Peripartum cardiomyopathy: a rare cause of acute heart failure
- 1 Department of Internal Medicine, Kantonsspital Graubunden, Chur, Switzerland
- 2 Department of Internal Medicine, Cardiology, Kantonsspital Graubunden, Chur, Switzerland
- Correspondence to Professor Thomas Fehr; Thomas.fehr@ksgr.ch
Abstract
A woman in her early 30s presented herself with acute dyspnoea and elevated D-dimers 5 weeks after delivery of her second child. Echocardiographic findings showed signs of acute left ventricular failure, and an MRI confirmed a non-ischaemic dilated left heart failure compatible with peripartum cardiomyopathy. The antihormonal therapy with bromocriptine during 6 weeks and an intensive heart failure therapy led to an amelioration of the heart function within 3 years, but full recovery was not yet observed.
Background
Peripartum cardiomyopathy (PPCM) is a non-ischaemic dilated heart disease presenting with left ventricular systolic dysfunction that occurs within 1 month before and 5 months after delivery.1 There is a wide range of incidence varying between 1 and 100 births in Nigeria, 1 and 5700–10 000 in Europe and 1 and 20 000 births in Japan. This may be related to ethnicity, but likely also due to underreporting in certain areas, as Mielniczuk et al suspected when observing a duplication of PPCM cases within 12 years in the USA.2–4 Published data are scarce particularly in Europe with only two studies from Denmark and Sweden reporting the incidence of PPCM. This suggests a lack of awareness and may affect adequate management and optimal outcome, leaving aside the high mortality of up to 50% if the condition is diagnosed.5
Case presentation
A woman in her early 30s was referred to the emergency department by her general practitioner with suspicion of pulmonary embolism, because she presented herself with acute dyspnoea and elevated D-dimers 5 weeks after giving birth to her second child. Family history revealed a sister with pulmonary embolism around the age of 20, but according to the patient's information, further evaluation did not show evidence for a hereditary thrombophilia.
On arrival at the emergency department the vital parameters showed an afebrile, slightly hypertensive woman with tachycardia and tachypnoea (pulse 136/min, respiratory rate 40 /min, blood pressure 149/90 mm Hg). The clinical examination showed discrete bibasal rales.
Investigations
Further investigations showed increased D-dimers (0.83 mg/L), only slightly elevated inflammation serum markers with a C reactive protein of 7.5 mg/L, a slight leucocytosis and cardiac volume overload with NT-pro-BNP at >4400 pg/mL. High sensitive troponin T was slightly elevated with 18 ng/L without further increase, and the creatin kinase value was normal. The ECG showed no pathological alterations apart from sinus tachycardia. With suspicion of pulmonary embolism a CT scan was performed. No pulmonary embolism was detected, but contrary to expectation signs of severe left heart failure such as prominent vascular markings and ground glass opacities in the lung, an enlarged left ventricle with a diameter of 6.8 cm and a convex shift of the septum interventriculare towards the right ventricle, and washback of contrast agent into the vena cava inferior were observed. The transthoracic echocardiogram showed a dilated left ventricle with diffuse hypokinesia, reduced systolic ejection fraction of 25% and a severe functional mitral valve regurgitation. Furthermore, an increased pulmonary pressure, a transtricuspid pressure gradient of 40 mm Hg, and a dilated and functionally impaired right ventricle was evident.
To further evaluate the still unclear aetiology of this unusual heart failure in this young woman, a cardiac MR tomography was performed (figure 1A–D) indicating a non-ischaemic dilated cardiomyopathy compatible with PPCM. To estimate the risk of arrhythmia a 24-hour-ECG was recorded showing a moderate number of ventricular extrasystoles, no blockages or pauses, but three non-continuous ventricular tachycardia runs.
(A–D) Findings in MR tomography; dilatation of all four chambers particularly of left ventricle. Severe restricted right and left ventricle function (left ventricle ejection fraction 33%). Significant functional mitral regurgitation. Unrestricted perfusion at rest (disclaim of stress perfusion testing), no late gadolinium enhancement. Legend yellow letters: A, anterior; P, posterior; L, left; R, right; H, head; F, feet.
Treatment
An intensive heart failure therapy with valsartan/sacubitril, metoprolol, spironolactone and torasemide was established. Furthermore an ablactating therapy with 5 mg bromocriptine for 6 weeks was introduced.
To prevent the potential risk of sudden cardiac death due to malignant arrhythmias, a ‘life vest’ west was customised and subcutaneous anticoagulation with a low molecular heparin was installed. After an in-hospital stay of 18 days the patient was discharged.
Outcome and follow-up
There was an intense medical follow-up from initial presentation up to now. Through its course the clinical symptoms recorded with NYHA (New York Heart Association) functional classification ameliorated from initially grade IV to I within 1 year. Correspondingly the levels of NT-pro-BNP decreased over time to normal values. Repeated transthoracic echocardiographs revealed a gradual improvement of the left ventricular ejection fraction, a decreasing end-diastolic volume, and also a decrease of the severity of mitral valve regurgitation (table 1). Furthermore, the established heart failure therapy could be gradually reduced without clinical relapse (figure 2). However, full recovery from heart failure has not occurred with respect to the echocardiographic findings, thus further follow-up is required.
Development of echocardiographic markers, the time specification refers to the initial presentation
| Date | LVEDVI mL/m2 | LVEDD mm | LVEF% | LAVI mL/m2 | RVEF | Mitral regurgitation |
| Initial presentation | 92 | 69 | 25 | 44 | Impaired | Severe |
| 1 month | 102 | 67 | 30 | 50 | Impaired | Severe |
| 2 months | 102 | 70 | 30 | 51 | Impaired | Severe |
| 5 months | 60 | 65 | 40 | 22 | Impaired | Moderate |
| 9 months | 67 | 63 | 50 | 34 | Preserved | Moderate |
| 13 months | 73 | 62 | 50 | 21 | Preserved | Moderate |
| 18 months | 80 | 62 | 50 | 33 | Preserved | Mild-moderate |
| 2 years | 70 | 60 | 50 | 28 | Preserved | Mild-moderate |
| 3 years | 79 | 62 | 55 | 35 | Preserved | Mild-moderate |
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LAVI, Left Atrial Volume Index; LVEDD, left ventricular end-diastolic diameter; LVEDVI, Left Ventricular End-Diastolic Volume Index; LVEF, left ventricular ejection fraction; RVEF, right ventricular ejection fraction.
(Created by TCEV): therapy regimen in milligrams, the time specification refers to the initial presentation.
Discussion
PPCM is a rare and especially in Europe not broadly reported cause of pregnancy-related acute heart failure, but it represents one of the three main aetiologies of pregnancy-associated heart failure as are pre-eclampsia and amniotic fluid embolism (table 2). The incidence of PPCM broadly differs between countries implying racial differences, but also incomplete registration/reporting.2 3 6 Because of the lack of clinical studies, the specific treatment strategy depends on expert opinions and preclinical study results and is therefore challenging for clinicians.7 8
Causes of pregnancy-related acute heart failure
| Aetiology of heart failure | Incidence/births or pregnancies | Pathophysiology | Echocardiography |
| PPCM1–3 14 | 1: 300–20 000 births | Endothelial cell apoptosis, disruption of capillary structures, myocyte dysfunction and apoptosis, oxidative stress | Dilated left ventricle with diffuse hypokinesia and systolic dysfunction |
| Amniotic fluid embolism15 | 1: 8000–800 000 births |
Trespassing of amniotic fluid into maternal circulation |
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| Spontaneous coronary artery dissection16 | 1: 64 000 pregnancies |
Oestrogen/progesterone induced structural changes cause weakness of tunica media |
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| Pre-eclampsia and eclampsia,14,17 | 1: 22 and 1:71 pregnancies |
Disruption of maternal endothelial function, systemic inflammatory response, increased systemic vascular resistance, increased filling pressure left atrium, diastolic dysfunction | Diastolic dysfunction of left ventricle |
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PPCM, peripartum cardiomyopathy.
The following risk factors for PPCM are mentioned in the literature: age above 30 years, black race, pre-eclampsia, hypertension, multiple pregnancies and multigestation.9 10 Our patient, a nordic blonde type with no medical history of hypertension and an unproblematic preceding pregnancy fulfilled only the risk factor of being over 30 years and secundigravida/secundipara.
Regarding laboratory testing, numerous blood markers like miRNA 146a (microRNA), 16 kDa Prolactine or sFLt-1 (soluble fms-like tyrosine kinase-1) are discussed as diagnostic tools for PPCM, but none of them was proven to be of clinical value so far.10 Elevated markers of inflammation, especially C reactive protein, have also been discussed as targets to optimise therapy by adding immunomodulatory substances such as pentoxifylline.11 NT-pro-BNP has been defined as a sensitive but unspecific marker in PPCM.12 In our case NT-pro-BNP was used as guidance for heart failure therapy during the follow-up.
Concerning imaging, echocardiography is used as the main tool to diagnose PPCM showing typical configurations of dilated cardiomyopathy with left ventricular dilatation, heart failure with reduced ejection fraction, right ventricular enlargement, mitral and tricuspid regurgitation, and pulmonary hypertension.9 Cardiac MRI is not an established diagnostic tool to identify the non-ischaemic nature of heart insufficiency of PPCM in clinical routine; however, we think that it can add valuable information, in particular for exclusion of ischaemic heart disease and myocarditis.
In the past years, treatment strategies—however still experimental—have focused on adding bromocriptine to the commonly applied heart failure therapy used for both ischaemic and other non-ischaemic forms of heart failure including PPCM:
Animal models suggest a potential role of prolactin secretion in the pathogenesis of PPCM in postpartal mice. The cleavage product of prolactine, 16 kDa prolactine is suspected to induce upregulation of microRNA 146a which is responsible, together with other proteins such as sFLT-1, for a myocardial capillary network impairment. A proof-of-concept study with 20 patients by Sliwa et al showed better recovery of left ventricular ejection fraction 6 months post partum in women suffering from PPCM when receiving bromocriptine compared with a control group only receiving conventional heart insufficiency therapy.13 Hilfiker-Kleiner et al showed that the addition of bromocriptine to standard heart failure therapy is associated with higher full left ventricular recovery compared with other cohorts, and that 8 weeks vs 1 week of bromocriptine treatment duration has no added benefit.8
In conclusion, PPCM is a form of cardiomyopathy leading to acute heart failure with globally differing incidences and remarkably few cases in Europe. Promotion of awareness might increase diagnosis frequency and therefore ameliorate treatment and outcome. Using echocardiography and cardiac MRI it can be clearly distinguished from ischaemic heart disease, myocarditis and other forms of cardiomyopathy. Apart from classical treatment of heart failure with reduced ejection fraction, the addition of bromocriptine is discussed to improve recovery, which however may need several years to occur.
Learning points
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Peripartum cardiomyopathy is a possibly under-reported form of dilated cardiomyopathy in Europe leading to acute heart failure.
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Echocardiography and cardiac MRI are good investigation techniques to distinguish between ischaemic heart disease, myocarditis and other forms of cardiomyopathy.
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The addition of bromocriptine to classical treatment of heart failure with reduced ejection fraction might improve recovery.
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Full recovery might take several years.
Ethics statements
Patient consent for publication
Footnotes
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Contributors TF: idea for the article, attending physician during inpatient care, theoretical supervision, text corrections. SS: specialist assessment during inpatient care, clinical follow-up and echocardiographic recording, text corrections. TCEV: attending physician during inpatient care, theoretical research, article writing, patient correspondance.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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