Familial occurrence of peripartum cardiomyopathy: Genetic origin, unrecognized dilated cardiomyopathy or chance effect?

Abstract

There have been rare case series with familial clustering of peripartum cardiomyopathy (PPCMP). Due to the concomitant occurrence of PPCMP and idiopathic dilated cardiomyopathy, it has been suggested that genetics might play a role in the pathogenesis of PPCMP. Herein, we report four cases of PPCMP in the same family, who showed full recovery of left ventricular function within a short period.

<Learning objective: Physicians caring for peripartum cardiomyopathy (PPCMP) patients should be aware that PPCMP may have a genetic background and guidelines for diagnosis of genetic cardiomyopathy should be considered.>

Introduction

Peripartum cardiomyopathy (PPCMP) is defined by the Heart Failure Association of the European Society of Cardiology as ‘an idiopathic cardiomyopathy presenting with heart failure secondary to left ventricular (LV) systolic dysfunction towards the end of pregnancy or in the months following delivery, where no determinable cause of heart failure is found. The LV may not be dilated but the ejection fraction (EF) is nearly always reduced below 45%’ [1]. The exact pathophysiology of PPCMP is unclear, and many potential causes have been proposed including genetics [2]. The frequency of mutations associated with familial dilated cardiomyopathy genes in patients with PPCMP suggests that there may be an overlap in the clinical spectrum of these two conditions 3, 4. A genetic basis for PPCMP is controversial, while some case reports noted familial inclination 5, 6, 7, as well as other large case series did not report family history as a PPCMP risk factor [8]. Herein, we present the case of two sisters from common parents with the diagnosis of PPCMP, who have fully recovered within 6 months. PPCMP was further diagnosed in two maternal cousins after a detailed family screening.

Case report

Two Caucasian sisters (both from common parents) with a history of PPCMP were admitted to our cardiology outpatient clinics due to routine control visits. Both sisters were primigravida, and experienced singleton pregnancy without any obstetrical complications. The first was diagnosed with PPCMP just after 3 months of the first labor at the age of 27 years. She had undergone normal spontaneous vaginal delivery at the 38th week of gestation. She had no systemic/cardiovascular disease, smoking history, medication, or PPCMP-associated risk factors. Her electrocardiography (ECG) showed sinus rhythm (72 bpm) with QRS duration of 120 ms. Her transthoracic echocardiography revealed a LVEF of 30%, LV end-diastolic diameter (LVEDD) of 60 mm and global LV hypokinesia. Although she had New York Heart Association (NYHA) class III symptoms at the time of diagnosis, she rapidly recovered in a 6-month period with medical therapy including ramipril, carvedilol, and digoxin. At 3rd year follow-up visit, she was asymptomatic with a LVEF of 58%, LVEDD of 52 mm, and on no medication. In the second sister, PPCMP was diagnosed at the 5th month of puerperium (first birth) at age 29 years. She had undergone normal spontaneous vaginal delivery at 37th week of gestation. She also had no systemic/cardiovascular disease, smoking history, medication or PPCMP-associated risk factors including obesity. Her ECG showed sinus rhythm (64 bpm) with QRS duration of 100 ms. Her transthoracic echocardiography revealed a LVEF of 40%, LVEDD of 56 mm, and global LV hypokinesia. At the time of diagnosis, she had NYHA class III symptoms and again recovered in an 8-month period with medical therapy including ramipril and carvedilol. At 2nd year follow-up visit, she was asymptomatic with a LVEF of 64%, LVEDD of 50 mm, and on no medical therapy. Because of such a clustering of PPCMP in this family, we screened the available 15 family members including their first-degree (parents, male sibling) and second-degree relatives with echocardiography. There was no pathological finding in the 15 family members except 4 with a history of myocardial infarction. Also 3rd and 4th generation family history assessment revealed that 2 cousins (maternal) had PPCMP history similarly (diagnosed after birth and recovered in a 6-month period) (Fig. 1). However, the patients and family members refused to participate in a genetic testing, so, we could not gain any data regarding the common genetic mutations among them.

Fig. 1.

Schematic of family pedigree of the patients affected by peripartum cardiomyopathy.

Discussion

PPCMP is a rarely seen idiopathic cardiomyopathy that affects women toward the end of pregnancy or in the months following delivery with unclear pathophysiological basis. Although approximately 50% of the patients recover, the clinical course is unpredictable and some patients develop refractory heart failure and persistent LV systolic dysfunction 1, 9. Although the exact etiology of PPCMP is unclear, different mechanisms are probable including genetics [2]. In small sample size studies, it has been shown for the first time that there might be a familial and genetic predisposition for PPCMP, activated during mid to late pregnancy 3, 4. However, a genetic basis for PPCMP has not been systematically studied. Also there may be a fact that some forms of familial PPCMP could be an unknown familial dilated cardiomyopathy unmasked by pregnancy. Herein, we presented the case of 2 sisters in the same family who developed PPCMP without any PPCMP-associated and other risk factors. Also a similar clinical scenario has been found in their 3rd generation family members. So, clustering of such a clinical finding cannot be explained by chance and also recovery of the disease in all those family members made us thought to exclude overlapping of PPCMP with familial dilated cardiomyopathy. In accordance with the suggestions of Morales et al. [4], we remind that physicians caring for PPCMP patients should be aware that PPCMP may have a genetic background and guidelines for diagnosis of genetic cardiomyopathy should be considered. Particularly, such an evaluation may include clinical screening (family history, medical history, ECG, echocardiography) of the patient and her/his first-degree relatives. Also, genetic counseling, including reproductive risk counseling about PPCMP, is recommended, in addition to consideration of genetic testing.

Conflict of interest

None declared.

Funding

None.