CHAPTER 1
Maternal heart health

Karen Sliwa1, John Anthony2, and Denise Hilfiker-Kleiner3

1 University of Cape Town, South Africa; University of the Witwatersrand, Johannesburg, South Africa

2 Department of Obstetrics & Gynaecology, Groote Schuur Hospital, Cape Town, South Africa

3 Department of Cardiology and Angiology, Medical School Hannover, Germany

1.0 Introduction

In this chapter, we first report upon a recent single-center prospective cohort study from Groote Schuur Hospital [13] in which the majority of maternal deaths observed were attributable to various forms of cardiomyopathy (CMO), with only two being related to complications of sepsis and thrombosis affecting prosthetic heart valves. Significantly, 8 out of the 9 deaths reported in this patient cohort of 152 patients with 6-month follow-up would not have been reported if the definition of death within 42 days had been applied, thereby underestimating the number of cardiac deaths related to pregnancy as a result of late presentation and deaths occurring among women with familial CMO or PPCMO.

The last decade has seen a steady increase in the institutional maternal mortality rate for cardiac disease in South Africa [14]. While the maternal mortality rate was 3.73 % per 100,000 live births during the period 2005 to 2007, this rose to 5.64 in 2008 to 2010 and further still to 6 % during 2011 to 2013. After nonpregnancy-related infections, cardiac disease is the second most common cause of indirect maternal death, with complications of rheumatic heart disease (RHD) and CMO being the most significant contributors to cardiac deaths. The fact that more than half of those cases occurred postpartum is noteworthy; it implies that the maternal death rate in South Africa-already estimated to be 176/100,000 [1]-is probably grossly underestimated, as death could only be reported until 42 days postpartum.

Valvular heart disease (VHD) in pregnant women, whether due to congenital or acquired etiologies such as RHD, poses a particular challenge to clinicians and their patients. Significant valve disease increases the risks associated with pregnancy to both mother and fetus and requires a careful preconception risk assessment as well as specialised care during gestation to minimize maternal and fetal morbidity and mortality. Ideally, all women with VHD would undergo preconception evaluation, including advice on risk prediction and contraception, by a joint cardiac-obstetric team seeking advice from other specialties [15]. Of note, recent findings from the Global Rheumatic Heart Disease Registry (REMEDY) (see Section 2) indicated that of 1,825 women with RHD in child-bearing age, only 3.6% were using contraception [16].

PPCMO is a disease particularly common in African women. It develops in previously healthy women peripartum and carries a mortality rate of approximately 15%. In a recent publication we summarize the prevalence, clinical presentation, and natural history of PPCMO treated with standard HF medication [17]. Close collaboration with basic scientists from Hannover University, Germany, gave rise to unique translational research involving several animal models and human biological samples, providing breakthrough evidence [18] on the pathogenesis of human PPCMO. Treatment of mice (which serve as a model for human PPCMO) with bromocriptine, a dopamine antagonist inhibiting prolactin, prevented the development of the disease. Figure 1.1 summarizes the possible metabolic events leading to PPCMO.

Figure 1.1 Basic mechanisms underlying peripartum cardiomyopathy.

Subsequent to this foundational research, a South African clinical trial in women with newly diagnosed PPCMO [19] was conducted. The trial showed significant clinical improvement in those treated with bromocriptine, compared to patients receiving only standard care. These initially positive results have since been confirmed via collaborative research in a German cohort [20], and this ongoing work was recently summarized in an invited review on this new treatment modality [21]. In conclusion, joint obstetric-medical-cardiac clinics will be the optimal approach for women presenting with cardiac disease in the peripartum period in sub-Saharan Africa. Appropriate guidance in referral to secondary and tertiary care hospitals with dedicated cardiac disease in maternity clinics should be implemented and is currently being explored in South Africa [13].

1.1 Spectrum of maternal cardiac disease in South Africa

Sliwa K, Libhaber E, Elliott C, Momberg Z, Osman A, Zühlke L, Lachmann T, Nicholson L, Thienemann F, Roos-Hesselink J, Anthony J. Spectrum of cardiac disease in maternity in a low-resource cohort in South Africa. Heart 2014; 100(24):1967-74. [13]

1.1.1 Background

Data focusing on the spectrum and characteristics of cardiovascular disease (CVD) among women in LMIC are limited, especially among those who are pregnant [22,23]. In sub-Saharan Africa this significant clinical research gap is exacerbated by a shortage of physicians and health care resources.

1.1.2 Study aims

The aims of this study were to examine the spectrum and characteristics of CVD presenting in the prepartum and postpartum period, as well as describe maternal and fetal outcomes, in a representative cohort of African women in Cape Town, South Africa.

1.1.3 Methods

1.1.3.1 Patient enrollment

During the period 1 July 2010 to 30 June 2012, 225 consecutive pregnant women with suspected or previously diagnosed CVD were assessed at their first visit to the joint cardiac-obstetric clinic, having been directed there via a referral algorithm from primary care and secondary care facilities in Cape Town and from within the tertiary hospital (see Figure 1.2). All referred patients were seen by a senior cardiology and obstetric consultant, and physicians from other disciplines (i.e., radiology, endocrinology, and anesthetics) were consulted. Patients were then assessed throughout their pregnancy, while those presenting postpartum were seen once at this clinic and subsequently managed at the general cardiac clinic or a dedicated CMO clinic, at Groote Schuur Hospital, Cape Town, South Africa. Patient appointments were scheduled according to standard management, which could entail a waiting period of up to 3 months. Patients with a history of CVD and a normal clinical inspection, along with minimal echocardiography changes, were seen only on one occasion early and subsequently referred to second-level obstetric care. Most patients were referred from peripheral hospitals; therefore, records were not available to document maternal and fetal outcomes. Those patients who presented with signs, symptoms, or a World Health Organization (WHO) classification stage of II-IV underwent clinical visits at <28 weeks (second trimester), 28 to 37 weeks (third trimester), onset of labor until hospital discharge (peripartum period), and at 6 weeks and 6 months postpartum.

Figure 1.2 Referral algorithm to joint Cardiac Maternity Clinic, Groote Schuur Hospital.

1.1.4 Results

As detailed in Table 1.1, patients of African ancestry were significantly more likely to present with advanced disease (WHO II-IV) than those of other ethnic groups (p < 0.0001). Patients in the modified WHO class II-IV exhibited significantly higher heart rate (p < 0.0001) and gravidity (p = 0.0002) than those in WHO class I. Comorbidity, including HIV infection, was associated with more severe cardiac disease (p < 0.0001). Overall, 73 (32.4%) patients were classified as WHO class I; of these, 27 (37.0%) had been referred for other reasons such as history of palpitations or the need for pre-conception counseling, 26 (35.6%) presented with minor or operated CHD and no significant residual structural abnormality, 16 (21.9%) had RHD, and 4 (5.5%) had chronic hypertension with no end-organ damage. The remaining 152 (67.6) patients were placed in WHO class II-IV and required close follow-up; of these, 21 (13.8%) presented with PPCMO, 15 (9.9%) with prior CHD surgical correction, 15 (9.9%) with prior surgery for RHD, 11 (7.2%) with idiopathic dilated CMO, 9 (5.9%) with hypertension-related CMO, 8 (5.3%) with atrial septal defect, 6 (4.0%) with ventricular septal defect, 5 (3.3%) with ventricular arrhythmias, 4 (2.6%) with Takayasu's disease, 4 (2.6%) with Marfan's disease, 3 (2.0%) with coarctation, and 3 (2.0%) with constrictive pericarditis. Notably, IHD was absent in this cohort. Figure 1.3 displays the distribution of patients per disease group.

Table 1.1 Patients' demographic and clinical characteristics according WHO functional class.