- Email: [email protected]
E′ in hypertensive heart failure
EJINME-03397; No of Pages 2 European Journal of Internal Medicine xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Differences in predictors of one-year mortality between patients with hypertensive and non-hypertensive acute heart failure: Usefulness of E/E′ in hypertensive heart failure Keywords: Heart failure Hypertension Mortality Blood pressure Echocardiogram
High blood pressure (BP) is an important factor causing acute decompensated heart failure (HF). An abrupt increase in BP has been associated with a surge in neurohormonal and cytokine activation, which is one of the triggers of acute decompensated HF and reported to induce redistribution of fluids from the systemic to pulmonary circulation, further neurohormonal activation, and increased left ventricular (LV) afterload [1]. On the other hand, long-standing hypertension leads to structural remodeling of the heart [2,3]. Although determinants of the LV functional and structural response to hypertension and interindividual variability thereof remain ill-defined [2], patients with hypertensive HF (HTNHF) may show certain clinical characteristics that are distinct from those in patients with non-hypertensive HF (nonHTNHF), and the underlying pathophysiology can differ between these patient groups. Assessing the clinical characteristics and mechanisms of HTNHF is thus an important research topic from the viewpoint of individualized medicine. Accordingly, we compared the prognostic factors for one-year mortality between patients with hypertensive and non-hypertensive acute decompensated HF in the present study. We retrospectively studied 436 consecutive patients who were admitted for acute decompensated HF to Kyorin University Hospital, Japan, from March 2009 to August 2013. Patients with acute coronary syndrome or hemodialysis were excluded from the study. HTNHF was defined as an elevated blood pressure of ≥140/ and/or ≥/90 at admission. Potential risk factors for one-year mortality were selected by univariate analyses; then multivariate Cox regression analysis with backward stepwise selection was performed for variables showing a statistical value of P b 0.10 in the univariate analyses to identify significant factors. All statistical analyses were performed using SPSS version 22 (IBM Japan, Tokyo, Japan). P b 0.05 was considered significant. This study was approved by the institutional ethics review board of Kyorin University School of Medicine, Japan. The clinical characteristics of the study subjects are summarized in Supplemental Table 1. We also evaluated antihypertensive medications at discharge (Supplemental Table 2). As shown in Supplemental Fig. 1, Patients with HTNHF exhibited a significantly lower one-year mortality than those with nonHTNHF (log-rank, P = 0.005). In the HTNHF group, univariate Cox regression analyses revealed that age (P = 0.030), serum sodium value at admission (P = 0.069), C-reactive protein at admission (P b 0.001), and the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/E′) determined by
echocardiogram (P = 0.033) were potential risk factors for one-year mortality (Supplemental Table 3). Subsequent multivariate Cox regression analysis with backward stepwise selection using variables with P b 0.10 in the univariate analyses identified older age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.03–1.25; P = 0.007], lower serum sodium value at admission (serum sodium value: HR, 0.64; 95% CI, 0.49–0.83; P = 0.001), and higher mitral E/E′ ratio (HR, 1.39; 95% CI, 1.11–1.74; P = 0.004) as significant risk factors for one-year mortality (Table 1). On the other hand, univariate Cox regression analyses revealed that age (P = 0.007), systolic BP at admission (P = 0.084), diastolic BP at admission (P = 0.002), serum creatinine levels at admission (P = 0.002), blood urea nitrogen levels at admission (P b 0.001), plasma B-type natriuretic peptide (P = 0.046), chronic obstructive pulmonary disease (P = 0.049), medication without diuretics at discharge (P = 0.003), medication without renin–angiotensin–aldosterone system inhibitors at discharge (P = 0.011), medication without beta blockers at discharge (P = 0.003), and medication without calcium channel blockers at discharge (P = 0.088) were potential risk factors for one-year mortality in nonHTNHF patients (Supplemental Table 3). Multivariate Cox regression analysis with backward stepwise selection for variables of P b 0.10 in the univariate analyses then showed that the significant risk factors for one-year mortality were older age (HR, 1.09; 95% CI, 1.03–1.15; P = 0.002), lower systolic BP at admission (systolic BP: HR, 0.96; 95% CI, 0.93–0.99; P = 0.009), higher serum creatinine level at admission (HR, 1.76; 95% CI, 1.21–2.55; P = 0.003), and medication without diuretics at discharge (HR, 4.27; 95% CI, 1.80–10.12; P = 0.001) in the nonHTNHF group (Table 1). The finding herein that E/E′ was a reliable predictor of mortality only in the HTNHF group is of note, and recognizing E/E′ as an indicator of the underlying pathophysiological mechanisms might have important implications for individualized medicine. Although E/E′ has been used to estimate pulmonary capillary wedge pressure (PCWP) in a wide range of cardiac patients [4], it remains contentious as to whether mitral
Table 1 Risk factors for one-year mortality in patients with HTNHF and nonHTNHF. Variable
HR (95% CI)
P-value
HTNHF
Age Serum sodium value E/E′
1.14 (1.03–1.25) 0.64 (0.49–0.83) 1.39 (1.11–1.74)
0.007 0.001 0.004
nonHTNHF
Age Systolic BP at admission Serum creatinine level at admission Medication without diuretics at discharge
1.09 (1.03–1.15) 0.96 (0.93–0.99) 1.76 (1.21–2.55) 4.27 (1.80–10.12)
0.002 0.009 0.003 0.001
Multivariate Cox regression analysis with backward stepwise selection was performed with variables showing a statistical value of P b 0.10 in the univariate analyses. Significant risk factors were defined as P b 0.05. BP, blood pressure; CI, confidence interval; E/E′, the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity; HTNHF, hypertensive heart failure; HR, hazard ratio; nonHTNHF, non-hypertensive heart failure.
http://dx.doi.org/10.1016/j.ejim.2016.10.018 0953-6205/© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Matsushita K, et al, Differences in predictors of one-year mortality between patients with hypertensive and nonhypertensive acute heart failure: Usefulness ..., Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.10.018
e2
Letter to the Editor
E/E′ is a reliable predictor of PCWP [5]. Therefore, assessing the usefulness of mitral E/E′ in HF is an important topic for research. Recently, we reported that E/E′ is useful for estimating PCWP in acute HF patients with preserved ejection fraction (EF), but possibly not so in those with reduced EF [6]. In the present study, E/E′ did not significantly differ between the HTNHF and nonHTNHF groups; however, the ratio of history of hypertension was significantly higher in the HTNHF group. In this context, Sharp et al. [7] reported that E/E′ was the only parameter to predict primary cardiac events in a hypertensive population. Thus, E/E′ might be a reliable tool for assessing structural and functional alterations in hypertensive heart, but not in non-hypertensive heart. The determinants of the LV structural and functional response to hypertension are still unclear and further studies are needed to progress the individualization of heart failure treatment. Another important finding of this study is that high serum creatinine levels at admission were significantly associated with one-year mortality only in the nonHTNHF group. In this context, cardiorenal syndrome (CRS) should also be considered. CRS is a complex disorder of the heart and kidneys, and it seems that some mechanisms differ among the types of HF [8,9]. For example, we previously reported significant differences between HF patients with preserved EF and reduced EF in terms of the way that hypertension was involved in CRS type 1 [10]. Based on the hypothesis by Gheorghiade et al. [1], control of congestion is more important in patients with nonHTNHF than in those with HTNHF. Taken together, these findings suggest that CRS may have more influence in patients with nonHTNHF than those with HTNHF. In conclusion, the present study demonstrated that patients with HTNHF exhibited a significantly lower one-year mortality than those with nonHTNHF and there were significant differences in the prognostic factors for one-year mortality between the HTNHF and nonHTNHF groups. E/E′ was a reliable predictor of one-year mortality only in the HTNHF group, while hyponatremia at admission was also significantly associated with mortality only in the HTNHF group. Renal impairment at admission and medication without diuretics at discharge were significantly associated with mortality only in the nonHTNHF group. Elucidation of the pathophysiological mechanisms behind these findings could lead to more effective individualized therapeutic strategies for patients with acute decompensated HF. Supplementary data to this article can be found online at doi:10. 1016/j.ejim.2016.10.018.
Acknowledgments The authors appreciate the help of Ms. Keiko Nishizawa for data collection. This work was supported, in part, by grants from the Japan Society for the Promotion of Science (KAKENHI 26461086; to Kenichi Matsushita) and Kyorin University School of Medicine (No. B102090002; to Kenichi Matsushita). References [1] Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, et al. Acute heart failure syndromes: current state and framework for future research. Circulation 2005;112:3958–68. [2] Santos M, Shah AM. Alterations in cardiac structure and function in hypertension. Curr Hypertens Rep 2014;16:428. [3] Weber KT, Sun Y, Guarda E. Structural remodeling in hypertensive heart disease and the role of hormones. Hypertension 1994;23:869–77. [4] Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009;10:165–93. [5] Mullens W, Borowski AG, Curtin RJ, Thomas JD, Tang WH. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation 2009;119:62–70. [6] Matsushita K, Minamishima T, Goda A, Ishiguro H, Kosho H, Sakata K, et al. Comparison of the reliability of E/E′ to estimate pulmonary capillary wedge pressure in heart failure patients with preserved ejection fraction versus those with reduced ejection fraction. Int J Cardiovasc Imaging 2015;31:1497–502. [7] Sharp AS, Tapp RJ, Thom SA, Francis DP, Hughes AD, Stanton AV, et al. Tissue Doppler E/E′ ratio is a powerful predictor of primary cardiac events in a hypertensive population: an ASCOT substudy. Eur Heart J 2010;31:747–52. [8] Matsushita K. Pathogenetic pathways of cardiorenal syndrome and their possible therapeutic implications. Curr Pharm Des 2016;22:4629–37. [9] Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol 2008;52:1527–39. [10] Yamagishi T, Matsushita K, Minamishima T, Goda A, Sakata K, Satoh T, et al. Comparison of risk factors for acute worsening renal function in heart failure patients with and without preserved ejection fraction. Eur J Intern Med 2015;26:599–602.
Kenichi Matsushita⁎ Toshinori Minamishima Konomi Sakata Toru Satoh Hideaki Yoshino Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan *Corresponding author at: Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan. E-mail address: [email protected] (K. Matsushita).
Conflict of interests The authors have no conflicts of interest to disclose.
19 October 2016 Available online xxxx
Please cite this article as: Matsushita K, et al, Differences in predictors of one-year mortality between patients with hypertensive and nonhypertensive acute heart failure: Usefulness ..., Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.10.018
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Letter to the Editor Differences in predictors of one-year mortality between patients with hypertensive and non-hypertensive acute heart failure: Usefulness of E/E′ in hypertensive heart failure Keywords: Heart failure Hypertension Mortality Blood pressure Echocardiogram
High blood pressure (BP) is an important factor causing acute decompensated heart failure (HF). An abrupt increase in BP has been associated with a surge in neurohormonal and cytokine activation, which is one of the triggers of acute decompensated HF and reported to induce redistribution of fluids from the systemic to pulmonary circulation, further neurohormonal activation, and increased left ventricular (LV) afterload [1]. On the other hand, long-standing hypertension leads to structural remodeling of the heart [2,3]. Although determinants of the LV functional and structural response to hypertension and interindividual variability thereof remain ill-defined [2], patients with hypertensive HF (HTNHF) may show certain clinical characteristics that are distinct from those in patients with non-hypertensive HF (nonHTNHF), and the underlying pathophysiology can differ between these patient groups. Assessing the clinical characteristics and mechanisms of HTNHF is thus an important research topic from the viewpoint of individualized medicine. Accordingly, we compared the prognostic factors for one-year mortality between patients with hypertensive and non-hypertensive acute decompensated HF in the present study. We retrospectively studied 436 consecutive patients who were admitted for acute decompensated HF to Kyorin University Hospital, Japan, from March 2009 to August 2013. Patients with acute coronary syndrome or hemodialysis were excluded from the study. HTNHF was defined as an elevated blood pressure of ≥140/ and/or ≥/90 at admission. Potential risk factors for one-year mortality were selected by univariate analyses; then multivariate Cox regression analysis with backward stepwise selection was performed for variables showing a statistical value of P b 0.10 in the univariate analyses to identify significant factors. All statistical analyses were performed using SPSS version 22 (IBM Japan, Tokyo, Japan). P b 0.05 was considered significant. This study was approved by the institutional ethics review board of Kyorin University School of Medicine, Japan. The clinical characteristics of the study subjects are summarized in Supplemental Table 1. We also evaluated antihypertensive medications at discharge (Supplemental Table 2). As shown in Supplemental Fig. 1, Patients with HTNHF exhibited a significantly lower one-year mortality than those with nonHTNHF (log-rank, P = 0.005). In the HTNHF group, univariate Cox regression analyses revealed that age (P = 0.030), serum sodium value at admission (P = 0.069), C-reactive protein at admission (P b 0.001), and the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity (E/E′) determined by
echocardiogram (P = 0.033) were potential risk factors for one-year mortality (Supplemental Table 3). Subsequent multivariate Cox regression analysis with backward stepwise selection using variables with P b 0.10 in the univariate analyses identified older age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.03–1.25; P = 0.007], lower serum sodium value at admission (serum sodium value: HR, 0.64; 95% CI, 0.49–0.83; P = 0.001), and higher mitral E/E′ ratio (HR, 1.39; 95% CI, 1.11–1.74; P = 0.004) as significant risk factors for one-year mortality (Table 1). On the other hand, univariate Cox regression analyses revealed that age (P = 0.007), systolic BP at admission (P = 0.084), diastolic BP at admission (P = 0.002), serum creatinine levels at admission (P = 0.002), blood urea nitrogen levels at admission (P b 0.001), plasma B-type natriuretic peptide (P = 0.046), chronic obstructive pulmonary disease (P = 0.049), medication without diuretics at discharge (P = 0.003), medication without renin–angiotensin–aldosterone system inhibitors at discharge (P = 0.011), medication without beta blockers at discharge (P = 0.003), and medication without calcium channel blockers at discharge (P = 0.088) were potential risk factors for one-year mortality in nonHTNHF patients (Supplemental Table 3). Multivariate Cox regression analysis with backward stepwise selection for variables of P b 0.10 in the univariate analyses then showed that the significant risk factors for one-year mortality were older age (HR, 1.09; 95% CI, 1.03–1.15; P = 0.002), lower systolic BP at admission (systolic BP: HR, 0.96; 95% CI, 0.93–0.99; P = 0.009), higher serum creatinine level at admission (HR, 1.76; 95% CI, 1.21–2.55; P = 0.003), and medication without diuretics at discharge (HR, 4.27; 95% CI, 1.80–10.12; P = 0.001) in the nonHTNHF group (Table 1). The finding herein that E/E′ was a reliable predictor of mortality only in the HTNHF group is of note, and recognizing E/E′ as an indicator of the underlying pathophysiological mechanisms might have important implications for individualized medicine. Although E/E′ has been used to estimate pulmonary capillary wedge pressure (PCWP) in a wide range of cardiac patients [4], it remains contentious as to whether mitral
Table 1 Risk factors for one-year mortality in patients with HTNHF and nonHTNHF. Variable
HR (95% CI)
P-value
HTNHF
Age Serum sodium value E/E′
1.14 (1.03–1.25) 0.64 (0.49–0.83) 1.39 (1.11–1.74)
0.007 0.001 0.004
nonHTNHF
Age Systolic BP at admission Serum creatinine level at admission Medication without diuretics at discharge
1.09 (1.03–1.15) 0.96 (0.93–0.99) 1.76 (1.21–2.55) 4.27 (1.80–10.12)
0.002 0.009 0.003 0.001
Multivariate Cox regression analysis with backward stepwise selection was performed with variables showing a statistical value of P b 0.10 in the univariate analyses. Significant risk factors were defined as P b 0.05. BP, blood pressure; CI, confidence interval; E/E′, the ratio of early transmitral velocity to tissue Doppler mitral annular early diastolic velocity; HTNHF, hypertensive heart failure; HR, hazard ratio; nonHTNHF, non-hypertensive heart failure.
http://dx.doi.org/10.1016/j.ejim.2016.10.018 0953-6205/© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Matsushita K, et al, Differences in predictors of one-year mortality between patients with hypertensive and nonhypertensive acute heart failure: Usefulness ..., Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.10.018
e2
Letter to the Editor
E/E′ is a reliable predictor of PCWP [5]. Therefore, assessing the usefulness of mitral E/E′ in HF is an important topic for research. Recently, we reported that E/E′ is useful for estimating PCWP in acute HF patients with preserved ejection fraction (EF), but possibly not so in those with reduced EF [6]. In the present study, E/E′ did not significantly differ between the HTNHF and nonHTNHF groups; however, the ratio of history of hypertension was significantly higher in the HTNHF group. In this context, Sharp et al. [7] reported that E/E′ was the only parameter to predict primary cardiac events in a hypertensive population. Thus, E/E′ might be a reliable tool for assessing structural and functional alterations in hypertensive heart, but not in non-hypertensive heart. The determinants of the LV structural and functional response to hypertension are still unclear and further studies are needed to progress the individualization of heart failure treatment. Another important finding of this study is that high serum creatinine levels at admission were significantly associated with one-year mortality only in the nonHTNHF group. In this context, cardiorenal syndrome (CRS) should also be considered. CRS is a complex disorder of the heart and kidneys, and it seems that some mechanisms differ among the types of HF [8,9]. For example, we previously reported significant differences between HF patients with preserved EF and reduced EF in terms of the way that hypertension was involved in CRS type 1 [10]. Based on the hypothesis by Gheorghiade et al. [1], control of congestion is more important in patients with nonHTNHF than in those with HTNHF. Taken together, these findings suggest that CRS may have more influence in patients with nonHTNHF than those with HTNHF. In conclusion, the present study demonstrated that patients with HTNHF exhibited a significantly lower one-year mortality than those with nonHTNHF and there were significant differences in the prognostic factors for one-year mortality between the HTNHF and nonHTNHF groups. E/E′ was a reliable predictor of one-year mortality only in the HTNHF group, while hyponatremia at admission was also significantly associated with mortality only in the HTNHF group. Renal impairment at admission and medication without diuretics at discharge were significantly associated with mortality only in the nonHTNHF group. Elucidation of the pathophysiological mechanisms behind these findings could lead to more effective individualized therapeutic strategies for patients with acute decompensated HF. Supplementary data to this article can be found online at doi:10. 1016/j.ejim.2016.10.018.
Acknowledgments The authors appreciate the help of Ms. Keiko Nishizawa for data collection. This work was supported, in part, by grants from the Japan Society for the Promotion of Science (KAKENHI 26461086; to Kenichi Matsushita) and Kyorin University School of Medicine (No. B102090002; to Kenichi Matsushita). References [1] Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, et al. Acute heart failure syndromes: current state and framework for future research. Circulation 2005;112:3958–68. [2] Santos M, Shah AM. Alterations in cardiac structure and function in hypertension. Curr Hypertens Rep 2014;16:428. [3] Weber KT, Sun Y, Guarda E. Structural remodeling in hypertensive heart disease and the role of hormones. Hypertension 1994;23:869–77. [4] Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 2009;10:165–93. [5] Mullens W, Borowski AG, Curtin RJ, Thomas JD, Tang WH. Tissue Doppler imaging in the estimation of intracardiac filling pressure in decompensated patients with advanced systolic heart failure. Circulation 2009;119:62–70. [6] Matsushita K, Minamishima T, Goda A, Ishiguro H, Kosho H, Sakata K, et al. Comparison of the reliability of E/E′ to estimate pulmonary capillary wedge pressure in heart failure patients with preserved ejection fraction versus those with reduced ejection fraction. Int J Cardiovasc Imaging 2015;31:1497–502. [7] Sharp AS, Tapp RJ, Thom SA, Francis DP, Hughes AD, Stanton AV, et al. Tissue Doppler E/E′ ratio is a powerful predictor of primary cardiac events in a hypertensive population: an ASCOT substudy. Eur Heart J 2010;31:747–52. [8] Matsushita K. Pathogenetic pathways of cardiorenal syndrome and their possible therapeutic implications. Curr Pharm Des 2016;22:4629–37. [9] Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol 2008;52:1527–39. [10] Yamagishi T, Matsushita K, Minamishima T, Goda A, Sakata K, Satoh T, et al. Comparison of risk factors for acute worsening renal function in heart failure patients with and without preserved ejection fraction. Eur J Intern Med 2015;26:599–602.
Kenichi Matsushita⁎ Toshinori Minamishima Konomi Sakata Toru Satoh Hideaki Yoshino Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan *Corresponding author at: Division of Cardiology, Second Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan. E-mail address: [email protected] (K. Matsushita).
Conflict of interests The authors have no conflicts of interest to disclose.
19 October 2016 Available online xxxx
Please cite this article as: Matsushita K, et al, Differences in predictors of one-year mortality between patients with hypertensive and nonhypertensive acute heart failure: Usefulness ..., Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.10.018