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Assessment of Arterial Elastance and Ventricular-Arterial Coupling in Patients with Systemic Lupus Erythematosus
504
Letters to the Editor
Assessment of Arterial Elastance and Ventricular-Arterial Coupling in Patients with Systemic Lupus Erythematosus Calvin Woon Loong Chin a,⁎, Thu Thao Le a, Fei Gao a,b, Marie Xin Ru Ng a, Chee Yang Chin a, Fei Qiong Huang a, Kok Yong Fong c, Julian Thumboo c, Ru San Tan a a b c
Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore Center for Quantitative Medicine, Duke-NUS Graduate Medical School Singapore, Singapore Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
a r t i c l e
i n f o
Article history: Received 23 May 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: Systemic lupus erythematosus non-invasive imaging arterial stiffness
To the Editor: Patients with systemic lupus erythematosus (SLE) are at increased risk of premature atherosclerosis, mediated by endothelial dysfunction and increased arterial stiffness [1]. The latter, most commonly assessed using carotid-femoral pulse wave velocity, is increased in patients with SLE and is associated with cardiovascular risk factors [1]. Recently, a more sensitive measure of arterial stiffness (effective arterial elastance; Ea), and ventricular-arterial coupling (ratio of arterial and end-systolic ventricular elastance; Ea/Ees) demonstrated incremental prognostic value in patients with chronic heart failure [2]. We aimed to assess the potential of Ea and Ea/Ees as novel biomarkers of cardiovascular risk in SLE women without ischemic heart disease. Women who satisfied the revised American College of Rheumatology classification criteria for SLE were prospectively recruited from the rheumatology clinics, as described previously [3]. Patients with recent active flares, ischemic heart disease (all patients underwent nuclear stress perfusion imaging as part of the study), cardiomyopathies (including myocarditis) and valvular heart disease of ≥ moderate severity were excluded. Cardiovascular risk was defined as history of hypertension, hyperlipidemia, diabetes mellitus, current tobacco use, cerebrovascular events, family history of coronary artery disease and secondary anti-phospholipid syndrome. Age-matched control women were recruited from the community. Left ventricular mass, diastolic function and systolic ejection fraction were assessed with echocardiography; Ea was estimated as 0.9 x (arm-cuff systolic pressure/Doppler stroke volume) and Ees was calculated by the wellvalidated approach of using arm-cuff pressures, Doppler stroke volumes, ejection fraction, pre-ejection and systolic periods [4,5]. The study was conducted in accordance with the Declaration of Helsinki and approved by the local research ethics committee. Written informed consent was obtained from all participants. Continuous variables were presented in mean±SD or median [interquartile range] and compared using either the Student t test or Mann-Whitney U test, as appropriate. The mean differences in Ea and Ea/Ees were adjusted for age, systolic ejection fraction and systolic blood pressure. We assessed associations using the Pearson (r) or Spearman (ρ) correlation, as appropriate. All statistical analyses were ⁎ Corresponding author at: National Heart Center Singapore, 5 Hospital Drive, 169609, Singapore. Tel.: + 65 6704 8000; fax: +65 6844 9030. E-mail address: [email protected] (C.W.L. Chin).
performed with the SPSS version 19 (SPSS Inc, Chicago, USA). A two-sided P b0.05 was considered statistically significant. Forty-eight patients with SLE (43±9 years old; disease duration of 14±6 years; 1 [0,2] risk factors) and 20 control women (42±9 years old) were recruited. There were no differences in left ventricular mass, diastolic function and Ees between SLE and control women (PN0.50 for all; Table 1). Compared to control individuals, patients with SLE had lower systolic ejection fraction, albeit a small difference (71±8 versus 75±7%; P=0.04). Despite similar systolic blood pressure compared with control women (116±12 versus 119±16 mmHg; P=0.52), patients with SLE had increased Ea (1.77±0.56 versus 1.37±0.27 mmHg/mL; adjusted mean difference 0.30 mmHg/ mL, 95% confidence interval [CI] 0.08 to 0.53 mmHg/mL, Pb0.001) and Ea/Ees (0.61±0.18 versus 0.50±0.07; adjusted mean difference 0.06, 95% CI 0.01 to 0.12, P=0.04). Furthermore, Ea was associated with increasing cardiovascular risk (ρ=0.35; P=0.02), systolic blood pressure (r=0.55, Pb0.001) and duration of prednisolone use (ρ=0.33, P=0.03).
Table 1 Characteristics of control individuals and patients with systemic lupus erythematosus (SLE).
Clinical characteristic Age, years History of hypertension History of diabetes mellitus History of hyperlipidemia Current tobacco use Family history of coronary artery disease History of cerebrovascular event Presence of secondary antiphosphoplipid syndrome Duration of SLE diagnosed, years SLICC/ACR damage index¶ Current prednisolone use Body mass index, kg/m2 Systolic blood pressure, mmHg Low density lipoprotein cholesterol, mmol/L High density lipoprotein cholesterol, mmol/L Echocardiographic characteristics Indexed left ventricular mass, g/m2 Diastolic function E/e’ Systolic ejection fraction, % Effective arterial elastance (Ea), mmHg/mL End-systolic elastance (Ees), mmHg/mL Ea/Ees
Control Individuals (n = 20)
Patients with SLE (n = 48)
P value
42±9 1 (5) 0 0 1 (5) 5 (25) 0 -
43±9 12 (25) 2 (4) 10 (21) 4 (8) 7 (15) 7 (15) 12 (25)
0.71 0.06 0.35 0.03 0.63 0.30 0.07 -
23.8±3.7 116±12 -
14±6 0 [0,1] 25 (52) 23.4±5.0 119±16 3.0±0.7
0.76 0.52 -
-
1.3±0.4
57 [52.72] 60 [52,77] 6.9 [5.7,8.0] 6.2 [4.9,8.3] 75±7 71±8 1.34 [1.25,1.49] 1.64 [1.42,1.95] 2.82 3.03 [2.36,3.19] [2.59,3.49] 0.49 0.56 [0.45,0.55] [0.51,0.64]
-
0.46 0.48 0.04 b 0.001 0.18 b 0.001
Results are presented in mean±SD, median [25th, 75th percentiles] or n (%). ¶ SLICC/ACR Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index assessed organ damage in 12 systems with a maximum score of 47.
Letters to the Editor
Over 3 years of follow-up (median 31 [17,37] months), 8% of patients with SLE developed cardiovascular events (event rate 3.2 per 100 person-years; non-fatal myocardial infarction, n=2; stroke, n=1; significant coronary artery disease, n=1). Importantly, compared to control individuals and patients without events, SLE patients with cardiovascular events had increased Ea (1.33 [1.25,1.49] versus 1.59 [1.40,1.93] versus 2.10 [1.59,2.98] mmHg/mL, respectively; Pb0.001) and Ea/Ees (0.49 [0.45,0.55] versus 0.55 [0.51,0.64] versus 0.59 [0.55,1.15], respectively; Pb0.01). By design, we had excluded patients with ischemic heart disease and cardiomyopathies, as the role of non-invasive vascular imaging will be of greater relevance in these patients. Therefore, it was not surprising that we did not see any difference in Ees, a marker of ventricular stiffness, between SLE and control women. This was also supported by the similar left ventricular mass and diastolic function between SLE and control women. The small difference in systolic ejection fraction was likely an event of chance and not of important clinical significance. Conversely, Ea was significantly increased in patients with SLE compared to control women despite similar and normal blood pressures. The combination of these changes account for the small magnitude of Ea/Ees effect sizes. The association between
505
Ea, Ea/Ees and adverse events is promising but we acknowledge this is exploratory and will require further validation in larger cohorts with longer follow-up. In conclusion, arterial elastance and ventricular-arterial coupling are associated with increased cardiovascular risk and are potential novel markers of adverse cardiovascular events in patients with SLE. The authors report no relationships that could be construed as a conflict of interest
References [1] Chin C, Tan RS, Thumboo J. Endothelial function and arterial stiffness assessment as early surrogate markers of vascular risk in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2013;31(2):295–301. [2] Ky B, French B, Khan AM, et al. Ventricular-Arterial Coupling, Remodeling, and Prognosis in Chronic Heart Failure. J Am Coll Cardiol 2013;62(13):1165–72. [3] Chin C, Chin CY, Ng MXR, et al. Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus. Rheumatol Int Feb 19 2014, doi:10.1007/s00296-014-2968-4. [4] Kelly RP, Ting CT, Yang TM, et al. Effective arterial elastance as index of arterial vascular load in humans. Circulation 1992;86(2):513–21. [5] Chen CH, Fetics B, Nevo E, et al. Noninvasive single-beat determination of left ventricular end-systolic elastance in humans. J Am Coll Cardiol 2001;38(7):2028–34.
http://dx.doi.org/10.1016/j.ijcard.2014.07.055 0167-5273/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Three-year clinical outcomes of staged, ad hoc and culprit-only percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction and multivessel disease Min Chul Kim, Myung Ho Jeong ⁎, Keun Ho Park, Doo Sun Sim, Nam Sik Yoon, Hyun Joo Yoon, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Youngkeun Ahn, Jeong Gwan Cho, Jong Chun Park Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea
a r t i c l e
i n f o
Article history: Received 19 May 2014 Accepted 5 July 2014 Available online 12 July 2014 Keywords: Myocardial infarction Coronary artery disease Percutaneous coronary intervention
Multivessel coronary artery disease (MVD) in ST-segment elevation myocardial infarction (STEMI) is a common clinical condition encountered by interventional cardiologists and it is associated with poorer clinical outcomes than single-vessel disease [1]. Current guidelines recommend culprit-vessel only revascularization (CVR) during primary angioplasty, except in patients that are hemodynamically unstable [2]. Several recent studies have reported promising results from CVR followed by elective second-stage PCI at non-infarct related arteries with significant stenosis. However, there are insuffi-
⁎ Corresponding author at: Principal Investigator of Korea Acute Myocardial Infarction Registry, Director of Heart Research Center of Korea Ministry of Health and Welfare, Chonnam National University Hospital, 42 Jaebongro, Dong-gu, Gwangju 501-757, Republic of Korea. Tel.: +82 62 220 6243; fax: +82 62 228 7174. E-mail address: [email protected] (M.H. Jeong).
cient data on the long-term outcomes of staged PCI in these patients. We investigated the long-term clinical outcomes of a staged PCI strategy compared to ad hoc PCI and CVR in patients with STEMI and MVD who underwent primary PCI. We enrolled 575 consecutive patients with STEMI and MVD who visited Chonnam National University Hospital from January 2006 to July 2009. All patients underwent primary PCI within 120 min after being admitted to the hospital. We selected 474 patients after exclusion of patients who presented with cardiogenic shock. Patients were divided into three groups based on the initial interventional strategy: staged PCI (initial index intervention and secondary elective staged PCI during index hospitalization, n = 252); ad hoc (simultaneous infarct-related and non infarct-related artery intervention during the index procedure, n = 67); and culprit-vessel only PCI (CVR, n = 155). The primary endpoint was composite outcome including death from all causes, myocardial infarction (MI) and repeat PCI during 3-year clinical follow-up visits. Repeat PCI included target lesion revascularization, target vessel revascularization and non-target vessel revascularization. Three-year composite outcomes and death from all causes or MI were evaluated using the Kaplan–Meier analysis and compared using a log-rank test. Cox regression analysis was used to identify the clinical impact of staged PCI with complete revascularization (CR) adjusted with clinically relevant covariates. All variables were considered significant when the p-value was b0.05. There were no significant differences in baseline and angiographic characteristics among groups except for more aged persons (staged vs. ad hoc vs. CVR; 68.8 ± 10.8 vs. 65.5 ± 12.8 vs. 70.7 ± 13.7, p = 0.012), more
Letters to the Editor
Assessment of Arterial Elastance and Ventricular-Arterial Coupling in Patients with Systemic Lupus Erythematosus Calvin Woon Loong Chin a,⁎, Thu Thao Le a, Fei Gao a,b, Marie Xin Ru Ng a, Chee Yang Chin a, Fei Qiong Huang a, Kok Yong Fong c, Julian Thumboo c, Ru San Tan a a b c
Department of Cardiovascular Medicine, National Heart Center Singapore, Singapore Center for Quantitative Medicine, Duke-NUS Graduate Medical School Singapore, Singapore Department of Rheumatology and Immunology, Singapore General Hospital, Singapore
a r t i c l e
i n f o
Article history: Received 23 May 2014 Accepted 5 July 2014 Available online 11 July 2014 Keywords: Systemic lupus erythematosus non-invasive imaging arterial stiffness
To the Editor: Patients with systemic lupus erythematosus (SLE) are at increased risk of premature atherosclerosis, mediated by endothelial dysfunction and increased arterial stiffness [1]. The latter, most commonly assessed using carotid-femoral pulse wave velocity, is increased in patients with SLE and is associated with cardiovascular risk factors [1]. Recently, a more sensitive measure of arterial stiffness (effective arterial elastance; Ea), and ventricular-arterial coupling (ratio of arterial and end-systolic ventricular elastance; Ea/Ees) demonstrated incremental prognostic value in patients with chronic heart failure [2]. We aimed to assess the potential of Ea and Ea/Ees as novel biomarkers of cardiovascular risk in SLE women without ischemic heart disease. Women who satisfied the revised American College of Rheumatology classification criteria for SLE were prospectively recruited from the rheumatology clinics, as described previously [3]. Patients with recent active flares, ischemic heart disease (all patients underwent nuclear stress perfusion imaging as part of the study), cardiomyopathies (including myocarditis) and valvular heart disease of ≥ moderate severity were excluded. Cardiovascular risk was defined as history of hypertension, hyperlipidemia, diabetes mellitus, current tobacco use, cerebrovascular events, family history of coronary artery disease and secondary anti-phospholipid syndrome. Age-matched control women were recruited from the community. Left ventricular mass, diastolic function and systolic ejection fraction were assessed with echocardiography; Ea was estimated as 0.9 x (arm-cuff systolic pressure/Doppler stroke volume) and Ees was calculated by the wellvalidated approach of using arm-cuff pressures, Doppler stroke volumes, ejection fraction, pre-ejection and systolic periods [4,5]. The study was conducted in accordance with the Declaration of Helsinki and approved by the local research ethics committee. Written informed consent was obtained from all participants. Continuous variables were presented in mean±SD or median [interquartile range] and compared using either the Student t test or Mann-Whitney U test, as appropriate. The mean differences in Ea and Ea/Ees were adjusted for age, systolic ejection fraction and systolic blood pressure. We assessed associations using the Pearson (r) or Spearman (ρ) correlation, as appropriate. All statistical analyses were ⁎ Corresponding author at: National Heart Center Singapore, 5 Hospital Drive, 169609, Singapore. Tel.: + 65 6704 8000; fax: +65 6844 9030. E-mail address: [email protected] (C.W.L. Chin).
performed with the SPSS version 19 (SPSS Inc, Chicago, USA). A two-sided P b0.05 was considered statistically significant. Forty-eight patients with SLE (43±9 years old; disease duration of 14±6 years; 1 [0,2] risk factors) and 20 control women (42±9 years old) were recruited. There were no differences in left ventricular mass, diastolic function and Ees between SLE and control women (PN0.50 for all; Table 1). Compared to control individuals, patients with SLE had lower systolic ejection fraction, albeit a small difference (71±8 versus 75±7%; P=0.04). Despite similar systolic blood pressure compared with control women (116±12 versus 119±16 mmHg; P=0.52), patients with SLE had increased Ea (1.77±0.56 versus 1.37±0.27 mmHg/mL; adjusted mean difference 0.30 mmHg/ mL, 95% confidence interval [CI] 0.08 to 0.53 mmHg/mL, Pb0.001) and Ea/Ees (0.61±0.18 versus 0.50±0.07; adjusted mean difference 0.06, 95% CI 0.01 to 0.12, P=0.04). Furthermore, Ea was associated with increasing cardiovascular risk (ρ=0.35; P=0.02), systolic blood pressure (r=0.55, Pb0.001) and duration of prednisolone use (ρ=0.33, P=0.03).
Table 1 Characteristics of control individuals and patients with systemic lupus erythematosus (SLE).
Clinical characteristic Age, years History of hypertension History of diabetes mellitus History of hyperlipidemia Current tobacco use Family history of coronary artery disease History of cerebrovascular event Presence of secondary antiphosphoplipid syndrome Duration of SLE diagnosed, years SLICC/ACR damage index¶ Current prednisolone use Body mass index, kg/m2 Systolic blood pressure, mmHg Low density lipoprotein cholesterol, mmol/L High density lipoprotein cholesterol, mmol/L Echocardiographic characteristics Indexed left ventricular mass, g/m2 Diastolic function E/e’ Systolic ejection fraction, % Effective arterial elastance (Ea), mmHg/mL End-systolic elastance (Ees), mmHg/mL Ea/Ees
Control Individuals (n = 20)
Patients with SLE (n = 48)
P value
42±9 1 (5) 0 0 1 (5) 5 (25) 0 -
43±9 12 (25) 2 (4) 10 (21) 4 (8) 7 (15) 7 (15) 12 (25)
0.71 0.06 0.35 0.03 0.63 0.30 0.07 -
23.8±3.7 116±12 -
14±6 0 [0,1] 25 (52) 23.4±5.0 119±16 3.0±0.7
0.76 0.52 -
-
1.3±0.4
57 [52.72] 60 [52,77] 6.9 [5.7,8.0] 6.2 [4.9,8.3] 75±7 71±8 1.34 [1.25,1.49] 1.64 [1.42,1.95] 2.82 3.03 [2.36,3.19] [2.59,3.49] 0.49 0.56 [0.45,0.55] [0.51,0.64]
-
0.46 0.48 0.04 b 0.001 0.18 b 0.001
Results are presented in mean±SD, median [25th, 75th percentiles] or n (%). ¶ SLICC/ACR Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index assessed organ damage in 12 systems with a maximum score of 47.
Letters to the Editor
Over 3 years of follow-up (median 31 [17,37] months), 8% of patients with SLE developed cardiovascular events (event rate 3.2 per 100 person-years; non-fatal myocardial infarction, n=2; stroke, n=1; significant coronary artery disease, n=1). Importantly, compared to control individuals and patients without events, SLE patients with cardiovascular events had increased Ea (1.33 [1.25,1.49] versus 1.59 [1.40,1.93] versus 2.10 [1.59,2.98] mmHg/mL, respectively; Pb0.001) and Ea/Ees (0.49 [0.45,0.55] versus 0.55 [0.51,0.64] versus 0.59 [0.55,1.15], respectively; Pb0.01). By design, we had excluded patients with ischemic heart disease and cardiomyopathies, as the role of non-invasive vascular imaging will be of greater relevance in these patients. Therefore, it was not surprising that we did not see any difference in Ees, a marker of ventricular stiffness, between SLE and control women. This was also supported by the similar left ventricular mass and diastolic function between SLE and control women. The small difference in systolic ejection fraction was likely an event of chance and not of important clinical significance. Conversely, Ea was significantly increased in patients with SLE compared to control women despite similar and normal blood pressures. The combination of these changes account for the small magnitude of Ea/Ees effect sizes. The association between
505
Ea, Ea/Ees and adverse events is promising but we acknowledge this is exploratory and will require further validation in larger cohorts with longer follow-up. In conclusion, arterial elastance and ventricular-arterial coupling are associated with increased cardiovascular risk and are potential novel markers of adverse cardiovascular events in patients with SLE. The authors report no relationships that could be construed as a conflict of interest
References [1] Chin C, Tan RS, Thumboo J. Endothelial function and arterial stiffness assessment as early surrogate markers of vascular risk in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2013;31(2):295–301. [2] Ky B, French B, Khan AM, et al. Ventricular-Arterial Coupling, Remodeling, and Prognosis in Chronic Heart Failure. J Am Coll Cardiol 2013;62(13):1165–72. [3] Chin C, Chin CY, Ng MXR, et al. Endothelial function is associated with myocardial diastolic function in women with systemic lupus erythematosus. Rheumatol Int Feb 19 2014, doi:10.1007/s00296-014-2968-4. [4] Kelly RP, Ting CT, Yang TM, et al. Effective arterial elastance as index of arterial vascular load in humans. Circulation 1992;86(2):513–21. [5] Chen CH, Fetics B, Nevo E, et al. Noninvasive single-beat determination of left ventricular end-systolic elastance in humans. J Am Coll Cardiol 2001;38(7):2028–34.
http://dx.doi.org/10.1016/j.ijcard.2014.07.055 0167-5273/© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Three-year clinical outcomes of staged, ad hoc and culprit-only percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction and multivessel disease Min Chul Kim, Myung Ho Jeong ⁎, Keun Ho Park, Doo Sun Sim, Nam Sik Yoon, Hyun Joo Yoon, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Youngkeun Ahn, Jeong Gwan Cho, Jong Chun Park Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic of Korea
a r t i c l e
i n f o
Article history: Received 19 May 2014 Accepted 5 July 2014 Available online 12 July 2014 Keywords: Myocardial infarction Coronary artery disease Percutaneous coronary intervention
Multivessel coronary artery disease (MVD) in ST-segment elevation myocardial infarction (STEMI) is a common clinical condition encountered by interventional cardiologists and it is associated with poorer clinical outcomes than single-vessel disease [1]. Current guidelines recommend culprit-vessel only revascularization (CVR) during primary angioplasty, except in patients that are hemodynamically unstable [2]. Several recent studies have reported promising results from CVR followed by elective second-stage PCI at non-infarct related arteries with significant stenosis. However, there are insuffi-
⁎ Corresponding author at: Principal Investigator of Korea Acute Myocardial Infarction Registry, Director of Heart Research Center of Korea Ministry of Health and Welfare, Chonnam National University Hospital, 42 Jaebongro, Dong-gu, Gwangju 501-757, Republic of Korea. Tel.: +82 62 220 6243; fax: +82 62 228 7174. E-mail address: [email protected] (M.H. Jeong).
cient data on the long-term outcomes of staged PCI in these patients. We investigated the long-term clinical outcomes of a staged PCI strategy compared to ad hoc PCI and CVR in patients with STEMI and MVD who underwent primary PCI. We enrolled 575 consecutive patients with STEMI and MVD who visited Chonnam National University Hospital from January 2006 to July 2009. All patients underwent primary PCI within 120 min after being admitted to the hospital. We selected 474 patients after exclusion of patients who presented with cardiogenic shock. Patients were divided into three groups based on the initial interventional strategy: staged PCI (initial index intervention and secondary elective staged PCI during index hospitalization, n = 252); ad hoc (simultaneous infarct-related and non infarct-related artery intervention during the index procedure, n = 67); and culprit-vessel only PCI (CVR, n = 155). The primary endpoint was composite outcome including death from all causes, myocardial infarction (MI) and repeat PCI during 3-year clinical follow-up visits. Repeat PCI included target lesion revascularization, target vessel revascularization and non-target vessel revascularization. Three-year composite outcomes and death from all causes or MI were evaluated using the Kaplan–Meier analysis and compared using a log-rank test. Cox regression analysis was used to identify the clinical impact of staged PCI with complete revascularization (CR) adjusted with clinically relevant covariates. All variables were considered significant when the p-value was b0.05. There were no significant differences in baseline and angiographic characteristics among groups except for more aged persons (staged vs. ad hoc vs. CVR; 68.8 ± 10.8 vs. 65.5 ± 12.8 vs. 70.7 ± 13.7, p = 0.012), more