Author + information
- Received September 4, 2013
- Revision received October 7, 2013
- Accepted October 17, 2013
- Published online May 13, 2014.
- Stephan H. Schirmer, MD, PhD∗ (, )
- Marwa M.Y.A. Sayed, MD,
- Jan-Christian Reil, MD,
- Christian Ukena, MD,
- Dominik Linz, MD, PhD,
- Michael Kindermann, MD,
- Ulrich Laufs, MD,
- Felix Mahfoud, MD and
- Michael Böhm, MD
- Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
- ↵∗Reprint requests and correspondence:
Dr. Stephan H. Schirmer, Klinik für Innere Medizin III (Kardiologie, Angiologie und Internistische Intensivmedizin) Universitätsklinikum des Saarlandes, Kirrberger Strasse, Gebäude 40, 66421 Homburg/Saar, Germany.
Objectives This study sought to investigate the interaction between blood pressure (BP) and heart rate (HR) reduction and changes in left ventricular (LV) structure and function following renal sympathetic denervation (RDN).
Background Hypertension results in structural and functional cardiac changes. RDN reduces BP, HR, and LV mass and improves diastolic dysfunction.
Methods We evaluated LV size, mass, and function before and 6 months after RDN in 66 patients with resistant hypertension and analyzed results in relation to systolic BP (SBP) and HR.
Results SBP decreased by 11 ± 3 mm Hg in the first, 18 ± 5 mm Hg in the second, and 36 ± 7 mm Hg in the third tertile of SBP at baseline (p < 0.001). HR decreased by 13 ± 4 beats/min, 8 ± 3 beats/min, and 11 ± 6 beats/min in tertiles of SBP (p for interaction between tertiles = 0.314). In all SBP tertiles, LV mass index (LVMI) decreased similarly (LVMI −6.3 ± 2.2 g/m2.7, −8.3 ± 2.1 g/m2.7, and −9.6 ± 1.9 g/m2.7; p for interaction = 0.639). LVMI decreased unrelated to HR at baseline (p for interaction = 0.471). The diastolic parameters E-wave deceleration time, isovolumetric relaxation time, and E′-wave velocity improved similarly in all tertiles of SBP and HR. Changes in LV mass and function were also unrelated to reduction in SBP or HR. Vascular compliance improved dependently on BP but independently of HR reduction.
Conclusions In patients with resistant hypertension, LV hypertrophy and diastolic function improved 6 months after RDN, without significant relation to SBP and HR. These findings suggest a direct effect of altered sympathetic activity in addition to unloading on cardiac hypertrophy and function.
Pressure overload in arterial hypertension leads to maladaptive myocardial remodeling associated with cardiac hypertrophy and later development of heart failure with preserved or reduced ejection fraction (1). Antihypertensive drugs reduce cardiac remodeling (2) and progression to heart failure (3). Resistant arterial hypertension is defined as insufficient office blood pressure (BP) control despite the use of ≥3 antihypertensive drugs at maximal tolerated doses, one being a diuretic (4). Renal artery sympathetic denervation (RDN) is a novel technique that has been shown to reduce BP and heart rate (HR) in patients with resistant hypertension (5–7). HR is associated with outcomes in hypertension (8) and heart failure (9), and HR reduction improves left ventricular (LV) remodeling (10) and outcomes (11) in heart failure. RDN has also been shown to reduce LV hypertrophy (LVH) and to improve diastolic and systolic LV function, also achieving a decrease of LV mass in some office BP nonresponders (<10 mm Hg decrease 6 months after RDN) (12). These findings attracted our attention to a possible BP-independent effect of RDN. In the present study, we thus investigated cardiac structure and function before and 6 months after RDN using transthoracic echocardiography and analyzed results in relation to BP and HR reduction.
This study was approved by the institutional medical ethics committee (No. 67/11) in accordance with the declaration of Helsinki. Sixty-six consecutive patients scheduled for RDN for treatment of resistant arterial hypertension (defined as office systolic BP [SBP] ≥140 mm Hg) were prospectively included using a prespecified analysis protocol (Symplicity extension NCT00664638, NCT00888433, and NCT01888315) if they were in sinus rhythm and did not suffer from systolic heart failure (ejection fraction <50%) or severe renal dysfunction (estimated glomerular filtration rate <45 ml/min/1.73 m2 as measured by cystatin C). Patients suffering from secondary causes of hypertension were excluded.
BP and HR
Following 10 min of supine rest, BP was measured in triplicate with an automatic oscillometric monitor and HR was obtained from a 12-lead electrocardiogram. Ambulatory BP monitoring (ABPM) was performed to exclude pseudoresistant hypertension (mean 24-h SBP <130 mm Hg) (13).
Transthoracic echocardiography was performed by the same operator (M.M.Y.A.S.), who was blinded to BP data and patient status, on a Vivid E9 (General Electric, Frankfurt, Germany) before and 6 months after RDN. The investigation included regular 2-dimensional echocardiography, Doppler, and tissue Doppler imaging according to the guidelines of the American Society of Echocardiography (14). All studies were read offline by an investigator blinded to patient status (S.H.S.). LV size was measured as left ventricular end-diastolic diameter (LVEDD) using M-mode. LV mass was calculated from the end-diastolic diameters of the interventricular septum (IVSd), left ventricular posterior wall (LVPWd), and LV cavity using the Devereux formula (15). Body surface area was calculated according to the Mosteller formula (16), and LV mass was indexed to height to the 2.7th power. Relative wall thickness was calculated as the sum of IVSd and LVPWd divided by LVEDD. LV diastolic function was assessed according to standardized criteria (17), using pulsed-wave (PW) Doppler of the mitral inflow and measuring deceleration time (DT) of the E-wave, E- to A-wave ratio (E/A), and isovolumetric relaxation time (IVRT) (time between closure of the aortic and opening of the mitral valve). Tissue Doppler was used for measurements of E′ septal and E′ lateral wave (peak early diastolic septal and lateral mitral annular velocities) and calculation of the ratio of the maximum E-wave velocity and the mean E′-wave. Other hemodynamic parameters were calculated as follows: stroke volume = π × VTILVOT × (diameterLVOT/2)2, for which VTI is velocity time integral and LVOT is LV outflow tract. Peripheral arterial compliance = stroke volume/(SBP − DBP), for which DBP is diastolic blood pressure. HR-corrected LV circumferential fiber shortening (VCFc) = FS/ET × (60/HR)1/2, for which FS is fractional shortening and ET is ejection time. End-systolic meridional wall stress (EsMWS) was calculated according to Grossman et al. (18) and Reicheck et al. (19) as follows: (0.334 × SBP × LVESD)/(LVPWs × [1 + LVPWs/LVESD]), for which LVESD is LV end-systolic diameter and LVPWs is LV posterior wall during systole.
Following renal artery angiography, RDN was performed using the Flex catheter system (Medtronic, Santa Rosa, California), as previously reported (7). In both renal arteries, radiofrequency ablations at a maximum power of 8 W lasting 2 min each were performed.
Data are presented as mean ± SEM. Data were analyzed for normal distribution using the Kolmogorov-Smirnov test. Normally distributed parameters were compared between baseline and 6-month follow-up using a paired Student t test or a Wilcoxon matched-pairs test if not normally distributed. Linear regression analyses were used to calculate the correlation between the change in BP and the change in echocardiographic parameters. Analysis of variance was performed with post-hoc testing for trend when the change in the 3 groups was compared. The Fisher exact test was used for testing associations in 2 × 2 contingency tables. Differences were considered significant if p was <0.05. SPSS version 18.0 (SPSS Inc., Chicago, Illinois) was used for statistical calculations.
Patients in the treatment group had a mean age of 63.5 ± 1.2 years. Thirty-six of the 66 study patients (54.5%) were male. Average body mass index was 29.4 ± 0.6 kg/m2. Patients were receiving 4.3 ± 0.1 antihypertensive drugs (Online Table 1). The RDN procedure was performed without complications in all patients.
RDN decreased BP, HR, and LV mass and improved diastolic LV function
Six months after RDN, SBP/DBP decreased from 172.9 ± 3.0/92.5 ± 2.3 mm Hg to 151.3 ± 3.2/85.5 ± 1.6 mm Hg (p < 0.001 for both), corresponding to a decrease of 21.6 ± 3.0/10.1 ± 2.0 mm Hg. Pulse pressure decreased from 81.8 ± 2.9 mm Hg to 69.0 ± 2.7 mm Hg (p < 0.001). Reduction of BP was confirmed by 24-h ABPM when completely available at both time points (n = 50). HR decreased from 67.7 ± 1.3 beats/min before to 60.5 ± 1.2 beats/min at 6 months (p < 0.001). LV mass index (LVMI) was reduced from 61.5 ± 2.0 g/m2.7 before to 53.4 ± 1.5 g/m2.7 at 6 months (p < 0.001). E/A in mitral PW Doppler as a measure of diastolic function increased from 0.84 ± 0.04 to 1.01 ± 0.06 (p = 0.001) (Fig. 1). DT of PW Doppler detected that E wave of the mitral inflow decreased from 252.0 ± 8.5 at baseline to 227.6 ± 5.7 ms at 6 months (p = 0.010). In tissue Doppler, an improvement of diastolic mitral annular movement was noted by an increase in E′ velocity (mean septal and lateral E′) from 6.73 ± 0.25 cm/s before RDN to 7.47 ± 0.26 cm/s at follow-up (p = 0.003). Maximum E-wave velocity increased from 66.9 ± 2.6 cm/s to 72.9 ± 2.1 cm/s (p = 0.013). Because of the increase of both E and E′, the ratio E/E′mean as an indicator of filling pressure was unchanged (10.6 ± 0.5 before, 10.4 ± 0.4 at follow-up).
SBP at baseline or SBP reduction did not influence LV mass regression or improvement of diastolic function
Tertiles were defined according to SBP at baseline (n = 22 patients each). In patients with a baseline pressure of 148.6 ± 1.6 mm Hg, SBP was reduced to 136.3 ± 2.9 mm Hg in those with a pressure of 169.5 ± 1.7 mm Hg to 153.2 ± 3.6 mm Hg and in those with a pressure of 200.5 ± 3.6 mm Hg to 164.4 ± 7.5 mm Hg (all p < 0.001; use-dependent effect, p for trend of SBP decrease = 0.002) (Fig. 2A). Patients were also divided into tertiles according to SBP reduction (n = 22 patients each). In the first tertile, SBP remained unchanged from baseline (166.5 ± 5 mm Hg) to 6 months' follow-up (170.8 ± 6.3 mm Hg; p = 0.081), constituting BP nonresponders (≤10 mm Hg reduction). In the second tertile, SBP was reduced by 18.6 ± 1.1 mm Hg from 161.7 ± 3.1 to 143.2 ± 3.2 mm Hg (p < 0.001). In the last tertile, SBP was reduced by 50.4 ± 3.9 mm Hg from 190.4 ± 5.1 to 140.0 ± 4.4 mm Hg (p < 0.001).
LVMI decreased by the same extent in all tertiles of baseline SBP (from 57.6 ± 3.2 g/m2.7 to 50.8 ± 2.3 g/m2.7 [p = 0.004] in the first, from 64.8 ± 3.3 g/m2.7 to 56.6 ± 2.4 g/m2.7 [p = 0.001] in the second, and from 62.2 g/m2.7 ± 3.7 to 52.6 ± 3.2 g/m2.7 [p < 0.001] in the third tertile [p for trend of LVMI decrease = 0.529]) (Fig. 2B). LVMI also regressed comparably in all tertiles of SBP reduction: from 64.0 ± 4.1 g/m2.7 to 53.2 ± 2.7 g/m2.7 (p < 0.001) in the first, from 59.6 ± 2.9 g/m2.7 to 51.6 ± 2.3 g/m2.7 (p < 0.001) in the second, and from 61.7 ± 3.3 g/m2.7 to 55.3 ± 3.0 g/m2.7 (p = 0.002) in the third tertile. Comparable LVMI regression was observed in all tertiles of 24-h BP at baseline and 24-h BP reduction (measured by ABPM) (Online Fig. 1). End-diastolic diameter of the interventricular septum and the LV posterior wall decreased accordingly in all tertiles. Linear regression analysis of the relative change in BP and the relative change in LVMI proved that there was no significant interaction of the change in SBP and LVMI regression (r2 = 0.024; p = 0.280). The number of patients with LVH (>44 g/m2.7 for women, >48 g/m2.7 for men) decreased from 55 patients at baseline to 39 patients at follow-up (p = 0.004). Similar to wall thickness, LVEDD decreased in all tertiles. LVESD and FS did not change significantly (data not shown).
Next, the relation of diastolic function with SBP was investigated. In the baseline SBP tertiles, E/A increased by 0.19 ± 0.09 (p = 0.018), 0.09 ± 0.05 (p = 0.064), and 0.09 ± 0.07 (p = 0.220), respectively (p for trend of E/A increase = 0.260) (Fig. 2C). DT and IVRT were reduced in all tertiles of baseline SBP. E/A, DT, and IVRT also improved in all tertiles of SBP reduction, and linear regression analyses confirmed lack of relation of improvement of mitral inflow parameters with SBP reduction (r2 = 0.001; p = 0.770) for DT, (r2 = 0.000; p = 0.907) for E/A, and (r2 = 0.014; p = 0.351) for IVRT. Also, E′ velocity increased comparably in all tertiles of SBP reduction.
HR at baseline or HR reduction does not predict LV mass regression or improvement of diastolic function
Although HR reduction correlated with baseline HR (Fig. 3A), it was similar in all tertiles of baseline SBP (data not shown). In the tertiles of SBP reduction, HR also decreased similarly from 69.1 ± 2.4 beats/min to 61.2 ± 2.3 beats/min (p < 0.001), from 64.6 ± 2.2 beats/min to 58.1 ± 2.3 beats/min (p = 0.009), and from 69.7 ± 2.3 beats/min to 62.3 ± 1.7 beats/min (p = 0.001) (i.e., by 9.1 ± 3.2, 10.8 ± 3.7, and 10.9 ± 3.1 beats/min, respectively). Linear regression analysis corroborated lack of association of HR reduction with BP reduction (r2 = 0.017; p = 0.314). We next analyzed the relation of HR reduction and change in LV mass. Decrease in LVMI was present to a similar extent in all tertiles of baseline HR and HR reduction (Fig. 3B). Increase of E/A (Fig. 3C) and decrease of IVRT also occurred to a similar extent in all tertiles of baseline HR and HR reduction.
SBP or HR reduction occurs independently of LVMI reduction or change in diastolic LV function
LVMI regression was present in all tertiles of LVMI at baseline but showed a use-dependent effect with stronger regression the higher the baseline LVMI was (p for trend < 0.001; data not shown). When the whole patient group was divided into tertiles according to LVMI regression, SBP decrease was similar across all tertiles of LVMI regression (decrease of 30.0 ± 5.4, 18.6 ± 6.0, and 18.8 ± 5.3 mm Hg, respectively; all p < 0.01) (Fig. 4A). We also observed HR reduction to be similar in all tertiles of LVMI reduction (Fig. 4B). Lack of correlation of HR and LVMI reduction was underlined in linear regression analysis (r = 0.008; p = 0.478). SBP and HR reduction occurred similarly in all tertiles of E/A increase (Figs. 4C and 4D). A calculation of 4 groups according to the presence of a decrease in BP and HR showed that LV mass regression was present in all groups independent of either BP or HR reduction (Fig. 5).
Functional cardiovascular parameters improve depending on BP reduction
Vascular compliance increased from 1.05 ± 0.05 before RDN to 1.39 ± 0.06 ml/mm Hg at 6 months (p < 0.001). Improvement in compliance was not evident in the first tertile of BP reduction (1.18 ± 0.10 ml/mm Hg before, 1.15 ± 0.09 ml/mm Hg 6 months after RDN; p = 0.890), more pronounced in the second tertile (increase from 1.17 ± 0.08 ml/mm Hg to 1.55 ± 0.09 ml/mm Hg; p = 0.005), and most pronounced in the tertile with strongest BP decrease (compliance increase from 0.93 ± 0.06 ml/mm Hg to 1.40 ± 0.09 ml/mm Hg; p < 0.001). In linear regression analysis, increase in compliance was dependent on BP decrease (r2 = 0.288; p < 0.001). VCFc was not affected by RDN (data not shown). EsMWS decreased from 66.9 ± 2.9 to 59.4 ± 2.2 × 103 dynes/cm2 (p = 0.042). Again, because of the dependency of the calculation of the parameter on BP, its decrease was present only in the tertile with greatest BP reduction (regression coefficient r2 = 0.130; p = 0.013). Interestingly, compliance and EsMWS were not associated with HR reduction. For calculation of contractile function independently of afterload, VCFc was correlated with EsMWS (20,21). The y-axis intercept, representing intrinsic contractility at a hypothesized afterload of zero, increased mildly but significantly following RDN (from 0.746 ± 0.062 before to 0.820 ± 0067 after RDN; p < 0.001) (Online Fig. 2).
In this prospective echocardiographic study, we observed a decrease in BP, a decline in HR, a regression of LV mass, an improvement of LV diastolic function, and an increase in vascular compliance following RDN. Interestingly, structural and functional cardiac changes were not exclusively related to BP or HR changes, suggesting a direct role of reducing the sympathetic nervous system activity on changes of the cardiac phenotype.
Patients in the present investigation had slightly lower baseline BP (173/95 mm Hg) than that in previous studies (5,12). Furthermore, we also included patients with less severe resistant hypertension with an office SBP ≥140 mm Hg (compared with ≥160 mm Hg in the Symplicity trials). Baseline BP has been identified as the strongest predictor of BP response after RDN (22), which might, in part, account for the relatively high rate of nonresponders (33%) found (<10 mm Hg SBP reduction 6 months after treatment). HR reduction as another measure of sympathetic activation unrelated to BP reduction, however, did occur with comparable efficacy in all patients undergoing RDN, suggesting that the definition of “nonresponse” may need to be extended beyond the BP definition. RDN also appeared to lead to LVH regression and improvement of diastolic function in patients with moderate resistant hypertension at baseline (baseline SBP ≥140 and <160 mm Hg).
Although pharmacological BP reduction can be achieved effectively with various types of antihypertensive drugs, their effects on LVH seem to differ, fueling discussions on antihypertrophic effects independent of BP reduction (23). Although some studies have reported comparable antihypertrophic effects of different antihypertensive regimens (24), others have shown that nonhypotensive doses of antihypertensive drugs already influence sympathetic (beta-adrenergic) myocardial signaling (25). The LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) study showed greater LVH regression with angiotensin receptor blockade than beta-blockade despite similar SBP reduction (26). Recently, inhibition of the renin-angiotensin-aldosterone system and the sympathetic nervous systems showed greater LVH regression than that produced by comparable BP reduction with other drugs (27). LVMI is known to predict cardiac events (28), and reversal of LVH is associated with improved survival independent of other risk factors (29). The present study showed for the first time that an interventional strategy designed for BP reduction in treatment-resistant hypertension can reverse cardiac remodeling and ameliorate cardiac function in a way unrelated to BP or HR reduction. Antihypertensive drug therapy was not to be changed during the study period. However, medication dosage was reduced during follow-up in 15 patients (23%), and antihypertensive dosage was increased in 8 patients (12%). In a sensitivity analysis, when these 23 patients were excluded, BP and HR changes were similar in the complete patient group. Particularly, BP- and HR-independent changes in LV hypertrophy remained unaffected after exclusion of these patients, making antihypertensive drug therapy unlikely to be the cause for the observed regression in LV mass.
In the present study, LVMI reduction was documented in the same order of magnitude as previously reported within 6 months after RDN (12). However, patients in the current analysis had more severe LVH, as demonstrated by a higher LVMI at baseline (61.5 vs. 53.9 g/m2.7) than in the study by Brandt et al. (12) and reached the same LV mass only at follow-up (53.4 g/m2.7). Although a mild reduction in LV mass could be observed without BP response, LV mass regression was most pronounced in patients with the strongest BP decrease. In the present investigation, LV mass regression was as strong among BP nonresponders (first tertile) as compared with the other tertiles. Thus, when BP was investigated according to tertiles of LV mass regression, BP decreased to the same extent in all tertiles. A lack of correlation between BP and LV mass provided statistical evidence that modulation of the sympathetic nervous system by RDN can reduce LV mass independently of BP. Although no correlation was observed between baseline SBP and LVMI, one cannot exclude that the missing correlation between the 2 deltas are influenced by their baseline interplay and regression to the mean, making mechanistic conclusions difficult. Nonetheless, in other investigations, a BP-independent effect of sympathectomy on LVH has been described in an animal model of abdominal aortic banding, when BP was unaffected by sympathectomy but LVH decreased significantly (30). Pilot clinical data point toward a reduction of total body (measured by muscle sympathetic nerve activity ) and renal sympathetic activity (measured by norepinephrine spillover ), which might have direct effects on myocardial structure. Additionally, experimental (33) and clinical data (34) using carvedilol, a combined alpha and beta receptor blocker, point toward an alpha receptor–mediated effect of antisympathetic treatment on LVH, which might also underlie the observed effects of RDN.
Reduction of HR as an indicator of cardiac autonomic activity was independent of BP reduction, confirming earlier observations (6). This is particularly relevant because HR has been identified to be an independent predictor of mortality in patients with arterial hypertension and heart failure (8,35). Importantly, the present data showed that LV mass regression and HR reduction can occur independently of each other. We therefore conclude that both HR reduction and LV mass regression, both of which reduce the number of cardiovascular events (10,29), can also occur independently of BP changes.
One could expect functional cardiac parameters in our study to change when BP changes. However, we observed both LVH regression and improvement of diastolic function independently of BP change. The linear regression analyses performed provided no evidence of BP dependency. Improvement of vascular compliance, which was dependent on BP reduction, was independent of HR at baseline or HR reduction, suggesting that this BP-dependent parameter is independent of cardiac autonomic activity.
Magnetic resonance imaging is considered the gold standard for the detection of LV mass (36). However, echocardiography as a widely accessible and inexpensive tool is known to provide valid and reproducible LVH measurements (15). Our data on LVH regression are confirmed by unpublished but presented magnetic resonance imaging data (37). Nevertheless, the present data are still preliminary because they are derived from a small single-center patient population. One cannot exclude that the differences in office BP and LVMI reductions found herein were partially influenced by other factors, including a possible regression to the mean of office BP readings over repeated visits.
Accurate assessment of LV filling pressure in a noninvasive approach has limitations. The combination of tissue Doppler and the mitral annulus and mitral inflow velocity curves has been proven to yield the most valid results when compared with invasive measurements of LV end-diastolic pressures in left heart catheterization (38). The fact that despite improvement in diastolic function (reduction in left atrial volume, DT, IVRT, increase in E/A), E/E′ remained unchanged in our study is due to a strong rise in E wave. The latter can be explained by the HR decline induced by RDN because HR reduction shifts ventricular filling toward the early phase (E wave) (39). A relevant direct effect of the decrease in BP on E/A is unlikely due to the lack of correlation.
RDN reduced LV mass and improved diastolic function independently of BP and HR reduction. The current data suggest a direct effect of the sympathetic nervous system on myocardial morphology and function. The present findings call for a prospective study investigating in detail the functional cardiovascular benefits of RDN beyond BP reduction.
For supplemental figures and a table, please see the online version of this article.
Dr. Schirmer is supported by the Deutsche Forschungsgemeinschaft (KFO 196) and the Deutsche Herzstiftung. Dr. Sayed is supported by the Deutsche Akademische Austauschdienst. Dr. Ukena is supported by the Deutsche Forschungsgemeinschaft (KFO 196); and has received speaker honoraria from Medtronic and St. Jude. Dr. Laufs is supported by the Deutsche Forschungsgemeinschaft (KFO 196); and has received speaker honoraria from Medtronic. Dr. Mahfoud is supported by the Hochdruckliga and the Deutsche Gesellschaft für Kardiologie; has received scientific support from Medtronic, St. Jude, ReCor, Vessix Vascular, and Cordis; and has received speaker honoraria from Medtronic, St. Jude, Cordis, and Vessix Vascular. Dr. Böhm is supported by the Deutsche Forschungsgemeinschaft (KFO 196); and has received scientific support and/or speaker honoraria from Medtronic, St. Jude, Cordis, Boston Scientific, and ReCor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- ambulatory blood pressure monitoring
- blood pressure
- diastolic blood pressure
- deceleration time
- E- to A-wave ratio
- end-systolic meridional wall stress
- fractional shortening
- heart rate
- isovolumetric relaxation time
- left ventricular
- left ventricular end-diastolic diameter
- left ventricular end-systolic diameter
- left ventricular hypertrophy
- left ventricular mass index
- left ventricular outflow tract
- left ventricular posterior wall during systole
- renal sympathetic denervation
- systolic blood pressure
- heart rate–corrected left ventricular circumferential fiber shortening
- Received September 4, 2013.
- Revision received October 7, 2013.
- Accepted October 17, 2013.
- American College of Cardiology Foundation
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