Peripartum Cardiomyopathy Reached Progressive Recovery Despites Poor Initial Ejection Fraction

Peripartum cardiomyopathy (PPCM) is a pregnancy-associated, idiopathic cardiomyopathy secondary to marked left ventricular dysfunction, which manifests between the last month of pregnancy and the first five months postpartum. While it is relatively rare, PPCM is associated with significant morbidity and can be fatal. Its diagnosis is often delayed because its symptoms closely resemble those within the normal spectrum of pregnancy and the postpartum period. When PPCM is misdiagnosed or is not diagnosed in time, the consequences for patients could be deadly. We present a rare case which was first misdiagnosed but had a continuous progressive recovery of LV systolic function (LVSF) within five years after it was finally diagnosed and treated. A 23 year-old female, P1A0, 8-weeks postpartum, was admitted to the emergency unit of our hospital because of dyspnea and fatigue, which developed three days after the delivery of her child. A week prior to delivery she was admitted to the hospital due to coughing, proteinuria and edema of her lower extremities. She was then diagnosed with severe preeclampsia. The patient, however, refused the administration of Magnesium-sulfate as a therapy because of personal reasons. 48 hours later, the patient was induced with oxytocin and she delivered a living female infant via vaginal delivery with no labor complications and was later discharged. Three days after delivery, the patient complained about having shortness of breath and fatigue. She went to a general practitioner who thought her symptoms were normal after a delivery. Two months later she went to an obstetric clinic for a check-up and was referred to the cardiology unit at our hospital. She stated that for the past two months, she had been experiencing symptoms such as exhaustion, palpitations, an inability to lay flat, decreased exercise tolerance and severe dyspnea. PPCM is a rare but potentially lethal disease that remains a challenge to diagnose, prognosticate, and treat. It is increasingly recognized that the condition is often diagnosed late which may indicate a poor prognosis. However, there are cases in which the initial severity of left ventricular dysfunction or dilatation is not necessarily predictive for long-term functional outcome.

General Physician at dr. H. Marsidi Judono Hospital, Belitung 2 Cardiologist at dr. H. Marsidi Judono Hospital, Belitung Introduction P eripartum cardiomyopathy (PPCM) is a pregnancy-associated, idiopathic cardio myopathy secondary to marked left ventricular dysfunction, which manifests between the last month of pregnancy and the first five months postpartum.While it is relatively rare, PPCM is associated with normal first and second heart sounds.No significant cardiac murmurs were detected.Vesicular breathing in both lungs with significant bilateral basal crackles was detected.Other physical findings include ascites and edema of the lower extremities.
Treatment of PPCM includes O2 therapy 3 l/min through nasal cannula, albumin correction with extra IV furosemide and oral potassium slow release, with maintenance furosemide dose of 20 mg/day, warfarin 2 mg/OD, Angiotensin Converting Enzyme Inhibitors (Captopril) 6.25 mg TDS, Digoxin 0.125 mg/BID, and Coenzyme Q 25 mg/BID.She was treated in the Intensive Care Unit for three days.During the treatment, the pulmonary edema regressed and the patient was discharged after one week from the hospital for out-patient treatment of heart failure.The patient was also advised against subsequent pregnancies.During the follow-up there was a continuous improvement of left ventricle dimensions and function.
Six months later, repeated 2D TTE showed normokinetic, normal-sized cardiac cavities, normalized diastolic and improved systolic function with LVEF of 53.1%.She was treated with Mineralocorticoid receptor Antagonists (Spironolactone) 12.5 mg OD, Angiotensin Converting Enzyme Inhibitors (Captopril) 6.25 mg TDS, B-blocker (Bisoprolol) 1.25 mg OD and Coenzyme Q 25mg/BID.Digoxin, warfarin and furosemide were all discontinued.The patient was then scheduled for monthly follow-ups to reassess the cardiac function.After five years of routine follow-ups, repeated echocardiography showed normal-sized cardiac cavities, fully recovered with LVEF of 71% with normal cardiac valves function as shown by Table 1 and Figure 1-4, the patient was then taken off any treatment regimes.significant morbidity and can be fatal.Its diagnosis is often delayed because its symptoms closely resemble those within the normal spectrum of pregnancy and the postpartum period.When PPCM is misdiagnosed or is not diagnosed in time, the consequences for patients could be deadly.We present a rare case which was first misdiagnosed but had a continuous progressive recovery of LV systolic function (LVSF) within five years after it was finally diagnosed and treated.

Case Illustration
A 23 year-old female, P1A0, 8-weeks postpartum, was admitted to the emergency unit of our hospital because of dyspnea and fatigue, which developed three days after the delivery of her child.A week prior to delivery she was admitted to the hospital due to coughing, proteinuria and edema of her lower extremities.She was then diagnosed with severe preeclampsia.The patient, however, refused the administration of Magnesium-sulfate as a therapy because of personal reasons.Forty eight hours later, the patient was induced with oxytocin and she delivered a living female infant via vaginal delivery with no labor complications and was later discharged.Three days after delivery, the patient complained about having shortness of breath and fatigue.She went to a general practitioner who thought her symptoms were normal after a delivery.Two months later she went to an obstetric clinic for a check-up and was referred to the cardiology unit at our hospital.She stated that for the past two months, she had been experiencing symptoms such as exhaustion, palpitations, an inability to lay flat, decreased exercise tolerance and severe dyspnea.The patient also complained of lower extremity edema.The patient denied ever having any heart problems before and was never diagnosed with any heart abnormalities nor had any family history of heart disease.The patient had regular antenatal care (ANC) with an OB-GYN, with data as follows: body weight=43 kg, height=152 cm, Body Mass Index (BMI)=18.6kg/m 2 , blood pressure (BP)=110/70, heart rate (HR)=82 beats/minute.The patient's body weight during 38 th week of the pregnancy was 58 kg, with a BMI of 25.1 kg/m 2 .
Initial vital signs were a BP of 118/78 mmHg, HR of 120 beats/minute, respiratory rate (RR) 28 rates/minute, temperature of 36.6 o C, and an oxygen saturation of 97%.Upon physical examination she had an apparent jugular venous distension.Cardiac auscultation showed

Discussion
Peripartum Cardiomyopathy (PPCM) is an uncommon disorder associated with pregnancy in which the heart dilates and weakens, leading to symptoms of heart failure.The incidence has been fully agreed upon but it estimated to be 0.025% to 0.03%, i.e. (1/4000) to (1/3000) births respectively. 1PPCM may be difficult to diagnose because symptoms of heart failure can mimic those of pregnancy.Affected women may recover normal heart function, stabilize on medicines, or progress to severe heart failure requiring mechanical support or heart transplantation.Even when the heart recovers, another pregnancy may be associated with a risk of recurrent heart failure. 2 This disorder carries a high mortality rate, since a misdiagnosis or a delayed diagnosis could consequently lead to death.[6][7][8][9][10] The underlying cause of PPCM remains unknown.A number of proposed mechanisms include: genetic, viral myocarditis, abnormal immune response, hemodynamic response to pregnancy, hormonal abnormalities, and malnutrition. 2However, none has emerged as a convincing single etiology.This may be because PPCM represents a heterogeneous group of disease process with a multifactorial etiology. 10,11lassic heart failure symptoms include dyspnea, dyspnea on exertion, lower extremity edema, and fatigue, and these are often presenting symptoms.Un-Unfortunately, these symptoms can be indistinguishable from symptoms common in late pregnancy and the postpartum period, making the diagnosis challenging and often missed, as shown by our case report. 12,13hysical exam findings in PPCM may reveal signs of volume overload such as pulmonary rales, increased  respiratory rate, tachycardia, pathologic S3 or S4 heart sounds, distended neck veins, and lower extremity edema. 2 While there are no specific electrocardiography (ECG) findings that are particularly helpful in diagnosing PPCM. 14As can be seen in this case, symptoms such as these can make diagnosis of PPCM difficult because some patients with preeclampsia may experience dyspnea, fatigue, and lower extremity edema. [15]he National Heart, Lung and Blood Institute (NHLBI) and the National Institutes of Health (NIH) in the U.S., published a diagnostic criteria for PPCM to direct more accurate research on epidemiology, pathophysiology, and outcomes.Current diagnosis of PPCM is based on the presence of four clinical criteria: (1) Development of heart failure (HF) in the last month of pregnancy or within five months after delivery; (2) Absence of an identifiable cause for HF; (3) Absence of recognizable heart disease prior to the last month of pregnancy; (4) Echocardiography (TTE) criteria of left ventricular systolic dysfunction (left ventricular ejection fraction, LVEF<45%), fractional shortening of<30%, or both. 4In this case, peripartum cardiomyopathy was diagnosed upon exclusion of other reasons for the heart failure, according to the diagnostic criteria of peripartum cardiomyopathy.
Treatment of PPCM is based on guidelines for standard HF treatment, including angiotensin converting enzyme (ACE) inhibitors, angiostensin receptor blockers (ARBs), beta-blockers, spironolactone, digoxin, diuretics, vasodilators and inotropes if needed.The mainstays of treatment for acute decompensated PPCM include diuretics and renin angiotensin inhibiting agents for patients that are hemodynamically stable.Once stabilized, betablockers, aldosterone-antagonists and additional therapies should be initiated and up-titrated as tolerated in the out-patient setting, particularly in the setting of persistent LV dysfunction. 10Although early improvement in EF (i.e.within the first 3-6 months) predicts a good outcome, some women will have slow, gradual improvement in EF over years. 12n important additional therapy that we considered for this patient is anticoagulation therapy.Considering that the patient is in a hypercoagulable state and the depressed systolic function caused by PPCM, she is at a higher risk for thrombus formation and thromboembolic events. 5,13,20Warfarin anticoagulation should be considered for prevention of morbidity or mortality from thromboembolism. 13  Since the patient had a poor initial LV ejection fraction (<25%), she was also given counseling against subsequent pregnancies in order to avoid risk of recurrence of heart failure. 13ecently, a growing body of evidence has pointed to abnormal prolactin metabolism as crucial in the etiology of PPCM, and prolactin inhibition is being explored as a novel treatment for PPCM. 12,14,16he basis for the use of Prolactin inhibition (e.g.Bromocriptine) in PPCM is based on the hypothesis that PPCM is originated by increased oxidative stress in the postpartum heart through the enhancement of the cathepsin D-mediated cleavage of prolactin into its 16-kDa subform.16-kDa prolactin has angiostatic and proapoptotic properties, which in turn, promotes vasoconstriction, inhibits endothelial cell proliferation and migration, and favors myocardial micro-vascular injury. 17However, a larger scale study is still needed to confirm the efficiency of prolactin inhibitors as a component of a treatment regime for PPCM.Other alternatives, such as pentoxifylline and intravenous immunoglobulin, are also being studied as other possible treatments for PPCM. 18,19he decision of when to discontinue medications depends not only on left-ventricular function and structure, but also on lingering symptoms, as proposed by the European Society of Cardiology (ESC) guideline. 10Digoxin had been given since patient was discharged but then switched to beta-blocker after 6-months of out-patient care and the patient is clinically stable and no longer shows any symptoms of congestion.Warfarin was also discontinued after the risk of thrombus formation is no longer prominent due to the gradual and consistent improvement of left ventricular function.B-blocker and ACE-inhibitor were continued as essential treatment of PPCM, along with mineralocorticoid receptor antagonist (MRA), with expectation of fully restoring the LV structure, as the patient still had LV structural problem (Table 1).
Prognosis of PPCM is positively related to the recovery of ventricular function. 3,20Effective treatment helps women recover cardiac function and reduces morbidity and mortality. 21Thus, it is important that general practitioners to be familiar with PPCM and therefore consider it when diagnosing dyspneic patients to ensure prompt medical treatment for a potentially lethal condition.
A fractional shortening less than 20% and a left ventricular diastolic dimension of 6 cm or greater at the time of diagnosis are associated with a more than three-fold higher risk for persistent cardiac dysfunction. 22he correlation between a depressed ejection fraction (EF) at the time of diagnosis and worse outcomes has been supported by several studies. 5,21,23,24However, other researchers have found no correlation between initial left-ventricular ejection fraction (LVEF) and survival, or recovery of LV function. 9,20,25,26In our case report, with an initial LVEF 14.2%, our patient managed to reach a better prognosis than expected.Thus, the initial severity of left ventricular dysfunction or dilatation is not necessarily predictive for long-term functional outcome. 20,27

Conclusion
PPCM is a rare but potentially lethal disease that remains a challenge to diagnose, prognosticate, and treat.It is increasingly recognized that the condition is often diagnosed late which may indicate a poor prognosis.However, there are cases in which the initial severity of left ventricular dysfunction or dilatation is not necessarily predictive for long-term functional outcome.

Figure 1 .
Figure 1.Improved LVEF and FS over course of treatment (in percentage) * LVEF: left-ventricular ejection fraction, FS: fractional shortening