Peripartum cardiomyopathy in patients with psychiatric disorders successfully treated with bromocriptine: Two case reports

Abstract

Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular systolic dysfunction and heart failure symptoms occur during the peripartum period. Inhibition of prolactin secretion by bromocriptine mediates beneficial effects on cardiac function in PPCM. Mental disorders are also associated with the onset of PPCM. Psychiatric medications for mental disorders would affect serotonin production and tryptophan and dopamine metabolism, and they are associated with PPCM. Conversely, bromocriptine affects psychiatric symptoms; therefore, the treatment of PPCM complicated by mental disorders using bromocriptine may be difficult. Herein, we report cases of two patients with PPCM and mental disorders successfully treated with bromocriptine therapy. The first case involved a 33-year-old woman with a history of atypical depression and anxiety disorder, who developed PPCM with a left ventricular ejection fraction (LVEF) of 19 %. The second case was that of a 42-year-old woman with a history of bipolar and panic disorders who developed PPCM with an LVEF of 18 %. Both patients were administered bromocriptine; however, psychiatric symptoms did not worsen and cardiac function improved. We also review the literature on the relationship between PPCM and mental disorders.

Learning objective

Mental disorders and psychiatric medications may be associated with the onset of peripartum cardiomyopathy (PPCM). Although bromocriptine has beneficial effects on PPCM, it has also been reported to increase the risk of worsening psychiatric symptoms; therefore, the efficacy and safety of bromocriptine in PPCM patients with mental disorders is controversial. Our cases showed that bromocriptine can be used safely without worsening psychiatric symptoms in PPCM with mental disorders.

Introduction

Peripartum cardiomyopathy (PPCM) is a rare disorder characterized by left ventricular (LV) systolic dysfunction and heart failure symptoms during the peripartum period. PPCM is defined as an idiopathic cardiomyopathy in which the patient shows a LV ejection fraction (LVEF) ≤45 % in the last month of pregnancy or up to five months postpartum [1]. Most patients with PPCM have a high potential for cardiac recovery [2]. While the etiology of PPCM is not entirely understood, one of the hypothesized mechanisms includes enhanced unbalanced oxidative stress levels and the subsequent generation of cleaved prolactin fragments [2,3]. Inhibition of prolactin secretion from the pituitary gland with bromocriptine (a dopamine D2 receptor agonist) mediates beneficial effects on cardiac function in preclinical models and is associated with cardiac recovery [4,5].

Mental disorders and cardiovascular diseases are common comorbidities [6]. Mental distress and depression are associated with physiological responses such as inflammation and oxidative stress and depressive symptoms may be associated with PPCM [7,8]. In addition, depressive symptoms are more prevalent in patients with PPCM who are more often treated with psychiatric medication during the preconception period than in controls [8]. Therefore, antidepressants or antipsychotics may affect the onset of PPCM. However, the relationship between PPCM and mental disorders has not yet been fully elucidated.

We report two cases of PPCM with mental disorders that were successfully treated with bromocriptine therapy and review the literature on the relationship between PPCM and mental disorders.

Case report

Case 1

A 33-year-old woman with a history of mental disorders presented with a one-month history of dyspnea. She was diagnosed with atypical depression and anxiety disorder at the age of 16 years and was treated with aripiprazole, duloxetine hydrochloride, flunitrazepam, triazolam, and etizolam. Her family history was unremarkable, and her LVEF had never been measured. She had a normal delivery without any complications in her previous pregnancy three years earlier. Two months prior to this presentation, she delivered a healthy second female infant vaginally without any obstetric complications. However, she developed progressive dyspnea one month after delivery, and her mental status deteriorated postpartum. She was initially diagnosed with postpartum depression; however, her symptoms did not improve with medication.

On arrival, her vital signs were as following: blood pressure, 140/100 mmHg; heart rate, 114 beats/min; and oxygen saturation, 97 % on room air. Physical examination revealed coarse crackles on auscultation, third heart sound, jugular vein distention, and leg edema. Electrocardiography revealed sinus tachycardia with ventricular bigeminy and poor R progression in leads V1–5 (Fig. 1A). Chest radiography revealed a high cardiothoracic ratio of 66 % and pulmonary edema (Fig. 1B). Laboratory data revealed elevated levels of troponin I (138.8 ng/L), B-type natriuretic peptide (BNP) (1567 pg/mL), and creatine kinase (465 U/L). Transthoracic echocardiography on admission showed severe LV dysfunction with an LVEF of 19 % and moderate functional mitral regurgitation. The LV diastolic dimension (LVDd) and LV systolic dimension (LVDs) were 69 mm and 63 mm, respectively. Only a small amount of pericardial effusion was observed without cardiac hypertrophy. The patient was diagnosed with acute decompensated heart failure due to PPCM and admitted.

Fig. 1.

Case 1 electrocardiogram on admission revealing sinus tachycardia with ventricular bigeminy and poor R progression in leads V1–5 (A) and chest radiograph on admission showing a large cardiothoracic ratio of 66 % and pulmonary edema (B). Case 2 electrocardiogram four weeks prior to admission (C) and at admission (D), and chest radiograph showing a cardiothoracic ratio of 56 % with pulmonary edema and pleural effusions bilaterally (E).

The clinical course is shown in Fig. 2. She was initially treated with diuretics (furosemide and spironolactone) and sacubitril/valsartan. Her symptoms subsided promptly and the BNP level gradually decreased. Bisoprolol was added on day 6 and the dose was gradually increased to 1.875 mg/day. Because of her low blood pressure, up-titration of bisoprolol and sacubitril/valsartan was difficult. However, a follow-up transthoracic echocardiogram on day 11 showed no significant improvement in the LVEF. Although she had schizophrenia and anxiety disorders, her mental condition was stable on admission. We consulted a psychiatrist to administer bromocriptine to treat PPCM. Bromocriptine administration was initiated on day 12 and continued at a dosage of 5 mg daily for two weeks, followed by 2.5 mg daily for six weeks. Even after the initiation of bromocriptine treatment, the patient's psychiatric symptoms did not worsen. The patient was discharged on day 28 without any complications. Dapagliflozin was added after discharge. At the follow-up four months after admission, her BNP level was 71 pg/mL and LVEF was 38 %.

Fig. 2.

Clinical course in case 1.

BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction.

Case 2

A 42-year-old pregnant woman at 37 weeks of gestation with a history of bipolar disorder, panic disorder, and recurrent cystitis presented with a four-month history of progressive palpitations and dyspnea. She was diagnosed with panic disorder at the age of 20 years, had been attending a psychiatrist and was being treated with quetiapine fumarate and lamotrigine. Her reproductive history included G12P2 (cesarean sections 2, still births 2, spontaneous abortions 4, artificial abortions 3). Prior to this presentation, she had two cesarean deliveries at the ages of 23 and 33 years; however, her previous pregnancies were uncomplicated and she had never been diagnosed with poor cardiac function or cardiac enlargement. The patient was referred to our department because of tachycardia.

Her vital signs were as following: blood pressure, 96/50 mmHg; heart rate, 150 beats/min; and oxygen saturation, 95 % on room air. Electrocardiography revealed sinus tachycardia with premature ventricular contractions (Fig. 1C). Transthoracic echocardiography showed severe LV dysfunction with an LVEF of 27 % and moderate functional mitral regurgitation. The LVDd and LVDs were 55 mm and 48 mm, respectively. BNP level was 95 pg/mL and thyroid function was normal. Because her cardiac function was poor, an emergency cesarean section was performed. She delivered a healthy female infant on catecholamine support. After delivery, her palpitations subsided and vital signs stabilized without catecholamines (blood pressure, 100/60 mmHg and heart rate, 90 beats/min). She was administered bisoprolol 0.625 mg, discharged 7 days after delivery, and was scheduled to undergo further cardiac evaluation.

However, she re-developed dyspnea and visited the hospital 3 weeks after discharge. Electrocardiography revealed sinus tachycardia with poor R progression in leads V1–3 (Fig. 1D). Chest radiography revealed a cardiothoracic ratio of 56 %, with bilateral pulmonary edema and pleural effusions (Fig. 1F). Laboratory data revealed an elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) level (11,792 pg/mL). Transthoracic echocardiography showed a worsened LVEF of 18 %. LVDd and LVDs were 59 mm and 54 mm, respectively. Based on the history, she was diagnosed with PPCM and admitted.

The clinical course of the patient is shown in Fig. 3. She was initially treated with diuretics (furosemide and spironolactone) and dobutamine. Although the initial response was good, her blood pressure was low and tachycardia sustained. Ivabradine was administered on day 5. However, the patient developed low output syndrome and required gradual increase of dobutamine. Her condition finally stabilized after the addition of pimobendan and bromocriptine. During hospitalization, the psychiatrist also observed the patient; however, her mental status was well-controlled under the original psychiatric treatments. Bromocriptine dose was decreased to 2.5 mg daily on day 38 and continued for six weeks. A repeat transthoracic echocardiogram on day 40 revealed poor LVEF of 18 %. Sodium-glucose cotransporter-2 inhibitor and angiotensin receptor neprilysin inhibitor were not used because of her history of recurrent cystitis and low blood pressure, respectively. The patient was discharged on day 42. At follow-up three months after discharge, her LVEF significantly improved to 60 % and her NT-proBNP level was normal (50 pg/mL).

Fig. 3.

Clinical course in case 2.

NT-proBNP, N-terminal pro B-type natriuretic peptide.

Discussion

Although both patients had a history of depression and were treated with psychiatric medications, they were treated with bromocriptine without worsening their mental status. To the best of our knowledge, these are the first reported cases of PPCM complicated by mental disorders in which bromocriptine was safely administered and was effective for heart failure symptoms.

Although the relationship between PPCM and mental disorders has not been fully elucidated, some studies have reported that mental disorders may be associated with the onset of PPCM [[7], [8], [9]]. Mental disorders, including depression, have been linked to impaired tryptophan metabolism, reduced levels of the anti-depressive neurotransmitter serotonin, and increased production of pro-inflammatory and mental disorder-promoting kynurenine. Patients with PPCM display elevated levels of serum kynurenine, reduced levels of serum serotonin, and elevated levels of plasma microRNA-30e, which has been found to promote severe depression [9]. In addition, the prevalence of major depressive disorders, posttraumatic stress disorders, and panic disorders was higher in patients with PPCM than in postpartum women without PPCM. Psychiatric treatment for mental disorders is another link between PPCM and mental disorders [8]. These medications affect serotonin production and tryptophan and dopamine metabolism, and they are associated with PPCM. Although bromocriptine, a dopamine D2 receptor agonist, has been reported to increase the risk of worsening psychosis, schizophrenia, and mania [10], our patients were able to use bromocriptine without worsening their psychiatric symptoms. A recent meta-analysis demonstrated that bromocriptine treatment for PPCM was associated with a significant improvement in LVEF without a significant reduction in all-cause mortality [5]. Therefore, physicians may consider bromocriptine in patients with PPCM, as our cases suggest that it can be used even in the presence of psychiatric complications.

In conclusion, we report two cases of PPCM with mental disorders that were successfully treated with bromocriptine. Because case studies of mental disorders complicated by PPCM are limited, future data on these case studies and treatment with bromocriptine are warranted.

Declaration of competing interest

The authors declare that there is no conflict of interest.