribution were compared using the one-way analysis of variance (ANOVA) test. Tukey’s test was performed to test the significance of pairwise differences by using Bonferroni correction to adjust for multiple comparisons. Categorical data were compared with the chi-square test. Spearman’s correlation coefficients were used to assess the relationship between continuous variables. A multivariate linear regression analysis was used to assess the relationship between several confounders and MTWA value. A p-value ⬍ 0.05 was considered statistically significant.
Results Baseline demographic, clinical and laboratory characteristics of patients based on their LV geometrical patterns were presented in Table I. There was no difference among the groups in terms of age, male gender, body mass index (BMI), smoking habit, diabetes mellitus (DM), medications, office SBP and DBP, and laboratory parameters (all p-values ⬎ 0.05). However, MTWA positivity was found to be significantly different among the groups (p ⬍ 0.001). In subgroup analysis, MTWA positivity was found to be significantly higher when the CHG was compared
Table I. Baseline demographic, clinical and laboratory characteristics of patients based on their left ventricular geometrical patterns.
Age (year) Sex, male (%) Body mass index (kg/m2) Creatinine (mg/dl) Smokers (%) Diabetes mellitus (%) Hematocrit (%) Glucose (mg/dl) Total cholesterol (mg/dl) HDL (mg/dl) LDL (mg/dl) TG (mg/dl) ARB⫹ ACE (%) CCB (%) Diuretics (%) Other antihypertensive drugs (%) Office Systolic BP (mmHg) Office Diastolic BP (mmHg) MTWA (positivity %)
Normal geometry group (n ⫽ 90)
Concentric remodeling group (n ⫽ 99)
Concentric hypertrophy group (n ⫽ 63)
Eccentric hypertrophy group (n ⫽ 58)
p-value
49.6 ⫾ 7.8 66.7 28.7 ⫾ 4.6 0.81 ⫾ 0.18 34.1 18.9 42.8 ⫾ 4.4 100.7 ⫾ 28.8 200.6 ⫾ 41.2 45 ⫾ 12.2 128.8 ⫾ 36.1 148.4 ⫾ 119 35.6 20 20.1 6.7 147.6 ⫾ 9.4 91 ⫾ 9.1 12.6
50.9 ⫾ 6.6 56.6 29.4 ⫾ 3.4 0.83 ⫾ 0.21 23.5 24.2 42.1 ⫾ 4.8 101.4 ⫾ 35.3 215.3 ⫾ 45.4 47 ⫾ 12.5 138.9 ⫾ 37.8 158.4 ⫾ 81.8 41.4 25.3 33.4 10.1 147.3 ⫾ 8.3 92 ⫾ 9.8 16.2
51.6 ⫾ 7.3 50.7 29.4 ⫾ 3.1 0.77 ⫾ 0.15 23.8 26.4 41.9 ⫾ 4.1 111.6 ⫾ 38.3 194 ⫾ 38.1 45.1 ⫾ 15.7 127.7 ⫾ 45.5 159.9 ⫾ 97.5 47.6 39.7 38.4 12.7 151.1 ⫾ 12.5 92 ⫾ 16 39.7
51.6 ⫾ 9.0 51.7 28.8 ⫾ 4.2 0.80 ⫾ 0.23 25.4 25 41.9 ⫾ 4.3 104.2 ⫾ 24.2 196.2 ⫾ 58.2 44.2 ⫾ 16.5 125.4 ⫾ 35.9 149.7 ⫾ 74.8 44.1 28.8 32.2 13.6 149.3 ⫾ 8.9 90 ⫾ 10.3 37.3
0.445 0.148 0.543 0.303 0.376 0.706 0.484 0.148 0.550 0.692 0.148 0.858 0.486 0.056 0.054 0.234 0.075 0.594 ⬍ 0.001
ACE, angiotensin converting enzyme blockers; ARB, angiotensin receptor blockers; BP, blood pressure; CCB, calcium channel blockers; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MTWA, microvolt T-wave alternance; TG, triglyceride.
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with the NGG (p ⬍ 0.001), the EHG was compared with the NGG (p ⬍ 0.001), the EHG was compared with the CRG (p ⫽ 0.003) and the CHG compared with the CRG (p ⫽ 0.001). On the other hand, MTWA positivity did not reach statistical significance between the NGG and CRG (p ⫽ 0.440), and the CHG and EHG (p ⫽ 0.786). The comparisons of the echocardiographic parameters of patients according to their LV geometrical patterns were reported in Table II. The LV ejection fraction (LVEF) was similar among the groups. LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum diameter (IVSd), PWd, RWT and LVMI values were statistically significant among the groups (all p-values ⬍ 0.05). When the comparison of echocardiographic parameters between different LV geometrical patterns was investigated with subgroup analysis, all groups were found to be significantly different between each other in terms of LVEDD (p ⬍ 0.001). LVESD was also significantly different among the groups (p ⬍ 0.001), except between the NGG and CHG (p ⫽ 0.374). Moreover, all group comparisons demonstrated significant differences between each other (for all p ⬍ 0.001) in terms of IVSd, except between the CRG and NGG (p ⫽ 0.063) and the EHG and CRG (p ⫽ 0.042). For PWd, all groups showed significant differences between each other, except between the CRG and EHG (p ⫽ 0.015). Also, LVMI was found to be significantly different among all groups (for all p-values ⬍ 0.001), except between the NGG and CRG (p ⫽ 0.379) and the CHG and EHG (p ⫽ 0.947). In addition, all groups demonstrated significant differences between each other in terms of RWT (for all, p ⬍ 0.001), except between the EHG and NGG (p ⫽ 0.222). When the relation of MTWA with clinical and echocardiographic parameters of patients was investigated, LVMI, LVEDD, LVESD IVSd, PWd and office SBP were found to be significantly positively correlated with MTWA. However, there was no correlation between age, office DBP, RWT and MTWA in patients with sustained hypertension (Table III).
Table III. The correlation between microvolt T-wave alternans and echocardiographic and clinical parameters of patients. Spearman’s correlation analysis
LVMI IVSd PWd LVEDD LVESD Age Office SBP Office DBP RWT
r
p
0.349 0.236 0.211 0.148 0.180 0.660 0.202 0.109 0.048
⬍ 0.001 ⬍ 0.001 ⬍ 0.001 0.009 0.001 0.244 ⬍ 0.001 0.056 0.396
DBP, diastolic blood pressure; IVSd, interventricular septum diameter; LVEDD, left ventricular end diastolic diameter; LVESD, left ventricular end systolic diameter; LVMI, left ventricular mass index; PWd, posterior wall diameter; RWT, relative wall thickness; SBP, systolic blood pressure.
Multivariate linear regression analysis showed a significant relation between LVMI and MTWA (R2 ⫽ 0.157, β ⫽ 0.348, p ⬍ 0.001). However, no association was found between RWT, gender, age, office systolic blood pressure, office diastolic blood pressure and MTWA. When this analysis was done among different LV geometrical pattern subgroups, only LVMI was found to be related with MTWA for the NGG (R2 ⫽ 0.348, β ⫽ 0.582, p ⬍ 0.001) and CHG (R2 ⫽ 0.218, β ⫽ 0.446, p ⫽ 0.001). Furthermore, LVMI and office systolic and diastolic BP were found to be associated with MTWA in the EHG (R2 ⫽ 0.357, β ⫽ 0.337, p ⫽ 0.009; β ⫽ 0.408, p ⫽ 0.003, β ⫽ ⫺ 0.303, p ⫽ 0.018, respectively). However, none of the parameters was found to be related with MTWA in the CRG (p ⬎ 0.05).
Discussion The present study demonstrated that there was a significant positive relation between LVMI and MTWA in all LV geometrical patterns in sustained hypertensives. This finding supports the important effect of LVH, defined as LVMI, on MTWA in patients with sustained hypertension. Moreover, both
Table II. The comparisons of the echocardiographic parameters of patients according to their left ventricular geometrical pattern.
Ejection fraction (%) Left ventricle mass index (g/m2) LVEDD (mm) LVESD (mm) IVSd (mm) PWd (mm) RWT
Normal geometry group (n ⫽ 90)
Concentric remodeling group (n ⫽ 99)
Concentric hypertrophy group (n ⫽ 63)
Eccentric hypertrophy group (n ⫽ 58)
p-value
65.8 ⫾ 5.7 92.7 ⫾ 8.5 50.3 ⫾ 3.4 31.1 ⫾ 3.6 10.6 ⫾ 1.3 9.2 ⫾ 0.8 0.37 ⫾ 0.04
64.5 ⫾ 3.9 89.1 ⫾ 11.9 45.4 ⫾ 3.0 28.1 ⫾ 3.4 11.3 ⫾ 1.2 10.6 ⫾ 0.7 0.47 ⫾ 0.04
63.8 ⫾ 3.6 123.1 ⫾ 19.9 48 ⫾ 4.2 30.1 ⫾ 4.3 13.5 ⫾ 2.0 12.1 ⫾ 1.35 0.51 ⫾ 0.07
64 ⫾ 3.6 121.5 ⫾ 21.2 53.3 ⫾ 3.3 33.4 ⫾ 3.7 11.7 ⫾ 2.2 10.1 ⫾ 0.91 0.38 ⫾ 0.03
0.068 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001 ⬍ 0.001
IVSd, interventricular septum diameter; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; PWd, posterior wall diameter; RWT, relative wall thickness.
LV geometry and microvolt T-wave alternans in sustained hypertension the eccentric and concentric LVH were found to be associated with raised MTWA levels in subgroup analyses. In chronic arterial hypertension, pressure and volume changes as well as structural alterations in myocardium often lead to an increase in LVM (4). An increase in LVM is defined as LVH. Independent of other risk factors, patients with increased LVM have remarkable risk of future cardiovascular morbidity and mortality (14). In different studies, it was reported that concentric hypertrophy was associated with the elevated risk of future cardiovascular events (2) with the evidence of increased progression to LV dilatation and ultimately heart failure in hypertensives (15,16). Increased LVM in concentric hypertrophy results in impaired coronary hemodynamics exerted by decreased coronary blood flow and flow reserve associated with increased coronary vascular resistance (17). Impaired coronary hemodynamics involve coronary arteriolar compression by the hypertrophied and stiffer LV produced by ventricular fibrosis, the increased arteriolar wall thickening and arteriolar wall-to-lumen diameter (18), insufficient sizing of coronary vessels (19), increased blood viscosity in hypertension (20) and the increased LV chamber diameters designating not only myocytic hypertrophy but also collagen deposition (21). For the reasons mentioned above, patients with arterial hypertension and LVH can experience numerous areas of supply–demand mismatch and this could lead to myocardial ischemia (22). MTWA is a well-established risk factor related to long-term susceptibility to ventricular tachyarrhythmia and sudden cardiac death (23). Positive MTWA has also been reported in acute coronary syndrome with chest pain and ST-T changes and ischemic and non-ischemic cardiomyopathy in human and animal models (24,25). Various studies in animals during coronary artery occlusion and in humans during angioplasty have demonstrated that myocardial ischemia can increase MTWA magnitude (26). In these experimental studies, in which heart rate was kept constant, it was found that myocardial ischemia provokes increases in MTWA magnitude in parallel with increased susceptibility to ischemia-induced ventricular fibrillation (27). This increase in MTWA was accompanied by parallel changes in T-wave complexity and heterogeneity (28). Myocardial ischemia may be responsible for positive MTWA in hypertensive patients with concentric hypertrophy. Myocardial structural changes also occur during genesis of LVH. Two important biological alterations, fibrosis and changes in membrane protein composition, have been observed in LVH (29). Ventricular fibrosis is a substantially well documented entity in LVH. In patients with arterial hypertension and LVH, an increase in collagen volume fraction has been revealed (30). There are also small clinical study
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in the literature concerning occurrence of ventricular arrhythmias in LVH settings (31). However, no attempt has been made to study the role of cardiac hypertrophy and fibrosis in the onset of arrhythmias. Re-entry may be one of the possible mechanisms for arrhythmias. Re-entry involves a conduction block in the normal conductive pathway together with slowed conduction; thus, the conduction time in the re-entry circuit exceeds the refractory period of the conducting tissue. Fibrosis can generate alternative pathway and conduction block, or can lead to slow conduction. In LVH, arrhythmias that originated from triggered activity or abnormal automaticity was also observed (32). In addition, LVH generates the lengthening of the action potential that causes the ventricular repolarization abnormalities on the ECG (33). Increased MTWA positivity, which predicts future ventricular arrhythmias, can be explained by increased fibrosis in patients with concentric hypertrophy. In our study, eccentric hypertrophy revealed an increase in MTWA positivity like concentric hypertrophy. In eccentric hypertrophy, in which an increase in LVM can occur, wall thickness remains normal, while the LV cavity dilates through myocyte elongation. Eccentric hypertrophy is usually observed in states of volume overload, such as mitral regurgitation, and aortic regurgitation. Moreover, it may represent the early manifestation of a cardiomyopathic process without an intervening phase of concentric hypertrophy in hypertensive settings. This alternative pathway for the development of heart failure in hypertension was supported by some previous studies. They have demonstrated the eccentric hypertrophy to be associated with more severe systolic dysfunction as compared with concentric hypertrophy (34,35). Moreover, it was reported that longitudinal systolic function was significantly impaired in both concentric and eccentric hypertrophy as compared with normal LV geometry. Also, in the same study, it was designated that patients with eccentric hypertrophy had worse longitudinal systolic function and lower EF compared with concentric hypertrophy (36). Because eccentric hypertrophy may be the precursor of heart failure, this may lead to an elevated MTWA in this patient population (36). Also, there are small studies reporting that eccentric hypertrophy is associated with higher risk of ventricular arrhythmia as compared with concentric hypertrophy (37). Study limitations This is a single-center study with a relatively small sample size, both of which limit the power of our research findings. In addition, our study provides no information regarding long-term outcomes. We also excluded patients with clinically overt cardiovascular disease (such as coronary artery disease, cerebrovascular disease and renal failure), and therefore our
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results cannot be extrapolated to all hypertensive subjects. Conclusion We demonstrated that increased LVMI is associated with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically significant LV geometric patterns including both concentric and eccentric hypertrophy, which play a pivotal role in the pathophysiology of myocardial ischemia, heart failure and fatal arrhythmias, are related with a raised MTWA positivity, which may lead to particular predilection to life-threatening ventricular arrhythmias and sudden cardiac death in sustained hypertension.
10.
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Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This study was not financially supported. The authors have no relevant conflicts of interest to disclose.
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