- Email: [email protected]
Right Ventricular Ejection Fraction in Ischemic Versus Nonischemic Cardiomyopathy
Right Ventricular Ejection Fraction in Ischemic Versus Nonischemic Cardiomyopathy Stephen Wasemiller, MDa,*, Tiffany Earle, MDa, Michael Kashner, PhDa,b, Gary Foster, MDa,b, and Helme Silvet, MDa,b The relation between the etiology of cardiomyopathy and the function of the right ventricle (RV) has not been well described in the current era of 3-dimensional cardiac imaging. New advances in cardiac imaging with computed tomography (CT) have allowed accurate measurements of ejection fraction (EF), often a challenging task considering the unique RV shape. We evaluated 130 patients at the Loma Linda Veterans Affairs Healthcare System with cardiomyopathy and a left ventricular (LV) EF £40%. Etiology of cardiomyopathy was determined by CT angiography as ischemic (n [ 56) or nonischemic (n [ 74). RV volumes and RVEF were calculated based on 3-dimensional data set from CT images. Baseline LVEF was similar with a mean LVEF of 28% (–6%) in the ischemic group and 28% (–9%) in the nonischemic group (p [ 0.46). RV function and volumes were moderately decreased in both cohorts, without significant difference between the groups (mean RVEF 34 – 11% in ischemic group and 32 – 10% in nonischemic group, p [ 0.26). In conclusion, most patients with LV dysfunction also have RV dysfunction. The degree of RV dysfunction is not dependent on the etiology of cardiomyopathy. Ó 2016 Elsevier Inc. All rights reserved. (Am J Cardiol 2016;117:278e281)
Cardiomyopathy associated with a low left ventricular (LV) ejection fraction (EF) is a common condition with known adverse prognosis.1,2 In practice, the etiology of cardiomyopathy is characterized as either ischemic or nonischemic based on the presence or absence of coronary artery disease.2e5 Patients with depressed LV systolic function often have depressed right ventricular (RV) systolic function, although the extent of dysfunction has not been well characterized in different types of cardiomyopathy.6,7 Earlier studies have suggested that RV function is more depressed in patients with idiopathic dilated cardiomyopathy compared with ischemic cardiomyopathy.8e10 However, these studies were limited by small sample sizes and by a lack of accurate RV measurement methods. Newer, 3-dimensional imaging modalities have greatly improved the accuracy of RV evaluation.11 Both cardiac magnetic resonance imaging and cardiac computed tomography (CT) have now been shown to accurately measure RV volumes and EF.12e18 The purpose of this study was to investigate RV function in a cohort of patients with both ischemic and nonischemic cardiomyopathy using cardiac CT to accurately evaluate RV volumes and RVEF. Methods We conducted a single-center, cross-sectional cohort study at the Loma Linda Veterans Affairs Healthcare System located in Loma Linda, California. Study protocol was approved by the a Loma Linda University Health and bVeterans Affairs Loma Linda Healthcare System, Loma Linda, California. Manuscript received July 22, 2015; revised manuscript received and accepted October 14, 2015. The authors of the article were solely responsible for the preparation, composition, and submission of this study. See page 280 for disclosure information. *Corresponding author: Tel: (701) 640-5679, (909) 583-6097; fax: (909) 777-3273. E-mail address: [email protected] (S. Wasemiller).
0002-9149/15/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.10.033
institutional review board. Patients were included in the study if they had pre-existing LV dysfunction and had a cardiac CT angiography study at the Loma Linda Veterans Affairs Hospital between 2005 and 2011. Cardiomyopathy was determined to be either ischemic or nonischemic in etiology based on data obtained from cardiac CT angiography. Inclusion criteria dictated that subjects have (1) LVEF of 40% confirmed by cardiac CT, (2) cardiac CT image quality adequate to evaluate for the presence or absence of flow-limiting coronary artery disease, and (3) adequate image quality for LV and RV volume analysis. Patients who did not have cardiac CT angiography images available for evaluation through the Veterans Affairs computer system were excluded from the study. Cardiac CT images were obtained using a Toshiba Aquilion 16-slice before September 2007 (Toshiba America Medical Systems, Tustin, California) and Siemens Definition 64-slice dual-source scanner after September 2007 (Siemens AG, Erlangen, Germany). The cardiac CT images were then evaluated for coronary artery stenosis and cardiac chamber sizing using a Vitrea 2 software and analysis package as part of usual care (Vital Images, Minnetonka, Minnesota). LV volumes were evaluated from gated 3-dimensional data sets by automated LV volume measurements, with manual corrections when needed. RV volumes were determined later as part of this research study by manually tracing the RV endocardial surface in the short-axis view at peak systole and at peak diastole from pre-existing CT data sets. From these measurements RVEF was calculated. This technique of using 16- and 64-slice CT images for RV volume assessment has been previously shown to be a reliable method compared with cardiac magnetic resonance, the gold standard for cardiac chamber volume assessment.18,19 Etiology of cardiomyopathy was determined by standard criteria based on coronary imaging on the same data set. Patients found to have a 70% stenotic lesion in a proximal or midsection of at least one major epicardial coronary artery www.ajconline.org
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Table 1 Prevalence and means of baseline clinical variables and their correlation with cardiomyopathy etiology Variable
Nonischemic (n ¼ 74)
Ischemic (n ¼ 56)
t e Test, (c2 test)*
p e Value
60 9 30 8 65 % 53 % 27 % 15 % 46 % 15 % 16 % 22 %
64 9 29 5 61 % 73 % 29 % 5% 43 % 5% 18 % 21 %
2.18 -0.76 0.09 4.83 0.00 2.09 0.03 3.22 0.06 0.00
0.03 0.35 0.71 0.02 0.85 0.09 0.86 0.09 0.82 1.00
5.6
0.35
Age (years) Body mass index (kg/m2) Hypertension Dyslipidemia Chronic obstructive pulmonary disease Obstructive sleep apnea Diabetes mellitus type 2 Chronic kidney disease Atrial fibrillation Smoking Alcohol Never used Former user Use 7 drinks per week Use >7 drinks per week
18 38 35 10
% % % %
34 34 27 5
% % % %
Results consider significant by p-value equal to or less than 0.05. * Chi-square test listed for categorical variables.
Table 2 Extent of coronary artery disease in patients in the ischemic cardiomyopathy cohort (n ¼ 56) Extent of Coronary Artery Disease Three-vessel disease Two-vessel disease One-vessel disease with proximal involvement of left anterior descending artery Other one-vessel disease with history of myocardial infarction Other one-vessel disease without history of myocardial infarction
n (%) 8 (14%) 24 (43%) 6 (11%) 20 (35%) 3 (5%)
evident on CT angiography were classified as having ischemic cardiomyopathy. Patients with no coronary disease evident on CT angiography, coronary disease with stenotic lesions of <70%, or coronary disease with a 70% stenotic lesion limited to a branch vessel were classified as having nonischemic cardiomyopathy. Analysis of coronary arteries on CT angiography was performed by a CT-qualified cardiologist at the Loma Linda Veterans Affairs Hospital. Demographic and clinical data were collected by patient phone calls and chart review from a computerized health record. Descriptive statistics included means and standard deviations for continuous variables and frequencies for ordinal and categorical variables. Between-group comparisons (ischemic and nonischemic cardiomyopathy) were evaluated by group means (t-statistic with unequal variance assumed) and cross tables (chi-square statistic with appropriate continuity corrections). p 0.05 was considered significant. Associations between RVEF and demographic and clinical variables were estimated using generalized linear models, with adjusted estimates for age and LVEF. Results One hundred thirty patients were included in the study. Baseline demographic and clinical variables in nonischemic
cardiomyopathy cohort (n ¼ 74) and ischemic cardiomyopathy cohort (n ¼ 56) are presented in Table 1. CT data describing the extent of coronary artery disease are presented in Table 2. LV and RV variables in nonischemic and ischemic groups are presented in detail in Table 3. LVEF was similar in both groups with a mean LVEF of 29% in the ischemic group and 28% in the nonischemic group (p ¼ 0.46). Despite the similarity in EF, LV end-diastolic volume and LV mass were significantly higher in the nonischemic group (p ¼ 0.04 and p ¼ 0.002, respectively), possibly representing a higher percentage of hypertensive cardiomyopathy in this cohort. Almost all patients in the study also had decreased RV function, with only 8 patients (6%) presenting with a normal RVEF 50%. RVEF or RV volumes did not differ significantly between the ischemic and nonischemic cohorts. Correlation between demographic and clinical variables and RV function in univariate and adjusted regression analysis is presented in Table 4. In both univariate and adjusted analysis, RVEF was correlated with LVEF. Poor RVEF was associated with younger age. Of clinical variables, only the presence of chronic obstructive pulmonary disease was found to be negatively correlated with RVEF (p ¼ 0.046). This correlation remained significant after adjusting for LVEF and age. When controlled for age and LVEF, RVEF did not correlate with the presence of coronary artery disease (p ¼ 0.44) or with the presence of right coronary artery disease (p ¼ 0.55). Additional correlation analyses performed in the ischemic and nonischemic subgroups did not yield any other significant variable correlations. Discussion Considering the evidence showing that RV failure is commonly caused by LV failure,11,20,21 it is not surprising to see the statistically significant correlation between RVEF and LVEF in our study. The unexpected finding in our study was the presence and extent of RV dysfunction in the population of patients with LV dysfunction. In patients with
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Table 3 Left ventricular and right ventricular baseline variables with correlation to cardiomyopathy etiology Variable
Nonischemic
Left ventricular ejection fraction Left ventricular end-diastolic volume (mL) Left ventricular end-systolic volume (mL) Left ventricle mass (g) Right ventricular ejection fraction Right ventricular end-diastolic volume (mL) Right ventricular end-systolic volume (mL)
28 246 177 251 32 233 162
9 77 78 60 10 77 69
Ischemic
teTest
peValue
0.75 - 2.09 - 1.92 - 3.16 1.13 - 0.33 - 0.40
0.46 0.04 0.06 0.002 0.26 0.74 0.69
28 221 155 219 34 228 156
6 54 50 56 12 90 88
Results consider significant by p-value equal to or less than 0.05.
Table 4 Correlation of right ventricular ejection fraction with selected clinical variables Variable
Age (years) Left ventricular ejection fraction Coronary artery disease Right coronary artery disease Hypertension Chronic obstructive pulmonary disease Obstructive sleep apnea Smoking Alcohol use†
Unadjusted
Adjusted*
b
95% CI
c
p - Value
b
95% CI
c2
p - Value
0.32 0.62 2.31 2.15 1.41 - 4.49
0.12 e 0.54 0.39 e 0.84 - 1.65 e 6.27 - 1.95 e 6.26 - 2.81 e 5.69 - 8.90 e (-0.07)
9.16 28.4 1.30 1.06 0.43 3.97
0.002 <0.001 0.25 0.30 0.51 0.046
0.25 0.57 1.38 1.10 - 0.68 - 4.87
0.06 - 0.45 0.34 e 0.80 - 2.10 e 4.87 - 2.52 e 4.72 - 4.56 e 3.20 - 8.88 e (-0.86)
6.50 22.92 0.60 0.36 0.12 5.67
0.01 <0.001 0.44 0.55 0.73 0.017
- 1.13 - 0.33
- 5.47 e 3.21 - 4.52 e 3.85
0.26 0.03 6.31
0.61 0.87 0.28
- 2.65 1.05
- 7.50 e 2.19 - 2.88 e 4.98
1.15 0.27 7.83
0.28 0.60 0.17
2
Results consider significant by p-value equal to or less than 0.05. * Adjusted for age and left ventricular ejection fraction. † Alcohol use in 6 categories: never used, former user, current user <4 drinks per week, current user 4 to 7 drinks per week, current user 8 to 14 drinks per week, current user >14 drinks per week.
cardiomyopathy, the evaluation of RV function is often an “afterthought” and is usually not performed with the same accuracy as the evaluation of LV function, mostly because of lack of convenient accurate modalities to do so. As a result, clinicians may not be aware of the presence of RV dysfunction. With the emergence of 3-dimensional modalities such as cardiac CT, 3-dimensional echocardiography and cardiac magnetic resonance imaging, accurate RV function and volume evaluation should become routine in future clinical practice. Previous studies have suggested that RV dysfunction may be a clinical marker for morbidity and mortality,22 making RV evaluation an even greater priority. Smaller studies in the past have suggested that poor RV function is more common in patients whose cardiomyopathy is of nonischemic etiology.10 Contrary to these findings, RVEF did not differ between ischemic and nonischemic cardiomyopathy in our cohort. LV dysfunction strongly predicted RV dysfunction in our cohort regardless of the etiology of cardiomyopathy, suggesting that it is the presence of LV dysfunction itself that is associated with RV dysfunction rather than the etiology of LV dysfunction. The pathophysiology of RV dysfunction in patients with cardiomyopathy is not well understood. Previous hypotheses explaining this disease process include pulmonary venous hypertension, ventricular interdependence, disruption of neurohormonal processes, and intrinsic derangements with the myocardium itself, including ischemia.20 It has been determined that these processes have the potential of
contributing to RV failure, which is suspected to be a final pathway in patients with cardiomyopathy.23 In our study, we did not see a correlation between RVEF and other parameters such as coronary artery disease, hypertension, alcohol use, or smoking; however, our study sample may have been too small to reliably evaluate this. Interestingly, RVEF did not correlate with the presence or absence of right coronary artery disease in contrast to previous studies.24e26 This may be due to a small sample size or LV dysfunction having a larger effect on RVEF than right coronary artery disease. The correlation between chronic obstructive pulmonary disease and reduced RVEF was expected as several studies have shown the causal relation between pulmonary disease and RV heart failure.27,28 Although our study looked at a relatively small patient population, our findings make a strong case for a more routine evaluation of RV function. More studies are needed to understand the prognostic implications of RV dysfunction in different types of cardiomyopathy. Management of RV pathology is not well addressed in current guidelines. This may be due to a lack of widely accepted standards in RV imaging as it is still a growing field. Disclosures The authors have no conflicts of interest to disclose. 1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ,
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Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Executive summary: heart disease and stroke statisticse2013 update: a report from the American Heart Association. Circulation 2013;127: 143e152. Shafazand M, Schaufelberger M, Lappas G, Swedberg K, Rosengren A. Survival trends in men and women with heart failure of ischaemic and non-ischaemic origin: data for the period 1987-2003 from the Swedish Hospital Discharge Registry. Eur Heart J 2009;30:671e678. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996;93:841e842. Felker MG, Shaw LK, O’Connor CM. A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol 2002;39:210e218. Bart BA, Shaw LK, McCants CB Jr, Fortin DF, Lee KL, Califf RM, O’Connor CM. Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am Coll Cardiol 1997;30:1002e1008. Meyer P, Filippatos GS, Ahmed MI, Iskandrian AE, Bittner V, Perry GJ, White M, Aban IB, Mujib M, Dell’Italia LJ, Ahmed A. Effects of right ventricular ejection fraction on outcomes in chronic systolic heart failure. Circulation 2010;121:252e258. Adhyapak SM. Effect of right ventricular function and pulmonary pressures on heart failure prognosis. Prev Cardiol 2010;13:72e77. La Vecchia L, Paccanaro M, Bonanno C, Varotto L, Ometto R, Vincenzi M. Left ventricular versus biventricular dysfunction in idiopathic dilated cardiomyopathy. Am J Cardiol 1999;83:120e122. La Vecchia L, Zanolla L, Varotto L, Bonanno C, Spadaro GL, Ometto R, Fontanelli A. Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction. Am Heart J 2001;142:181e189. Juillière Y, Buffet P, Marie PY, Berder V, Danchin N, Cherrier F. Comparison of right ventricular systolic function in idiopathic dilated cardiomyopathy and healed anterior wall myocardial infarction associated with atherosclerotic coronary artery disease. Am J Cardiol 1994;73:588e590. Haddad F, Hunt S, Rosenthal D, Murphy D. Right ventricular function in cardiovascular disease, Part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008;117: 1436e1448. Markiewicz W, Sechtem U, Higgins C. Evaluation of the right ventricle by magnetic resonance imaging. Am Heart J 1987;113:8e15. Pattynama P, Lamb H, Van der Velde E, Van der Geest R, Van der Wall E, De Roos A. Reproducibility of MRI-derived measurements of right ventricular volumes and myocardial mass. Magn Reson Imaging 1995;13:53e63. Suzuki J, Caputo GR, Masui T, Chang JM, O’Sullivan M, Higgins CB. Assessment of right ventricular diastolic and systolic function in
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patients with dilated cardiomyopathy using cine magnetic resonance imaging. Am Heart J 1991;122:1035e1040. Pickett CA, Cheezum MK, Kassop D, Villines TC, Hulten EA. Accuracy of cardiac CT, radionucleotide and invasive ventriculography, two- and three-dimensional echocardiography, and SPECT for left and right ventricular ejection fraction compared with cardiac MRI: a meta-analysis. Eur Heart J Cardiovasc Imaging 2015;16: 848e852. Maffei E, Messalli G, Martini C, Nieman K, Catalano O, Rossi A, Seitun S, Guaricci AI, Tedeschi C, Mollet NR, Cademartiri F. Left and right ventricle assessment with cardiac CT: validation study vs. cardiac MR. Eur Radiol 2012;22:1041e1049. Dupont M, Dragean C, Coche E. Right ventricle function assessment by MDCT. AJR Am J Roentgenol 2011;196:77e86. Plumhans C, Mühlenbruch G, Rapaee A, Sim KH, Seyfarth T, Günther R, Mahnken A. Assessment of global right ventricular function on 64-MDCT compared with MRI. AJR Am J Roentgenol 2008;190: 1358e1361. Koch K, Oellig F, Oberholzer K, Kunz P, Mildenberger P, Hake U, Kreitner KF, Thelen M. Assessment of right ventricular function by 16-detector-row CT: comparison with magnetic resonance imaging. Eur Radiol 2005;15:312e318. Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 2008;117: 1717e1731. Juilliere Y, Barbier G, Feldmann L, Grentzinger A, Danchin N, Cherrier F. Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J 1997;18:276e280. Cameli M, Righini FM, Lisi M, Bennati E, Navarri R, Lunghetti S, Padeletti M, Cameli P, Tsioulpas C, Bernazzali S, Maccherini M, Sani G, Henein M, Mondillo S. Comparison of right versus left ventricular strain analysis as a predictor of outcome in patients with systolic heart failure referred for heart transplantation. Am J Cardiol 2013;112: 1778e1784. Voelkel NF, Quaife RA, Leinwand LA, Barst RJ, McGoon MD, Meldrum DR, Dupuis J, Long CS, Rubin LJ, Smart FW, Suzuki YJ, Gladwin M, Denholm EM, Gail DB. Right ventricular function and failure: report of a National Heart, Lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure. Circulation 2006;114:1883e1891. Goldstein JA. Pathophysiology and management of right heart ischemia. J Am Coll Cardiol 2002;40:841e853. Kinch JW, Ryan TJ. Right ventricular infarction. N Engl J Med 1994;330:1211e1217. Bowers TR, O’Neill WW, Pica M, Goldstein JA. Patterns of coronary compromise resulting in acute right ventricular ischemic dysfunction. Circulation 2002;106:1104e1109. MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1994;150:833e852. Brent BN, Berger HJ, Matthay RA, Mahler D, Pytlik L, Zaret BL. Physiologic correlates of right ventricular ejection fraction in chronic obstructive pulmonary disease: a combined radionuclide and hemodynamic study. Am J Cardiol 1982;50:255e262.
Cardiomyopathy associated with a low left ventricular (LV) ejection fraction (EF) is a common condition with known adverse prognosis.1,2 In practice, the etiology of cardiomyopathy is characterized as either ischemic or nonischemic based on the presence or absence of coronary artery disease.2e5 Patients with depressed LV systolic function often have depressed right ventricular (RV) systolic function, although the extent of dysfunction has not been well characterized in different types of cardiomyopathy.6,7 Earlier studies have suggested that RV function is more depressed in patients with idiopathic dilated cardiomyopathy compared with ischemic cardiomyopathy.8e10 However, these studies were limited by small sample sizes and by a lack of accurate RV measurement methods. Newer, 3-dimensional imaging modalities have greatly improved the accuracy of RV evaluation.11 Both cardiac magnetic resonance imaging and cardiac computed tomography (CT) have now been shown to accurately measure RV volumes and EF.12e18 The purpose of this study was to investigate RV function in a cohort of patients with both ischemic and nonischemic cardiomyopathy using cardiac CT to accurately evaluate RV volumes and RVEF. Methods We conducted a single-center, cross-sectional cohort study at the Loma Linda Veterans Affairs Healthcare System located in Loma Linda, California. Study protocol was approved by the a Loma Linda University Health and bVeterans Affairs Loma Linda Healthcare System, Loma Linda, California. Manuscript received July 22, 2015; revised manuscript received and accepted October 14, 2015. The authors of the article were solely responsible for the preparation, composition, and submission of this study. See page 280 for disclosure information. *Corresponding author: Tel: (701) 640-5679, (909) 583-6097; fax: (909) 777-3273. E-mail address: [email protected] (S. Wasemiller).
0002-9149/15/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.10.033
institutional review board. Patients were included in the study if they had pre-existing LV dysfunction and had a cardiac CT angiography study at the Loma Linda Veterans Affairs Hospital between 2005 and 2011. Cardiomyopathy was determined to be either ischemic or nonischemic in etiology based on data obtained from cardiac CT angiography. Inclusion criteria dictated that subjects have (1) LVEF of 40% confirmed by cardiac CT, (2) cardiac CT image quality adequate to evaluate for the presence or absence of flow-limiting coronary artery disease, and (3) adequate image quality for LV and RV volume analysis. Patients who did not have cardiac CT angiography images available for evaluation through the Veterans Affairs computer system were excluded from the study. Cardiac CT images were obtained using a Toshiba Aquilion 16-slice before September 2007 (Toshiba America Medical Systems, Tustin, California) and Siemens Definition 64-slice dual-source scanner after September 2007 (Siemens AG, Erlangen, Germany). The cardiac CT images were then evaluated for coronary artery stenosis and cardiac chamber sizing using a Vitrea 2 software and analysis package as part of usual care (Vital Images, Minnetonka, Minnesota). LV volumes were evaluated from gated 3-dimensional data sets by automated LV volume measurements, with manual corrections when needed. RV volumes were determined later as part of this research study by manually tracing the RV endocardial surface in the short-axis view at peak systole and at peak diastole from pre-existing CT data sets. From these measurements RVEF was calculated. This technique of using 16- and 64-slice CT images for RV volume assessment has been previously shown to be a reliable method compared with cardiac magnetic resonance, the gold standard for cardiac chamber volume assessment.18,19 Etiology of cardiomyopathy was determined by standard criteria based on coronary imaging on the same data set. Patients found to have a 70% stenotic lesion in a proximal or midsection of at least one major epicardial coronary artery www.ajconline.org
Cardiomyopathy/Right Ventricular Ejection Fraction
279
Table 1 Prevalence and means of baseline clinical variables and their correlation with cardiomyopathy etiology Variable
Nonischemic (n ¼ 74)
Ischemic (n ¼ 56)
t e Test, (c2 test)*
p e Value
60 9 30 8 65 % 53 % 27 % 15 % 46 % 15 % 16 % 22 %
64 9 29 5 61 % 73 % 29 % 5% 43 % 5% 18 % 21 %
2.18 -0.76 0.09 4.83 0.00 2.09 0.03 3.22 0.06 0.00
0.03 0.35 0.71 0.02 0.85 0.09 0.86 0.09 0.82 1.00
5.6
0.35
Age (years) Body mass index (kg/m2) Hypertension Dyslipidemia Chronic obstructive pulmonary disease Obstructive sleep apnea Diabetes mellitus type 2 Chronic kidney disease Atrial fibrillation Smoking Alcohol Never used Former user Use 7 drinks per week Use >7 drinks per week
18 38 35 10
% % % %
34 34 27 5
% % % %
Results consider significant by p-value equal to or less than 0.05. * Chi-square test listed for categorical variables.
Table 2 Extent of coronary artery disease in patients in the ischemic cardiomyopathy cohort (n ¼ 56) Extent of Coronary Artery Disease Three-vessel disease Two-vessel disease One-vessel disease with proximal involvement of left anterior descending artery Other one-vessel disease with history of myocardial infarction Other one-vessel disease without history of myocardial infarction
n (%) 8 (14%) 24 (43%) 6 (11%) 20 (35%) 3 (5%)
evident on CT angiography were classified as having ischemic cardiomyopathy. Patients with no coronary disease evident on CT angiography, coronary disease with stenotic lesions of <70%, or coronary disease with a 70% stenotic lesion limited to a branch vessel were classified as having nonischemic cardiomyopathy. Analysis of coronary arteries on CT angiography was performed by a CT-qualified cardiologist at the Loma Linda Veterans Affairs Hospital. Demographic and clinical data were collected by patient phone calls and chart review from a computerized health record. Descriptive statistics included means and standard deviations for continuous variables and frequencies for ordinal and categorical variables. Between-group comparisons (ischemic and nonischemic cardiomyopathy) were evaluated by group means (t-statistic with unequal variance assumed) and cross tables (chi-square statistic with appropriate continuity corrections). p 0.05 was considered significant. Associations between RVEF and demographic and clinical variables were estimated using generalized linear models, with adjusted estimates for age and LVEF. Results One hundred thirty patients were included in the study. Baseline demographic and clinical variables in nonischemic
cardiomyopathy cohort (n ¼ 74) and ischemic cardiomyopathy cohort (n ¼ 56) are presented in Table 1. CT data describing the extent of coronary artery disease are presented in Table 2. LV and RV variables in nonischemic and ischemic groups are presented in detail in Table 3. LVEF was similar in both groups with a mean LVEF of 29% in the ischemic group and 28% in the nonischemic group (p ¼ 0.46). Despite the similarity in EF, LV end-diastolic volume and LV mass were significantly higher in the nonischemic group (p ¼ 0.04 and p ¼ 0.002, respectively), possibly representing a higher percentage of hypertensive cardiomyopathy in this cohort. Almost all patients in the study also had decreased RV function, with only 8 patients (6%) presenting with a normal RVEF 50%. RVEF or RV volumes did not differ significantly between the ischemic and nonischemic cohorts. Correlation between demographic and clinical variables and RV function in univariate and adjusted regression analysis is presented in Table 4. In both univariate and adjusted analysis, RVEF was correlated with LVEF. Poor RVEF was associated with younger age. Of clinical variables, only the presence of chronic obstructive pulmonary disease was found to be negatively correlated with RVEF (p ¼ 0.046). This correlation remained significant after adjusting for LVEF and age. When controlled for age and LVEF, RVEF did not correlate with the presence of coronary artery disease (p ¼ 0.44) or with the presence of right coronary artery disease (p ¼ 0.55). Additional correlation analyses performed in the ischemic and nonischemic subgroups did not yield any other significant variable correlations. Discussion Considering the evidence showing that RV failure is commonly caused by LV failure,11,20,21 it is not surprising to see the statistically significant correlation between RVEF and LVEF in our study. The unexpected finding in our study was the presence and extent of RV dysfunction in the population of patients with LV dysfunction. In patients with
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Table 3 Left ventricular and right ventricular baseline variables with correlation to cardiomyopathy etiology Variable
Nonischemic
Left ventricular ejection fraction Left ventricular end-diastolic volume (mL) Left ventricular end-systolic volume (mL) Left ventricle mass (g) Right ventricular ejection fraction Right ventricular end-diastolic volume (mL) Right ventricular end-systolic volume (mL)
28 246 177 251 32 233 162
9 77 78 60 10 77 69
Ischemic
teTest
peValue
0.75 - 2.09 - 1.92 - 3.16 1.13 - 0.33 - 0.40
0.46 0.04 0.06 0.002 0.26 0.74 0.69
28 221 155 219 34 228 156
6 54 50 56 12 90 88
Results consider significant by p-value equal to or less than 0.05.
Table 4 Correlation of right ventricular ejection fraction with selected clinical variables Variable
Age (years) Left ventricular ejection fraction Coronary artery disease Right coronary artery disease Hypertension Chronic obstructive pulmonary disease Obstructive sleep apnea Smoking Alcohol use†
Unadjusted
Adjusted*
b
95% CI
c
p - Value
b
95% CI
c2
p - Value
0.32 0.62 2.31 2.15 1.41 - 4.49
0.12 e 0.54 0.39 e 0.84 - 1.65 e 6.27 - 1.95 e 6.26 - 2.81 e 5.69 - 8.90 e (-0.07)
9.16 28.4 1.30 1.06 0.43 3.97
0.002 <0.001 0.25 0.30 0.51 0.046
0.25 0.57 1.38 1.10 - 0.68 - 4.87
0.06 - 0.45 0.34 e 0.80 - 2.10 e 4.87 - 2.52 e 4.72 - 4.56 e 3.20 - 8.88 e (-0.86)
6.50 22.92 0.60 0.36 0.12 5.67
0.01 <0.001 0.44 0.55 0.73 0.017
- 1.13 - 0.33
- 5.47 e 3.21 - 4.52 e 3.85
0.26 0.03 6.31
0.61 0.87 0.28
- 2.65 1.05
- 7.50 e 2.19 - 2.88 e 4.98
1.15 0.27 7.83
0.28 0.60 0.17
2
Results consider significant by p-value equal to or less than 0.05. * Adjusted for age and left ventricular ejection fraction. † Alcohol use in 6 categories: never used, former user, current user <4 drinks per week, current user 4 to 7 drinks per week, current user 8 to 14 drinks per week, current user >14 drinks per week.
cardiomyopathy, the evaluation of RV function is often an “afterthought” and is usually not performed with the same accuracy as the evaluation of LV function, mostly because of lack of convenient accurate modalities to do so. As a result, clinicians may not be aware of the presence of RV dysfunction. With the emergence of 3-dimensional modalities such as cardiac CT, 3-dimensional echocardiography and cardiac magnetic resonance imaging, accurate RV function and volume evaluation should become routine in future clinical practice. Previous studies have suggested that RV dysfunction may be a clinical marker for morbidity and mortality,22 making RV evaluation an even greater priority. Smaller studies in the past have suggested that poor RV function is more common in patients whose cardiomyopathy is of nonischemic etiology.10 Contrary to these findings, RVEF did not differ between ischemic and nonischemic cardiomyopathy in our cohort. LV dysfunction strongly predicted RV dysfunction in our cohort regardless of the etiology of cardiomyopathy, suggesting that it is the presence of LV dysfunction itself that is associated with RV dysfunction rather than the etiology of LV dysfunction. The pathophysiology of RV dysfunction in patients with cardiomyopathy is not well understood. Previous hypotheses explaining this disease process include pulmonary venous hypertension, ventricular interdependence, disruption of neurohormonal processes, and intrinsic derangements with the myocardium itself, including ischemia.20 It has been determined that these processes have the potential of
contributing to RV failure, which is suspected to be a final pathway in patients with cardiomyopathy.23 In our study, we did not see a correlation between RVEF and other parameters such as coronary artery disease, hypertension, alcohol use, or smoking; however, our study sample may have been too small to reliably evaluate this. Interestingly, RVEF did not correlate with the presence or absence of right coronary artery disease in contrast to previous studies.24e26 This may be due to a small sample size or LV dysfunction having a larger effect on RVEF than right coronary artery disease. The correlation between chronic obstructive pulmonary disease and reduced RVEF was expected as several studies have shown the causal relation between pulmonary disease and RV heart failure.27,28 Although our study looked at a relatively small patient population, our findings make a strong case for a more routine evaluation of RV function. More studies are needed to understand the prognostic implications of RV dysfunction in different types of cardiomyopathy. Management of RV pathology is not well addressed in current guidelines. This may be due to a lack of widely accepted standards in RV imaging as it is still a growing field. Disclosures The authors have no conflicts of interest to disclose. 1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ,
Cardiomyopathy/Right Ventricular Ejection Fraction
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