Peripartum Cardiomyopathy Characteristics and Outcomes in Canadian Aboriginal and Non-Aboriginal Women

Accepted Manuscript Peripartum Cardiomyopathy Characteristics and Outcomes in Canadian Aboriginal and Non-Aboriginal Women Shuangbo Liu, MD FRCPC, Sobia A. Zuberi, MB Bch BAO NUI (LRCP & LRCS), Amrit A. Malik, MD FRCPC, Brett M. Hiebert, MSc, Allan Schaffer, MD FRCPC, Shelley Zieroth, MD FRCPC, Francisco J. Cordova, MD, FACC PII:

S0828-282X(16)31084-4

DOI:

10.1016/j.cjca.2016.11.001

Reference:

CJCA 2297

To appear in:

Canadian Journal of Cardiology

Received Date: 13 November 2015 Revised Date:

2 November 2016

Accepted Date: 6 November 2016

Please cite this article as: Liu S, Zuberi SA, Malik AA, Hiebert BM, Schaffer A, Zieroth S, Cordova FJ, Peripartum Cardiomyopathy Characteristics and Outcomes in Canadian Aboriginal and Non-Aboriginal Women, Canadian Journal of Cardiology (2016), doi: 10.1016/j.cjca.2016.11.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

RI PT

PERIPARTUM CARDIOMYOPATHY CHARACTERISTICS AND

OUTCOMES IN CANADIAN ABORIGINAL AND NON-ABORIGINAL

M AN U

SC

WOMEN

Shuangbo Liu MD FRCPC,1 Sobia A. Zuberi MB Bch BAO NUI (LRCP & LRCS),2 Amrit A. Malik, MD FRCPC,1 Brett M. Hiebert MSc,1 Allan Schaffer, MD FRCPC,1

TE D

Shelley Zieroth, MD FRCPC,1 Francisco J Cordova, MD, FACC1

1

AC C

EP

Short title: Peripartum Cardiomyopathy in Canadian Women

Section of Cardiology, Rady Faculty of Health Sciences and Max Rady College of

Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 2

Department of Internal Medicine, Rady Faculty of Health Sciences and Max Rady

College of Medicine, University of Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.

Page 1 of 25

ACCEPTED MANUSCRIPT

Address of correspondence to: Dr. Francisco J. Cordova, MD, FACC

RI PT

Assistant Professor, Section of Cardiology, Department of Internal Medicine College of Medicine, Faculty of Health Sciences, University of Manitoba

Room Y3005 Bergen Cardiac Care Centre, St. Boniface General Hospital

SC

409 Tache Avenue, Winnipeg, Manitoba, Canada, R2H 2A6 204-238-1266

M AN U

[email protected]

AC C

EP

TE D

Word Count: 3885

Page 2 of 25

ACCEPTED MANUSCRIPT

BRIEF SUMMARY Peripartum cardiomyopathy (PPCM) is characterized by heart failure and left

RI PT

ventricular dysfunction in the absence of an alternative cause and a previous diagnosis of cardiomyopathy. The Aboriginal population often have barriers to healthcare. We performed a retrospective study that demonstrated PPCM Aboriginal women are more likely to present with lower LVEF, a more dilated LV and require more symptomatic

SC

management. This is the first description and contrast of PPCM between Aboriginal and

AC C

EP

TE D

M AN U

non-Aboriginal Canadians.

Page 3 of 25

ACCEPTED MANUSCRIPT

ABSTRACT Background: Peripartum cardiomyopathy (PPCM) is a heterogeneous condition

RI PT

characterized by heart failure and left ventricular dysfunction (LVEF<45%) in the absence of an alternative cause and a previous diagnosis of cardiomyopathy. The Aboriginal population (Inuit, First Nations, Metis) of Canada often has barriers to healthcare, which can lead to delays in diagnosis and treatment. Our objectives are to

SC

describe PPCM in a Canadian population, and to determine if Canadian Aboriginal

M AN U

women have worse clinical outcomes than non-Aboriginal women.

Methods: A retrospective study was performed at a single tertiary care center, between 2008-2014. Demographics, symptoms of presentation, medical history, discharge

collected.

TE D

medications, blood work, echocardiographic parameters and follow up information were

Results: A total of 177 women were screened, and 23 were included in the study (52%

EP

were Aboriginal). Aboriginal women were found to have higher rates of gravidity and

AC C

parity, and higher incidence of tobacco smoking than non-Aboriginal women, and were more likely to be discharged on diuretics. At diagnosis, Aboriginal women were more likely to have a lower LVEF (20% (IQR 15-23%) vs 40% (IQR 30-42%), p=0.02) and a more dilated LV (LVEDD 64mm (IQR 57-74mm) vs 54mm (IQR 50-57mm), p<0.01). Recovery rate, defined as LVEF>50%, was similar (46% in Aboriginal patients and 60% in non-Aboriginal patients).

Page 4 of 25

ACCEPTED MANUSCRIPT

Conclusion: Our findings support that Aboriginal women with PPCM are more likely to present with lower LVEF and a more dilated LV, as well, require more symptomatic management. This is the first description and contrast of PPCM between Aboriginal and

RI PT

non-Aboriginal Canadians.

AC C

EP

TE D

M AN U

SC

Word count= 249

Page 5 of 25

ACCEPTED MANUSCRIPT

INTRODUCTION Peripartum cardiomyopathy (PPCM) is a heterogeneous condition characterized

RI PT

by heart failure (HF) and left ventricular systolic dysfunction (LV ejection fraction <45%) in the absence of an alternative cause and a previous diagnosis of cardiomyopathy1. The incidence of PPCM varies depending on the study population, ranging from 1:300 in Haiti2 to 1:4,0253. In 2006, Mielniczuk et al reported a trend

SC

towards increase in incidence over time in the United States2. Certain high-risk

M AN U

populations have also been identified to have a poor prognosis, such as AfricanAmericans4,5. The incidence of PPCM in the Canadian population has not yet been characterized.

The Aboriginal population (Inuit, First Nations, Metis)6 of Canada often has

TE D

barriers to healthcare, which can lead to delays in diagnosis and treatment7. A Health Canada publication on the determinants of health in 2010 described 38.6% of First Nations adults living in First Nations communities believed they had less access to health

EP

services compared to Canadians generally8. A publication examining the outcomes of Aboriginal patients diagnosed with HF showed that this patient population have increased

AC C

short and long-term mortality, when compared to white HF patients9. The health status of the Aboriginal population remains below that of the general Canadian population, as measured by most major indicators of health. In 2000, the estimated life expectancy at birth for the Aboriginal population was 8.1 years and 5.5 years less than the Canadian population for males and females, respectively8.

Page 6 of 25

ACCEPTED MANUSCRIPT

The objectives of our project are to describe PPCM in a Canadian population, and to determine if Canadian Aboriginal women have worse clinical outcomes than non-

AC C

EP

TE D

M AN U

SC

RI PT

Aboriginal women, in this cohort.

Page 7 of 25

ACCEPTED MANUSCRIPT

METHODS Study Population

RI PT

A retrospective study was performed in 2014, at a single tertiary care center using the Winnipeg St. Boniface Hospital Heart Failure Clinic Patient Data Registry (as part of the Canadian Congestive Heart Failure Clinics Network). The St. Boniface Heart Failure Clinic is the larger of only two heart failure clinics in the province of Manitoba, with a

SC

catchment area of 1.5 million inhabitants (including Manitoba, parts of Nunavut and

M AN U

western Ontario). All female patients under the age of 55 years seen in the heart failure clinic between July 1st, 2008 to June 30th, 2014 were reviewed to determine whether they fulfilled the diagnostic criteria for PPCM as per the Canadian Cardiology Society guidelines.1 If there was any ambiguity regarding the diagnosis of PPCM, the patient’s chart was reviewed in detail to assess for any history of pregnancy. Demographics,

TE D

symptoms of presentation, past medical history, medications at discharge, blood work, echocardiographic parameters and follow up information, including recovery which was defined a priori as LVEF >50% based on review of the literature, were collected.

EP

Ethnicity was recorded based on patient self-report as taken from the Patient Data

AC C

Registry and patient chart.

Ethics approval was obtained from the University of Manitoba Research Ethics

Board as well as the St. Boniface Hospital Research Ethics Board. A letter was also written to the Assembly of Manitoba Chiefs to obtain their support of the project.

Page 8 of 25

ACCEPTED MANUSCRIPT

Standard transthoracic echocardiography (TTE) was performed at the time of diagnosis to assess LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD) and LV ejection fraction (LVEF). TTE, multi-gated acquisition scans (MUGA)

RI PT

and/or cardiac magnetic resonance imaging (CMR) were used for reassessment of the LVEF.

SC

Statistical Analysis

Several demographic and clinical parameters were compared between those who

M AN U

recovered from low LVEF at baseline. Continuous variables were expressed as median and interquartile range (IQR), and compared using the Mann Whitney Test. Categorical variables were expressed as N (%) and compared using a Fisher’s Exact Test or ChiSquare Test where appropriate. Similar comparisons were made between Aboriginal and

TE D

non-Aboriginal populations to identify the clinical differences between both patient populations. All comparisons were two-tailed and the significance was ascribed to a pvalue <0.05. Variables associated with LVEF recovery were identified using univariate

AC C

EP

analysis. Due to the small sample size, multivariate analysis was not possible.

Page 9 of 25

ACCEPTED MANUSCRIPT

RESULTS Study Population

RI PT

A total of 177 women under the age of 55 years were screened, and 23 were included in the analysis (52% were Aboriginal). Patients were excluded if an alternate etiology for their cardiomyopathy was identified (Figure 1). The baseline clinical characteristics of the study population are summarized in Table 1. The median age for the

SC

study population was 31 years (IQR 28-37 years). The median age was 30 years (IQR 26-

M AN U

35 years) for the Canadian Aboriginal patients and 33 years (IQR 30-38 years) and for non-Aboriginal patients (p=0.20). Canadian Aboriginal women were found to have higher rates of gravidity (5, IQR 4–8 vs 2, IQR 1-2, p<0.01) and parity (4, IQR 2-6 vs 1, IQR 1-2, p<0.01). The New York Heart Association (NYHA) Functional Class (FC) distribution at presentation is summarized in Figure 2 (p=0.35). The majority of non-

TE D

Aboriginal patients presented as FC III (45%), whereas most of the Canadian Aboriginal patients presented as FC II (58%). NYHA FC at last visit (p=0.85) and change in FC (p=0.25) were not statistically significant between the two groups. The majority of the

EP

patients in both patient populations had NYHA FC I symptoms at the time of the last

AC C

visit. Symptoms at presentation did not differ between the two groups.

As described in Table 1, the only statistically significant difference in the past

medical history between the two groups was a higher incidence of tobacco smoking in the Canadian Aboriginal population compared to the non-Aboriginal population (67% vs 9%, p<0.01). The rate of appropriate HF medical therapy did not significantly vary between the two patient populations. Diuretic use was the only statistically significant difference

Page 10 of 25

ACCEPTED MANUSCRIPT

in medications at discharge. Canadian Aboriginal patients were more likely to be discharged from the hospital on Furosemide (92% vs 18%, p<0.01). The mean follow-up time was 102 weeks (52 weeks for Aboriginal patients and 135 weeks for non-Aboriginal

RI PT

patients, p=0.60).

At the time of diagnosis, the Canadian Aboriginal women in this cohort were

SC

more likely to have a lower LVEF (20%, IQR 15-23% vs 40%, IQR 30-42%, p=0.02) than non-Aboriginal women. They also presented with a more dilated LV (LVEDD 64

M AN U

mm, IQR 57-74 mm vs 54 mm, IQR 50-57 mm, p<0.01, and LVESD 56 mm, IQR 48-67 mm vs 44 mm, IQR 41-45 mm vs, p<0.01) on TTE (Table 2). There was no significant difference in the incidence of LV thrombus between the Canadian Aboriginal and nonAboriginal populations (8% and 10%, respectively, p=1.00). Canadian non-Aboriginal

TE D

patients were more likely to have a CMR compared to Canadian Aboriginal patients (55% vs 0%, p<0.01). The rate of LVEF recovery (defined as LVEF >50%)1 was not statistically different between the two groups (46% in Aboriginal and 60% in non-

EP

Aboriginal patients, p=0.68). Figure 3 describes the change in LVEF between diagnosis and reassessment for the study cohort (28%, IQR 18-40% at diagnosis and 45%, IQR 31-

AC C

56% at reassessment, p<0.001), Canadian Aboriginal patients (22%, 30-42% at diagnosis and 40%, IQR 27-55% at reassessment, p=0.004) and non-Aboriginal patients (33.9%, 30-42% at diagnosis and 51%, IQR 55-60% at reassessment, p=0.004), respectively. The time to LVEF reassessment was similar between the two populations (41 weeks for Aboriginal patients, 47 weeks for non-Aboriginal patients, p=0.76).

Page 11 of 25

ACCEPTED MANUSCRIPT

Table 3 describes some of the factors associated with LVEF recovery in our Canadian PPCM patients. LVEDD (68 mm in patients with no LVEF recovery and 55 mm in patients with LVEF recovery, p=0.01) and LVESD (57 mm in patients with no

RI PT

LVEF recovery and 45 mm in patients with LVEF recovery, p=0.01) were associated with LVEF recovery. All examined variables are available in Supplementary Table 1. Two sensitivity analyses were performed: with LVEF recovery defined as LVEF>45%

SC

where LVEDD (p=0.02) and LVESD (p=0.01) were still associated with LVEF recovery (Supplementary Table 2); with LVEF recovery defined as LVEF>55% where LVESD

M AN U

(p<0.01) was still associated with LVEF recovery however LVEDD (p=0.1) was no

AC C

EP

TE D

longer associated (Supplementary Table 3).

Page 12 of 25

ACCEPTED MANUSCRIPT

DISCUSSION Peripartum cardiomyopathy is defined as a dilated cardiomyopathy with a LVEF

RI PT

< 45%, with the development of heart failure in the last month of pregnancy or within 5 months after delivery.1 Our study demonstrated that the Canadian Aboriginal patients in our cohort were more likely to have a higher gravidity and parity, and to be discharged from the hospital on diuretics, when compared to the non-Aboriginal patients. Our study

SC

also showed that despite a lower LVEF and a more dilated LV at diagnosis in the

M AN U

Aboriginal patients, there was no difference in the rate of recovery between the two cohorts.

In our study, the median gravidity of Canadian Aboriginal women was significantly higher than non-Aboriginal women [5 (IQR 4-8), 2 (IQR 1-2), respectively,

TE D

p<0.01]. As well, the parity was higher for Canadian Aboriginal patients compared with non-Aboriginal patients [4, (IQR 3-6), 1 (1-2), respectively, p<0.01]. This is consistent with previous reports, that higher risk PPCM patient populations have a higher gravidity

EP

and parity10-13, and multiparity is a known risk factor for PPCM14. In the United States,

AC C

Elkayam et al have reported a mean gravidity of 2.6 with 37% being primigravidas11. For patients at a higher risk of worse prognosis (South Africans and Haitians), the reported gravidity and parity rates have been higher (3 with 20% primigravidas and 4 with 24.5% primigravidas, respectively)10-11,15-16. Our study population’s Canadian Aboriginal PPCM patients have comparable gravidity and parity with those reported for women of AfricanAmerican descent.

Page 13 of 25

ACCEPTED MANUSCRIPT

We found that Canadian Aboriginal patients in our cohort were more likely to be discharged on diuretics, suggesting that they are more symptomatic. However, Canadian Aboriginal patients in our study do not have a worse NYHA FC at presentation. We

RI PT

propose the following theories as possible explanations for this finding. First, studies have shown that despite a higher prevalence of symptoms (such as pain) in Aboriginal patients, they are more likely to underemphasize their symptoms.17-20 There is also

SC

suggestion that terminology, word usage and narrative styles are different in Aboriginal patients, and this can lead to miscommunication in healthcare.21-22 Second, NYHA FC is

M AN U

subjective and due to the above differences in communication patterns for Aboriginal patients, it may not be the most accurate assessment of symptom limitations. Therefore, the way we traditionally establish NYHA functional class may under-estimate the severity of symptom limitations. The 6-minute walk test is a validated tool in establishing

TE D

the functional capacity in the heart failure patient population.22-24 It may be helpful to investigate the application of more objective validated tools, such as the 6-minute walk

EP

test in the PPCM patient population.

We demonstrated that the Aboriginal patients in our study presented with a lower

AC C

LVEF and a more dilated LV. This could be secondary to later diagnosis (and therefore more time for remodeling), or this may imply that Aboriginal patients remodel quicker than non-Aboriginal patients, and therefore have a more dilated LV. Left ventricular dimensions have also been studied as a prognostic factor for LVEF recovery.10,20,25-30 In our study, we found that irrespective of ethnicity, patients with a more dilated LV were less likely to recover. This is in keeping with previous studies, where patients with a

Page 14 of 25

ACCEPTED MANUSCRIPT

LVEDD >55 mm was less likely to recover31. In contrast to previous studies, for our study population, the LVEF at diagnosis did not influence the recovery rate5, 25-28. It is possible that we could not show a statistically significant difference due our limited

RI PT

sample size. Another possible explanation is that we did not examine the clinical outcomes of Canadian Aboriginal patients in contrast with the clinical outcomes of Caucasian patients, but rather, the clinical outcomes of all non-Aboriginal patients in our

SC

database. For certain non-Aboriginal non-Caucasian ethnicities the rates of LVEF recovery may vary5,10,14. Despite starting at a lower baseline LVEF, the rates of LVEF

M AN U

recovery for Canadian Aboriginal patients were similar to those of non-Aboriginal patients, perhaps due to optimal medical therapy.

Study Limitations

TE D

There are limitations to the current study that should be mentioned. First, this was a retrospective, observational study at a single tertiary care center. While we attempted to ensure that we included all cases of PPCM, we were limited by patient referral to our

EP

center. Second, the study sample size is small which can limit the interpretation of the results. Due to the modest sample size of our study, it would have been difficult to

AC C

analyze the clinical outcomes of the Aboriginal population separately by First Nations, Inuit or Metis. There may be a genetic difference in these populations. Similarly, a multivariable analysis was not performed due to sample size restrictions. Third, although the imaging modality of choice at diagnosis was TTE, due to local practice, reassessment of the LVEF was often performed with other imaging modalities: MUGA (which is preferred for a more accurate LVEF in our center) and CMR (which is reserved for more

Page 15 of 25

ACCEPTED MANUSCRIPT

accurate LVEF and whenever we intend to exclude other potential cardiac pathology and/or better assess the cardiac structure). The wait times for these studies, which are significantly lower than wait times for a TTE at our center, may vary. The LVEF may

RI PT

also vary slightly between image modalities, but this variability is generally accepted in clinical practice when reassessing the LVEF in HF patients. Given the young patient population and rarity of angina, our patients did not undergo routine coronary angiogram.

M AN U

Research and Future Directions

SC

This is a minor limitation to our study.

Through this retrospective single center study, we have found a signal that Aboriginal PPCM patients may present with a more remodelled LV and a decreased LV systolic function. A national multicenter collaborative study is needed to assess this

TE D

association as well as to evaluate the incidence, characteristics and prognosis of PPCM in

AC C

EP

the Canadian population.

Page 16 of 25

ACCEPTED MANUSCRIPT

CONCLUSION Peripartum cardiomyopathy is an important diagnosis to consider in the

RI PT

appropriate clinical setting, as a delay in diagnosis can lead to increased morbidity and mortality. Our findings support that Canadian Aboriginal women with PPCM may be more likely to present with a more dilated LV and a lower LVEF. In our study, smaller LV dimensions at presentation were associated with LVEF recovery. We did not find the

SC

LVEF at diagnosis to be a good predictor of LVEF recovery. This is the first description

M AN U

and contrast of clinical outcomes in Canadian Aboriginal and non-Aboriginal PPCM patients. Future studies are required to further characterize clinical outcomes in the

AC C

EP

TE D

Canadian population.

Page 17 of 25

ACCEPTED MANUSCRIPT

ACKNOWLEDGEMENTS

RI PT

We would like to acknowledge the interdisciplinary healthcare team at the St. Boniface Hospital Heart Failure Clinic. We would also like to acknowledge the Federation of Medical Women in Canada and the Maude Abbott Research Fund for

AC C

EP

TE D

M AN U

SC

supporting this research project.

Page 18 of 25

ACCEPTED MANUSCRIPT

FUNDING SOURCES

AC C

EP

TE D

M AN U

SC

RI PT

The Federation of Medical Women of Canada - Maude Abbott Research Fund.

Page 19 of 25

ACCEPTED MANUSCRIPT

DISCLOSURES

AC C

EP

TE D

M AN U

SC

RI PT

No conflicts of interest to disclose.

Page 20 of 25

ACCEPTED MANUSCRIPT

REFERENCES

RI PT

1. Howlett JG, McKelvie RS, Costigan J, Ducharme A, Estrella-Holder E, Ezekowitz JA, Giannetti N, Haddad H, Heckman GA, Herd AM, Isaac D, Kouz S, Leblanc K, Liu P, Mann E, Moe GW, O’Meara E, Rajda Miroslav, Siu S, Stolee P, Swiggum E, Zieroth S. The 2010 Canadian Cardiovascular Society guidelines

SC

for the diagnosis and management of heart failure update: heart failure in ethnic

M AN U

minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance programs. Can J Cardiol. 2010;26(4):185-202 2. Mielniczuk LM, Williams K, Davis DR, Tang AS, Lemery R, Green MS, Gollob MH, Haddad H, Birnie DH. Frequency of peripartum cardiomyopathy. Am J Cardiol. 2006;97(12):1765-8

TE D

3. Brar SS, Khan SS, Sandhu GK, Jorgensen MB, Parikh N, Hsu JW, Shen AY. Incidence, mortality and racial differences in peripartum cardiomyopathy. Am J Cardiol. 2007;100(2):302-4

EP

4. Sliwa K, Skudicky D, Bergemann A, Candy G, Puren A, Sareli P. Peripartum

AC C

cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1. J Am Coll Cardiol. 2000;35(3):701-5

5. McNamara DM, Elkayam U, Alharethi A, Damp J, Hsich E, Ewald G, Modi K, Alexis JD, Ramani GV, Semigran MJ, Haythe J, Markham DW, Marek J, Gorcsan J 3rd, WU WC, Lin Y, Halder I, Pisarcik J, Cooper LT, Fett JD; IPAC Investigators. Clinical outcomes for peripartum cardiomyopathy in North

Page 21 of 25

ACCEPTED MANUSCRIPT

America: Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol. 2015;66(8):905-14

Terminology (2012, October). https://www.aadnc-

RI PT

6. Government of Canada, Aboriginal Affairs and Northern Development Canada:

aandc.gc.ca/eng/1100100014642/1100100014643) Accessed September 27, 2015. 7. Health Canada. First Nations and Inuit Health Strategic Plan: A shared path to

SC

improved health (2012). http://www.hc-sc.gc.ca/fniah-

August 12, 2015

M AN U

spnia/alt_formats/pdf/pubs/strat-plan-2012/strat-plan-2012-eng.pdf Accessed

8. Health Canada. First Nations and Inuit Health (2005). http://www.hcsc.gc.ca/fniah-spnia/diseases-maladies/2005-01_health-sante_indicat-eng.php Accessed August 12, 2015

TE D

9. Lyons KJ, Ezekowitz JA, Liu W, McAlister FA, Kaul P. Mortality outcomes among Aboriginals and whites with heat failure. Can J. Cardiol 2014;30:619-626 10. Elkayam U. Clinical characteristics of peripartum cardiomyopathy in the United

EP

States: diagnosis, prognosis and management. J Am Coll Cardiol 2011;58:659-70 11. Elkayam U, Akhter MW, Singh HS, Khan S, bitar F, Hameed A, Shotan A.

AC C

Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation. Circulation. 2005; 111(16): 2050–55,

12. Sliwa K, Skudick D, Bergmann A, Candy G, Puren A, Sareli P. Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/Apo-1. J Am Coll Cardiol. 2000;35(3):701-05

Page 22 of 25

ACCEPTED MANUSCRIPT

13. Kao DP, Hsich E, Lindenfeld J. Characteristics, adverse events, and racial differences among delivering mothers with peripartum cardiomyopathy. JACC Heart Fail. 2013;1(5):409-16

RI PT

14. Ntsui NBA, Mayosi BM. Aetiology and risk factors of peripartum

cardiomyopathy: A systematic review. Int J Cardiol. 2009 (131):168-179 15. Fett JD, Carraway RD, Dowell DL, King ME, Pierre R. Peripartum

SC

cardiomyopathy in the Hospital Albert Schweitzer District of Haiti. Am J Obstet Gynecol. 2002;186:1005–10.

M AN U

16. Fett JD, Christie LG, Carraway RD, Murphy JG. Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Proceed. 2005;80:1602–06

17. Jimenez N, Garroutte E, Kundu A, Morales L, Buchwald D. A review of the

TE D

experience, epidemiology, and management of pain among American Indian, Alaska Native, and Aboriginal Canadian peoples. J Pain. 2011;12(5):511-22 18. Kramer BJ, Harker JO, Wong AL. Descriptions of joint pain by American

EP

Indians: comparison of inflammatory and noninflammatory arthritis. Arthritis Rheum. 2002;47(20:149-54

AC C

19. Kramer BJ, Harker JO, Wong AL. Arthritis beliefs and self-care in an urban American Indian population. Arthritis Rheum. 2002;47(6);588-94

20. Barkwell D. Cancer pain: voices of the Ojibway people. J Pain Symptom Manage. 2005;30(5):454–464.

21. Garroutte EM, Kunovich RM, Buchwald D, Goldberg J. Medical communication with American Indian older adults: Implications for models of racial/ethnic health

Page 23 of 25

ACCEPTED MANUSCRIPT

disparities. Paper presented at the Annual Meeting of the American Sociological Association; August 14, 2004.

medical interview. Med Anthropol Q. 1995;9:503–509

RI PT

22. Woolfson P, Hood V, Secker-Walker R, Macauley AC. Mohawk English in the

23. Shah MR, Hasselblad V, Gheorghiade M, Adams KF, Swedberg K, Califf RM, O’Connor CM. Prognostic usefulness of the six-minute walk in patients with

SC

advanced congestive heart failure secondary to ischemic or nonischemic cardiomyopathy. Am J Cardiol. 2001;88:987-993,

M AN U

24. Passantino A, Lagioia R, Mastropasqua F, Scrutinio D. Short-term change in distance walked in 6 min is an indicator of outcome in patients with chronic heart failure in clinical practice. J Am Coll Cardiol. 2006;48:99-105 25. Duran N, Gunes H, Duran I, Biteker M, Ozkan M. Predictors of prognosis in

TE D

patients with peripartum cardiomyopathy. Int J of Gynecol and Obstet. 2008;101(2):137-140

26. Habli M, O’Brien T, Nowack E, Khoury S, Barton JR, Sibai B. Peripartum

EP

cardiomyopathy: prognostic factors for long-term maternal outcome. Am J of Obstet Gynecol. 2008;199(4):415.e1-5

AC C

27. Chapa JB, Heiberger HB, Weinert L, Decara J, Lang RM, Hibbard JU. Prognostic value of echocardiography in peripartum cardiomyopathy. Obstet Gynecol 2005;105(6):1303-8

28. 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(1):27-31

Page 24 of 25

ACCEPTED MANUSCRIPT

29. Blauwet LA, Libhaber E, Forster O, Tibazarwa K, Mebazaa A, Hilfiker-Kleiner D, Sliwa K. Predictors of outcome in 176 South African patients with peripartum cardiomyopathy. Heart. 2013;99(5):308-313

RI PT

30. Horgan SJ, Margey R, Brenna DJ, O’Herlihy C, Mahon NG. Natural history,

management, and outcomes of peripartum cardiomyopathy: an Irish single-center cohort study. J Matern Fetal and Neonatal Med. 2013;26(2):161-5

SC

31. Goland S, Bitar F, Modi K Safirstein J, Ro A, Mirocha J, Khatri N, Elkayam U.

Evaluation of the clinical relevance of baseline left ventricular ejection fraction as

M AN U

a predictor of recovery or persistence of severe dysfunction in women in the

AC C

EP

TE D

United States with peripartum cardiomyopathy. J Card Fail. 2011;17(5):426-30

Page 25 of 25

ACCEPTED MANUSCRIPT

Table 1: Baseline demographics in Aboriginal and non-Aboriginal women with PPCM

Aboriginal

n = 11

n = 12

33 (30 – 38)

30 (26 – 35)

0.20

Gravidity

2 (1 – 2)

5 (4 – 8)

<0.01

Parity

1 (1 – 2)

4 (3 – 6)

<0.01

Multifetal pregnancy

1 (9%)

0 (0%)

0.48

7 (64%)

4 (33%)

0.15

3 (27%)

2 (17%)

0.64

3 (27%)

3 (25%)

1.00

1 (9%)

8 (67%)

<0.01

8 (73%)

11 (92%)

0.32

8 (73%)

11 (92%)

0.32

0 (0%)

0 (0%)

1.00

Furosemide

2 (18%)

11 (92%)

<0.01

Spironolactone

1 (9%)

2 (17%)

1.00

Anticoagulation

0 (0%)

3 (25%)

0.22

Cardiac MRI (CMR)

6 (55%)

0 (0%)

<0.01

Mean follow-up time (weeks)

79

53

0.57

Age at diagnosis (years)

Delivery via Cesarean section Past Medical History Hypertension

Smoker

TE D

Diabetes

M AN U

Pregnancy Related

p-value

RI PT

Non-Aboriginal

SC

Clinical Variable

Beta-blockers ACEI or ARB

AC C

Digoxin

EP

Medications at discharge from hospital

ACCEPTED MANUSCRIPT

ACEI = Angiotensin converting enzyme inhibitor; ARB = Angiotensin receptor blocker; LV = Left ventricle; LVEDD = Left ventricular end diastolic dimension; LVEF = Left

RI PT

ventricular ejection fraction; LVESD = Left ventricular end systolic dimension; NYHA =

AC C

EP

TE D

M AN U

SC

New York Heart Association; MRI = Magnetic resonance imaging

ACCEPTED MANUSCRIPT

Table 2: Assessment of LVEF at diagnosis and follow-up in Canadian Aboriginal and non-Aboriginal peripartum cardiomyopathy patients.

Aboriginal

n = 11

n = 12

LVEF (%)

40 (30 – 42)

20 (15 – 23)

0.02

LVEDD (mm)

54 (50 – 57)

64 (57 – 74)

<0.01

LVESD (mm)

44 (41 - 45)

56 (48 – 67)

<0.01

55 (55 – 60)

48 (27 – 55)

<0.001

60

46

0.68

M AN U

Echocardiographic parameters at diagnosis

LVEF at follow-up

AC C

EP

TE D

Recovery of LVEF (%)

p-value

RI PT

Non-Aboriginal

SC

Clinical Variable

ACCEPTED MANUSCRIPT

Table 3: Factors associated with LVEF recovery in Canadian peripartum cardiomyopathy women.

LVEF Recovery

n = 10

n = 13

Age at diagnosis

29 (25 – 33)

36 (30 – 37)

0.07

Aboriginal ethnicity

6 (60%)

6 (46.2%)

0.68

Gravidity

4 (2 – 4)

2 (1 – 6)

0.75

Parity

3 (2 – 4)

1 (1 – 4)

0.31

LVEF at time of diagnosis

25 (15 – 30)

30 (15 – 43)

0.23

LVEDd (mm)

68 (59 – 75)

55 (52 – 59)

0.01

LVESd (mm)

57 (47 – 68)

45 (42 – 48)

0.01

LVEF < 25%

5 (50%)

6 (46.2%)

1.00

EP AC C

P value

M AN U

SC

RI PT

No LVEF Recovery

TE D

Clinical Variable

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT