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Differences in Clinical Profile of African-American Women With Peripartum Cardiomyopathy in the United States
Journal of Cardiac Failure Vol. 19 No. 4 2013
Clinical Investigations
Differences in Clinical Profile of African-American Women With Peripartum Cardiomyopathy in the United States SOREL GOLAND, MD,1 KALGI MODI, MD,2 PARTA HATAMIZADEH, MD,3 AND URI ELKAYAM, MD3 Rehovot, Israel; Shreveport, Louisiana; and Los Angeles, California
ABSTRACT Background: Peripartum cardiomyopathy (PPCM) is a rare and heterogeneous disease with a higher prevalence in African Americans (AAs) in the USA. The clinical features and prognosis of PPCM in AAs have not been sufficiently characterized. Methods: We studied 52 AA patients with PPCM and compared clinical characteristics and outcome with those of 104 white patients. Results: AA patients were significantly younger (26 6 7 vs 30 6 6 years; P ! .001), had a higher prevalence of gestational hypertension (61% vs 41%; P 5 .03), and were diagnosed more commonly postpartum rather then antepartum (83% vs 64%; P 5 .03). The rate of left ventricular (LV) recovery (LV ejection fraction [LVEF] $50%) was significantly lower in AAs (40% vs 61%; P 5 .02). AA women also had a larger LV end-diastolic diameter (57 6 10 vs 51 6 6 mm; P 5 .004) as well as lower LVEF (40% 6 16.7% vs 46% 6 14%; P 5 .002) at the last follow-up. Moreover, AA patients had a significantly higher incidence of the combined end points of mortality and cardiac transplantation (P 5 .03) and showed a strong trend (P 5 .09) for increased mortality. Conclusions: AA patients with PPCM in the USA have a different clinical profile and worse prognosis compared with white patients. Further research to evaluate potentially correctable causes for these differences is warranted. (J Cardiac Fail 2013;19:214e218) Key Words: Peripartum cardiomyopathy, racial differences, African American.
differences in presentation as well as outcome between AA patients and women of other ethnic groups.2,3,8,9 Better definition of such differences may be of great importance and can serve to improve diagnostic as well as therapeutic strategies for this patient population. The purpose of the present study was, therefore, to compare the clinical profile of AA patients with PPCM and that of white patients, in an attempt to identify differences in clinical characteristics of PPCM in AA women in the USA.
Peripartum cardiomyopathy (PPCM) is a relatively rare form of cardiac failure associated with pregnancy; it can lead to severe and lasting morbidity and is an important cause of maternal mortality.1e3 This disease shows a rising incidence and is estimated to affect w1,300 new cases annually in the USA.1,4 Although PPCM can involve women of different ethnic backgrounds,3,5,6 the prevalence among African American (AA) patients has been reported to be considerably higher compared with other ethnic groups in the USA.3,5e7 In addition, preliminary data have suggested
Methods 1
From the Department of Cardiology, Kaplan Medical Center, Rehovot, Israel; 2Louisiana State University Health Science Center, Shreveport, Louisiana and 3Heart Failure Program, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. Manuscript received December 15, 2012; revised manuscript received March 5, 2013; revised manuscript accepted March 6, 2013. Reprint requests: Uri Elkayam, MD, LAC/USC Medical Center, 2020 Zonal Avenue, Los Angeles, CA 90033. E-mail: [email protected] See page 217 for disclosure information. 1071-9164/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2013.03.004
This is a retrospective analysis of data obtained in 187 patients diagnosed with PPCM. One hundred fifty-three patients were part of the database established at the University of Southern California from 1994 to 2007, and 34 patients were diagnosed and cared for at the Louisiana State University Health Science Center, Shreveport, Louisiana (1993e2000). Relevant information was collected through review of records as well as interviews of some of the patients and/or their referring physicians. The study was conducted with approval of the respective Institutional Review Boards.
214
PPCM in African-American Women The diagnosis of PPCM was based on recommended criteria by a workshop convened by the National Heart Lung and Blood Institute and the Office of Rare Diseases of the National Institutes of Health11: 1) development of congestive heart failure during pregnancy or the first 5 months after delivery; 2) absence of an identifiable cause for cardiac failure; 3) absence of recognizable heart disease before pregnancy; and 4) left ventricular (LV) systolic dysfunction with ejection fraction (EF) !45%.10,11 Patient with preexisting cardiac disease or LVEF O45% were excluded. Statistical Analysis This was a retrospective analysis designed to describe differences between AA and white patients with PPCM in clinical characteristics, as well as outcome criteria, including LV recovery, a number of major adverse events as well as death and a combined rate of death and heart transplantation. Variables used for the statistical analysis included the mean age, mean index pregnancy, twin pregnancy, history of hypertension during pregnancy, use of tocolytic therapy, the occurrence of symptoms of heart failure before delivery (antepartum) and after delivery (postpartum), New York Heart Association (NYHA) functional class, rate of cesarean section, mean LV end-diastolic dimension (LVEDD), and mean LVEF as measured by echocardiography. In addition, the rate of complications including death, transplantation, circulatory support, cardiopulmonary arrest, thromboembolic events, and serious brady- or tachyarrhythmias requiring pacemaker and automatic implanted cardiac defibrillator (AICD) were also included. Summary statistics for numeric variables were presented as mean 6 SD. Summary statistics for categoric variables were presented as n (%). Two-group differences on continuous outcome measures were assessed by the t test or Mann-Whitney test, as appropriate. Two-group differences on categoric outcomes were assessed by the Fisher exact test. Survival curves were estimated by the Kaplan-Meier method. Group differences in survival were assessed by the log-rank test. A P value of !.05 was regarded to be statistically significant. Statistical calculations were performed using the statistical software package SPSS version 11.5 statistical software.
Results
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recovery of LV function (EF $50%) was observed in 55% of patients. Differences in Baseline Clinical Characteristics Between AA and White Patients With PPCM
The baseline clinical characteristics of both groups are presented in Table 1. AA patients were significantly younger as represented by a lower mean age (26 6 7% vs 30 6 6 years; P ! .001) as well as by a larger number of patients older than 30 years (29% vs 55%; P 5 .002). The development of symptoms and time of diagnosis occurred after the delivery in the great majority of AA patients (83%) compared with 64% of white patients (P 5 .03). In addition, the number of patients with severe symptoms at the time of diagnosis was higher in AAs, with 72% presenting with NYHA functional class III and IV compared with 42% of whites (P 5 .008; Fig. 1). There were no significant differences in other characteristics, including index pregnancy, prevalence of twin pregnancy, use of tocolytic therapy, and rate of cesarean section. Differences in Left Ventricular Function and Size
Degree of LV systolic dysfunction was similar at the time of diagnosis between AA and white patients (Table 1, Fig. 1) as reflected by the group mean LVEF values (2.83 6 10.5% vs 27.8 6 10.0%; P 5 .8.) and the proportion of patients with LVEF !25% (54% vs 47%; P 5 .5). However, AAs had significantly larger LV size (60 6 6 mm vs 56 6 7 mm; P 5 .001). Improvement of LV function occurred in both groups over time, but to a lesser degree in AAs (Fig. 1). At the last follow-up (13.0 6 10.4 months for whites and 14.9 6 13.7 months for AAs), LVEF was significantly lower (39 6 17% vs 46 6 14%; P 5 .002) and LVEDD was significantly larger (57 6 10 mm vs 51 6 6 mm; P 5 .004) in AAs. In addition, AA patients had a significantly lower rate of complete recovery of LV function (LVEF O50%): only 40% compared with 61% of Table 1. Comparison Between Clinical Characteristics of African-American (AA) and White PPCM Patients
Clinical Characteristics of All PPCM Patients
One hundred four of the patients were white, 52 AA, 23 Hispanic, and 8 Asian. Because of the small numbers, Hispanic and Asian patients were excluded from the analysis. The mean age for the entire patient population (156 patients) was 29 6 7 years. Mean index pregnancy was 1.9 6 1.7, and 16% of patients had twin pregnancies. History of hypertension during pregnancy was obtained in 46% of the patients, and use of tocolytic therapy was reported in 20%. The occurrence of symptoms before delivery was reported in 32%. Mean LVEDD, as measured by echocardiography, was 58 6 7 mm at time of diagnosis, and mean LVEF was 28 6 10%. LVEF increased to 43 6 16% at the last follow-up (136 surviving patients with an echocardiogram $3 months after diagnosis, mean 14 6 13 months) and
Age (y) Age O30 y Gestational hypertension Twin pregnancy Index pregnancy Multiparous Tocolysis Cesarian delivery Symptoms postpartum NYHA IIIeIV LVEF baseline (%) LVEF #25% LVEDD baseline (mm)
White (n 5 104)
AA (n 5 52)
P Value
30 6 6 55% 41% 19% 2.0 6 1.7 51% 18% 44% 64% 44% 28.3610.5 47% 56 6 6
26 6 7 29% 61% 13% 1.8 6 1.6 40% 25% 40% 83% 72% 27.8 6 10.0 53% 60 6 8
!.001 .002 .03 .5 .2 .3 .4 .7 .03 .008 .8 .5 .001
PPCM, peripartum cardiomyopathy; NYHA, New York Heart Association functional class; LVEF, left ventricular ejection fraction; LVDD, left ventricular end-diastolic diameter. Data are presented as mean 6 SD or %.
216 Journal of Cardiac Failure Vol. 19 No. 4 April 2013 of cardiac transplantation and mortality compared with white patients (9/52 [17.3%] vs 7/104 [6.7%]; P 5 .03). Discussion
Fig. 1. Comparison of left ventricular ejection fraction (LVEF) at the time of the diagnosis and at follow-up between AfricanAmerican and white (‘‘Caucasian’’) women with peripartum cardiomyopathy.
white patients (P 5 .02). When comparing the AAs from the Louisiana database and USC, a trend to lower LVEF was observed in the USC group compared with the Louisiana patients (25 6 7% vs 29 6 10%, P 5 .08). No difference between LVEDD between these 2 patient populations was observed (59 6 7 mm vs 59 6 6 mm; P 5 .55). Complications and Survival in AA and White Patients With PPCM (Fig. 2)
The reported mean follow-up for the entire group of patients with PPCM was 19 6 14 months. There was a strong trend for higher incidence of serious complications, including death, transplantation, circulatory support, cardiopulmonary arrest, thromboembolic events, and serious brady- or tachyarrhythmias requiring pacemaker and AICD insertion among AA patients compared with whites (18/104 whites [17.3%] vs 16/52 AAs [30.8%]; P 5 .07). No significant difference in survival was found between the 2 groups; however, AA patients had a clear trend for higher mortality (6/52 [11.5%] vs 5/104 [4.8%]; P 5 .09) and a significantly higher incidence of the combined rate
Fig. 2. Comparison in rate of complications, mortality, and combined end points of mortality and cardiac transplantation in African-American and white (‘‘Caucasian’’) women with peripartum cardiomyopathy.
The results of the present study demonstrate significant and important differences in the clinical profile and outcome of AA women compared with white women with PPCM in the USA. Although PPCM has been shown to be associated with older maternal age,1,3,5,6 the age of AA women included in this study was significantly younger compared with white women. A possible explanation of this finding could be the higher national rate of pregnancies at younger age in AA women.12 This assumption may be supported by the finding of similar parity in AA patients with PPCM in the present study despite their younger age. A strong association has also been reported between a history of gestational hypertension and the development of PPCM in the USA.1,3,5,6,8,13 The results of the present study, as well as earlier studies,9 indicate that this association is particularly strong in the AA population. A significant difference was also noted in the timing of symptomatic presentation and diagnosis of PPCM, with a great majority of AA patients (83%) presenting postpartum compared with white women, in whom more than one-third were diagnosed antepartum. In addition, the development of PPCM in the AA patients was associated with more severe symptoms of heart failure, with O70% of the patients presenting with moderate to severe (NYHA functional III or IV) symptoms compared with fewer than one-half of the white patients. Our analysis also indicated important differences in outcome between the 2 groups. There was a strong trend for higher incidence of serious complications, including death, heart transplantation, use of circulatory support, cardiopulmonary arrest, and thromboembolic events, as well as pacemaker and AICD insertion for serious arrhythmias, among AA compared with white patients. In addition, there was a strong trend for increased mortality rate in AA patients and a statistically significant lower rate of heart transplantationefree survival. These findings of higher incidence of complications and worse outcome in AA women with PPCM are strongly supported by earlier studies. Whitehead et al,2 who used data from the Centers for Disease Control to examined pregnancy-related deaths due to cardiomyopathy from 1991 to 1997, reported a 6.4-fold increased risk of death in AA compared with white patients. More recently Harper et al,3 who performed an epidemiologic study of residences of North Carolina, found almost 4-fold increased fatality in black non-Hispanic women with PPCM compared with white women. In our previously published study,14 we found the delay of diagnosis to be an independent predictor of major adverse events in patients with PPCM. Unfortunately, we did not have information on the time delay between onset of symptoms and diagnosis in all patients analyzed for the purpose of the present study. Further investigation of the reasons for late diagnosis of
PPCM in African-American Women
PPCM in AA patients, especially if the delay is related to preventable factors, is important. Recovery of LV systolic function has been reported in O50% of women with PPCM in the USA, with the majority occurring within 2e6 months after diagnosis.8,15 Earlier studies have demonstrated a strong relationship between the degree of LVEF at time of diagnosis and recovery.16 Although LVEF at the time of diagnosis was similar between the 2 groups included in the present study, rate and magnitude of recovery of LV function was significantly lower in AA women. These findings are strongly supported by a recent study by Amos et al,8 who reported on 55 women with PPCM and described a significantly lower rate of LV functional recovery in AA compared with white patients (41% vs 74%; P 5 .03). Based on our results AAs had higher prevalence of gestational hypertension (61% vs 41%; P 5 .03) but lower rates of LV recovery. This observation is at variance with a report recently published by Safirstein et al,17 who found gestational hypertension, in mostly white women with PPCM, to be significantly associated with recovery of systolic function. Similarly, Kamiya et al reported gestational hypertension to be independently associated with a shorter hospital stay and a higher LVEF at last follow-up in a Japanese population.18 Although an explanation of the clear differences in the phenotypic presentation of PPCM in AA compared with white women in the USA is not readily available, these differences may be multifactorial, including genetic variations as well as socioeconomic causes which may account for some of the differences in epidemiology, LV recovery, and outcome between the 2 groups. Genetic differences may be supported by other reported unique characteristics in AA women with PPCM, such as a substantially increased incidence of this condition compared with women of other ethnic groups in the USA.3,5e7 In addition, timing of presentation, lower rate of recovery of LV function, and higher mortality rate of AA women demonstrated in our study are similar to those described in black patients in Haiti and South Africa.19,20 Other potential causes for differences in outcome in AA women with PPCM may be related to disparities in the utilization and quality of medical care.21 Earlier studies have provided evidence that AA patients in the USA are less likely to receive effective treatment for other cardiac conditions and have less frequent access to newer and costly cardiac procedures, such as cardiac catheterization, percutaneous interventions, coronary artery bypass surgery, and use of cardiac resynchronization therapy.22,23 Additional reports have also demonstrated that AA patients are less likely to achieve guideline-recommended therapeutic goals of proven therapy for conditions such as hyperlipidemia and hypertension.24,25 Further investigations are therefore required to better understand the causes for differences in outcome between AA and white women with PPCM in the USA in an attempt to identify potentially correctable sources that might reduce the ethnic differences demonstrated in the present study.
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Study Limitations The results of this study are based on a retrospective review of patients’ records and reports by physicians and patients. The data could, therefore, be influenced by referral as well as reporting bias and may be incomplete. The study can not provide an explanation for the differential racial outcomes, which are likely to be multifactorial, including potential genetic and physiologic variances as well as possible differences in health care. The study, however, includes the largest group of patients with PPCM reported to date in the USA and strongly supports earlier data from smaller groups, suggesting racial differences in both the presentation and outcome of PPCM in the USA. Further research is needed to identify possible modifiable factors that can lead to prevention of complications and to improved outcome of AA patients with PPCM in the USA. Conclusion The present study clearly demonstrates racial differences in clinical profile as well as outcomes of patients diagnosed with PPCM in the USA. Peripartum cardiomyopathy in AA women occurred at younger age and had stronger association with gestational hypertension compared with white women. There was a significant difference in the timing of presentation relative to time of delivery and in severity of symptoms. Whereas more than one-third of white women were diagnosed before delivery, AA patients were more likely to present postpartum and with more severe symptoms of heart failure. Although LV function was similar in both groups at time of diagnosis, rate of recovery of LVEF was significantly lower in AA patients. This difference in recovery of cardiac function was associated with worse outcome with a strong trend for higher mortality rate and a significantly higher incidence of the combined end point of mortality and cardiac transplantation. These findings strongly suggest that PPCM in AA patients in the USA is associated with a different clinical presentation and worse outcomes. Further studies are warranted to investigate potential correctable causes of these differences in an attempt to potentially improve the outcome of PPCM in AA patients. Disclosures None. References 1. Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the US: diagnosis, prognosis and management J. Am Coll Cardiol 2011;58:659e70. 2. Whitehead SJ, Berg CJ, Chang J. Pregnancy-related mortality due to cardiomyopathy: United States, 1991e1997. Obstet Gynecol 2003; 102:1326e31.
218 Journal of Cardiac Failure Vol. 19 No. 4 April 2013 3. Harper MA, Meyer RE, Berg CJ. Peripartum cardiomyopathy population-based birth prevalence 7eyear mortality. Obstet Gynecol 2012;120:1013e9. 4. Mielniczuk LM, Williams K, Davis DR, et al. Frequency of peripartum cardiomyopathy. Am J Cardiol 2006;97:1965e8. 5. Brar SS, Khan SS, Sandhu GK, et al. Incidence, mortality, and racial differences in peripartum cardiomyopathy. Am J Cardiol 2007;100: 302e4. 6. Gunderson EP, Croen LA, Chiang V, Yoshida CK, Walton D, Go AS. Epidemiology of peripartum cardiomyopathy incidence, predictors and outcomes. Obstet Gynecol 2011;118:583e91. 7. Gentry MB, Dias JK, Luis A, Patel R, Thornton J, Reed GL. African American women have a higher risk for developing peripartum cardiomyopathy. J Am Coll Cardiol 2010;55:654e9. 8. Amos AM, Jaber WA, Russell SD. Improved outcomes in peripartum cardiomyopathy with contemporary. Am Heart J 2006;152: 509e13. 9. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an ominous diagnosis. Am J Obstet Gynecol 1997;176:182e8. 10. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on etiology, diagnosis, management and therapy of peripart cardiomyopathy: a position statement from the Heart Failure Association of European Society of Cardiology Working Group on Peripartum Cardiomyopathy. Eur J Heart Failure 2010;12:767e78. 11. Pearson GD, Veille J-C, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000;283:1183e8. 12. Rost K, Henshaw S. U.S. teenage pregnancies, births and abortion, 2008: national trends by age, race and ethnicity. Guttmacher Institute. February 2012. 13. Patten IS, Rana S, Shahul S, et al. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 2012;485:333e9. 14. Goland S, Modi K, Bitar F, et al. Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Failure 2009; 15:645e50.
15. Elkayam U, Akhter MW, Singh H, et al. Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation 2005;111:2050e5. 16. Goland S, Bitar F, Modi K, et al. Evaluation of the clinical relevance of baseline left ventricular ejection fraction as a predictor of recovery or persistence of severe dysfunction in women in the United States with peripartum cardiomyopathy. J Cardiac Fail 2011;17:426e30. 17. Safirstein JG, Ro AS, Grandhi S, Wang L, Fett JD, Staniloae C. Predictors of left ventricular recovery in a cohort of peripartum cardiomyopathy patients recruited via the internet. Int J Cardiol 2012;154:27e31. 18. Kamiya CA, Kitakaze M, Ishibashi-Ueda H, et al. Different characteristics of peripartum cardiomyopathy between patients complicated with and without hypertensive disorders. Results from the Japanese Nationwide Survey of Peripartum Cardiomyopathy. Circ J 2011;75:1975e81. 19. Fett JD, Sammon H, Thelisma E, et al. Recovery from severe heart failure following peripartum cardiomyopathy. Int J Gynaecol Obstet 2009;104:125e7. 20. Blauwet LA, Libhaber E, Forster O, et al. Predictors of outcome in 176 South African patients with peripartum cardiomyopathy. Heart 2013;99:308e13. 21. Yancy CW, Wang TY, Ventura HO, et al. The Coalition to Reduce Racial and Ethnic Disparities in Cardiovascular Disease Outcomes (CREDO): why CREDO matters to cardiologists. J Am Coll Cardiol 2011;57:245e52. 22. Cram P, Bayman L, Popescu I, Vaughan-Sarrazin MS. Racial disparities in revascularization rates among patients with similar insurance coverage. J Natl Med Assoc 2009;101:1132e9. 23. Farmer SA, Kirkpatrick JN, Heidenreich PA, Curtis JP, Wang Y, Groenevld PW. Ethnic and racial disparities in cardiac resynchronization therapy. Heart Rhythm 2009;6:325e31. 24. Kaplan RC, Bhalodkar NC, Brown DL, White J, Brown EJ Jr. Difference by age and race, ethnicity in knowledge about hypercholesterolemia. Cardiol Rev 2006;14:1e6. 25. U.S. Department of Health and Human Services. The seventh report of the Joint National Committee in Prevention, Detection, Evaluation and Treatment of High Blood Pressure. NIH publication no. 04e5230. August 2004.
Clinical Investigations
Differences in Clinical Profile of African-American Women With Peripartum Cardiomyopathy in the United States SOREL GOLAND, MD,1 KALGI MODI, MD,2 PARTA HATAMIZADEH, MD,3 AND URI ELKAYAM, MD3 Rehovot, Israel; Shreveport, Louisiana; and Los Angeles, California
ABSTRACT Background: Peripartum cardiomyopathy (PPCM) is a rare and heterogeneous disease with a higher prevalence in African Americans (AAs) in the USA. The clinical features and prognosis of PPCM in AAs have not been sufficiently characterized. Methods: We studied 52 AA patients with PPCM and compared clinical characteristics and outcome with those of 104 white patients. Results: AA patients were significantly younger (26 6 7 vs 30 6 6 years; P ! .001), had a higher prevalence of gestational hypertension (61% vs 41%; P 5 .03), and were diagnosed more commonly postpartum rather then antepartum (83% vs 64%; P 5 .03). The rate of left ventricular (LV) recovery (LV ejection fraction [LVEF] $50%) was significantly lower in AAs (40% vs 61%; P 5 .02). AA women also had a larger LV end-diastolic diameter (57 6 10 vs 51 6 6 mm; P 5 .004) as well as lower LVEF (40% 6 16.7% vs 46% 6 14%; P 5 .002) at the last follow-up. Moreover, AA patients had a significantly higher incidence of the combined end points of mortality and cardiac transplantation (P 5 .03) and showed a strong trend (P 5 .09) for increased mortality. Conclusions: AA patients with PPCM in the USA have a different clinical profile and worse prognosis compared with white patients. Further research to evaluate potentially correctable causes for these differences is warranted. (J Cardiac Fail 2013;19:214e218) Key Words: Peripartum cardiomyopathy, racial differences, African American.
differences in presentation as well as outcome between AA patients and women of other ethnic groups.2,3,8,9 Better definition of such differences may be of great importance and can serve to improve diagnostic as well as therapeutic strategies for this patient population. The purpose of the present study was, therefore, to compare the clinical profile of AA patients with PPCM and that of white patients, in an attempt to identify differences in clinical characteristics of PPCM in AA women in the USA.
Peripartum cardiomyopathy (PPCM) is a relatively rare form of cardiac failure associated with pregnancy; it can lead to severe and lasting morbidity and is an important cause of maternal mortality.1e3 This disease shows a rising incidence and is estimated to affect w1,300 new cases annually in the USA.1,4 Although PPCM can involve women of different ethnic backgrounds,3,5,6 the prevalence among African American (AA) patients has been reported to be considerably higher compared with other ethnic groups in the USA.3,5e7 In addition, preliminary data have suggested
Methods 1
From the Department of Cardiology, Kaplan Medical Center, Rehovot, Israel; 2Louisiana State University Health Science Center, Shreveport, Louisiana and 3Heart Failure Program, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. Manuscript received December 15, 2012; revised manuscript received March 5, 2013; revised manuscript accepted March 6, 2013. Reprint requests: Uri Elkayam, MD, LAC/USC Medical Center, 2020 Zonal Avenue, Los Angeles, CA 90033. E-mail: [email protected] See page 217 for disclosure information. 1071-9164/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.cardfail.2013.03.004
This is a retrospective analysis of data obtained in 187 patients diagnosed with PPCM. One hundred fifty-three patients were part of the database established at the University of Southern California from 1994 to 2007, and 34 patients were diagnosed and cared for at the Louisiana State University Health Science Center, Shreveport, Louisiana (1993e2000). Relevant information was collected through review of records as well as interviews of some of the patients and/or their referring physicians. The study was conducted with approval of the respective Institutional Review Boards.
214
PPCM in African-American Women The diagnosis of PPCM was based on recommended criteria by a workshop convened by the National Heart Lung and Blood Institute and the Office of Rare Diseases of the National Institutes of Health11: 1) development of congestive heart failure during pregnancy or the first 5 months after delivery; 2) absence of an identifiable cause for cardiac failure; 3) absence of recognizable heart disease before pregnancy; and 4) left ventricular (LV) systolic dysfunction with ejection fraction (EF) !45%.10,11 Patient with preexisting cardiac disease or LVEF O45% were excluded. Statistical Analysis This was a retrospective analysis designed to describe differences between AA and white patients with PPCM in clinical characteristics, as well as outcome criteria, including LV recovery, a number of major adverse events as well as death and a combined rate of death and heart transplantation. Variables used for the statistical analysis included the mean age, mean index pregnancy, twin pregnancy, history of hypertension during pregnancy, use of tocolytic therapy, the occurrence of symptoms of heart failure before delivery (antepartum) and after delivery (postpartum), New York Heart Association (NYHA) functional class, rate of cesarean section, mean LV end-diastolic dimension (LVEDD), and mean LVEF as measured by echocardiography. In addition, the rate of complications including death, transplantation, circulatory support, cardiopulmonary arrest, thromboembolic events, and serious brady- or tachyarrhythmias requiring pacemaker and automatic implanted cardiac defibrillator (AICD) were also included. Summary statistics for numeric variables were presented as mean 6 SD. Summary statistics for categoric variables were presented as n (%). Two-group differences on continuous outcome measures were assessed by the t test or Mann-Whitney test, as appropriate. Two-group differences on categoric outcomes were assessed by the Fisher exact test. Survival curves were estimated by the Kaplan-Meier method. Group differences in survival were assessed by the log-rank test. A P value of !.05 was regarded to be statistically significant. Statistical calculations were performed using the statistical software package SPSS version 11.5 statistical software.
Results
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recovery of LV function (EF $50%) was observed in 55% of patients. Differences in Baseline Clinical Characteristics Between AA and White Patients With PPCM
The baseline clinical characteristics of both groups are presented in Table 1. AA patients were significantly younger as represented by a lower mean age (26 6 7% vs 30 6 6 years; P ! .001) as well as by a larger number of patients older than 30 years (29% vs 55%; P 5 .002). The development of symptoms and time of diagnosis occurred after the delivery in the great majority of AA patients (83%) compared with 64% of white patients (P 5 .03). In addition, the number of patients with severe symptoms at the time of diagnosis was higher in AAs, with 72% presenting with NYHA functional class III and IV compared with 42% of whites (P 5 .008; Fig. 1). There were no significant differences in other characteristics, including index pregnancy, prevalence of twin pregnancy, use of tocolytic therapy, and rate of cesarean section. Differences in Left Ventricular Function and Size
Degree of LV systolic dysfunction was similar at the time of diagnosis between AA and white patients (Table 1, Fig. 1) as reflected by the group mean LVEF values (2.83 6 10.5% vs 27.8 6 10.0%; P 5 .8.) and the proportion of patients with LVEF !25% (54% vs 47%; P 5 .5). However, AAs had significantly larger LV size (60 6 6 mm vs 56 6 7 mm; P 5 .001). Improvement of LV function occurred in both groups over time, but to a lesser degree in AAs (Fig. 1). At the last follow-up (13.0 6 10.4 months for whites and 14.9 6 13.7 months for AAs), LVEF was significantly lower (39 6 17% vs 46 6 14%; P 5 .002) and LVEDD was significantly larger (57 6 10 mm vs 51 6 6 mm; P 5 .004) in AAs. In addition, AA patients had a significantly lower rate of complete recovery of LV function (LVEF O50%): only 40% compared with 61% of Table 1. Comparison Between Clinical Characteristics of African-American (AA) and White PPCM Patients
Clinical Characteristics of All PPCM Patients
One hundred four of the patients were white, 52 AA, 23 Hispanic, and 8 Asian. Because of the small numbers, Hispanic and Asian patients were excluded from the analysis. The mean age for the entire patient population (156 patients) was 29 6 7 years. Mean index pregnancy was 1.9 6 1.7, and 16% of patients had twin pregnancies. History of hypertension during pregnancy was obtained in 46% of the patients, and use of tocolytic therapy was reported in 20%. The occurrence of symptoms before delivery was reported in 32%. Mean LVEDD, as measured by echocardiography, was 58 6 7 mm at time of diagnosis, and mean LVEF was 28 6 10%. LVEF increased to 43 6 16% at the last follow-up (136 surviving patients with an echocardiogram $3 months after diagnosis, mean 14 6 13 months) and
Age (y) Age O30 y Gestational hypertension Twin pregnancy Index pregnancy Multiparous Tocolysis Cesarian delivery Symptoms postpartum NYHA IIIeIV LVEF baseline (%) LVEF #25% LVEDD baseline (mm)
White (n 5 104)
AA (n 5 52)
P Value
30 6 6 55% 41% 19% 2.0 6 1.7 51% 18% 44% 64% 44% 28.3610.5 47% 56 6 6
26 6 7 29% 61% 13% 1.8 6 1.6 40% 25% 40% 83% 72% 27.8 6 10.0 53% 60 6 8
!.001 .002 .03 .5 .2 .3 .4 .7 .03 .008 .8 .5 .001
PPCM, peripartum cardiomyopathy; NYHA, New York Heart Association functional class; LVEF, left ventricular ejection fraction; LVDD, left ventricular end-diastolic diameter. Data are presented as mean 6 SD or %.
216 Journal of Cardiac Failure Vol. 19 No. 4 April 2013 of cardiac transplantation and mortality compared with white patients (9/52 [17.3%] vs 7/104 [6.7%]; P 5 .03). Discussion
Fig. 1. Comparison of left ventricular ejection fraction (LVEF) at the time of the diagnosis and at follow-up between AfricanAmerican and white (‘‘Caucasian’’) women with peripartum cardiomyopathy.
white patients (P 5 .02). When comparing the AAs from the Louisiana database and USC, a trend to lower LVEF was observed in the USC group compared with the Louisiana patients (25 6 7% vs 29 6 10%, P 5 .08). No difference between LVEDD between these 2 patient populations was observed (59 6 7 mm vs 59 6 6 mm; P 5 .55). Complications and Survival in AA and White Patients With PPCM (Fig. 2)
The reported mean follow-up for the entire group of patients with PPCM was 19 6 14 months. There was a strong trend for higher incidence of serious complications, including death, transplantation, circulatory support, cardiopulmonary arrest, thromboembolic events, and serious brady- or tachyarrhythmias requiring pacemaker and AICD insertion among AA patients compared with whites (18/104 whites [17.3%] vs 16/52 AAs [30.8%]; P 5 .07). No significant difference in survival was found between the 2 groups; however, AA patients had a clear trend for higher mortality (6/52 [11.5%] vs 5/104 [4.8%]; P 5 .09) and a significantly higher incidence of the combined rate
Fig. 2. Comparison in rate of complications, mortality, and combined end points of mortality and cardiac transplantation in African-American and white (‘‘Caucasian’’) women with peripartum cardiomyopathy.
The results of the present study demonstrate significant and important differences in the clinical profile and outcome of AA women compared with white women with PPCM in the USA. Although PPCM has been shown to be associated with older maternal age,1,3,5,6 the age of AA women included in this study was significantly younger compared with white women. A possible explanation of this finding could be the higher national rate of pregnancies at younger age in AA women.12 This assumption may be supported by the finding of similar parity in AA patients with PPCM in the present study despite their younger age. A strong association has also been reported between a history of gestational hypertension and the development of PPCM in the USA.1,3,5,6,8,13 The results of the present study, as well as earlier studies,9 indicate that this association is particularly strong in the AA population. A significant difference was also noted in the timing of symptomatic presentation and diagnosis of PPCM, with a great majority of AA patients (83%) presenting postpartum compared with white women, in whom more than one-third were diagnosed antepartum. In addition, the development of PPCM in the AA patients was associated with more severe symptoms of heart failure, with O70% of the patients presenting with moderate to severe (NYHA functional III or IV) symptoms compared with fewer than one-half of the white patients. Our analysis also indicated important differences in outcome between the 2 groups. There was a strong trend for higher incidence of serious complications, including death, heart transplantation, use of circulatory support, cardiopulmonary arrest, and thromboembolic events, as well as pacemaker and AICD insertion for serious arrhythmias, among AA compared with white patients. In addition, there was a strong trend for increased mortality rate in AA patients and a statistically significant lower rate of heart transplantationefree survival. These findings of higher incidence of complications and worse outcome in AA women with PPCM are strongly supported by earlier studies. Whitehead et al,2 who used data from the Centers for Disease Control to examined pregnancy-related deaths due to cardiomyopathy from 1991 to 1997, reported a 6.4-fold increased risk of death in AA compared with white patients. More recently Harper et al,3 who performed an epidemiologic study of residences of North Carolina, found almost 4-fold increased fatality in black non-Hispanic women with PPCM compared with white women. In our previously published study,14 we found the delay of diagnosis to be an independent predictor of major adverse events in patients with PPCM. Unfortunately, we did not have information on the time delay between onset of symptoms and diagnosis in all patients analyzed for the purpose of the present study. Further investigation of the reasons for late diagnosis of
PPCM in African-American Women
PPCM in AA patients, especially if the delay is related to preventable factors, is important. Recovery of LV systolic function has been reported in O50% of women with PPCM in the USA, with the majority occurring within 2e6 months after diagnosis.8,15 Earlier studies have demonstrated a strong relationship between the degree of LVEF at time of diagnosis and recovery.16 Although LVEF at the time of diagnosis was similar between the 2 groups included in the present study, rate and magnitude of recovery of LV function was significantly lower in AA women. These findings are strongly supported by a recent study by Amos et al,8 who reported on 55 women with PPCM and described a significantly lower rate of LV functional recovery in AA compared with white patients (41% vs 74%; P 5 .03). Based on our results AAs had higher prevalence of gestational hypertension (61% vs 41%; P 5 .03) but lower rates of LV recovery. This observation is at variance with a report recently published by Safirstein et al,17 who found gestational hypertension, in mostly white women with PPCM, to be significantly associated with recovery of systolic function. Similarly, Kamiya et al reported gestational hypertension to be independently associated with a shorter hospital stay and a higher LVEF at last follow-up in a Japanese population.18 Although an explanation of the clear differences in the phenotypic presentation of PPCM in AA compared with white women in the USA is not readily available, these differences may be multifactorial, including genetic variations as well as socioeconomic causes which may account for some of the differences in epidemiology, LV recovery, and outcome between the 2 groups. Genetic differences may be supported by other reported unique characteristics in AA women with PPCM, such as a substantially increased incidence of this condition compared with women of other ethnic groups in the USA.3,5e7 In addition, timing of presentation, lower rate of recovery of LV function, and higher mortality rate of AA women demonstrated in our study are similar to those described in black patients in Haiti and South Africa.19,20 Other potential causes for differences in outcome in AA women with PPCM may be related to disparities in the utilization and quality of medical care.21 Earlier studies have provided evidence that AA patients in the USA are less likely to receive effective treatment for other cardiac conditions and have less frequent access to newer and costly cardiac procedures, such as cardiac catheterization, percutaneous interventions, coronary artery bypass surgery, and use of cardiac resynchronization therapy.22,23 Additional reports have also demonstrated that AA patients are less likely to achieve guideline-recommended therapeutic goals of proven therapy for conditions such as hyperlipidemia and hypertension.24,25 Further investigations are therefore required to better understand the causes for differences in outcome between AA and white women with PPCM in the USA in an attempt to identify potentially correctable sources that might reduce the ethnic differences demonstrated in the present study.
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Study Limitations The results of this study are based on a retrospective review of patients’ records and reports by physicians and patients. The data could, therefore, be influenced by referral as well as reporting bias and may be incomplete. The study can not provide an explanation for the differential racial outcomes, which are likely to be multifactorial, including potential genetic and physiologic variances as well as possible differences in health care. The study, however, includes the largest group of patients with PPCM reported to date in the USA and strongly supports earlier data from smaller groups, suggesting racial differences in both the presentation and outcome of PPCM in the USA. Further research is needed to identify possible modifiable factors that can lead to prevention of complications and to improved outcome of AA patients with PPCM in the USA. Conclusion The present study clearly demonstrates racial differences in clinical profile as well as outcomes of patients diagnosed with PPCM in the USA. Peripartum cardiomyopathy in AA women occurred at younger age and had stronger association with gestational hypertension compared with white women. There was a significant difference in the timing of presentation relative to time of delivery and in severity of symptoms. Whereas more than one-third of white women were diagnosed before delivery, AA patients were more likely to present postpartum and with more severe symptoms of heart failure. Although LV function was similar in both groups at time of diagnosis, rate of recovery of LVEF was significantly lower in AA patients. This difference in recovery of cardiac function was associated with worse outcome with a strong trend for higher mortality rate and a significantly higher incidence of the combined end point of mortality and cardiac transplantation. These findings strongly suggest that PPCM in AA patients in the USA is associated with a different clinical presentation and worse outcomes. Further studies are warranted to investigate potential correctable causes of these differences in an attempt to potentially improve the outcome of PPCM in AA patients. Disclosures None. References 1. Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the US: diagnosis, prognosis and management J. Am Coll Cardiol 2011;58:659e70. 2. Whitehead SJ, Berg CJ, Chang J. Pregnancy-related mortality due to cardiomyopathy: United States, 1991e1997. Obstet Gynecol 2003; 102:1326e31.
218 Journal of Cardiac Failure Vol. 19 No. 4 April 2013 3. Harper MA, Meyer RE, Berg CJ. Peripartum cardiomyopathy population-based birth prevalence 7eyear mortality. Obstet Gynecol 2012;120:1013e9. 4. Mielniczuk LM, Williams K, Davis DR, et al. Frequency of peripartum cardiomyopathy. Am J Cardiol 2006;97:1965e8. 5. Brar SS, Khan SS, Sandhu GK, et al. Incidence, mortality, and racial differences in peripartum cardiomyopathy. Am J Cardiol 2007;100: 302e4. 6. Gunderson EP, Croen LA, Chiang V, Yoshida CK, Walton D, Go AS. Epidemiology of peripartum cardiomyopathy incidence, predictors and outcomes. Obstet Gynecol 2011;118:583e91. 7. Gentry MB, Dias JK, Luis A, Patel R, Thornton J, Reed GL. African American women have a higher risk for developing peripartum cardiomyopathy. J Am Coll Cardiol 2010;55:654e9. 8. Amos AM, Jaber WA, Russell SD. Improved outcomes in peripartum cardiomyopathy with contemporary. Am Heart J 2006;152: 509e13. 9. Witlin AG, Mabie WC, Sibai BM. Peripartum cardiomyopathy: an ominous diagnosis. Am J Obstet Gynecol 1997;176:182e8. 10. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al. Current state of knowledge on etiology, diagnosis, management and therapy of peripart cardiomyopathy: a position statement from the Heart Failure Association of European Society of Cardiology Working Group on Peripartum Cardiomyopathy. Eur J Heart Failure 2010;12:767e78. 11. Pearson GD, Veille J-C, Rahimtoola S, et al. Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000;283:1183e8. 12. Rost K, Henshaw S. U.S. teenage pregnancies, births and abortion, 2008: national trends by age, race and ethnicity. Guttmacher Institute. February 2012. 13. Patten IS, Rana S, Shahul S, et al. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 2012;485:333e9. 14. Goland S, Modi K, Bitar F, et al. Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Failure 2009; 15:645e50.
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